WO2011130880A1

WO2011130880A1 - Detection method of fetal chromosomal aneuploidy

Info

Publication number: WO2011130880A1
Application number: PCT/CN2010/000568
Authority: WO
Inventors: 李英睿; 李松岗; 杨广霞; 蒋馥蔓; 张秀清; 玄兆伶; 陈芳; 林静蓉
Original assignee: 深圳华大基因科技有限公司
Priority date: 2010-04-23
Filing date: 2010-04-23
Publication date: 2011-10-27
Also published as: CN102753703A; CN102753703B

Abstract

The invention provides a detection method of fetal chromosomal aneuploidy, wherein the prenatal diagnosis of the fetal chromosomal aneuploidy is carried out using the values of amounts of nucleic acid molecules in the first kind of chromosome windows and the values of amounts of nucleic acid molecules in the corresponding windows of the second kind of chromosome, and the function relation between them.

Description

胎儿染色体非整倍性的检测方法技术领域 Method for detecting fetal chromosome aneuploidy

本发明涉及医疗检测领域，具体地涉及胎儿染色体非整倍体性的检测方法，通过第一类染色体窗口组合的核酸分子量的值与其在第二类染色体上的对应窗口的核酸分子的量，及其间的函数关系来检测产前胎儿染色体非整倍性。 The present invention relates to the field of medical detection, and in particular to a method for detecting aneuploidy of a fetal chromosome, the value of the molecular weight of the nucleic acid combined by the first type of chromosome window and the amount of the nucleic acid molecule of the corresponding window on the second type of chromosome, and A functional relationship between them to detect prenatal fetal chromosome aneuploidy.

背景技术 Background technique

胎儿非整倍体染色体是指染色体或染色体的某一区域的量的异常。这个异常的量可以是异常的高，如胎儿 21号三体，即是比正常的二倍体胎儿多了一条 21号染色体；或者异常低，如特纳综合征患者就是缺了一条或部分 X染色体。 A fetal aneuploid chromosome refers to an abnormality in the amount of a chromosome or a certain region of a chromosome. The amount of this abnormality can be abnormally high, such as the fetal No. 21 trisomy, which is a chromosome 21 more than the normal diploid fetus; or abnormally low, such as Turner syndrome patients are missing one or part of X chromosome.

传统中使用如绒毛膜绒毛取样（CVS)或羊膜穿刺术的方法，获得从胎儿处分离得到细胞，可以使用这些细胞进行常规产前诊断。虽然用这种方法来诊断胎儿非整倍体的准确性较高，然而，这些方法是侵入性的，对母亲和胎儿具有明显的危险性。（Tabor A， et al. Randomised control led trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986, 1: 1287 -1293). Conventional methods such as chorionic villus sampling (CVS) or amniocentesis are used to obtain cells isolated from the fetus, which can be used for routine prenatal diagnosis. Although the accuracy of this method for diagnosing fetal aneuploidy is high, however, these methods are invasive and have significant risks to the mother and fetus. (Tabor A, et al. Randomised control led trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986, 1: 1287 -1293).

在母体血浆和血清中发现有非细胞的循环胎儿 DNA, 这为非侵入性产前诊断提供了无限可能性。 Rossa W.LChiu等人在 PNAS 2008, 105： 20458-20463, 杂志上的文章 "利用大规模高通量测序的方法来进行非整倍体染色体的无创产前诊断" 详^介绍了利用这种方法来进行无创胎儿非整倍体的诊断，并且指出通过测序的手段可以最大程度的获得外周血里面核酸分子的信息，特别是在提取的母体样本里所含的来源于胎儿染色体的核酸分子相对于背景母体核酸分子的量来说是相当少的情况下（Rossa W.K.Chiu ，et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternalplasma. PNAS, 2008, 105: 20458- 20463)。所述的方法为：先提取出孕妇外周血血浆中的核酸分子，再经过大规模高通量第二代测序仪进行测序，得到 DNA片断的序列信息及序列落在哪一条染色体上的位置信息。 Dennis Lo 等人基于这一基本信息，然后统计来源于有医学意义的染色体（如 21 号， 18号， 13号染色体)上的核酸分子的量及来源于作为背景染色体的核酸分子的量，通过这两个量，可以得到一个参数，然后将这一参数与由正常样本所建得的一个或多个域值做比照，进而发现在有医学意义染色体上有异常的样本的这个参数与多种域值存在着较大的差异 (Denni s Lo, e t a l. Presence of feta l DNA in ma terna l p lasma and serum. Lancet 1997, 350: 485-487)。由此，这种方法可用来检测胎儿的非整倍体。 Non-cellular circulating fetal DNA is found in maternal plasma and serum, providing unlimited possibilities for non-invasive prenatal diagnosis. Rossa W. LChiu et al., PNAS 2008, 105: 20458-20463, article "Using large-scale, high-throughput sequencing for non-invasive prenatal diagnosis of aneuploid chromosomes" The method was used to diagnose the aneuploidy of non-invasive fetuses, and pointed out that the information of nucleic acid molecules in peripheral blood can be obtained by means of sequencing, especially the nucleic acid molecules derived from fetal chromosomes contained in the extracted maternal samples. In the case where the amount of background parent nucleic acid molecules is relatively small (Rossa WK Chiu, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. PNAS, 2008, 105: 20458-20463). The method comprises the following steps: first extracting nucleic acid molecules in the plasma of the peripheral blood of the pregnant woman, and then performing sequencing by a large-scale high-throughput second-generation sequencer to obtain sequence information of the DNA fragment and position information on which chromosome the sequence falls on. . Based on this basic information, Dennis Lo et al. then counted the amount of nucleic acid molecules derived from medically meaningful chromosomes (such as chromosomes 21, 18, and 13) and the amount of nucleic acid molecules derived from the background chromosome. These two quantities, you can get a parameter, and then this parameter and one or more built by the normal sample The domain values were compared, and it was found that this parameter with abnormal samples on medically meaningful chromosomes differed greatly from various domain values (Denni s Lo, eta l. Presence of feta l DNA in ma terna lp lasma and Serum. Lancet 1997, 350: 485-487). Thus, this method can be used to detect aneuploidy in the fetus.

然而，这一方法存在着自身的局限性。首先它对于每一个样本的检测都依赖于通过 N个（N大于 20个）标准阴性对照样本的序列分布数量所建立的正常对照值，即上面所提到的域值。基于这些正常对照值，才可能分析出所检测样本的情况。也就是说为了做出正确判断，所测得的各样本的值之间的相互依赖性比较明显，因为要通过比较样本与样本之间的值的差别才有可能做出正确的判断。 However, this method has its own limitations. First, its detection for each sample relies on the normal control value established by the number of sequence distributions of N (N greater than 20) standard negative control samples, i.e., the domain values mentioned above. Based on these normal control values, it is possible to analyze the condition of the sample being tested. That is to say, in order to make a correct judgment, the interdependence between the measured values of the samples is obvious, because it is possible to make a correct judgment by comparing the difference between the values of the samples and the samples.

因此，由于样本间需要相互比较的关系，这种方法所要求的各批次样本所采用的实验条件较为严格，若实验条件差距较大，将很难得到较为可信的正常对照值或是样本值。这个实验条件包括前期的样本制备，所用试剂的批次及种类，测序 GC偏向，体系温度等，也就是说，各种实验条件的变化都应控制在相当小的范围内，否则会导致各阴性对照样本间的值的方差增大，或者各阴性对照样本的值的相互之间的较大偏差，有些阴性样本的值甚至可能脱离正常值范围内，成为离群值。同理，这一方法也依赖于待检测样本的值的准确性，为获得准确值，制备该样本及所用的试剂及测序条件，包括测序 GC偏向，体系温度等，都应该与实施阴性对照样本的尽量保持一致。只有这样，才能较为理想并可信的统计出异常样本在所研究的染色体上的分布数量的异常，并且保证其值为可信的。 Therefore, due to the need to compare the samples, the experimental conditions for each batch of samples required by this method are strict. If the experimental conditions are large, it will be difficult to obtain a more reliable normal control value or sample. value. The experimental conditions include pre-sample preparation, batch and type of reagents used, sequencing GC bias, system temperature, etc. In other words, changes in various experimental conditions should be controlled within a relatively small range, otherwise each negative will result. The variance of the values between the control samples is increased, or the values of the respective negative control samples are greatly deviated from each other, and the values of some of the negative samples may even fall out of the normal value range and become outliers. Similarly, this method also depends on the accuracy of the value of the sample to be tested. In order to obtain accurate values, the preparation of the sample and the reagents used and sequencing conditions, including sequencing GC bias, system temperature, etc., should be performed with negative control samples. Try to be consistent. Only in this way can it be more ideal and credible to count the anomalies of the distribution of abnormal samples on the chromosomes studied, and to ensure that their values are credible.

但是，要保证实验及测序条件下各微观体系条件的一致性不是太简单的事情，因为实验过程中会有其它干扰因素，所以往往会导致实验数据不太理想，或者各样本之间数据差异较大，一方面，一旦数据缺乏一致性，其检测结果的可信度也随之降低，而产生假阳性或假阴性的结果；另一方面，如若数据由于实脸条件的变化因素所致差距较大，更会使之成为离群值而被抛弃不用。众所周知，测序成本目前还是较高的，这样把离群值抛弃不用理所当然会造成相当的浪费。 However, it is not too simple to ensure the consistency of the micro-system conditions under the experimental and sequencing conditions. Because there are other interference factors in the experiment, the experimental data is often not ideal, or the data difference between the samples is different. Large, on the one hand, once the data lacks consistency, the credibility of the test results is also reduced, resulting in false positive or false negative results; on the other hand, if the data is due to differences in real face conditions Large, it will make it an outlier and will be abandoned. As we all know, the cost of sequencing is still relatively high, so it is quite wasteful to abandon the outliers.

正如前面所说的目前比较先进的通过测序方法来进行胎儿染色体非整倍性的诊断方法中，对样本制备或测序等的实验条件要求比较严格，因为在本质上来说，它依赖于样本与样本之间的比较。正常样本与异常样本在所要研究的值上是有显著差异的，然而一旦由于样本之间实验条件的不一样所引入的差异大于异常样本与正常样本间的差异的时候，就会出现判断错误的情况，降低检脸的可信度。发明内容 As mentioned above, in the current advanced diagnostic method for fetal chromosome aneuploidy by sequencing, the experimental conditions for sample preparation or sequencing are more stringent, because in essence, it depends on the sample and the sample. The comparison between. There is a significant difference between the normal sample and the abnormal sample in the value to be studied. However, once the difference introduced by the experimental conditions between the samples is greater than the difference between the abnormal sample and the normal sample, a judgment error occurs. In case of situation, reduce the credibility of the face. Summary of the invention

本发明所要解决的技术问题： Technical problems to be solved by the present invention:

针对这一情况，发明人进行了多方面深入的研究，终于研发出一种样本自身比照的方法，即不再通过样本之间的对比来做出决定，而是通过比较来源于样本本身的相关值来做出判断。这样消除了对实验条件的依赖性，这样提供了可用于胎儿染色体非整倍性的无创检测新方法，其消除了对实脸条件的依赖性。 In response to this situation, the inventor conducted in-depth research in various aspects, and finally developed a method of self-comparison of samples, that is, no longer make decisions through comparison between samples, but by comparing the correlations from the samples themselves. Value to make a judgment. This eliminates dependence on experimental conditions, which provides a novel approach to non-invasive detection of fetal chromosome aneuploidy that eliminates dependence on real face conditions.

本发明所采用的技术手段 Technical means adopted by the present invention

具体而言，发明人基于测序数据，发现染色体间具有相互对应的核酸量的相关性，根据这种相关性提供了下迷方法，依据本发明的数据采集和处理方法检测胎儿染色体的非整倍性。 Specifically, based on the sequencing data, the inventors found that there is a correlation between the amounts of nucleic acids corresponding to each other between chromosomes, and according to this correlation, a method for detecting aneuploidy of fetal chromosomes according to the data acquisition and processing method of the present invention is provided. Sex.

具体地，发明人的方法包括步骤： Specifically, the inventor's method includes the steps of:

1.检测个体染色体非整倍性的方法，包括： 1. A method of detecting an individual aneuploidy of an individual, comprising:

对全基因组进行测序，将作为研究对象的待研究染色体定义为笫一类染色体，全基因组中其余染色体定义为笫二类染色体；依据第二类染色体片段与笫一类染色体片段的行为值的相关性，在全基因组上建立数学模型； The whole genome is sequenced, and the chromosome to be studied as the research object is defined as a chromosome of the same type, and the remaining chromosomes in the whole genome are defined as the second type chromosome; the correlation between the second type of chromosome fragment and the behavioral value of the first-class chromosome fragment Sex, build mathematical models on the whole genome;

对待测个体进行全基因组测序，进而得到待检测个体本身的的第一类染色体和第二类染色体的行为值，如果在一定的置信水平上的行为值不满足前述数学模型，则可以确定待测个体的染色体是非整倍性的。 The whole genome is sequenced, and then the behavior values of the first type chromosome and the second type chromosome of the individual to be detected are obtained. If the behavior value at a certain confidence level does not satisfy the aforementioned mathematical model, the test can be determined. The chromosome of an individual is aneuploidy.

2.项目 1的方法，所迷方法包括： 2. The method of Project 1, the methods include:

将全部染色体分别切割成相互重叠或者不重叠的片段，每个片段定义为一个窗口；通过测序统计来自无染色体缺陷的正常个体样本的染色体各窗口的核酸分子的量，将该量定义为行为值； The entire chromosome is cut into overlapping or non-overlapping segments, each segment is defined as a window; the amount of nucleic acid molecules in each window of the chromosome from a normal individual sample without chromosomal defects is counted by sequencing, and the amount is defined as a behavior value. ;

依据行为值，通过数学统计方法寻找第二类染色体上的与笫一类染色体有强相关性的窗口或其组合，建立函数关系式； According to the behavior value, a mathematical correlation method is used to find a window or a combination thereof which has strong correlation with the first-class chromosome on the second chromosome, and a functional relationship is established;

依据函数关系式和待检测样本中第二类染色体各窗口中真实的核酸分子的量，在一定置信水平下，得到待研究第一类染色体的行为值的模拟值置信区间； According to the functional relationship and the amount of real nucleic acid molecules in each window of the second type of chromosome in the sample to be detected, at a certain confidence level, a confidence interval of the simulated value of the behavior value of the first type of chromosome to be studied is obtained;

通过判断检测样本的第一类染色体的行为值与其模拟值置信区间的关系，判定笫一类染色体是否异常。 3.项目 1的方法，包括建模步骤（1) - (4)和检测步骤（5) - (8) , 具体如下: By judging the relationship between the behavior value of the first type of chromosome of the test sample and the confidence interval of the simulated value, it is determined whether the chromosome of the first type is abnormal. 3. The method of item 1, including modeling steps (1) - (4) and detection steps (5) - (8), as follows:

(1)选择来自无染色体缺陷的正常个体的全基因組进行测序，将作为研究对象的待研究染色体定义为第一类染色体，其余染色体定义为笫二类染色体； (1) selecting the whole genome of a normal individual without chromosomal defects for sequencing, and defining the chromosome to be studied as the first chromosome, and the remaining chromosomes as the second chromosome;

(2)将（1)中的所有染色体切割成相互重叠或者不重叠的片段，每个片段定义为一个窗口； (2) cutting all the chromosomes in (1) into overlapping or non-overlapping segments, each segment being defined as a window;

(3)统计在多个不同实验奈件下多个样本染色体各窗口的核酸分子的量，定义为行为值；(3) counting the amount of nucleic acid molecules in each window of a plurality of sample chromosomes under a plurality of different experimental conditions, defined as a behavior value;

(4)依据（3)中的行为值，通过数学统计法寻找（1)中的第二类染色体上的与（1)中的第一类染色体有强相关性的窗口或其组合，建立第一类染色体的窗口和所找到的有强相关性窗口或其组合的函数关系式 A, 由此完成建模步骤； (4) According to the behavior value in (3), find a window or a combination thereof on the second type of chromosome in (1) that has a strong correlation with the first type of chromosome in (1) by mathematical statistics. a functional relationship between a window of a type of chromosome and a found strong correlation window or a combination thereof, thereby completing the modeling step;

(5)对待检测个体的样本的全基因组的所有染色体进行测序，其中作为研究对象的待研究染色体同样被定义为第一类染色体，其是与（1)中的第一类染色体对应相同编号的染色体，其余染色体作为第二类染色体； (5) sequencing all chromosomes of the whole genome of the sample to be tested, wherein the chromosome to be studied as the research object is also defined as the first type of chromosome, which is the same number as the first type of chromosome in (1). Chromosome, the remaining chromosomes as the second type of chromosome;

(6)按照（2)中同样的窗口规格切割（5)中待检测样本的染色体，统计第一类染色体和第二类染色体的行为值； (6) cutting the chromosome of the sample to be detected in (5) according to the same window specification in (2), and counting the behavior values of the first type chromosome and the second type chromosome;

(7)将（6)中的第二类染色体各窗口的行为值引入到关系式 A中，设定置信水平，计算得到第一类染色体行为值的理论区间； (7) Introducing the behavior value of each window of the second type of chromosome in (6) into relation A, setting a confidence level, and calculating a theoretical interval of the first type of chromosome behavior value;

(8)如果（6)中统计的笫一类染色体的行为值不在（7)中的行为值的理论区间范围内，则认为待研究的笫一类染色体异常。 (8) If the behavioral value of the scorpion chromosome in (6) is not within the theoretical interval of the behavioral value in (7), then the chromosomal abnormality of the scorpion to be studied is considered.

4. 项目 3的方法，其中将步骤（1) - (4)的关系式在不同待测样本的检测中重复使用，不需要每次样本检测时都重复测定，通过进行步骤（5) - (8)测定染色体的非整倍性。 4. The method of item 3, wherein the relationship of steps (1) - (4) is repeated in the detection of different samples to be tested, and the measurement is not repeated every time the sample is detected, by performing step (5) - ( 8) Determination of aneuploidy of chromosomes.

上述的 "置信区间" 包括各窗口的置信区间和整条染色体的置信区间。 The above "confidence interval" includes the confidence interval of each window and the confidence interval of the entire chromosome.

上述的 "不同实猃条件" 主要包括测序 GC含量不一致，试剂条件不一样，实验制备方法有差别等情况。 The above "different actual conditions" mainly include inconsistent sequencing GC content, different reagent conditions, and different experimental preparation methods.

本发明提供了一种方法，该方法使用来源于孕妇的单一样本，并根据其染色体数据，判断胎儿染色体是否为非整倍性。由此方法，发明最终获得了一组笫一类染色体窗口组合，和在第二类染色体中与其呈现强相关性的模拟窗口組合，以及在一定置信水平下校正后的函数关系式。通过这些窗口和函数关系式，可以判断具体样本的第一类染色体是否为非整倍性。 The present invention provides a method of using a single sample derived from a pregnant woman and determining whether the fetal chromosome is aneuploid based on its chromosomal data. In this way, the invention ultimately obtains a set of chromosome-like window combinations, and a combination of analog windows that are strongly correlated with the second type of chromosome, and a functional relationship that is corrected at a certain confidence level. Through these window and function relationships, it can be determined whether the first type of chromosome of a particular sample is aneuploid.

本发明的建模过程一旦确定，即不再需要大量的正常样本进行建模，只需将每次待检测样本的自身的第二类染色体的行为值代入在建模过程确定的关系式 A中，即可判断第一类染色体是否正常. Once the modeling process of the present invention is determined, that is, no longer a large number of normal samples are required for modeling, it is only necessary to treat each time. The behavior value of the second type of chromosome of the test sample is substituted into the relation A determined in the modeling process, and it can be judged whether the first type chromosome is normal.

本发明的技术效果 Technical effect of the present invention

本发明的方法可以用于非整倍体产前诊断。本发明的方法摆脱了原方法对于严格控制实验条件的较强依赖，可适用于修正由于实猃条件变动所导致的离群值样本，从而减小浪费. 本发明的方法可以通过样本自身对照，而不依赖于其它样本的值，给判断胎儿染色体是否为非整倍性提供重要依据；本发明的方法同时也避免侵入性方法而导致的风险。本发明方法基于测序不但可以用来诊断染色体是否为非整倍性，更能够用于未知实驗条件下或实验条件控制不好的情况下所获得的孤立样本的染色体非整倍性诊断，而且可与背景技术中的方法结合一起使用，互为验证，从而进一步提高检验的准确度，从大的影响上来看，可以有效地控制包括 21号三体在内的非整倍体染色体胎儿的出生率。另外本发明的方法建立了一种数据处理方法，灵活多变，可模拟 21号染色体，即找出与 21号染色体的最优行为值一致内对照窗口组合，也可以推广到所有感兴趣的染色体，如 18号染色体， 13号染色体等第一类染色体, 甚至一些感兴趣的染色体片断，从而增加该方法的应用范围。 The method of the invention can be used for prenatal diagnosis of aneuploidy. The method of the invention is free from the strong dependence of the original method for strictly controlling the experimental conditions, and can be applied to correct outlier samples due to changes in the actual conditions, thereby reducing waste. The method of the present invention can be controlled by the sample itself. Without relying on the values of other samples, an important basis for determining whether a fetal chromosome is aneuploidy is provided; the method of the present invention also avoids the risk of invasive methods. The method of the invention is based on sequencing not only for diagnosing whether a chromosome is aneuploidy, but also for chromosomal aneuploidy diagnosis of an isolated sample obtained under unknown experimental conditions or under poor control of experimental conditions, and Used in combination with the methods in the background art, mutual verification, thereby further improving the accuracy of the test, and from a large influence, can effectively control the birth rate of the aneuploid chromosome fetus including the No. 21 trisomy. In addition, the method of the invention establishes a data processing method, which is flexible and can simulate chromosome 21, that is, finds the inner control window combination consistent with the optimal behavior value of chromosome 21, and can also be extended to all interested chromosomes. For example, chromosome 18, chromosome 13 and other first chromosomes, and even some chromosome fragments of interest, thereby increasing the scope of application of the method.

附图简述 BRIEF DESCRIPTION OF THE DRAWINGS

图 1 : 用来演示本发明在全基因组（除待研究的第一类染色体）中寻找并确定与第一类染色体各窗口组合有极强相关性的模拟窗口組合的方法的流程图，记为方法 100。 Figure 1 is a flow chart showing the method of the present invention for finding and determining a combination of simulation windows that are strongly correlated with each window combination of the first type of chromosome in the whole genome (except for the first type of chromosome to be studied), Method 100.

图 2: 用来演示本发明诊断孕妇所孕胎儿是否为染色体非整倍性的方法的流程图，记为方法 200。 Figure 2: A flow chart showing the method of the present invention for diagnosing whether a fetus in a pregnant woman is chromosomal aneuploidy, as method 200.

图 3: 显示窗口间线性相关性的散点图。通过对表 3所统计的来自于基因组窗口标号为（chr4，642) 窗口区域上的核酸分子的量值（89个行为值 x i ) ，与来自基因组窗口标号为（chr21 , 180) 窗口区域上的核酸分子的量值（89个行为值 y i )，利用统计学上的相关性分析，计算两窗口间的相关系数，及关系函数，图上显示的 R²为 0. 9724，说明两窗口相关性很好。 Figure 3: A scatter plot showing the linear correlation between windows. The magnitude of the nucleic acid molecule (89 behavioral values xi) from the window region labeled (chr4, 642) from the genomic window as counted in Table 3, and the window region from the genome window labeled (chr21, 180) The magnitude of the nucleic acid molecule (89 behavioral values yi), using a statistical correlation analysis, calculates the correlation coefficient between the two windows, and the relationship function, the R ² shown on the graph is 0. 9724, indicating the correlation between the two windows well.

图 4: 显示窗口间线性相关关系的散点图。通过对表 3 所统计的来自基因組窗口标号为（chrl， 256) 窗口区域上的核酸分子的量值（ 89个行为值 xi ) ，与来自基因组窗口标号为（chr21，180) 窗口区域上的核酸分子的量值（89个行为值 yi ) , 利用统计学上的相关性分析，计算两窗口间的相关关系系数 R，由于相关系数 R²仅仅只有 0. 6 , 由图可以看出两窗口线性关系不好。 Figure 4: A scatter plot showing the linear correlation between windows. The number of nucleic acid molecules (89 behavioral values xi) on the window region labeled (chrl, 256) from the genomic window as summarized in Table 3, and the nucleic acid on the window region labeled (chr21, 180) from the genome window The magnitude of the molecule (89 behavioral values yi ), using statistical Correlation analysis, calculate the correlation coefficient R between the two windows, because the correlation coefficient R ² is only 0.6. From the figure, it can be seen that the linear relationship between the two windows is not good.

图 5 : 显示窗口间线性相关性的散点图。通过对表 7 所统计的来自基因组窗口标号为（chr8，710) 窗口区域上的核酸分子的量值（89个行为值 x i ) ，与来自基因组窗口标号为（chr l 8, 259) 窗口区域上的核酸分子的量值（53个行为值 yi )，利用统计学上的相关性分析，计算两窗口间的相关系数，及关系函数。图上显示的 R²为 0. 9816，说明两窗口相关性很好。 Figure 5: A scatter plot showing the linear correlation between windows. The amount of nucleic acid molecules (89 behavioral values xi ) on the window region labeled (chr8, 710) from the genomic window, as summarized in Table 7, and the window region from the genome window labeled (chr l 8, 259) The magnitude of the nucleic acid molecule (53 behavioral values yi), using statistical correlation analysis, calculates the correlation coefficient between the two windows, and the relationship function. The R ² shown on the graph is 0. 9816, indicating that the two windows are well correlated.

图 6: 显示窗口间线性相关关系的散点图。通过对表 7 所统计的来自基因组窗口标号为（chrlj) 窗口区域上的核酸分子的量值（53个行为值 x i ) , 与来自基因組窗口标号为（chr l 8，259) 窗口区域上的核酸分子的量值（ 53个行为值 yi ) , 利用统计学上的相关性分析，计算两窗口间的相关关系系数 R，由于相关系数 R²仅仅只有 0. 0043 , 由图可以看出两窗口线性关系不好。 Figure 6: A scatter plot showing the linear correlation between windows. The amount of nucleic acid molecules (53 behavioral values xi ) on the window region labeled (chrlj) from the genomic window as summarized in Table 7 and the nucleic acid on the window region labeled (chr l 8,259) from the genome window The magnitude of the numerator (53 behavioral values yi), using the statistical correlation analysis, calculates the correlation coefficient R between the two windows. Since the correlation coefficient R ² is only 0. 0043, the two windows are linear. bad relationship.

图 7: 显示正常样本与异常样本的真实值与各自的模拟值置信区间的关系的图。具体显示 4个来自孕妇外周血核酸样本，.样本 1与样本 2的真实值在各自的模拟值置信区间之外，样本为 21号染色体非整倍性；而样本 5与样本 6的真实值在各自的模拟值置信区间之内，样本正常。 Figure 7: A graph showing the relationship between the true values of normal and abnormal samples and their respective confidence intervals for analog values. Specifically, four nucleic acid samples from pregnant women's peripheral blood were displayed. The true values of samples 1 and 2 were outside the respective confidence interval of the simulated value, and the sample was aneuploidy of chromosome 21; and the true values of samples 5 and 6 were Within the confidence interval of each analog value, the sample is normal.

图 8: 显示正常样本与异常样本的真实值与各自的模拟值置信区间的关系的图，显示 4个来自孕妇外周血核酸样本，样本 3与样本 4的真实值在各自的模拟值置信区间之外，样本为 21号染色体非整倍性；而样本 7与样本 8的真实值在各自的模拟值置信区间之内，样本正常。 Figure 8: A graph showing the relationship between the true values of normal and abnormal samples and their respective simulated value confidence intervals, showing four nucleic acid samples from pregnant women's peripheral blood. The true values of samples 3 and 4 are in their respective simulated confidence intervals. In addition, the sample is aneuploidy on chromosome 21; and the true values of samples 7 and 8 are within the respective confidence intervals of the simulated values, and the samples are normal.

图 9: 显示正常样本与异常样本的真实值与各自的模拟值置信区间的关系的图。具体显示 4个来自孕妇外周血核酸样本，样本 1，样本 2与样本 3的真实值在各自的模拟值置信区间之内，样本为 18号染色体正常；而样本 4的真实值在各自的模拟值置信区间之外，为 18号染色体非整倍性。 Figure 9: A graph showing the relationship between the true values of normal and abnormal samples and their respective confidence intervals for analog values. Specifically, four nucleic acid samples from pregnant women's peripheral blood were sampled. Sample 1, the true values of samples 2 and 3 were within the respective confidence intervals of the simulated values, and the samples were normal for chromosome 18; and the true values of sample 4 were at their respective simulated values. Beyond the confidence interval, chromosome 18 is aneuploidy.

图 10: 显示正常样本与异常样本的真实值与各自的模拟值置信区间的关系的图. 显示 2个来自孕妇外周血核酸样本，样本 5与样本 6的真实值在各自的模拟值置信区间之外,样本为 18号染色体非整倍性。 Figure 10: A graph showing the relationship between the true values of normal and abnormal samples and their respective simulated value confidence intervals. Two nucleic acid samples from pregnant women's peripheral blood are shown. The true values of samples 5 and 6 are in their respective simulated confidence intervals. In addition, the sample is chromosome 18 aneuploidy.

定义为了更清楚地阐述本发明，在本发明中使用的术语定义如下。 Definition In order to explain the present invention more clearly, the terms used in the present invention are defined as follows.

"非整倍体染色体" 或 "染色体非整倍性" 是指某条染色体相对于正常的二倍体基因组上的这条染色体存在着整条或部分缺失或冗余。通常情况是，有额外的一奈染色体或其中的一条染色体丢失。染色体非整倍性的最常见情况是三体，即有一条额外的染色体。例如， 21号染色体三体就是在细胞中发现第三条 21号染色体的一种染色体异常. "Aneuploid chromosome" or "chromosomal aneuploidy" means that a chromosome has a whole or partial deletion or redundancy relative to the chromosome on the normal diploid genome. Usually, there is an extra one chromosome or one of the chromosomes is missing. The most common case of chromosomal aneuploidy is the trisomy, which has an additional chromosome. For example, chromosome 13 is a chromosomal abnormality found in the cell for the third chromosome 21.

"生物样本"是指来源于对象（如孕妇）的包含感兴趣的核酸分子的样本，如血浆，血清或其它含有核酸分子的生物样本， "Biological sample" means a sample containing a nucleic acid molecule of interest, such as plasma, serum or other biological sample containing nucleic acid molecules, derived from a subject, such as a pregnant woman.

"正常样本"是指没有出现任何染色体有非整倍体异常的孕妇外周血样本。 "Normal sample" refers to a peripheral blood sample of a pregnant woman who does not have any aneuploidy abnormality on any chromosome.

"核酸分子"是指提取的生物样本里所含有的脱氧核糖核苷酸分子，在这里是指生物样本里含有的，来源于人的 3亿基因组碱基对的核酸分子。 "Nucleic acid molecule" refers to a deoxyribonucleotide molecule contained in an extracted biological sample, and herein refers to a nucleic acid molecule contained in a biological sample derived from human's 300 million genomic base pairs.

"核酸片段分子" 是指生物样本经过制备等步骤后，能够通过测序手段获得其序列信息及其在基因组上的位置信息并可以代表与其相对应的核酸分子的片段核酸分子。 The "nucleic acid fragment molecule" refers to a fragment nucleic acid molecule which can obtain its sequence information and its position information on the genome by sequencing means after the preparation and the like, and can represent the nucleic acid molecule corresponding thereto.

"Unique核酸分子，，是指测序后信息分析表明该核酸分子在人类基因组上有且仅有一个分布的位置。 "Unique nucleic acid molecule means that post-sequencing information analysis indicates that the nucleic acid molecule has a position on the human genome and has only one distribution.

"窗口" 是指可以将染色体或染色体区域根据人为定义的单位核酸序列长度分割成有重叠区域或没有重叠区域的片段，而每个窗口都对应着这条染色体或染色体区域上唯一的一段，位置信息唯一。 "Window" means that a chromosome or a chromosomal region can be segmented into a segment having overlapping regions or no overlapping regions according to an artificially defined unit nucleic acid sequence length, and each window corresponds to a unique segment of the chromosome or chromosome region, the position Information is unique.

"核酸分子的量",也称行为值，依据核酸片段分子基于测序定位到各染色体具***置后，统计而得的定位在这个区域的核酸片段分子^条数或者是能够反映有多少核酸分子分布于这个区域的值，比如说将统计所得的可以定位在这个区域的核酸片段分子的条数，或者来自这个区域核酸分子的条数除以所有被统计或部分被统计的核酸分子的条数所获得的一个比值或者核酸片段分子长度的累积值等，总之，对于一次实猃样本来说，在某一窗口区域里，只要这个值能够反映核酸分子在这个窗口的分布的量的情况，这个值就可以称为行为值或者来源于该窗口的核酸分子的量。 The "amount of nucleic acid molecule", also called the behavior value, is based on the position of the nucleic acid fragment molecule based on sequencing to the specific position of each chromosome, and the number of nucleic acid fragments located in this region can be statistically reflected or how many nucleic acid molecules can be distributed. The value in this region, for example, the number of nucleic acid fragment molecules that can be located in this region, or the number of nucleic acid molecules from this region divided by the number of all statistically or partially counted nucleic acid molecules. A ratio obtained or a cumulative value of the molecular length of the nucleic acid fragment, etc. In short, for a real sample, in a window region, as long as the value reflects the amount of distribution of the nucleic acid molecule in the window, this value This can be referred to as the behavioral value or the amount of nucleic acid molecule derived from the window.

"来源于某一窗口的核酸分子的量，，（窗口的行为值）是指依据核酸片段分子基于测序定位到各染色体具***置后，统计所得的可以定位在这个区域的核酸片段分子的条数或者是能够反映到底有多少核酸分子分布于这个区域的值，比如说将统计所得的可以定位在这个区域的核酸片段分子的条数，或者来自同一区域核酸分子的条数除以所有被统计或部分被统计的核酸分子的条数所获得的一个比值或者核酸片段分子长度的累积量等，总之，对于一次实验样本来说，只要这个值能够反映核酸分子在这个窗口的分布的量的情况，这个值就可以称为行为值或者来源于该窗口的核酸分子的量。 "The amount of nucleic acid molecule derived from a certain window, (the behavioral value of the window) refers to the number of nucleic acid fragment molecules that can be located in this region after the nucleic acid fragment molecule is located at the specific position of each chromosome based on sequencing. Or a value that reflects how many nucleic acid molecules are distributed in this region, such as the number of nucleic acid fragment molecules that can be located in this region, or the number of nucleic acid molecules from the same region divided by all statistics. Or a fraction of the number of nucleic acid molecules counted or the cumulative amount of the length of the nucleic acid fragment, etc. In summary, for an experimental sample, as long as this value reflects the amount of distribution of the nucleic acid molecule in this window This value can be called the behavior value or the amount of nucleic acid molecules derived from the window.

"行为值一致 "是指两行为值，其中的一个行为值发生变化，另一行为值同时发生可以用函数关系式近似表达的变化。 "Consistent behavior values" refers to two behavioral values, one of which changes in behavior, and the other behavioral value that occurs simultaneously with a functional relationship.

"真实值"指来源于第一类染色体的窗口的核酸分子的量。 "Real value" refers to the amount of nucleic acid molecule derived from the window of the first type of chromosome.

"第一类染色体" 是指有临床研究价值的全部或部分核酸序列，或者说在医学上，经常用这些染色体的不平衡来检测某些不正常的症状。例如 21 号染色体序列， 18 号染色体序列， 1 3号染色体序列， X染色体序列或 Y染色体序列等。 "First type of chromosome" refers to all or part of a nucleic acid sequence of clinical research value, or medically, the imbalance of these chromosomes is commonly used to detect certain abnormal symptoms. For example, chromosome 21 sequence, chromosome 18 sequence, chromosome 1 sequence, X chromosome sequence or Y chromosome sequence.

"第二类染色体" 是指基因组上除去第一类染色体的其他染色体，本发明中指具体实施中除去待研究第一类染色体的其他染色体。 "Second type chromosome" refers to other chromosomes on the genome from which the first type of chromosome is removed, and in the present invention refers to other chromosomes in which the first type of chromosome to be studied is removed in a specific embodiment.

"第一类染色体窗口组合" 是指由若干个有重叠或无重叠窗口所构成的窗口組合，这一窗口组合可以覆盖整个或部分笫一类染色体。 "The first type of chromosome window combination" refers to a combination of windows consisting of several overlapping or non-overlapping windows that can cover all or part of a class of chromosomes.

"与第一类染色体的窗口有极强相关性的模拟窗口（模拟窗口组合) "是指在研究基因组中，存在于除当前研究的第一类染色体外其它染色体上的特定模拟窗口，该特定模拟窗口与当前研究下的第一类染色体窗口存在着强相关性，其表现为：对于其中的每一个正常生物样本来说，总是存在着这样一种关系，即在这个样本中来源于第一类染色体窗口的核酸分子的量若发生变化，则来源于与第一类染色体窗口有极相关性的模拟窗口 (模拟窗口组合）的核酸分子量也发生相应的变化，而且这种一个量发生变化另一量也发生变化的相关关系可以通过相关函数表达式近似表达出来。模拟窗口（模拟窗口组合）的选定见方法 100。 "A simulation window (simulation window combination) that has a strong correlation with the window of the first type of chromosome" refers to a specific simulation window present on the chromosome other than the first type of chromosome currently studied in the study genome, the specific There is a strong correlation between the simulation window and the first type of chromosome window under the current study. It is expressed as follows: For each of the normal biological samples, there is always a relationship that is derived from this sample. If the amount of a nucleic acid molecule of a type of chromosome window changes, the molecular weight of the nucleic acid derived from the analog window (simulation window combination) which is highly correlated with the first type of chromosome window also changes correspondingly, and this amount changes. Correlation in which another quantity also changes can be approximated by a correlation function expression. See Method 100 for the selection of the simulation window (simulation window combination).

"待研究染色体行为值的置信区间 "是指通过来源于第一类染色体的窗口组合的核酸分子的量和与其对应的函数关系式算得的在一定置信水平下，该笫一类染色体（染色体窗口）的置信区间。若两窗口间表达关系式为 y=ax+b，则此时统计所得的来源于与第一类染色体窗口有极相关关系模拟窗口的核酸分子的量为 X,根据函数关系式可以算得模拟值 y,再根据统计学知识可以获得相应的置信区间。 The "confidence interval of the chromosomal behavior value to be studied" refers to the chromosomal window at a certain confidence level calculated by the amount of the nucleic acid molecule combined with the window derived from the first type of chromosome and its corresponding functional relationship. Confidence interval. If the expression relationship between the two windows is y=ax+b, then the amount of the nucleic acid molecule derived from the analog window having a correlation with the first type of chromosome window is X, and the analog value can be calculated according to the functional relationship. y, according to statistical knowledge, you can get the corresponding confidence interval.

"不平衡" 在这里是指通过比较真实值不在根据模拟窗口和函数关系式计算得到的置信区间内，认为此时检测的生物样本在所研究的第一类染色体或第一类染色体区域存在着不平衡， "Unbalanced" here means that the biological sample detected at this time is stored in the first type of chromosome or the first type of chromosome region studied by comparing the true value in the confidence interval calculated according to the simulation window and the function relation. In an imbalance,

本发明中的 "Chr" 是 "染色体" 的缩写，例如 "Chr 18" 代表笫 18号染色体。染色体双螺旋链包括一正链，一反链，正反链是互补的，即一条链碱基序列确定，另外一条互补链的碱基序列也确定。因此，其中的每一个位置碱基成对出现，且碱基对是互补的： A与 T互补， C与 G互补。在人类的染色体上，以正链的碱基位置为基准，任何一个位置都是指一对碱基对，既包含了正链上的碱基，同时也包含了反链上的互补碱基，在本发明中的定位位置，都是以 bp为单位的，即 base pa i r缩写（碱基对）。例如 chr21: 150 - 450kbp , 代表 21号染色体上处于 150000碱基对到 450000碱基对的窗口。若要区分方向的话，正链是指 5， -3 ，的那条链，反链是与其互补的那条链，而方向应该是 3，-5，。我们通常都是以正链碱基位置为基准，这里处于 chr21: 150bp的碱基是指，从正链，方向 5， -3 ，，第 1个碱基开始数，处于 150号的那个碱基对；从负链，方向 3， -5，，第 1 个碱基开始数，处于 150号的那个碱基对. "Chr" in the present invention is an abbreviation for "chromosome", for example, "Chr 18" represents 笫 chromosome 18. The dye double helix chain includes a positive strand, a reverse strand, and the forward and reverse strands are complementary, that is, one strand base sequence is determined, and the base sequence of the other complementary strand is also determined. Thus, each of these positions appears in pairs in pairs, and the base pairs are complementary: A is complementary to T and C is complementary to G. On a human chromosome, based on the base position of a positive strand, any position refers to a pair of base pairs, including both bases in the positive strand and complementary bases in the reverse strand. The positioning positions in the present invention are all in units of bp, that is, abbreviations of base pa ir (base pairs). For example, chr21: 150 - 450kbp represents a window of 150000 bases to 450000 base pairs on chromosome 21. To distinguish the direction, the positive chain refers to the chain of 5, -3, the reverse chain is the one complementary to it, and the direction should be 3, -5. We usually use the base position of the positive strand as the reference. Here, the base of chr21: 150 bp refers to the base from the positive strand, the direction 5, -3, the first base, and the base at 150. Right; from the negative chain, direction 3, -5, the number of the first base starts, the base pair at 150.

在本发明的实施方案中，提供一种寻找与第一类染色体窗口组合有极相关性的模拟窗口或窗口组合的方法。所述的 "寻找模拟窗口或窗口组合" 的方法的本质是通过创新性的各窗口间行为值的相关性分析找出与第一类染色体窗口或窗口组合有极强相关性的模拟窗口或模拟窗口組合，例如，所选的可以称为是第一类染色体窗口组合的模拟窗口组合里的窗口与其所对应的笫一类染色体窗口之间的行为值相关系数接近于 1 , 且能够获得一个普遍的函数关系式，用来表述两窗口行为值之间的相关关系。 In an embodiment of the invention, a method of finding a combination of analog windows or windows that is highly correlated with a first type of chromosome window combination is provided. The essence of the method of "looking for a simulated window or window combination" is to find a simulation window or simulation that has a strong correlation with the first type of chromosome window or window combination through an innovative correlation analysis of behavior values between windows. A window combination, for example, a behavioral value correlation coefficient between a window in a simulated window combination that can be referred to as a first type of chromosome window combination and a corresponding class of chromosome window is close to 1, and can be obtained universally The function relation is used to express the correlation between the behavior values of the two windows.

当第一类染色体的窗口只找到一个第二类染色体窗口与之有强相关性时，函数关系式为二者之间的一元函数关系式，如果找到了多个强相关性窗口时，函数关系式为拟合优化后的多元函数关系式。 When the window of the first type of chromosome only finds a strong correlation between the second type of chromosome window, the function relation is a unary function relationship between the two. If multiple strong correlation windows are found, the function relationship The formula is to fit the optimized multivariate function relation.

本发明的实施方案，提供了下述的诊断方法，通过判断来源于同一样本的笫一类染色体窗口组合的核酸分子的量是否在置信区间内来诊断非整倍体染色体，置信区间由来源于前述寻找确定的模拟窗口组合的行为值及各相应窗口间的相关关系共同决定。 According to an embodiment of the present invention, there is provided a diagnostic method for diagnosing aneuploid chromosomes by judging whether the amount of a nucleic acid molecule combined with a steroid-like chromosome window derived from the same sample is within a confidence interval, and the confidence interval is derived from The behavior value of the above-mentioned search for the determined simulation window combination and the correlation between the respective windows are determined together.

实施例 Example

以下的实施例仅用来解释本发明，而不是用来限制本发明的保护范围，任何与本发明的方法等价的变体都包括在本发明当中. The following examples are merely illustrative of the invention and are not intended to limit the scope of the invention, and any variant equivalent to the method of the invention is included in the invention.

实施例一 - ^v ^ υ ο 步骤 1:获得建模所需测序数据 Embodiment 1 - ^v ^ υ ο Step 1: Obtain the sequencing data required for modeling

选择 89个正常样本，对这些样本在有差异的实验条件下制备并测序。 89 normal samples were selected and prepared and sequenced under differential experimental conditions.

简要地说，先制备 DNA文库，再将核酸片段分子连接到 So lexa测序接头上，然后分离纯化核酸片段长度在 150到 300碱基对的核酸分子。连上接头的核酸分子可以与 f low ce l l表面互补接头杂交，在一定条件下，核酸分子成簇生长，然后在 I l lumina Genome Ana lyzer上通过 36轮测序循环，即相当于每个核酸分子测得了 35个碱基对的核酸片段。接下来测得的序列信息经过一个 P i pel ine过程，最终可以获得以 NCBI里的人类基因组序列为参照序列的 ELAND比对结果。 Briefly, a DNA library is prepared, and the nucleic acid fragment molecule is ligated to a So lexa sequencing linker, and then the nucleic acid molecule having a purified nucleic acid fragment of 150 to 300 base pairs in length is isolated. The nucleic acid molecule linked to the adaptor can hybridize with the surface complement of the f low ce ll. Under certain conditions, the nucleic acid molecules grow in clusters and then pass through 36 cycles of sequencing on the Illumina Genome Analyzer, which is equivalent to each nucleic acid molecule. A 35 base pair nucleic acid fragment was detected. The sequence information measured is subjected to a P i pel ine process, and finally the ELAND alignment result using the human genome sequence in NCBI as a reference sequence can be obtained.

在研究中，为避免一些重复序列的干扰，发明人将那些处于基因组串联重复及转座重复的核酸分子片段剔除, 只统计那些可以定位到基因組唯一位置的核酸片段分子。这样说来，在所有测出来的核酸分子中，大概只有四分之一到三分之一的核酸分子是可以定位到基因组唯一位置。此时这些被统计的核酸分子称为 Unique核酸分子，而这个统计所得的 Unique核酸分子的量依然代表分布在基因组特定区域的核酸分子的量 In the study, in order to avoid interference from some repetitive sequences, the inventors knocked out fragments of nucleic acid molecules that are in tandem repeats and transpositions of the genome, and only counted those nucleic acid fragment molecules that can be located at unique positions in the genome. In this way, only about one-quarter to one-third of all nucleic acid molecules detected can be located in a unique location in the genome. At this time, these statistical nucleic acid molecules are called Unique nucleic acid molecules, and the amount of this unique nucleic acid molecule still represents the amount of nucleic acid molecules distributed in specific regions of the genome.

该步骤对应于图 1的 110， 120步。 This step corresponds to steps 110, 120 of Fig. 1.

步骤 2:建立 21号染色体检测模型 Step 2: Establish a chromosome 21 detection model

根据图 1的流程图进行，数学模型建立的过程由计算机程序优化完成。计算机程序通过不同的参数选择，完成相关性窗口的寻找，寻找最优参数，建立第一类染色体窗口与第二类染色体窗口的函数关系式。 According to the flow chart of Fig. 1, the process of establishing the mathematical model is optimized by computer program. The computer program completes the correlation window search through different parameter selections, finds the optimal parameters, and establishes a functional relationship between the first type of chromosome window and the second type of chromosome window.

在 130步中，基于测序，可以通过生物信息分析的手段将所测得的每条核酸片段分子定位到基因组的确切位置上. In step 130, based on sequencing, each of the measured nucleic acid fragment molecules can be mapped to the exact position of the genome by means of bioinformatics analysis.

在 140步中，对每个样本进行切割窗口。将构成基因组的每条染色体分割成若干窗口序列. 将整个基因组切割成合适大小的窗口，相当于将每条染色体看成由一些有重叠区域或无重叠区域的窗口的组合。如 21 号染色体总共有约 47Mega 的碱基对，如果以 l OMega大小为一个窗口，而每次窗口开始的位置向后滑动 lMega大小的话，则 21号染色体对应着 47个有重叠的 l OMega大小的窗口。可以人为定义想要的窗口长度大小及窗口重叠区序列的长度，并也为窗口编号，产生一对窗口编号到窗口在基因组上各染色体上的真实坐标的映射， In step 140, a cutting window is performed for each sample. Each chromosome constituting the genome is segmented into several window sequences. Cutting the entire genome into windows of appropriate size is equivalent to treating each chromosome as a combination of windows with overlapping or non-overlapping regions. For example, chromosome 21 has a total of about 47 Mega base pairs. If the size of l OMega is a window, and the position of the beginning of each window slides back to the size of lMega, then chromosome 21 corresponds to 47 overlapping OMega sizes. Window. The length of the desired window and the length of the window overlap region can be artificially defined, and also the window number, which produces a mapping of the pair of window numbers to the true coordinates of the window on each chromosome on the genome.

实施例中以 300k为窗口大小， 150k为 over lap切分窗口（即每个窗口的起始端为前一个窗口起始端向后滑动 150k ) ，表 1显示了切割 21号染色体后的 40个窗口。若一个窗口对应的窗口标号为 chr21， 2 ，则其对应的在基因组上的位置为 chr21 : 150 - 45 O In the embodiment, 300k is the window size, and 150k is the over lap splitting window (that is, the starting end of each window is the front The beginning of a window slides back 150k). Table 1 shows the 40 windows after cutting chromosome 21. If the window corresponding to a window is labeled chr21, 2 , its corresponding position on the genome is chr21 : 150 - 45 O

表 1展示了通过人为切割 21号染色体所获得的窗口的标号及窗口在基因组上的位置坐标，表里仅显示 40个窗口。如窗口标号为（chr21 , 180)，表示它是切割 21号染色体后的第 180个窗口，在 21号染色体上的具***置即坐标为（chr21 : 26850 - 27150kbp) , 即处于 21号染色体的 26850000碱基对及 27150000碱基对之间。由此，每一个窗口标号都代表着所对应染色体的映射位置，即一段人为切割的染色体区域。 Table 1 shows the labels of the windows obtained by artificially cutting chromosome 21 and the position coordinates of the window on the genome. Only 40 windows are shown in the table. For example, if the window is labeled (chr21, 180), it means that it is the 180th window after cutting chromosome 21, and the specific position on chromosome 21 is the coordinates (chr21: 26850 - 27150kbp), which is 2,658,500 on chromosome 21. Base pair and between 2,725,500 base pairs. Thus, each window label represents the mapped position of the corresponding chromosome, that is, an artificially cut chromosomal region.

实施例中， 4号染色体是一条非第一类染色体，若以 300k碱基对大小为一个窗口，而每次窗口开始的位置向后滑动 150k碱基对的方式同理可以切割成若干窗口，表 2列出 - 二十个窗口标号及在染色体上的位置信息即窗口坐标。如一个窗口对应的窗口标号为 chr4, 2 ，则其对应的在基因组上的位置为 chr4: 150 - 450kbp。窗口标号窗口坐标窗口标号窗口坐标 chr4，1 chr4 0~300kbp chr4,640 chr4:95850~96150kbp chr4,2 chr4 150~450kbp chr4,641 chr4:96000~96300kbp chr4,3 chr4 300~600kbp chr4,642 chr4:96150~96450kbp chr4,4 chr4 450~750kbp chr4,643 chr4:96300~96600kbp chr4,5 chr4 600~900kbp chr4,644 chr4:96450~96750kbp chr4,6 chr4 750~1050kbp chr4,645 chr4:96600~96900kbp chr4,7 chr4 900~1200kbp chr4,646 chr4:96750~97050kbp chr4，8 chr4 1050~1350kbp chr4,647 chr4:96900~97200kbp chr4,9 chr4 1200~1500kbp chr4,648 chr4:97050~97350kbp chr4,10 chr4 1350~1650kbp chr4,649 chr4:97200~97500kbp 表 2 中展示了通过人为切割笫 4号染色体所获得的窗口的标号及代表其在基因组上的位置的窗口坐标，仅显示其中的 20个窗口。如窗口标号为（chr4, 643) ,表示它是切割 4号染色体后在其上第 180个窗口，在 4号染色体上的具***置即坐标为（chr4: 96300 - 96600kbp) , 即处于 4号染色体的 96330000碱基对及 96600000碱基对之间。 In the embodiment, the chromosome 4 is a non-first type chromosome, and if the size of the 300k base pair is a window, and the position of each window starts to slide backward by 150k base pairs, the same manner can be cut into several windows. Table 2 lists - twenty window labels and positional information on the chromosome, ie window coordinates. If the window corresponding to a window is labeled chr4, 2, its corresponding position on the genome is chr4: 150 - 450kbp. Window label window coordinate window label window coordinate chr4,1 chr4 0~300kbp chr4,640 chr4:95850~96150kbp chr4,2 chr4 150~450kbp chr4,641 chr4:96000~96300kbp chr4,3 chr4 300~600kbp chr4,642 chr4: 96150~96450kbp chr4,4 chr4 450~750kbp chr4,643 chr4:96300~96600kbp chr4,5 chr4 600~900kbp chr4,644 chr4:96450~96750kbp chr4,6 chr4 750~1050kbp chr4,645 chr4:96600~96900kbp chr4, 7 chr4 900~1200kbp chr4,646 chr4:96750~97050kbp chr4,8 chr4 1050~1350kbp chr4,647 chr4:96900~97200kbp chr4,9 chr4 1200~1500kbp chr4,648 chr4:97050~97350kbp chr4,10 chr4 1350~1650kbp Chr4, 649 chr4: 97200~97500kbp Table 2 shows the label of the window obtained by artificially cutting the chromosome 4 and the window coordinates representing its position on the genome. Only 20 of them are displayed. For example, if the window is labeled (chr4, 643), it means that it is the 180th window on which chromosome 4 is cut, and the specific position on chromosome 4 is the coordinates (chr4: 96300 - 96600kbp), that is, on chromosome 4. Between 963,300 base pairs and 966,000 base pairs.

在 150步，对这些在有差异的条件下制备及测序的样本，基于测序所得信息，分别统计各样本来源于各窗口序列的核酸片段分子的量。 At step 150, based on the information obtained by sequencing, the samples prepared and sequenced under different conditions were counted for the amount of nucleic acid fragment molecules derived from each window sequence.

如 21号染色体的窗口，如前所述是指有临床研究价值的染色体的窗口组合。假设这一窗口组合中某一窗口的坐标为（chr21: 89000 - 89200bp) , 说明它处于 21号染色体上，并且这个窗口区域从第 89000个碱基对开始到笫 89200个碱基对结束，而此时，测得的某一核酸片段分子的起始坐标为 chr21： 89100, 而所测得的分子片段长度为 35个碱基对，那么，这个核酸片段分子的序列位置刚好在这个窗口坐标之内，则说明这一条核酸片段分子来源于此窗口区域，如可以统计一个样本的所有序列位置处于这一窗口的核酸分子的条数，那么这个条数可以称为来源于这一窗口的核酸分子的量。然后将构成这个笫一类染色体窗口組合的窗口的核酸片段分子的量合起来，就可以得到来源于第一类染色体窗口组合的核酸分子量，这里要强调的是这个第一类染色体窗口组合可以根据情况部分或整体地覆盖第一类染色体一次或多次。 For example, the window of chromosome 21, as mentioned above, refers to the window combination of chromosomes with clinical research value. Suppose the coordinates of a window in this window combination are (chr21: 89000 - 89200bp), indicating that it is on chromosome 21, and this window region ends from the 8890th base pair to the 笫89200 base pairs. At this time, the measured starting coordinate of a certain nucleic acid fragment molecule is chr21: 89100, and the measured molecular fragment length is 35 base pairs, then the sequence position of the nucleic acid fragment molecule is just at the window coordinate Inside, it indicates that the nucleic acid fragment molecule is derived from this window region. For example, the number of nucleic acid molecules in which all sequence positions of a sample are located in this window can be counted, and the number of nucleic acids can be called the nucleic acid molecule derived from this window. The amount. Then, by combining the quantities of the nucleic acid fragment molecules constituting the window of the chromosome-like window combination, the molecular weight of the nucleic acid derived from the first type of chromosome window combination can be obtained. It should be emphasized that the first type of chromosome window combination can be based on The condition partially or collectively covers the first type of chromosome one or more times.

在 160步，对于 21号染色体的每一个窗口，在整个基因組（除 21号染色体)上的窗口分析与这一窗口的相关性，选择极强相关性的窗口组保留，并确定其间的函数关系式，这时， 21号染色体的单个窗口可能会对应多个相关窗口，组成相关窗口组合。设统计所得的来源于第二类染色体窗口的核酸分子量为 X i , 统计所得来源于第一类染色体窗口的核酸分子量为 Y i， i代表样本编号，则观测样本为（XI, Yl) , (X2，Y2)， ...（Χη, Υη) .此时，根据这些数据，可以算得这两组数据的相关系数的平方。相关系数的平方越接近 1 , 截距接近于 0，说明相关性越高。每一个 21号染色体与其单个相关窗口都能确定一个函数关系式。 In step 160, for each window of chromosome 21, the window analysis on the entire genome (except chromosome 21) is related to this window, select the window group retention with strong correlation, and determine the functional relationship between them. formula, At this time, a single window of chromosome 21 may correspond to multiple related windows to form a related window combination. Let the statistically derived nucleic acid derived from the second type of chromosome window have a molecular weight of Xi, and the statistically derived nucleic acid derived from the first type of chromosome window has a molecular weight of Y i, and i represents a sample number, and the observed sample is (XI, Yl), ( X2, Y2), ...(Χη, Υη) At this time, based on these data, the square of the correlation coefficient of the two sets of data can be calculated. The closer the square of the correlation coefficient is to 1, the intercept is close to 0, indicating that the correlation is higher. Each chromosome 21 and its individual correlation window can determine a functional relationship.

实施例中，准备了 89个在有差异的实验条件及测序条件下进行样本制备及测序的生物样本，分别统计各样本来源于各窗口区域序列的核酸片段的量，即对每个样本，其在基因组上切割的每个窗口都对应着一个行为值。对于 89个样本来说，每个窗口里有 89 个行为值。 In the examples, 89 biological samples for sample preparation and sequencing under different experimental conditions and sequencing conditions were prepared, and the amount of nucleic acid fragments derived from each window region sequence of each sample was separately counted, that is, for each sample, Each window cut on the genome corresponds to a behavior value. For 89 samples, there are 89 behavior values in each window.

在这个实施例中，对于 21号染色体的每一个窗口，同时在基因组（除 21号染色体）上搜索与这一个窗口相关性极高的一个窗口。为方便说明，在这里仅取三个窗口用来说明，见表 5 , 一个来源于笫一类染色体窗口组合的窗口，编号为（chr21，180) ,两个来源于非第一类染色体的窗口，编号分别为窗口（chr l， 256)，窗口（chr4, 642)。见表 3, 所示第一行，显示样本编号，即本方法所研究的 89个样本的编号；第二行展示了样本编号对应的 89 个样本中的每个样本的来自基因組窗口标号为（chr l, 256)窗口上的核酸分子的量值，即 89个行为值，记为 X' i， i值从 1取到 89。笫三行展示了样本编号对应的 89 个样本中的每个样本的来自基因组窗口标号为（chr4， 642)窗口上的核酸分子的量值，也是 89个行为值，记为 xi，i值从 1取到 89。第四行展示样本编号对应的 89个样本中的每个样本的来自基因组窗口标号为（chr21，180)窗口上的核酸分子的量值，也是 89 个行为值，记为 y i, i值从 1取到 89 , In this embodiment, for each window of chromosome 21, a window with a very high correlation with this window is searched for on the genome (except chromosome 21). For convenience of explanation, only three windows are used here for illustration. See Table 5, a window derived from a combination of chromosomes of the first class, numbered (chr21, 180), and two windows derived from non-first chromosomes. , the numbers are window (chr l, 256), window (chr4, 642). See Table 3, the first row shown, showing the sample number, which is the number of the 89 samples studied in this method; the second row shows that each of the 89 samples corresponding to the sample number is labeled from the genome window ( Chr l, 256) The magnitude of the nucleic acid molecule on the window, that is, 89 behavioral values, denoted as X' i, and the value of i is taken from 1 to 89. The third line shows the magnitude of the nucleic acid molecule from the genomic window labeled (chr4, 642) in each of the 89 samples corresponding to the sample number, which is also 89 behavioral values, denoted as xi, i values from 1 is taken to 89. The fourth row shows the magnitude of the nucleic acid molecule from the genomic window labeled (chr21, 180) window for each of the 89 samples corresponding to the sample number, which is also 89 behavioral values, denoted as yi, i value from 1 Get 89,

表 3 table 3

首先研究窗口（chr4， 642)与窗口（chr21，180)的相关关系，此时观测样本为 First, the correlation between the window (chr4, 642) and the window (chr21, 180) is studied.

(XI , YD , (X2. Y2) , ... (Χη, Υη) , 在这个实施例中， η可以取到 89,研究两列数值的相关系数，相关系数的平方越接近 1，说明相关性越高，即当一个窗口的行为值变动时，另一个窗口也会发生相应的变动。当相关系数接近 1 时，可以根据观测样本研究两窗口的行为是否服从线性关系，表 3表示出的窗口（chr4，642)与窗口（chr21 , 180)的行为值服从线性关系，并且可以获得其线性方程的表达式和相关系数 R 的平方。见图 3 , 在这个实施例中，可以看出两窗口，窗口 (chr4, 642)与窗口 (chr21， 180) ,的行为值存在着极强的线性相关性，且相关表达式为： y=0. 7564-0. 6487, R²=0. 9724 „ 显然 R还是比较接近 1 的，则这个窗口（chr4, 642)可以选定作为与实施例窗口（chr21，180)相对应的有极强相关性的模拟窗口。再来研究窗口（chr l , 256)与窗口（chr21， 180)，见图 4，其 R²=0. 6214，则认为两窗口行为值不是很相关，以后可以不考虑该窗口。就这样, 对于第一类染色体窗口组合中的窗口都可以用这样的方法去寻得一个或多个相关性极强的模拟窗口。以后就只需要已知一个 X值，即只需要统计好来源于这个与实施例窗口相对应的有极强相关性的模拟窗口的量，就可以通过关系式计算出一个模拟值或模拟值置信区间。 (XI , YD , (X2. Y2) , ... (Χη, Υη) , In this embodiment, η can be taken to 89, and the correlation coefficient of the two columns of values is studied. The closer the square of the correlation coefficient is to 1, the correlation is The higher the sex, that is, when the behavior value of one window changes, the other window will change accordingly. When the correlation coefficient is close to 1, it can be studied according to the observation sample whether the behavior of the two windows obeys the linear relationship, as shown in Table 3. The behavior values of the window (chr4, 642) and the window (chr21, 180) obey the linear relationship, and the expression of the linear equation and the square of the correlation coefficient R can be obtained. See Fig. 3, in this embodiment, it can be seen that There is a strong linear correlation between the behavior values of windows, windows (chr4, 642) and windows (chr21, 180), and the correlation expression is: y=0. 7564-0. 6487, R ² =0. 9724 „ Obviously R is still close to 1, then this window (chr4, 642) can be selected as the analog window with strong correlation corresponding to the embodiment window (chr21, 180). Then study the window (chr l , 256) ) and the window (chr21, 180), see Figure 4, where R ² =0. 621 4, it is considered that the behavior value of the two windows is not very relevant, and the window can be ignored later. In this way, the window in the first type of chromosome window combination can be used to find one or more highly correlated ones. The simulation window. In the future, only one X value needs to be known, that is, only the amount of the analog window derived from the window corresponding to the embodiment window is calculated, and an analog value can be calculated by the relation or Analog value confidence interval.

如表 4公布了通过方法 100流程步骤所选得的与第一类窗口组合有极强相关性的散布在基因组其它位置的模拟窗口组合，表中仅显示由 20个窗口所组成的组合。第一列显示位于第一类染色体上的窗口标号，第二列显示其窗口坐标；第三列显示与相应的第一类染色体有极强相关性的模拟窗口的窗口标号，笫四列显示对应的模拟窗口坐标；第五列显示窗口与相关模拟窗口的关系表达式；第六列显示相关系数的平方值，即 R方值， R 平方值越接近 1，说明两窗口间相关性越高，即其中来源于一个窗口的核酸分子量发生变化，则来源于另一窗口核酸分子量会发生相应的变化。 Table 4 discloses a combination of simulation windows scattered at other locations in the genome that are strongly correlated with the first type of window combination selected by the method 100 process steps, and only a combination of 20 windows is shown in the table. The first column shows the window label on the first type of chromosome, the second column shows its window coordinates; the third column shows the corresponding first The chromosomes of the simulation window with extremely strong correlations, the four columns display the corresponding simulation window coordinates; the fifth column shows the relational expression of the window and the related simulation window; the sixth column shows the square of the correlation coefficient, ie R The square value, the closer the R squared value is to 1, indicates that the higher the correlation between the two windows, that is, the molecular weight of the nucleic acid derived from one window changes, the molecular weight of the nucleic acid derived from another window will change accordingly.

表 4 Table 4

接着可以将与 21号染色体窗口组合有极强相关性的模拟窗口组合起来，共同构成模拟窗口组合，再根据来源于模拟窗口或模拟窗口组合的核酸分子的量算得一个修正过的置信区间，用于方法 200对染色体非整倍性的判断， Then, the simulation windows with strong correlation with the chromosome 21 window combination can be combined to form a simulation window combination, and a modified confidence interval is calculated according to the amount of the nucleic acid molecules derived from the combination of the simulation window or the simulation window. Method 200 for the determination of chromosome aneuploidy,

在 170步，由于 21号染色体上的每个窗口可能有多个窗口与之相关，所以为充分使用测序数据，提高检测准确性，将这些窗口的相关函数关系式进行拟合，并根据实际数据，进行校正，最终确定 21号染色体中，能在基因组上找到强相关性的每个窗口的函数关系式。 In step 170, since each window on chromosome 21 may have multiple windows associated with it, in order to fully use the sequencing data, the detection accuracy is improved, and the correlation function relationships of these windows are fitted, and according to the actual data. Correction is performed to finally determine the functional relationship of each window in chromosome 21 that can find a strong correlation on the genome.

步骤 3:对待检测样本测序 Step 3: Sequencing the test sample

8 个孕妇志愿者参与本项检测，所获得的样本编号分别为样本 1-8。四个孕妇怀有 21号染色体三体胎儿，四个孕妇怀有 21号染色体正常胎儿。收集每个孕妇外周血，并对进行离心，取血浆，然后再从血浆中提取核酸分子，通过 I l lumina公司的测序仪对这些核酸分子进行大规模高通量测序。根据图 2的 200方法的流程图进行，具体地，在 210步，从孕妇处获得生物样本，这个生物样本可以是血浆或其它合适的样本。这种生物样本包含着来源于孕妇以及胎儿的核酸分子。 Eight pregnant women volunteers participated in the test, and the sample numbers obtained were samples 1-8. Four pregnant women harbored the 21st chromosome trisomy, and four pregnant women harbored the normal fetus of chromosome 21. The peripheral blood of each pregnant woman was collected, centrifuged, plasma was taken, and then nucleic acid molecules were extracted from the plasma, and these nucleic acid molecules were subjected to large-scale high-throughput sequencing by an Illumina sequencer. According to the flow chart of the 200 method of Fig. 2, specifically, at step 210, a biological sample is obtained from a pregnant woman, which may be plasma or other suitable sample. This biological sample contains nucleic acid molecules derived from pregnant women as well as fetuses.

在 220步，对样本中的核酸分子进行随机测序。被测序的核酸片段分子代表着整个基因组的一部分，可以定位在各条染色体上，样本中的核酸分子可以只测一端（如测一端 35个碱基对）或测两端，或者将整条核酸分子都测出来。 At step 220, the nucleic acid molecules in the sample are randomly sequenced. The sequenced nucleic acid fragment molecule represents a part of the entire genome and can be localized on each chromosome. The nucleic acid molecule in the sample can be measured only at one end (such as measuring 35 base pairs at one end) or both ends, or the entire nucleic acid The molecules are all measured.

测序可以通过大规模高通量平行测序仪测序，如 454, So lexa, SOL iD***，以及单分子测序或纳米孔测序等。在一个实施例中我们通过 I l lumina公司的 so lexa测序仪来对核酸分子进行一端测序。 Sequencing can be sequenced by large-scale, high-throughput parallel sequencers such as the 454, So lexa, SOL iD systems, and single-molecule sequencing or nanopore sequencing. In one embodiment, we performed one-end sequencing of nucleic acid molecules by Illumina's so lexa sequencer.

虽然样本制备以及实验的大概流程相同，为了验证本发明方法适合实验条件不太一致的情况，即具有对实验条件要求不是很严格的优势，所述的实验条件包括使用不同的试剂，测序 GC偏向不一致等。特分为两组，样本 1,样本 2，样本 5，样本 6为一组实验条件（A组）；样本 3,样本 4,样本 7,样本 8为另一组实验条件（B组）。 A组为抽取 5ml孕妇血浆，使用 QIAamp DNA Mi cro k i t (QIAGEN, 56304)提取游离 DNA,按照 I l lumina/Solexa 建库流程使用 NEB试剂构建 SE文库，上 SE36测序， B組抽取 600ul孕妇血浆使用 TIANamp Mi cro DNA Ki t ( Tiangen DP316)提取游离 DNA, 按照 I l lumina/Solexa 建库流程使用 Enzyma t ics试剂构建 PEI文库，上 SE36+7测序。 Although the approximate procedure of sample preparation and experiment is the same, in order to verify that the method of the present invention is suitable for a case where the experimental conditions are not consistent, that is, it has an advantage that the experimental conditions are not very strict, and the experimental conditions include using different reagents, sequencing GC bias Inconsistent, etc. Divided into two groups, sample 1, sample 2, sample 5, sample 6 is a set of experimental conditions (group A); sample 3, sample 4, sample 7, sample 8 is another set of experimental conditions (group B). In group A, 5 ml of maternal plasma was extracted, free DNA was extracted using QIAamp DNA Mi cro kit (QIAGEN, 56304), SE library was constructed using NEB reagent according to the Illumina/Solexa library procedure, SE36 was sequenced, and group B was used to extract 600 ul of maternal plasma. TIANamp Mi cro DNA Ki t (Tiangen DP316) was used to extract free DNA, and the PEI library was constructed using Enzymatics reagent according to the Illumina/Solexa library procedure, and sequenced on SE36+7.

此步骤如图 2的 210， 220步。 This step is shown in steps 210 and 220 of Figure 2.

步骤四：检测样本，根据图 2的流程图进行。 Step 4: Detect the sample, according to the flow chart of Figure 2.

在 230步中，基于测序，可以通过生物信息分析的手段将所测得的每条核酸片段分子定位到基因组的确切位置上。如表 1其显示了通过测序所测得的可以定位到各条染色体的核酸片段分子其在该染色体上的起始位置坐标。 In step 230, based on sequencing, each of the measured nucleic acid fragment molecules can be localized to the exact location of the genome by means of bioinformatics analysis. As shown in Table 1, the positional coordinates of the nucleic acid fragment molecules which can be localized to each chromosome as determined by sequencing on the chromosome are shown.

表 5显示了生物样本样本 1和样本 2测序后所得到的一些核酸分子定位到 4号染色体和 21号染色体上的前十个起始位点的位置信息。 Table 5 shows the positional information of some nucleic acid molecules obtained after sequencing of biological samples 1 and 2 to the first ten starting sites on chromosome 4 and chromosome 21.

由表 5可以看出，对于样本 1而言，其可以定位到 21号染色体上的第一条核酸片段分子的起始点位置为 9797443 , 即这条核酸片段分子的起始点位于 21 号染色体的笫 9797443碱基对位置。同理，其可以定位到 4 号染色体上的第一条核酸片段分子的起始点位置为 19219，即这条核酸片段分子的起始点位于 4号染色体的第 19219碱基对位置。

As can be seen from Table 5, for sample 1, the starting point of the first nucleic acid fragment molecule that can be mapped to chromosome 21 is 997943, that is, the starting point of the nucleic acid fragment molecule is located on chromosome 21 9797443 base pair position. Similarly, the starting point of the first nucleic acid fragment molecule that can be mapped to chromosome 4 is 19219, that is, the starting point of the nucleic acid fragment molecule is located at the 19th pair of base pairs of chromosome 4.

在 240步中, 和建立模型中一样，用 300k为窗口大小, 150k为 over lap对 8个待检测样本的所有染色体分别切割窗口. 在 250步中，基于核酸片段位置信息，统计来源于 21号染色体各窗口的核酸片段分子的量。在 260步中，基于核 Ml!MJMd Mil酸三三三三... 片段位置信息，统计体体体体 In step 240, as in the model building, 300k is the window size, and 150k is the overlap to cut the window for all the chromosomes of the 8 samples to be detected. In the 250 step, based on the position information of the nucleic acid fragment, the statistics are from the 21st. The amount of nucleic acid fragment molecules in each window of the chromosome. In step 260, based on the core Ml! MJMd Mil acid three three three three... Fragment position information, statistics body body

来源于每个样本的与 21号染色体窗口有强相关性的模拟窗口组合的核酸分子的量，并依据函数关系式算出置信区间。在 270步中，通过判定每个样本的第 250步胎胎胎胎所2 222The amount of nucleic acid molecules combined from the analog window of each sample that has a strong correlation with the chromosome 21 window, and the confidence interval is calculated according to the functional relationship. In step 270, by determining the 250th tire of each sample, 2 222

/, J获 II II 1 l 得的来源三三三三 Ϊ3§ί33! 于 21号染色体窗口的核酸片段分子的量是否在同一样本的第 260步中所获得的置ε4*_εκ- .··.·.常常常常信区间内，可以判断胎儿是否在 21号染色体存在非整倍性的高风险， /, J is the source of II II 1 l 3 3 3 3 3 §ί33! Whether the amount of the nucleic acid fragment molecule in the chromosome 21 window is ε4*_εκ- obtained in step 260 of the same sample. .. often often believe that the fetus is at high risk of aneuploidy on chromosome 21.

表 6：用本发明方法检测实施例中的八个样本所得到的结果样品真实值 Y 模拟值 95%置信区间 HITable 6: Results obtained by detecting the eight samples in the examples by the method of the present invention Sample Real value Y Analog value 95% confidence interval HI

Samplel 53182 [43741.8577333385,49180.4533039014] 2 12 Samplel 53182 [43741.8577333385,49180.4533039014] 2 12

Sample2 58357 [50652.113474583,55849.319880917] 21： Sample2 58357 [50652.113474583,55849.319880917] 21:

Sample3 27972 [24280.9213020507,27555.3170942193] 21Z Sample3 27972 [24280.9213020507,27555.3170942193] 21Z

Sample4 28149 [23685.2145432661 ,26901.8699143739] 21： Sample4 28149 [23685.2145432661,26901.8699143739] 21:

Sampled 60366 [56287.8434307435,62016.0997439065] 21 Sampled 60366 [56287.8434307435,62016.0997439065] 21

Sample6 56548 [52747.7578964899,58146.06907256] 21 Sample6 56548 [52747.7578964899,58146.06907256] 21

Sample7 34747 [32444.1196306556,36615.1903005244] 21 Sample7 34747 [32444.1196306556,36615.1903005244] 21

Sample8 23258 [21945.9756617287,24982.0017753413] 21 Sample8 23258 [21945.9756617287, 24982.0017753413] 21

表 6中的真实值 Y列，是统计所得的来源于各样本 21号染色体窗口组合的核酸分子量；统计该样本中与 21号染色体窗口组合有强相关性的模拟窗口组合的核酸分子量及相关关系表达式（如表 4 所示），再通过统计学知识所得到的一个置信区间（置信水平： 95% ) . 对于一个研究的样本来说，当它的真实值存在于计算得到的置信区间内时，可以认为所研究的样本是正常的可能性很大，反之，若真实值存在于模拟值置信区间之外，则说明该样本是正常的可能性很小。如样本 1，样本 2，样本 3，样本 4,它们的真实值即来源于 21号染色体组合的核酸分子量都在置信区间范围之外，则用本方法所获得的结论为它们为 21三体胎儿样本，该结果得到了核型分析结果的证明。 The true value Y column in Table 6 is the statistically derived molecular weight of the nucleic acid derived from the chromosome 21 window combination of each sample; the nucleic acid molecular weight and phase of the simulated window combination with strong correlation with the chromosome 21 window combination in the sample are counted. A relational expression (as shown in Table 4), followed by a confidence interval (confidence level: 95%) obtained from statistical knowledge. For a sample of a study, when its true value exists in the calculated confidence In the interval, it can be considered that the sample under study is normal. On the contrary, if the true value exists outside the confidence interval of the analog value, it is unlikely that the sample is normal. For example, sample 1, sample 2, sample 3, and sample 4, whose true values are derived from the molecular weight of the chromosome 21 combination are outside the confidence interval, the conclusion obtained by this method is that they are 21 trisomy The sample, the result is proved by the results of the karyotype analysis.

通过比较上述的各样本来源于第一类染色体窗口組合的核酸片段分子的量的值（真实值）与所获得的模拟值置信区间，判断是否存在着在第一类染色体上的胎儿非整倍体染色体或非整倍体染色体区域，如表 6所示，可以看到 21号染色体三体的真实值在模拟值置倌区间之外，而正常两倍体样本其真实值在模拟值置信区间范围之内。图 7，显示四个来自孕妇外周血核酸样本，样本 1与样本 2的真实值在各自的模拟值置信区间之上，可以确定为 21号染色体非整倍性；而样本 5与样本 6的真实值在各自的模拟值置信区间之内，可以认为样本正常。图 8 , 图示正常样本与异常样本的真实值与各自的模拟值置信区间的关系。显示四个来自孕妇外周血核酸样本，样本 3与样本 4的真实值在各自的模拟值置信区间之上，可以确定为 21号染色体非整倍性；而样本 7与样本 8的真实值在各自的模拟值置信区间之内，可以认为样本正常。 By comparing the value (true value) of the amount of the nucleic acid fragment molecule of each sample derived from the first type of chromosome window combination with the obtained confidence interval of the simulated value, it is determined whether there is fetal aneuploidy on the first type of chromosome. The chromosome or aneuploid chromosomal region, as shown in Table 6, can be seen that the true value of the trisomy of chromosome 21 is outside the interval of the simulated value, while the true value of the normal double-body sample is within the confidence interval of the simulated value. Within the scope. Figure 7 shows four samples of nucleic acid from pregnant women's peripheral blood. The true values of samples 1 and 2 are above the confidence interval of their respective simulated values, which can be determined as chromosome 21 aneuploidy; while sample 5 and sample 6 are true. The values are within the confidence interval of the respective analog values and the sample can be considered normal. Figure 8 shows the relationship between the true values of normal and abnormal samples and their respective analog value confidence intervals. Four nucleic acid samples from pregnant women's peripheral blood are displayed. The true values of samples 3 and 4 are above the confidence interval of their respective simulated values, which can be determined as chromosome 21 aneuploidy; and the true values of samples 7 and 8 are in their respective Within the confidence interval of the analog value, the sample can be considered normal.

实施例二 Embodiment 2

步骤 1 :获得建模所需测序数据 Step 1: Get the sequencing data needed for modeling

选择 53个正常样本，对这些样本在有差异的实验条件下制备并测序。 53 normal samples were selected and prepared and sequenced under differential experimental conditions.

根据图 1 的流程图进行，数学模型建立的过程由计算机程序优化完成。计算机程序通过不同的参数选择，完成相关性窗口的寻找，寻找最优参数，建立笫一类染色体窗口与第二类染色体窗口的函数关系式。 According to the flow chart of Fig. 1, the process of establishing the mathematical model is optimized by computer program. The computer program completes the correlation window search through different parameter selections, finds the optimal parameters, and establishes a functional relationship between the chromosome window of the first class and the chromosome window of the second type.

在 1 30步中，基于测序，可以通过生物信息分析的手段将所测得的每条核酸片段分子定位到基因组的确切位置上。 In step 1 30, based on sequencing, each of the measured nucleic acid fragment molecules can be mapped to the exact location of the genome by means of bioinformatics analysis.

在 140步中，对每个样本进行切割窗口。将构成基因组的每条染色体分割成若干窗口序列。实施例中以 300k为窗口大小， 150k为 over l ap切分窗口（即每个窗口的起始端为前一个窗口起始端向后滑动 150k ) 。 In step 140, a cutting window is performed for each sample. Each chromosome constituting the genome is divided into a number of window sequences. In the embodiment, 300k is the window size, and 150k is the over l ap segmentation window (that is, the start of each window). The end slides 150k backwards at the beginning of the previous window.

在 160步，对于 18号染色体的每一个窗口，在整个基因组（除 21号染色体）上的窗口分析与逸一窗口的相关性，选择极强相关性的窗口组保留，并确定其间的函数关系式，这时， 18号染色体的单个窗口若对应多个相关窗口，组成相关窗口组合。 In step 160, for each window of chromosome 18, the window analysis on the entire genome (except chromosome 21) is related to the Yiyi window, select the window group retention with strong correlation, and determine the functional relationship between them. In this case, if a single window of chromosome 18 corresponds to multiple related windows, a related window combination is formed.

实施例二中，准备了 53个在有差异的实验条件及测序条件下进行样本制备及测序的生物样本，分别统计各样本来源于各窗口区域序列的核酸片段的量，即对每个样本，其在基因组上切割的每个窗口都对应着一个行为值。对于 53个样本来说，每个窗口里有 53 个行为值。如表 7 所示，选取 3 个窗口，分别来自于（chrl 8, 259) , (chrl, 8) , (chr8， 710)。所示第一行，显示样本编号，即本实施例中所研究的 53个样本的编号；第二行展示了样本编号对应的 53 个样本中的每个样本的来自基因组窗口标号为（chrl， 8) 窗口上的核酸分子的量值，即 53个行为值，记为 4， 1值从1取到 53。第三行展示了样本编号对应的 53 个样本中的每个样本的来自基因组窗口标号为（chrl 8， 259) 核酸分子的量（53个行为值），记为 xi， i值从 1取到 53, 第四行展示样本编号对应的 53个样本中的每个样本的来自基因组窗口标号为（chrl 8， 259) 核酸分子的量（53个行为值），记为 yi， i值从 1取到 53。 In the second embodiment, 53 biological samples for sample preparation and sequencing under different experimental conditions and sequencing conditions were prepared, and the amount of nucleic acid fragments derived from each window region sequence of each sample was separately counted, that is, for each sample, Each window it cuts on the genome corresponds to a behavior value. For 53 samples, there are 53 behavior values in each window. As shown in Table 7, three windows are selected, which are from (chrl 8, 259), (chrl, 8), (chr8, 710). In the first row shown, the sample number is displayed, which is the number of the 53 samples studied in this example; the second row shows that the sample from the 53 samples corresponding to the sample number is labeled (chrl, 8) The magnitude of the nucleic acid molecule on the window, ie 53 behavioral values, is recorded as 4, and the value of 1 is taken from 1 to 53. The third row shows the amount of nucleic acid molecules (53 behavior values) from the genomic window labeled (chrl 8, 259) for each of the 53 samples corresponding to the sample number, denoted xi, and the value of i is taken from 1 53, the fourth row shows the amount of nucleic acid molecules (53 behavior values) from the genomic window labeled (chrl 8, 259) for each of the 53 samples corresponding to the sample number, denoted as yi, and the value of i is taken from 1. To 53.

表 7 Table 7

首先研究窗口（chr8， 710)与窗口（chrl 8， 259)的相关关系，此时观测样本为 (XI, YD , (X2. Y2) , ... (Χη, Υη) , 在这个实施例中， η可以取到 53，研究两列数值的相关系数，得到窗口（chr8, 710)与窗口（chrl 8, 259)的行为值存在着强相关性，且相关表达式为： y= - 9. 18452 + 0. 98295x, R²=0. 9816 , 见图 5 。显然 R²还是比较接近 1 的，则这个窗口 (chr8， 710)可以选定作为与实施例窗口（chrl 8, 259)相对应的有强相关性的窗口。再研究窗口（chrl j)与窗口（chr8， 259)，见图 6，其 R²=0. 004344,则认为两窗口行为值不相关，以后可以不考虑该窗口，如此，可以在基因组（除 18 号染色体）上选定一个或多个与 18号染色体相关性强的窗口。以后就只需要已知一个 X值，即只需要统计好来源于这个与实施例窗口相对应的有极强相关性的模拟窗口的量，就可以通过函数关系式计算出一个置信区间。 First, the correlation between the window (chr8, 710) and the window (chrl 8, 259) is studied. At this time, the observed samples are (XI, YD, (X2. Y2), ... (Χη, Υη), in this embodiment. , η can be taken to 53, to study the relationship between the two columns of values There is a strong correlation between the number of the obtained window (chr8, 710) and the window (chrl 8, 259), and the correlation expression is: y= - 9. 18452 + 0. 98295x, R ² =0. 9816 , See Figure 5. Obviously R ² is still close to 1, then this window (chr8, 710) can be selected as a strongly correlated window corresponding to the embodiment window (chrl 8, 259). Re-study window (chrl j) and window (chr8, 259), see Figure 6, where R ² =0. 004344, it is considered that the behavior values of the two windows are irrelevant, and the window can be ignored later, so that it can be in the genome (except One or more windows with a strong correlation with chromosome 18 are selected on chromosome 18. In the future, only one X value needs to be known, that is, only the amount of the analog window derived from the window corresponding to the embodiment window is calculated, and a confidence interval can be calculated by the function relation.

如表 8公布了通过方法 100流程所选得上面步骤所选得的与 18号染色体有极强相关性的散布在基因组其它位置的窗口组合，图中仅显示其中 20 个窗口。第一列显示位于 18号染色体上的窗口标号，笫二列显示其窗口坐标；第三列显示与相应的 18 号染色体有强相关性的窗口的标号，第四列显示对应的窗口坐标；第五列显示窗口与相关窗口的关系表达式；第六列显示相关系数的平方值，即 R². Table 8 discloses the combination of windows scattered at other locations in the genome that are strongly correlated with chromosome 18 selected by the above steps selected by the method 100, and only 20 of them are shown. The first column shows the window label on chromosome 18, the second column shows its window coordinates, the third column shows the label of the window with strong correlation with the corresponding chromosome 18, and the fourth column shows the corresponding window coordinates. The relationship between the five columns of display windows and the associated window; the sixth column shows the square of the correlation coefficient, ie R ² .

表 8 Table 8

接着可以将与 18号染色体窗口组合有极强相关性的窗口组合起来，再根据来源于各窗口的核酸分子的量算得一个修正过的置信区间，用于方法 200对染色体非整倍性的判断。

Then, a window with a strong correlation with the chromosome 18 window combination can be combined, and a modified confidence interval is calculated according to the amount of the nucleic acid molecules derived from each window, and the method 200 is used to judge the chromosome aneuploidy. .

步骤 3:对待检测样本测序 Step 3: Sequencing the test sample

6个孕妇志愿者参与本项检测，所获得的样本编号分别为样本 1-6。收集每个孕妇外周血，并对进行离心，取血浆，然后再从血浆中提取核酸分子，通过 I l lumina公司的测序仪对这些核酸分子进行大规模高通量测序。 Six pregnant women volunteers participated in the test, and the sample numbers obtained were samples 1-6. The peripheral blood of each pregnant woman is collected, centrifuged, plasma is taken, and then nucleic acid molecules are extracted from the plasma, and these nucleic acid molecules are subjected to large-scale high-throughput sequencing by an Illumina sequencer.

根据图 2的 200方法的流程图进行，具体地，在 210步，从孕妇处获得生物样本。这个生物样本可以是血浆或其它合适的样本，这种生物样本包含着来源于孕妇以及胎儿的核酸分子。 According to the flow chart of the 200 method of Fig. 2, specifically, at step 210, a biological sample is obtained from a pregnant woman. The biological sample can be plasma or other suitable sample containing nucleic acid molecules derived from pregnant women and fetuses.

在 220步，对样本中的核酸分子进行随机测序。被测序的核酸片段分子代表着整个基因组的一部分，可以定位在各条染色体上。实施例中我们通过 I l lumina公司的 solexa 测序仪来对核酸分子进行一端测序。 At step 220, the nucleic acid molecules in the sample are randomly sequenced. The sequenced nucleic acid fragment molecules represent a portion of the entire genome and can be localized on each chromosome. In the examples, we performed one-end sequencing of nucleic acid molecules by Illumina's solexa sequencer.

特分为两组，样本 1,样本 2,样本 4为一组实验条件（ A组）；样本 3,样本 5,样本 6 为另一组实验条件（B 组）， A 组为抽取 5ml 孕妇血浆，使用 QIAamp DNA Mi cro k i t (QIAGEN, 56304)提取游离 DNA，按照 1 1 lumina/Solexa建库流程使用 NEB试剂构建 SE 文库，上 SE36测序，Β组抽取 600ul孕妇血浆使用 TIANamp Mi cro DNA K i t( T iangen DP316) 提取游离 DNA, 按照 I I lumina/Solexa建库流程使用 Enzyma t ics试剂构建 PEI文库，上 SE36+7测序。 Divided into two groups, sample 1, sample 2, sample 4 is a set of experimental conditions (group A); sample 3, sample 5, sample 6 is another set of experimental conditions (group B), group A is to extract 5ml maternal plasma The free DNA was extracted using QIAamp DNA Mi cro kit (QIAGEN, 56304), and the SE library was constructed using NEB reagent according to the 1 1 lumina/Solexa library procedure. SE36 was sequenced and the sputum group was used to extract 600 ul maternal plasma using TIANamp Mi cro DNA K it ( T iangen DP316) The free DNA was extracted and the PEI library was constructed using Enzymatics reagent according to the II lumina/Solexa library procedure, and sequenced on SE36+7.

此步骤如图 2的 210 , 220步。 This step is shown in steps 210 and 220 of Figure 2.

步骤 4: 检测样本 Step 4: Test the sample

根据图 2的流程图进行. According to the flow chart of Figure 2.

在 230步中，基于测序，可以通过生物信息分析的手段将所测得的每条核酸片段分子定位到基因組的确切位置上。如表 1其显示了通过测序所测得的可以定位到各奈染色体的核酸片段分子其在该染色体上的起始位置坐标。 In step 230, based on sequencing, each of the measured nucleic acid fragment molecules can be localized to the exact location of the genome by means of bioinformatics analysis. As shown in Table 1, the coordinates of the starting position of the nucleic acid fragment molecule which can be localized to each of the nemeric chromosomes measured by sequencing on the chromosome are shown.

在 240步中，和建立模型中一样，用 300k为窗口大小， 150k为 over l ap对 6个待检测样本的所有染色体分别切割窗口， In step 240, as in the model building, 300k is the window size, and 150k is over l ap to cut the window for all the chromosomes of the six samples to be tested.

在 250步中，基于核酸片段位置信息，统计来源于 18号染色体各窗口的核酸片段分子的量。 In step 250, based on the nucleic acid fragment position information, the nucleic acid fragment derived from each window of chromosome 18 is counted. The amount of children.

在 260步中，基于核酸片段位置信息，统计来源于每个样本的与 18号染色体窗口有强相关性的窗口组合的核酸分子的量，并依据函数关系式算出置信区间。 In step 260, based on the nucleic acid fragment position information, the amount of nucleic acid molecules derived from the window of each sample having a strong correlation with the chromosome 18 window is counted, and the confidence interval is calculated according to the functional relationship.

在 270步中，通过判定每个样本的第 250步所获得的来源于 21号染色体窗口的核酸片段分子的量是否在同一样本的第 260步中所获得的置信区间内，可以判断胎儿是否在 18号染色体存在非整倍性的高风险。 In step 270, by determining whether the amount of the nucleic acid fragment molecule derived from the chromosome 21 window obtained in step 250 of each sample is within the confidence interval obtained in step 260 of the same sample, it can be determined whether the fetus is Chromosome 18 has a high risk of aneuploidy.

表 9: 用本发明方法检测实施例中的八个样本所得到的结果 Table 9: Results obtained by testing the eight samples in the examples using the method of the invention

表 9中的真实值（第二列），是统计所得的来源于各样本 18号染色体窗口组合的核酸分子量；统计该样本中与 18号染色体窗口组合有强相关性的模拟窗口组合的核酸分子量及相关函数表达式（如表 8所示），再通过统计学知识所得到的一个置信区间（置信水平： 95% )。对于一个研究的样本来说，当它的真实值存在于计算得到的置信区间内时，可以认为所研究的样本是正常的可能性很大，反之，若真实值存在于模拟值置信区间之外，则说明该样本是非整倍体的风险很大。如样本 4，样本 5，样本 6，它们的真实值即来源于 21号染色体组合的核酸分子量都在置信区间范围之外，则用本方法所获得的结论为它们为 18号染色体非整倍性胎儿样本，该结果得到了核型分析结果的证明。 The true value in Table 9 (second column) is the statistically derived molecular weight of the nucleic acid derived from the chromosome 18 window combination of each sample; the nucleic acid molecular weight of the simulated window combination with strong correlation with the chromosome 18 window combination in the sample is counted. And related function expressions (as shown in Table 8), and then a confidence interval (confidence level: 95%) obtained through statistical knowledge. For a sample of a study, when its true value exists within the calculated confidence interval, it can be considered that the sample under study is normal, and conversely, if the true value exists outside the confidence interval of the analog value , the risk that the sample is aneuploid is very high. For example, sample 4, sample 5, and sample 6, whose true values are derived from the molecular weight of the chromosome 21 combination are outside the confidence interval, the conclusion obtained by this method is that they are chromosome 18 aneuploidy. Fetal samples, the results were confirmed by the results of the karyotype analysis.

通过比较上述的各样本来源于第一类染色体窗口组合的核酸片段分子的量的值（真实值）与所获得的模拟值置信区间，判断是否存在着在第一类染色体上的胎儿非整倍体染色体或非整倍体染色体区域。如表 9所示，可以看到 18号染色体三体的真实值在模拟值置信区间之外，而正常两倍体样本其真实值在模拟值置信区间范围之内。图 9和图 10, 显示了 6个来自孕妇外周血核酸样本，样本 1，样本 2与样本 3的真实值在各自的模拟值置信区间之内，可以认为样本正常，而样本 4，样本 5与样本 6的真实值在各自的置信区间之外，认为 18号染色体非整倍性风险很高。 By comparing the value (true value) of the amount of the nucleic acid fragment molecule of each sample derived from the first type of chromosome window combination with the obtained confidence interval of the simulated value, it is determined whether there is fetal aneuploidy on the first type of chromosome. A chromosome or aneuploid chromosome region. As shown in Table 9, it can be seen that the true value of the trisomy of chromosome 18 is outside the confidence interval of the analog value, while the true value of the normal double-body sample is within the range of the confidence interval of the analog value. Figure 9 and Figure 10 show six nucleic acid samples from pregnant women's peripheral blood. Sample 1, sample 2 and sample 3 are within the confidence interval of their respective simulated values. The sample can be considered normal, while sample 4, sample 5 and The true value of sample 6 is outside the respective confidence intervals, and the risk of aneuploidy on chromosome 18 is considered to be high.

Claims

1. 检测个体染色体非整倍性的方法，包括： 1. A method of detecting an individual aneuploidy of an individual, comprising:

对全基因组进行测序，将作为研究对象的待研究染色体定义为第一类染色体，全基因組中其余染色体定义为第二类染色体；依据第二类染色体片段与第一类染色体片段的行为值的相关性，在全基因组上建立数学模型； The whole genome is sequenced, and the chromosome to be studied as the research object is defined as the first chromosome, and the remaining chromosomes in the whole genome are defined as the second chromosome; according to the correlation between the behavior of the second chromosome fragment and the first chromosome fragment Sex, build mathematical models on the whole genome;

对待测个体进行全基因组测序，进而得到待检测个体本身的的笫一类染色体和第二类染色体的行为值，如果在一定的置信水平上的行为值不满足前述数学模型，则可以确定待测个体的染色体是非整倍性的。 Perform genome-wide sequencing of the individual to be tested, and then obtain the behavior values of the first-class chromosome and the second-type chromosome of the individual to be detected. If the behavior value at a certain confidence level does not satisfy the aforementioned mathematical model, the test can be determined. The chromosome of an individual is aneuploidy.

2. 权利要求 1的方法，所述方法包括： 2. The method of claim 1, the method comprising:

依据行为值，通过数学统计方法寻找第二类染色体上的与第一类染色体有强相关性的窗口或其组合，建立函数关系式； According to the behavior value, a mathematical correlation method is used to find a window or a combination thereof on the second type of chromosome which has strong correlation with the first type of chromosome, and a function relationship is established;

依据函数关系式和待检测样本中第二类染色体各窗口中真实的核酸分子的量，在一定置信水平下，得到待研究笫一类染色体的行为值的模拟值置信区间； According to the functional relationship and the amount of real nucleic acid molecules in each window of the second type of chromosome in the sample to be detected, at a certain confidence level, a confidence interval of the simulated value of the behavior value of the chromosome to be studied is obtained;

通过判断检测样本的笫一类染色体的行为值与其模拟值置信区间的关系，判定第一类染色体是否异常。 It is determined whether the first type of chromosome is abnormal by judging the relationship between the behavior value of the chromosome of the test sample and the confidence interval of the analog value.

3.权利要求 1的方法，包括建模步骤（1) - (4)和检测步骤（5) - (8) , 所述步骤如下： 3. The method of claim 1 comprising modeling steps (1) - (4) and detecting steps (5) - (8), said steps being as follows:

(1)选择来自无染色体缺陷的正常个体样本的全基因组进行测序，将作为研究对象的待研究染色体定义为第一类染色体，其余染色体定义为第二类染色体； (1) selecting a whole genome from a sample of a normal individual without chromosomal defects for sequencing, and defining the chromosome to be studied as the first chromosome, and the remaining chromosomes as the second chromosome;

(2)将（1)中的所有染色体分别切割成相互重叠或者不重叠的片段，每个片段定义为一个窗口； (2) cutting all the chromosomes in (1) into overlapping or non-overlapping segments, each segment being defined as a window;

(3)统计在多个不同实验条件下多个正常个体样本染色体各窗口的核酸分子的量，将该量定义为行为值； (3) counting the amount of nucleic acid molecules in each window of a plurality of normal individual sample samples under a plurality of different experimental conditions, and defining the amount as a behavior value;

(4)依据（3)中的行为值，通过数学统计法寻找（1)中的第二类染色体上的与（1)中的笫一类染色体有强相关性的窗口或其组合，建立第一类染色体的窗口和所找到的有强相关性窗口或其组合的函数关系式 A，由此完成建模步骤； (4) According to the behavior value in (3), find a window or a combination of a strong correlation between the chromosomes of the second type (1) and the chromosomes of (1) in the (1) by mathematical statistics. The window of a type of chromosome and the strong phase found a functional relationship A of the closed window or a combination thereof, thereby completing the modeling step;

(7)将 (6)中的第二类染色体各窗口的行为值引入到关系式 A中，设定置信水平，计算得到第一类染色体行为值的理论区间； (7) Introducing the behavior value of each window of the second type of chromosome in (6) into relation A, setting a confidence level, and calculating a theoretical interval of the first type of chromosome behavior value;

(8)如果（6)中统计的第一类染色体的行为值不在（7)中的行为值的理论区间范围内，则认为待研究的第一类染色体异常。 (8) If the behavior value of the first type of chromosome counted in (6) is not within the theoretical interval of the behavior value in (7), then the first type of chromosome abnormality to be studied is considered.

4. 权利要求 3的方法，其中将步骤（1) - (4)的关系式在不同待测样本的检测中重复使用，不需要每次样本检测时都重复测定，通过进行步骤（5) - (8)测定染色体的非整倍性。 4. The method of claim 3, wherein the relationship of steps (1) - (4) is repeated in the detection of different samples to be tested, and the measurement is not repeated every time the sample is detected, by performing step (5) - (8) Determination of aneuploidy of chromosomes.

5.权利要求 1的方法，将待检样本全基因组染色体切割成和正常样本中参数一致的窗口。 5. The method of claim 1 wherein the whole genome chromosome of the sample to be examined is cut into a window that is consistent with parameters in the normal sample.

6. 权利要求 3的方法，其中所述函数关系式可以是一个方程式或者多个方程式的组。 6. The method of claim 3, wherein the functional relationship can be an equation or a group of equations.

7.权利要求 5的方法，其中所述函数关系式是一元函数式或是多元函数式。 7. The method of claim 5, wherein the functional relationship is a one-way function or a multi-function.

8.权利要求 3的方法，其中所述待检测个体的样本是来自孕妇的含有胎儿的 DNA的生物样本。 8. The method of claim 3, wherein the sample of the individual to be detected is a biological sample of fetal-containing DNA from a pregnant woman.

9. 权利要求 8的方法，其中所述的来自孕妇的含有胎儿的 DNA的生物样本选自血浆、血清、尿液和唾液。 9. The method of claim 8, wherein said biological sample of fetal-containing DNA from a pregnant woman is selected from the group consisting of plasma, serum, urine, and saliva.

10.权利要求 8的方法，其中所述的来自孕妇的含有胎儿的 DNA的生物样本选自子宫颈脱落细胞和子宫颈沖洗液。 10. The method of claim 8 wherein said biological sample of fetal-containing DNA from a pregnant woman is selected from the group consisting of cervical detachment cells and cervical lavage fluid.

11. 权利要求 1或 3的方法，其中的第一类染色体选自 21号染色体序列， 18号染色体序列， 1 3号染色体序列， X染色体序列和 Y染色体序列或其片段序列， 11. The method of claim 1 or 3, wherein the first type of chromosome is selected from the group consisting of chromosome 21 sequence, chromosome 18 sequence, chromosome 1 sequence, X chromosome sequence and Y chromosome sequence or fragment sequence thereof,

12.权利要求 3的方法，正常个体样本的选择来自不同实验条件下多个样本。 12. The method of claim 3, wherein the selection of the normal individual sample is from a plurality of samples under different experimental conditions.

13.权利要求 1或 3的方法，其中数学模型的建立由计算机程序优化完成。 13. The method of claim 1 or 3, wherein the establishing of the mathematical model is accomplished by computer program optimization.

14.权利要求 1 3的方法，其中计算机程序通过不同的参数选择，完成相关性窗口的寻找，寻找最优参数，建立第一类染色体窗口与第二类染色体窗口的函数关系式。 14. The method of claim 13 wherein the computer program selects the correlation window by different parameter selections, finds the optimal parameters, and establishes a functional relationship between the first type of chromosome window and the second type of chromosome window.

15.权利要求 1或 14的方法，其中所迷参数选自窗口大小和 over l ap大小. 15. The method of claim 1 or 14, wherein the parameters are selected from a window size and an over l ap size.

16.权利要求 15的方法，其中的窗口大小选自 300kb和 500kb，对应的 over l ap大小分别为 150kb 和 250kb。 ' 16. The method of claim 15 wherein the window size is selected from the group consisting of 300 kb and 500 kb, and the corresponding over l ap sizes are 150 kb and 250 kb, respectively. '

17.权利要求 3的方法，其中所迷置信水平为 90%置信区间、 95½置信区间或 99%置信区间。 17. The method of claim 3 wherein the confidence level is a 90% confidence interval, a 951⁄2 confidence interval, or a 99% confidence interval.

18.权利要求 17的方法，其中所述置信区间包括每个检测窗口的置信区间和整条染色体的置信区间。 18. The method of claim 17, wherein said confidence interval comprises a confidence interval for each detection window and a confidence interval for the entire chromosome.

19. 权利要求 3的方法，当窗口为 300kb时， over l ap为 150kb，其中有极强相关性窗口组合选自下述窗口组合： 19. The method of claim 3, when the window is 300 kb, the over l ap is 150 kb, wherein the combination of extremely strong correlation windows is selected from the following window combinations:

当第一类染色体的窗口是第 21号染色体的碱基位置为 14400 k - 14700 k的窗口时，其对应的笫二类染色体窗口是第 1 3号染色体的碱基位置为 37050 k-37350 k的窗口；当第一类染色体的窗口是第 21号染色体的碱基位置为 14550 k-14850 k的窗口时，其对应的笫二类染色体窗口是第 5号染色体的碱基位置为 88050 k-88350 k的窗口；当第一类染色体的窗口是第 21号染色体的碱基位置为 14700 k - 15000 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 16500 k-16800 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 14850 k - 15150 k的窗口时，其对应的笫二类染色体窗口是笫 12号染色体的碱基位置为 1 6500 k-16800 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15000 k - 15300 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 144300 k-144600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15150 k - 15450 k的窗口时，其对应的笫二类染色体窗口是第 2号染色体的碱基位置为 144300 k-144600 k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 15300 k - 15600 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 145050 k-145350 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15450 k - 15750 k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 56400 k-56700 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15600 k - 15900 k的窗口时，其对应的第二类染色体窗口是笫 3号染色体的碱基位置为 21750 k-22050 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15750 k - 16050 k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 1 05150 k-1 05450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 15900 k - 16200 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 50850 k-51150 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16050 k - 16350 k的窗口时, 其对应的第二类染色体窗口是第 12号染色体的碱基位置为 77850 k-78150 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16200 k - 16500 k的窗口时, 其对应的第二类染色体窗口是笫 4号染色体的碱基位置为 1 12800 k-11 3100 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16350 k - 16650 k的窗口时, 其对应的第二类染色体窗口是第 5号染色体的碱基位置为 83250 k-83550 k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 16500 k - 16800 k的窗口时，其对应的笫二类染色体窗口是第 3号染色体的碱基位置为 76200 k-76500 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16650 k - 16950 k的窗口时，其对应的第二类染色体窗口是笫 9号染色体的碱基位置为 74850 k-75150 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16800 k - 17100 k的窗口时，其对应的第二类染色体窗口是笫 5号染色体的碱基位置为 50700 k-51000 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 16950 k - 17250 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 1 38600 k-1 38900 k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 17100 k - 17400 k的窗口时, 其对应的第二类染色体窗口是第 8号染色体的碱基位置为 77100 k-77400 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 17250 k - 17550 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 1 38450 k-1 38750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 17700 k - 18000 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 111750 k-112050 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18000 k - 18300 k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 36150 k-36450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18150 k - 18450 k的窗口时, 其对应的第二类染色体窗口是笫 4号染色体的碱基位置为 119250 k-119550 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18300 k - 18600 k的窗口时, 其对应的第二类染色体窗口是第 3号染色体的碱基位置为 450 k-750 k的窗口； When the window of the first type of chromosome is the window of the chromosome 21 with the base position of 14400 k - 14700 k, the corresponding chromosome 2 window is the base position of chromosome 13 is 37050 k-37350 k When the window of the first type of chromosome is the window of the chromosome 21 with the base position of 14550 k-14850 k, the corresponding chromosome of the second chromosome is the base position of the chromosome 5 is 88050 k- a window of 88350 k; when the window of the first type of chromosome is a window with a base position of chromosome 21 of 14700 k - 15000 k, the corresponding second type of chromosome window is the base position of the chromosome 12 is 16500 The window of the k-16800 k; when the window of the first type of chromosome is the window of the chromosome 21 with the base position of 14850 k - 15150 k, the corresponding chromosome of the chromosome 2 is the base position of the chromosome 12 1 6500 k-16800 k window; the first chromosome window is the window of the chromosome 21 with a base position of 15000 k - 15300 k, the corresponding second chromosome window is the base of chromosome 2 The location is 144300 k-144600 k The first type of chromosome window is the window of the chromosome 21 with a base position of 15150 k - 15450 k, and its corresponding chromosome 2 window is the base position of chromosome 2 is 144300 k-144600 k The window of the first type of chromosome is when the base position of chromosome 21 is 15300 k - 15600 k, and the corresponding second type of chromosome window is the base position of chromosome 2 is 145050 k-145350 The window of k; the window of the first type of chromosome is the window of chromosome 21 with a base position of 15450 k - 15750 k, and its corresponding second type of chromosome window is the base position of chromosome 17 is 56400 k- The window of the first type of chromosome is the window of the chromosome 21 with a base position of 15600 k - 15900 k. The corresponding second type of chromosome window is the base position of the chromosome 3 is 21750 k a window of -22050 k; the window of the first type of chromosome is a window of chromosome 15 with a base position of 15750 k - 16050 k, and the corresponding second type of chromosome window is the base position of chromosome 8 is 1 05150 k-1 05450 k The window of the first type of chromosome is when the base position of chromosome 21 is 15900 k - 16200 k The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 50850 k-51150 k; the window of the first type of chromosome is when the base position of chromosome 21 is 16050 k - 16350 k The corresponding second type of chromosome window is a window with a base position of chromosome 19 of 77850 k-78150 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 16200 k - 16500 k The corresponding second type of chromosome window is a window with a base position of 124 chromosome of 1 12800 k-11 3100 k; the window of the first type of chromosome is the base position of chromosome 21 of 16350 k - 16650 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 5 is 83250 k-83550 k; the window of the first chromosome is the base position of chromosome 21 is 16500 k - When the window is 16800 k, the corresponding chromosome 2 window is the window with the base position of chromosome 3 being 76200 k-76500 k; the window of the first chromosome is the base position of chromosome 21 is 16650 k - 16950 k when the window is right The second type of chromosome window is the window of the base position of the chromosome 9 is 74850 k-75150 k; the window of the first type of chromosome is the window of the chromosome 21 with the base position of 16800 k - 17100 k. The corresponding second type of chromosome window is a window with a base position of 7005 chromosome of 50700 k-51000 k; the window of the first type of chromosome is when the base position of chromosome 21 is 16950 k - 17250 k The corresponding second type of chromosome window is a window with the base position of chromosome 4 being 1 38600 k-1 38900 k; the window of the first chromosome is the base position of chromosome 21 is 17100 k - 17400 k The window of the second type of chromosome is the window of the chromosome 8 with a base position of 77100 k-77400 k; the window of the first chromosome is the base position of chromosome 21 is 17250 k - 17550 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 4 is 1 38450 k-1 38750 k; the window of the first chromosome is the base position of chromosome 21 is 17700 k - 18000 k when the window, its The second type of chromosome window is a window with a base position of chromosome 7 of 111750 k-112050 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 18000 k - 18300 k, The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 36150 k-36450 k; the window of the first type of chromosome is when the base position of chromosome 21 is 18150 k - 18450 k The corresponding second type of chromosome window is a window with a base position of 1194 chromosome of 119250 k-119550 k; the window of the first type of chromosome is a window with a base position of chromosome 18 of 18300 k - 18600 k The corresponding second type of chromosome window is a window with a base position of chromosome 3 of 450 k-750 k;

第一类染色体的窗口是第 21号染色体的碱基位置为 18450 k - 18750 k的窗口时, 其对应的第二类染色体窗口是第 6号染色体的碱基位置为 69300 k-69600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18600 k - 18900 k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 69450 k-69750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18750 k - 19050 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 62400 k-62700 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 18900 k - 19200 k的窗口时，其对应的第二类染色体窗口是笫 4号染色体的碱基位置为 62250 k-62550 k的窗口; 第一类染色体的窗口是第 21号染色体的碱基位置为 19050 k - 19350 k的窗口时，其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 1 35300 k-135600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19200 k - 19500 k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 1 03350 k-1 03650 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19350 k - 19650 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 125550 k-125850 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19500 k - 19800 k的窗口时，其对应的第二类染色体窗口是笫 3号染色体的碱基位置为 85350 k-85650 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19650 k - 19950 k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 166650 k-166950 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19800 k - 201 00 k的窗口时，其对应的第二类染色体窗口是笫 1 3号染色体的碱基位置为 67350 k-67650 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 19950 k - 20250 k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 167250 k- 167550 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20100 k - 20400 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 62400 k-62700 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20250 k - 20550 k的窗口时，其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 62400 k-62700 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20400 k - 20700 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 12150 k-12450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20550 k - 20850 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 125550 k-125850 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20700 k - 21 000 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 1 18050 k-118350 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 20850 k - 21 150 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 81750 k-82050 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21000 k - 21 300 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 112650 k-112950 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21150 k - 21450 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 81750 k-82050 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21 300 k - 21600 k的窗口时，其对应的笫二类染色体窗口是第 5号染色体的碱基位置为 83250 k-83550 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21450 k - 21750 k的窗口时, 其对应的第二类染色体窗口是第 12号染色体的碱基位置为 84450 k-84750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21600 k - 21900 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 84450 k-84750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21750 k - 22050 k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 82650 k-82950 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 21900 k - 22200 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 141150 k-141450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22050 k - 22350 k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 51450 k-51750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22200 k - 22500 k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 51450 k-51750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22500 k - 22800 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 1 35150 k-135450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22650 k - 22950 k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 105300 k-105600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22800 k - 23100 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 184950 k-185250 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 22950 k - 23250 k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 141000 k-141 300 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 23100 k - 23400 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 141600 k-141900 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 23250 k - 23550 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 82350 k-82650 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 26700 k - 27000 k的窗口时, 其对应的第二类染色体窗口是第 8号染色体的碱基位置为 93450 k-93750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 26850 k - 27150 k的窗口时, 其对应的第二类染色体窗口是第 1 3号染色体的碱基位置为 46800 k-47100 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 31200 k - 31500 k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 47100 k-47400 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 31350 k - 31650 k的窗口时，其对应的第二类染色体窗口是第 18号染色体的碱基位置为 41100 k-41400 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 31500 k - 31800 k的窗口时, 其对应的第二类染色体窗口是第 12号染色体的碱基位置为 87600 k-87900 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 2i l 650 k - 31950 k的窗口时, 其对应的第二类染色体窗口是第 15号染色体的碱基位置为 60300 k-60600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 31950 k - 32250 k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 38850 k-39150 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 32100 k - 32400 k的窗口时，其对应的第二类染色体窗口是第 1 3号染色体的碱基位置为 97650 k-97950 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 32250 k - 32550 k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 169500 k-169800 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 32400 k - 32700 k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 20850 k-21150 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 32550 k - 32850 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 1500 k-1800 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 33000 k - 33300 k的窗口时，其对应的第二类染色体窗口是第 18号染色体的碱基位置为 71550 k-71850 k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 33150 k - 33450 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 52350 k-52650 k的窗口；笫一类染色体的窗口是第 21号染色体的碱基位置为 33300 k - 33600 k的窗口时，其对应的第二类染色体窗口是第 18号染色体的碱基位置为 52350 k-52650 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 33600 k - 33900 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 24600 k-24900 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 33750 k - 34050 k的窗口时，其对应的笫二类染色体窗口是笫 11号染色体的碱基位置为 84900 k-85200 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 33900 k - 34200 k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 120300 k-120600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 34050 k - 34350 k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 165450 k-165750 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 34200 k - 34500 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 45600 k-45900 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 3⁴350 k - 34650 k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 105300 k-105600 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 34500 k - 34800 k的窗口时，其对应的笫二类染色体窗口是第 21号染色体的碱基位置为 24750k-25050 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 34650k - 34950k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 60450k-60750 k的窗口； The window of the first type of chromosome is when the base position of chromosome 21 is 18450 k - 18750 k. The corresponding second type of chromosome window is a window with the base position of chromosome 6 being 69300 k-69600 k; the window of the first type of chromosome is when the base position of chromosome 21 is 18600 k - 18900 k The corresponding second type of chromosome window is a window with the base position of chromosome 6 being 69450 k-69750 k; the window of the first type of chromosome is a window with the base position of chromosome 21 being 18750 k - 19050 k The corresponding second type of chromosome window is a window with a base position of chromosome 4 of 62400 k-62700 k; the window of the first type of chromosome is the base position of chromosome 21 of 18900 k - 19200 k In the window, the corresponding second type of chromosome window is the window with the base position of chromosome 4 being 62250 k-62550 k; the window of the first chromosome is the base position of chromosome 21 is 19050 k - 19350 k When the window is located, the corresponding chromosome 2 window is the window with the base position of chromosome 4 being 1 35300 k-135600 k; the window of the first chromosome is the base position of chromosome 21 is 19200 k - 19500 k when the window, its The second type of chromosome window should be the window with the base position of chromosome 5 being 1 03350 k-1 03650 k; the window of the first chromosome is the window with the base position of chromosome 21 being 19350 k - 19650 k The corresponding second type of chromosome window is a window with the base position of chromosome 7 being 125550 k-125850 k; the window of the first type of chromosome is the base position of chromosome 21 being 19500 k - 19800 k In the window, the corresponding second type of chromosome window is the window with the base position of chromosome 3 being 85350 k-85650 k; the window of the first chromosome is the base position of chromosome 21 is 19650 k - 19950 k In the window, the corresponding second type of chromosome window is the window of chromosome 3 with a base position of 166650 k-166950 k; the window of the first type of chromosome is the base position of chromosome 21 is 19800 k - 201 In the window of 00 k, the corresponding second type of chromosome window is the window of the base position of chromosome 13 of the 笫1 3 chromosome is 67350 k-67650 k; the window of the first type of chromosome is the base position of the chromosome 21 is 19950 k - 20250 k window The corresponding second type of chromosome window is a window with the base position of chromosome 3 being 167250 k-167550 k; the window of the first type of chromosome is when the base position of chromosome 21 is 20100 k - 20400 k The corresponding second type of chromosome window is a window with a base position of chromosome 4 of 62400 k-62700 k; the window of the first type of chromosome is a window with a base position of chromosome 20 of 20250 k - 20550 k When the corresponding chromosome 2 window is the window of the chromosome 4 with a base position of 62400 k-62700 k; the window of the first chromosome is the base position of the chromosome 21 is 20400 k - 20700 k In the window, the corresponding second type of chromosome window is a window with the base position of chromosome 7 being 12150 k-12450 k; the window of the first chromosome is the base position of chromosome 21 is 20550 k - 20850 k Window when The corresponding second type of chromosome window is a window with the base position of chromosome 7 being 125550 k-125850 k; the window of the first type of chromosome is the window with the base position of chromosome 21 being 20700 k - 21 000 k The corresponding second type of chromosome window is a window with the base position of chromosome 7 being 1 18050 k-118350 k; the window of the first chromosome is the base position of chromosome 21 is 20850 k - 21 150 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 12 is 81750 k-82050 k; the window of the first chromosome is the base position of chromosome 21 is 21000 k - In the case of a window of 21 300 k, the corresponding second type of chromosome window is a window with a base position of chromosome 4 of 112650 k-112950 k; the window of the first type of chromosome is the base position of chromosome 21 of 21150. When the window of k - 21450 k, the corresponding second type of chromosome window is the window of the chromosome 4 with the base position of 81750 k-82050 k; the window of the first type of chromosome is the base position of the chromosome 21 21 300 k - 21600 k window When the corresponding chromosome 2 window is the window of the chromosome 5 whose base position is 83250 k-83550 k; the window of the first chromosome is the base position of chromosome 21 is 21450 k - 21750 k In the window, the corresponding second type of chromosome window is the window of the chromosome 12 with the base position of 84450 k-84750 k; the window of the first type of chromosome is the base position of the chromosome 21 is 21600 k - 21900 k The window of the second type is the window of the chromosome 12 with the base position of 84450 k-84750 k; the window of the first chromosome is the base position of chromosome 21 is 21750 k - 22050 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 3 is 82650 k-82950 k; the window of the first chromosome is the base position of chromosome 21 is 21900 k - In the window of 22200 k, the corresponding second type of chromosome window is the window with the base position of chromosome 2 being 141150 k-141450 k; the window of the first chromosome is the base position of chromosome 21 is 22050 k - 22350 k window when The corresponding second type of chromosome window is a window with a base position of the chromosome 5 of 51450 k-51750 k; the window of the first type of chromosome is a window with a base position of the chromosome 21 of 22200 k - 22500 k The corresponding second type of chromosome window is a window with the base position of chromosome 5 being 51450 k-51750 k; the window of the first type of chromosome is the base position of chromosome 21 being 22500 k - 22800 k In the window, the corresponding second type of chromosome window is a window with the base position of chromosome 4 being 1 35150 k-135450 k; the window of the first chromosome is the base position of chromosome 21 is 22650 k - 22950 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 5 is 105300 k-105600 k; the window of the first chromosome is the base position of chromosome 21 is 22800 k - 23100 k window, The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 184950 k-185250 k; the window of the first type of chromosome is when the base position of chromosome 21 is 22950 k - 23250 k The corresponding second type of chromosome window is a window with a base position of chromosome 2 of 141000 k-141 300 k; the window of the first type of chromosome is the base position of chromosome 21 of 23100 k - 23400 k In the window, the corresponding second type of chromosome window is the window with the base position of chromosome 2 being 141600 k-141900 k; the window of the first type of chromosome is the base position of chromosome 21 is 23250 k - 23550 k The window of the second type of chromosome is the window of the chromosome 12 with a base position of 82350 k-82650 k; the window of the first chromosome is the base position of chromosome 21 is 26700 k - 27000 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 8 is 93450 k-93750 k; the window of the first chromosome is the base position of chromosome 21 is 26850 k - 27150 k when the window, its The corresponding second type of chromosome window is a window with the base position of chromosome 13 being 46800 k-47100 k; the window of the first type of chromosome is when the base position of chromosome 21 is 31200 k - 31500 k The corresponding second type of chromosome window is a window with a base position of chromosome 6 of 47100 k-47400 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 31350 k - 31650 k The corresponding second type of chromosome window is a window with a base position of chromosome 18 of 41100 k-41400 k; the window of the first type of chromosome is the base position of chromosome 21 of 31500 k - 31800 k In the window, the corresponding second type of chromosome window is a window with the base position of chromosome 12 being 87600 k-87900 k; the window of the first type of chromosome is the base position of chromosome 21 being 2i l 650 k - In the window of 31950 k, the corresponding second type of chromosome window is the window of chromosome 15 with the base position of 60300 k-60600 k; the window of the first chromosome is the base position of chromosome 21 is 31950 k - 32250 k when the window, its The second type of chromosome window should be a window with a base position of chromosome 38 of 38850 k-39150 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 32100 k - 32400 k, The corresponding second type of chromosome window is a window with the base position of chromosome 13 being 97650 k-97950 k; the window of the first type of chromosome is the window with the base position of chromosome 21 being 32250 k - 32550 k The corresponding second type of chromosome window is a window with the base position of chromosome 5 being 169500 k-169800 k; the window of the first chromosome is the base position of chromosome 21 being 32400 k - 32700 k In the window, the corresponding second type of chromosome window is the window with the base position of chromosome 8 being 20850 k-21150 k; the window of the first type of chromosome is the base position of chromosome 21 is 32550 k - 32850 k Window when The corresponding second type of chromosome window is a window with the base position of chromosome 12 being 1500 k-1800 k; the window of the first type of chromosome is when the base position of chromosome 21 is 33000 k - 33300 k The corresponding second type of chromosome window is a window with a base position of the chromosome 18 of 71550 k-71850 k; the window of the first type of chromosome is a window with a base position of the chromosome 21 of 33150 k - 33450 k The corresponding second type of chromosome window is a window with the base position of chromosome 12 being 52350 k-52650 k; the window of the first chromosome is the base position of chromosome 21 being 33300 k - 33600 k In the window, the corresponding second type of chromosome window is the window with the base position of chromosome 18 being 52350 k-52650 k; the window of the first chromosome is the base position of chromosome 21 is 33600 k - 33900 k The window of the second type is the window of the chromosome 4 with a base position of 24600 k-24900 k; the window of the first chromosome is the base position of chromosome 21 is 33750 k - 34050 K when the window, its The corresponding 笫 second-class chromosome window is a window with a base position of 84911 chromosome of 84900 k-85200 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 33900 k - 34200 k, The corresponding second type of chromosome window is a window with a base position of chromosome 12 of 120300 k-120600 k; the window of the first type of chromosome is when the base position of chromosome 21 is 34050 k - 34350 k The corresponding second type of chromosome window is a window with a base position of chromosome 165450 k-165750 k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 34200 k - 34500 k The corresponding second type of chromosome window is a window with a base position of chromosome 2 of 45600 k-45900 k; the window of the first type of chromosome is the base position of chromosome 21 of 3 ⁴ 350 k - 34650 When the window of k is the corresponding second type of chromosome window, the base position of chromosome 2 is 105300 k-105600 k; the window of the first chromosome is the base position of chromosome 21 is 34500 k - 34800 k window time The corresponding chromosome 2 window is the window of the chromosome 21 with the base position of 24750k-25050 k; the window of the first chromosome is the window of the chromosome 21 with the base position of 34650k - 34950k, the corresponding The second type of chromosome window is a window with a base position of the second chromosome of 60450k-60750k;

第一类染色体的窗口是第 21号染色体的碱基位置为 34800k - 35100k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 157⁹50k-158²50 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 34950k - 35250k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 157950k-158250 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 35100k - 35400k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 8100k-8400 k的窗口；笫一类染色体的窗口是笫 21号染色体的碱基位置为 35250k - 35550k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 72600k-72900 k的窗口； The window of the first type of chromosome is when the base position of chromosome 21 is 34800k - 35100k, and the corresponding second type of chromosome window is the base position of chromosome 6 is 157 ⁹ 50k-158 ² 50 k Window; the window of the first type of chromosome is the window of the chromosome 21 with the base position of 34950k - 35250k, and the corresponding second type of chromosome window is the window of the chromosome 6 with the base position of 157950k-158250k; The window of the first type of chromosome is when the base position of the chromosome 21 is 35100k - 35400k, The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 8100k-8400 k; the window of the first chromosome is the window with the base position of chromosome 21 being 35250k - 35550k, and its corresponding The second type of chromosome window is a window with a base position of chromosome 5 of 72600k-72900k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 35400k - 35700k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 83550k-83850 k的窗口； The window of the first type of chromosome is when the base position of chromosome 21 is 35400k - 35700k, and the corresponding second type of chromosome window is the window of the chromosome 4 whose base position is 83550k-83850 k;

第一类染色体的窗口是第 21号染色体的碱基位置为 35550k - 35850k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 73500k-73800 k的窗口； When the window of the first type of chromosome is the window of chromosome 21 with a base position of 35550k - 35850k, the corresponding second type of chromosome window is a window with a base position of chromosome 3 of 73500k-73800 k;

第一类染色体的窗口是第 21号染色体的碱基位置为 35700k - 36000k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 56100k-56400 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 35850k - 36150k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 174150k-174450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 36000k - 36300k的窗口时，其对应的第二类染色体窗口是第 15号染色体的碱基位置为 58950k-59250 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 36150k - 36450k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 15000k-15300 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 36300k - 36600k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 157950k-158250 k的窗口；笫一类染色体的窗口是第 21号染色体的碱基位置为 36600k - 36900k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位直为 12150k-12450 k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 36750k - 37050k的窗口时，其对应的第二类染色体窗口是第 15号染色体的碱基位置为 77100k-77400k的窗口； The window of the first type of chromosome is a window with a base position of chromosome 21 of 35700k - 36000k, and the corresponding second type of chromosome window is a window with a base position of chromosome 12 of 56100k-56400 k; When the chromosome-like window is a window with a base position of chromosome 35 of 35850k - 36150k, the corresponding second type of chromosome window is a window with a base position of chromosome 174150k-174450 k; the first type of chromosome The window of the chromosome 21 is a window with a base position of 36000k - 36300k, and the corresponding second type of chromosome window is a window with a base position of chromosome 15 of 58950k-59250 k; the window of the first chromosome When the base position of chromosome 21 is 36150k - 36450k, the corresponding second type of chromosome window is a window with a base position of chromosome 17 of 15000k-15300 k; the window of the first chromosome is the first When the base position of chromosome 21 is 36300k - 36600k, the corresponding second type of chromosome window is the base position of chromosome 6 is 157950k-158250 k Window; The window of a genus of chromosomes is the window of chromosome 21 with a base position of 36600k - 36900k, and its corresponding second type of chromosome window is a window with the base of chromosome 11 being directly 12150k-12450 k The window of the first type of chromosome is the window of the chromosome 21 with the base position of 36750k - 37050k, and the corresponding second type of chromosome window is the window of the chromosome 15 with the base position of 77100k-77400k;

第一类染色体的窗口是第 21号染色体的碱基位置为 36900k - 37200k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 120150k-120450k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 37050k - 37350k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 37500k-37800k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 36900k - 37200k, and the corresponding second type of chromosome window is the window of the chromosome 11 with the base position of 120150k-120450k; When the chromosome window is a window with a base position of chromosome 37 of 37050k - 37350k, the corresponding second type of chromosome window is a window with a base position of chromosome 3 of 37500k-37800k;

第一类染色体的窗口是第 21号染色体的碱基位置为 37200k - 37500k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 42600k-42900k的窗口； When the window of the first type of chromosome is a window with a base position of chromosome 21 of 37200k - 37500k, the corresponding second type of chromosome window is a window with a base position of chromosome 2 of 42600k-42900k;

第一类染色体的窗口是第 21号染色体的碱基位置为 37350k - 37650k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 186150 k -186450k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 37500k - 37800k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 20100 k -20400k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 37650k - 37950k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 54900 k -55200k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 37800k - 38100k的窗口时，其对应的第二类染色体窗口是第 15号染色体的碱基位置为 78750 k -79050k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 37950k - 38250k的窗口时，其对应的第二类染色体窗口是笫 12号染色体的碱基位置为 118350 k -118650k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 38100k - 38400k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 93450 k -93750k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 38250k - 38550k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 66150 k -66450k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 38400k - 38700k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 30300 k -30600k的窗口；笫一类染色体的窗口是第 21号染色体的碱基位置为 38550k - 38850k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 1 00800 k -1011 00k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 38700k - 39000k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 96600 k -96900k的窗口；笫一类染色体的窗口是第 21号染色体的碱基位置为 38850k - 39150k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 1 30650k -130950k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 39000k - 39300k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 1050k -1 350k的窗口； The window of the first type of chromosome is when the base position of the chromosome 21 is 37350k - 37650k, The corresponding second type of chromosome window is a window with a base position of chromosome 186150 k -186450k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 37500k - 37800k, corresponding to The second type of chromosome window is a window with a base position of chromosome 20 of 20100 k -20400 k; the window of the first type of chromosome is a window with a base position of the chromosome 21 of 37650 k - 37950 k, which corresponds to the second The chromosome-like window is the window of the chromosome 3 with a base position of 54900 k -55200 k; the window of the first chromosome is the window of the chromosome 21 with a base position of 37800k - 38100k, and the corresponding second chromosome The window is the window of the chromosome 15 with the base position of 78750 k -79050k; the window of the first chromosome is the window of the chromosome 21 with the base position of 37950k - 38250k, and the corresponding second type of chromosome window is The base position of chromosome 12 is 118350 k -118650k; the window of the first chromosome is the window of chromosome 21 with the base position of 38100k - 38400k. The second type of chromosome window is the window of the chromosome 12 with the base position of 93450 k -93750k; the window of the first type of chromosome is the window of the chromosome 21 with the base position of 38250k - 38550k, the corresponding second The chromosome-like window is a window with the base position of chromosome 12 being 66150 k -66450k; the window of the first chromosome is the window of the second chromosome of chromosome 21 when the base position of the chromosome is 38400k - 38700k The window is a window with a base position of chromosome 3 of 30300 k -30600k; when the window of a chromosome of chromosome 1 is a window with a base position of 38550k - 38850k, the corresponding second type of chromosome window is The base position of chromosome 9 is a window of 1 00800 k -1011 00k; when the window of the first type of chromosome is a window with a base position of chromosome 21 of 38700k - 39000k, the corresponding second type of chromosome window is The base position of chromosome 9 is a window of 96600 k -96900k; the window of a chromosome of the first chromosome is the window with the base position of chromosome 21 being 38850k - 39150k, which corresponds to the second The chromosome window is a window with the base position of chromosome 11 being 1 30650k -130950k; the window of the first chromosome is the window of the second chromosome of the chromosome 21 with the base position of 39000k - 39300k Is a window with a base position of chromosome 10 of 1050k -1 350k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 39150k - 39450k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 169800k -170100k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 39300k - 39600k的窗口时，其对应的笫二类染色体窗口是第 3号染色体的碱基位置为 43200k -43500k的窗口； The window of the first type of chromosome is a window with a base position of 39150k - 39450k, and the corresponding second type of chromosome window is a window with a base position of chromosome 169800k - 170100k; When the chromosome window is a window with the base position of chromosome 21 being 39300k - 39600k, the corresponding chromosome 2 window is the window with the base position of chromosome 3 being 43200k -43500k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 39450k - 39750k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 25650k -25950k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 39750k - 40050k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 173700k -174000k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 39900k - 40200k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 29550k -29850k的窗口； The window of the first type of chromosome is when the base position of the chromosome 21 is 39450k - 39750k, The corresponding second type of chromosome window is a window with a base position of chromosome 6 of 25550k -25950k; the window of the first type of chromosome is a window with a base position of chromosome 31 of 39750k - 40050k, the corresponding The second type of chromosome window is a window with the base position of chromosome 5 being 173700k -174000k; the window of the first type of chromosome is the window of the second type of chromosome when the base position of chromosome 21 is 39900k - 40200k The window is a window with a base position of chromosome 2 of 29550k -29850k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 40200k - 40500k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 104700k -105000k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 40350k - 40650k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 92100k -92400k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 40500k - 40800k的窗口时，其对应的第二类染色体窗口是第 18号染色体的碱基位置为 70650k -70950k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 40650k - 40950k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 1 3950k -14250k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 40800k - 41100k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 9900k -1 0200k的窗口； The window of the first type of chromosome is a window with a base position of 40200k - 40500k on the chromosome 21, and the corresponding second type of chromosome window is a window with a base position of the chromosome 2 of 104700k - 105000k; When the chromosome window is a window with a base position of 40350k - 40650k, the corresponding second chromosome window is a window with a base position of chromosome 11 of 92100k - 92400k; the window of the first chromosome When the base position of chromosome 21 is 40500k - 40800k, the corresponding second type of chromosome window is the window of the chromosome 18 with the base position of 70650k - 70950k; the window of the first chromosome is the 21st. When the base position of the chromosome is 40650k - 40950k, the corresponding second type of chromosome window is the window of the chromosome 12 with the base position of 1 3950k -14250k; the window of the first chromosome is the 21st chromosome When the base position is 40800k - 41100k, the corresponding second type of chromosome window is the base position of chromosome 8 is 9900k -1 0200k Window;

第一类染色体的窗口是第 21号染色体的碱基位置为 40950k - 41250k的窗口时，其对应的第二类染色体窗口是第 18号染色体的碱基位置为 40650k -40950k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 41100k - 41400k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 9750k -1 0050k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 40950k - 41250k, and the corresponding second type of chromosome window is the window of the chromosome 18 with the base position of 40650k -40950k; When the chromosome window is a window with the base position of chromosome 21 being 41100k - 41400k, the corresponding second type of chromosome window is a window with the base position of chromosome 8 being 9750k -1 0050k;

第一类染色体的窗口是第 21号染色体的碱基位置为 41250k - 41550k的窗口时，其对应的第二类染色体窗口是第 20号染色体的碱基位置为 22350k -22650k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 41400k - 41700k的窗口时，其对应的笫二类染色体窗口是第 16号染色体的碱基位置为 55350k -55650k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 41550k - 41850k的窗口时，其对应的第二类染色体窗口是第 15号染色体的碱基位置为 99750k -100050k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 41700k - 42000k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 170700k -171000k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 41850k - 42150k的窗口时，其对应的第二类染色体窗口是第 16号染色体的碱基位置为 48000k -48300k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 42000k - 42300k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 Ok -300k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 41250k - 41550k, and the corresponding second type of chromosome window is the window of the chromosome 20 with the base position of 22350k -22650k; When the chromosome window is a window with the base position of chromosome 21 being 41400k - 41700k, the corresponding chromosome 2 window is the window with the base position of chromosome 16 being 55350k -55650k; the window of the first chromosome When the base position of chromosome 21 is 41550k - 41850k, the corresponding second type of chromosome window is the window of the chromosome 15 with the base position of 99750k - 100050k; the window of the first chromosome is the 21st When the base position of the chromosome is 41700k - 42000k, the corresponding second type of chromosome window is the window of the chromosome 5 with the base position of 170700k -171000k; the window of the first chromosome is the chromosome 21 When the base position is a window of 41850k - 42150k, The corresponding second type of chromosome window is a window with a base position of chromosome 4 of 48000k -48300k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 42000k - 42300k, the corresponding The second type of chromosome window is a window of the chromosome 12 whose base position is Ok -300k;

第一类染色体的窗口是第 21号染色体的碱基位置为 42150k - 42450k的窗口时，其对应的第二类染色体窗口是第 16号染色体的碱基位置为 48000k -48300k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 42300k - 42600k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 73200k -73500k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 42450k - 42750k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 73050k -73350k的窗口；笫一类染色体的窗口是第 21号染色体的碱基位置为 42600k - 42900k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 17550k -17850k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 42750k - 43050k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 120750k -121050k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 42900k - 43200k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 69300k -69600k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 43200k - 43500k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 240450k -240750k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 43350k - 43650k的窗口时，其对应的笫二类染色体窗口是第 21号染色体的碱基位置为 38100k -38400k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 43500k - 43800k的窗口时，其对应的笫二类染色体窗口是第 16号染色体的碱基位置为 83850k -84150k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 43650k - 43950k的窗口时，其对应的第二类染色体窗口是第 16号染色体的碱基位置为 3450k -3750k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 42150k - 42450k, and the corresponding second type of chromosome window is the window of the chromosome 16 with the base position of 48000k -48300k; When the chromosome window is a window with a base position of chromosome 21 of 42300k - 42600k, the corresponding second type of chromosome window is a window with a base position of chromosome 17 of 73200k - 73500k; the window of the first type of chromosome When the base position of chromosome 21 is 42450k - 42750k, the corresponding second type of chromosome window is the window of the 17th chromosome with the base position of 73050k -73350k; the window of the first chromosome is 21st. When the base position of the chromosome is 42600k - 42900k, the corresponding second type of chromosome window is the window of the chromosome 11 with the base position of 17550k -17850k; the window of the first chromosome is the chromosome 21 When the base position is 42750k - 43050k, the corresponding second type of chromosome window is the base position of chromosome 2 is 120750k -121050k Window; the window of the first type of chromosome is the window of the chromosome 21 with a base position of 42900k - 43200k, and the corresponding second type of chromosome window is a window with the base position of the chromosome 11 being 69300k -69600k; The window of a type of chromosome is a window with a base position of chromosome 21 of 43200k - 43500k, and the corresponding second type of chromosome window is a window with a base position of the second chromosome of 240450k - 240750k; The window is the window where the base position of chromosome 21 is 43350k - 43650k, and the corresponding chromosome 2 window is the window with the base position of chromosome 21 being 38100k - 38400k; the window of the first chromosome is When the base position of chromosome 21 is 43500k - 43800k, the corresponding chromosome 2 window is the window of chromosome 16 with the base position of 83850k -84150k; the window of the first chromosome is the 21st When the base position of the chromosome is 43650k - 43950k, the corresponding second type of chromosome window is the base position of chromosome 16 is 3450k -3750k window;

第一类染色体的窗口是第 21号染色体的碱基位置为 43800k - 44100k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 46800k -47100k的窗口； When the window of the first type of chromosome is a window with a base position of chromosome 21 of 43800k - 44100k, the corresponding second type of chromosome window is a window with a base position of chromosome 3 of 46800k - 47100k;

笫一类染色体的窗口是第 21号染色体的碱基位置为 43950k - 44250k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 70950k -71250k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 44100k - 44400k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 156900k -157200k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 44250k - 44550k的窗口时，其对应的第二类染色体窗口是笫 5号染色体的碱基位置为 1350k -1650k的窗口； When the window of the chromosome of the first chromosome is the window of the chromosome 21 with the base position of 43950k - 44250k, the corresponding chromosome window of the second type is the window of the base of the chromosome 17 is 70950k - 71250k; When the chromosome window is a window with a base position of chromosome 21 of 44100k - 44400k, The corresponding second type of chromosome window is a window with a base position of chromosome 156900k -157200k; the window of the first type of chromosome is a window with a base position of chromosome 21 of 44250k - 44550k, the corresponding The second type of chromosome window is a window with a base position of 笫5 chromosome of 1350k -1650k;

第一类染色体的窗口是第 21号染色体的碱基位置为 44400k - 44700k的窗口时，其对应的第二类染色体窗口是第 19号染色体的碱基位置为 1950k -2250k的窗口； When the window of the first type of chromosome is a window with a base position of chromosome 44 of 44400k - 44700k, the corresponding second type of chromosome window is a window with a base position of chromosome 19 of 1950k - 2250k;

第一类染色体的窗口是第 21号染色体的碱基位置为 44550k - 44850k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 136350k -136650k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 44700k - 45000k的窗口时，其对应的第二类染色体窗口是笫 2号染色体的碱基位置为 219900k -220200k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 44850k - 45150k的窗口时，其对应的第二类染色体窗口是第. 2号染色体的碱基位置为 219900k -220200k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 45000k - 45300k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 750k -1050k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 44550k - 44850k, and the corresponding second type of chromosome window is the window of the chromosome 9 with the base position of 136350k - 136650k; When the chromosome window is a window with a base position of chromosome 21 of 44700k - 45000k, the corresponding second type of chromosome window is a window with a base position of 219900k - 220200k on the chromosome 2; a window of the first type of chromosome When the base position of chromosome 21 is 44850k - 45150k, the corresponding second type of chromosome window is the window of chromosome 2 with the base position of 219900k - 220200k; the window of the first chromosome is the first When the base position of chromosome 21 is a window of 45000k - 45300k, the corresponding second type of chromosome window is a window with a base position of chromosome 7 of 750k - 1050k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 45150k - 45450k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 239550k -239850k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 45300k - 45600k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 238950k -239250k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 45450k - 45750k的窗口时，其对应的笫二类染色体窗口是第 20号染色体的碱基位置为 61050k -61350k的窗口；第一类染色体的窗口是笫 21号染色体的碱基位置为 45600k - 45900k的窗口时，其对应的第二类染色体窗口是笫 7号染色体的碱基位置为 1950k -2250k的窗口； The window of the first type of chromosome is a window with a base position of 45150k - 45450k, and the corresponding second type of chromosome window is a window with a base position of chromosome 239550k -239850k; When the chromosome window is a window with a base position of chromosome 22 of 45300k - 45600k, the corresponding second type of chromosome window is a window with a base position of chromosome 238950k -239250k; the window of the first type of chromosome When the base position of chromosome 21 is 45450k - 45750k, the corresponding chromosome 2 window is the window of chromosome 20 with the base position of 61050k -61350k; the window of the first chromosome is 笫21 When the base position of the chromosome is 45600k - 45900k, the corresponding second type of chromosome window is a window with the base position of chromosome 7 being 1950k - 2250k;

第一类染色体的窗口是笫 21号染色体的碱基位置为 45750k - 46050k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 135000k -135300k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 45900k - 46200k的窗口时，其对应的第二类染色体窗口是笫 19号染色体的碱基位置为 38700k -39000k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 46050k - 46350k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 139800k -140100k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 46200k - 46500k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 750k -1 050k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 46350k - 46650k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 1 350k -1650k的窗口； The window of the first type of chromosome is a window with a base position of 45750k - 46050k on chromosome 21, and the corresponding second type of chromosome window is a window with a base position of chromosome 9 of 135000k - 135300k; When the chromosome window is a window with the base position of chromosome 21 being 45900k - 46200k, the corresponding second type of chromosome window is the window of the base position of chromosome 19 of 38700k - 39000k; the window of the first type of chromosome When the base position of chromosome 21 is 46050k - 46350k, the corresponding second type of chromosome window is the window of chromosome 9 with the base position of 139800k - 140100k; the window of the first chromosome is the 21st When the base position of the chromosome is 46200k - 46500k, its The corresponding second type of chromosome window is a window with the base position of chromosome 7 being 750k -1 050k; the window of the first type of chromosome is when the base position of chromosome 21 is 46350k - 46650k, the corresponding The second type of chromosome window is a window with a base position of chromosome 5 of 1 350k - 1650k;

第一类染色体的窗口是第 21号染色体的碱基位置为 46500k - 46800k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 46350k -46650k的窗口；第一类染色体的窗口是第 21号染色体的碱基位置为 46650k - 46950k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 1650k -1950k的窗口； The window of the first type of chromosome is the window of the chromosome 21 with the base position of 46500k - 46800k, and the corresponding second type of chromosome window is the window of the chromosome 12 with the base position of 46350k - 46650k; When the chromosome window is a window with the base position of chromosome 21 being 46650k - 46950k, the corresponding second type of chromosome window is a window with the base position of chromosome 8 being 1650k -1950k;

当第一类染色体的窗口是第 18号染色体的碱基位置为 1050 k - 1 350 k的窗口时，其对应的第二类染色体窗口是笫 4号染色体的碱基位置为 178050k-178350k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 1200 k - 1500 k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 6450k-6750k的窗口； When the window of the first type of chromosome is the window of the chromosome 18 with the base position of 1050 k - 1 350 k, the corresponding second type of chromosome window is the window of the base position of the chromosome 4 of 178050k-178350k. When the window of the first type of chromosome is a window with the base position of chromosome 18 being 1200 k - 1500 k, the corresponding second type of chromosome window is a window with the base position of chromosome 3 being 6450k-6750k. ;

当第一类染色体的窗口是第 18号染色体的碱基位置为 1 350 k - 1650 k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱 '基位置为 125700k-126000k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 1500 k - 1800 k的窗口时，其对应的第二类染色体窗口是第 1 3号染色体的碱基位置为 53550k-53850k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 1650 k - 1950 k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 177450k-177750k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 1800k - 2100 k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 122250k-122550k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 1950k - 2250 k的窗口时，其对应的第二类染色体窗口是笫 6号染色体的碱基位置为 18900k-19200k的窗口； When the window of the first type of chromosome is a window with the base position of chromosome 18 being 1 350 k - 1650 k, the corresponding second type of chromosome window is the base 'base position of chromosome 7 is 125700k-126000k. Window; when the window of the first type of chromosome is the window of the chromosome 18 with a base position of 1500 k - 1800 k, the corresponding second type of chromosome window is the base position of the chromosome 1 is 53550k-53850k The window of the first type of chromosome is the window of chromosome 18 with a base position of 1650 k - 1950 k, and its corresponding second type of chromosome window is the base position of chromosome 3 is 177450k-177750k The window of the first type of chromosome is the window of the chromosome 18 with a base position of 1800k - 2100 k, and the corresponding second type of chromosome window is the base position of the chromosome 4 is 122250k-122550k. Window; when the window of the first type of chromosome is the window of the chromosome 18 with the base position of 1950k - 2250 k, the corresponding second type of chromosome window is the base position of the chromosome 6 is 18900 K-19200k window;

当第一类染色体的窗口是第 18号染色体的碱基位置为 2100k - 2400 k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 32400 k -32700k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 2250 k - 2550 k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 9600 k -9900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 2400k - 2700k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 1 30650 k -1 30950 k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 2550k - 2850k的窗口吋，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 48000 k -48300 k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 4200k - 4500k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 192450k -192750 k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 4350k - 4650k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 145800k -146100 k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 4650k - 4950k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 1 07550k -107850 k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 4800k - 5100k的窗口时，其对应的第二类染色体窗口是笫 12号染色体的碱基位置为 38100k -38400 k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 4950k - 5250k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 39000k -39300 k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 5100k - 5400k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 164550k -164850 k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 9000k - 9300k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 91050k -91 350 k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 16800k - 171 00k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 39150k -39450k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 16950k - 17250k的窗口时，其对应的第二类染色体窗口是笫 1 1号染色体的碱基位置为 32850k -33150k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 17100k - 17400k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 19950k -20250k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 17250k - 17550k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 39600k -39900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 17400k - 17700k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 80850k -81150k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 18450k - 18750k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 64350k -64650k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 18600k - 18900k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 19500k -19800k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 21750k - 22050k的窗口时，其对应的笫二类染色体窗口是笫 4号染色体的碱基位置为 148350k -148650k的窗口; 当第一类染色体的窗口是第 18号染色体的碱基位置为 21900k - 22200k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 1 3800k -14100k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 22800k - 23100k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 120150k -120450k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 23250k - 23550k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 153450k —153750k的窗口; 当第一类染色体的窗口是第 18号染色体的碱基位置为 23550k - 23850k的窗口时，其对应的笫二类染色体窗口是笫 12号染色体的碱基位置为 15450k -15750k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 24000k - 24300k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 125700k -126000k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 24150k - 2450k的窗口时，其对应的第二类染色体窗口是笫 12号染色体的碱基位置为 80100k -80400k的窗口; 当第一类染色体的窗口是笫 18号染色体的碱基位置为 24300k - 24600k的窗口时，其对应的第二类染色体窗口是第 17号染色体的碱基位置为 48150k -48450k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 24450k - 24750k的窗口时，其对应的第二类染色体窗口是第 11号染色体的碱基位置为 26250k -26550k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 24600k - 24900k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 62550k -62850k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 24750k - 25050k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 47550k -47850k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 24900k - 25200k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 1 0050k -10350k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 25050k - 25350k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 84300k -84600k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 25200k - 25500k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 70800k -71100k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 25350k - 25650k的窗口时, 其对应的第二类染色体窗口是第号染色体的碱基位置为 119100k -119400k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 25500k - 25800k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 119100k -119400k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 25650k - 25950k的窗口时, 其对应的第二类染色体窗口是第号染色体的碱基位置为 51300k -51600k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 25800k - 26100k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 145200k -145500k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 25950k - 26250k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 125550k -125850k的窗口；当第一类染色体的窗口是笫 8号染色体的碱基位置为 26100k - 26400k的窗口时，其对应的第二类染色体窗口是第 1号染色体的碱基位置为 16500k -16800k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 26250k - 26550k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 6000k -96300k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 26400k - 26700k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 95850k -96150k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 26550k - 26850k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 61350k -61650k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 26700k - 27000k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 92850k -93150k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 26850k - 27150k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 89700k -90000k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 27000k - 27300k的窗口时，其对应的第二类染色体窗口是笫 7号染色体的碱基位置为 25050k -25350k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 27150k - 27450k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 88050k -88350k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 28650k - 28950k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 92400k ■ -92700k的窗口；当笫一类染色体的窗口是笫 18号染色体的碱基位置为 28800k - 29100k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 52050k - -52350k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 28950k - 29250k的窗口时, 其对应的第二类染色体窗口是第 4号染色体的碱基位置为 138300k -138600k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 29100k - 29400k的窗口时, 其对应的第二类染色体窗口是第 7号染色体的碱基位置为 144450k -144750k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 29250k - 29550k的窗口时, 其对应的第二类染色体窗口是第 7号染色体的碱基位置为 115200k -115500k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 29550k - 29850k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 92250k - -92550k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 29700k - 30000k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 62250k - -62550k的窗口; 当第一类染色体的窗口是笫 18号染色体的碱基位置为 29850k - 30150k的窗口时, 其对应的笫二类染色体窗口是第 8号染色体的碱基位置为 84900k - -85200k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 30000k - 30300k的窗口时, 其对应的第二类染色体窗口是第 7号染色体的碱基位置为 82650k - -82950k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 30150k - 30450k的窗口时, 其对应的第二类染色体窗口是第 7号染色体的碱基位置为 93600k - -93900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 30300k - 30600k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 103950k -104250k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 32700k - 33000k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 77100k - -77400k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 33900k - 34200k的窗口时，其对应的第二类染色体窗口是第 9号染色体的碱基位置为 76200k - -76500k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 34800k - 35100k的窗口时, 其对应的第二类染色体窗口是第 8号染色体的碱基位置为 106350k -106650k的窗口; 当第一类染色体的窗口是第 18号染色体的碱基位置为 35550k - 35850k的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 35400k -35700k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 36450k - 36750k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 145050k -145350k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 36600k - 36900k的窗口时，其对应的第.二类染色体窗口是第 3号染色体的碱基位置为 103050k -103350k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 36750k - 37050k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 83250k -83550k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 36900k - 37200k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 34650k -34950k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 37800k - 38100k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 93300k -93600k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 38400k - 38700k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 50100k -50400k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 38550k - 38850k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 83100k -83400k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 38700k - 39000k的窗口时，其对应的笫二类染色体窗口是笫号染色体的碱基位置为 106350k -106650k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 38850k - 39150k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 141000k -141300k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 39000k - 39300k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 64050k -64350k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 39150k - 39450k的窗口时, 其对应的第二类染色体窗口是第号染色体的碱基位置为 69450k -69750k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 39300k - 39600k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 105150k -105450k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 39450k - 39750k的窗口时, 其对应的第二类染色体窗口是第 1号染色体的碱基位置为 29400k -29700k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 39600k - 39900k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 88950k -89250k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 39750k - 40050k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 71550k -71850k的窗口; 当笫一类染色体的窗口是第 8号染色体的碱基位置为 39900k - 40200k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 163200k -163500k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 44850k - 45150k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 112950k -113250k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 45000k - 45300k的窗口时，其对应的第二类染色体窗口是第 1号染色体的碱基位置为 32850k -33150k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 48600k - 48900k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 76800k -77100k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 48750k - 49050k的窗口时，其对应的第二类染色体窗口是第 1号染色体的碱基位置为 40800k -41100k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 49350k - 49650k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 38850k -39150k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 49650k - 49950k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 39900k -40200k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 49800k - 50100k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 130350k -130650k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 49950k - 50250k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 106350k -106650k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 50100k - 50400k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 87150k -87450k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 50250k - 50550k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 79350k -79650k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 52350k - 52650k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 70950k -71250k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 55950k - 56250k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 103800k -104100k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 56100k - 56400k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 172650k -172950k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 56250k - 56550k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 10050k -10350k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 56400k - 56700k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 90150k -90450k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 56550k - 56850k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 126750k -127050k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 57750k - 58050k的窗口时，其对应的第二类染色体窗口是第 2号染色体的碱基位置为 79350k -79650k的窗口；当笫一类染色体的窗口是第 8号染色体的碱基位置为 57900k - 58200k的窗口时，其对应的笫二类染色体窗口是第号染色体的碱基位置为 101700k -102000k的窗口；当第一类染色体的窗口是笫 8号染色体的碱基位置为 60000k - 60300k的窗口时，其对应的第二类染色体窗口是第 3号染色体的碱基位置为 77700k -78000k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60150k - 60450k的窗口时, 其对应的第二类染色体窗口是第号染色体的碱基位置为 126450k -126750k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60300k - 60600k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 167100k -167400k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60450k - 60750k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 123300k -123600k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60600k - 60900k的窗口时，其对应的第二类染色体窗口是笫号染色体的碱基位置为 34800k -35100k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60750k - 61050k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 145950k -146250k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 60900k - 61200k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 93900k -94200k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 61050k - 61350k的窗口时，其对应的第二类染色体窗口是笫 8号染色体的碱基位置为 116550k -116850k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 61200k - 61500k的窗口时，其对应的第二类染色体窗口是第 12号染色体的碱基位置为 27000k -27300k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 61 350k - 61650k的窗口时, 其对应的第二类染色体窗口是第 3号染色体的碱基位置为 85950k -86250k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 61500k - 61800k的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 81600k -81900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 61650k - 61950k的窗口时，其对应的笫二类染色体窗口是第 11号染色体的碱基位置为 89700k -90000k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 61800k - 621 00k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 83700k -84000k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 61950k - 62250k的窗口时，其对应的第二类染色体窗口是笫 1 3号染色体的碱基位置为 81600k -81900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 62100k - 62400k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 78450k -78750k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 62250k - 62550k的窗口时, 其对应的第二类染色体窗口是第 3号染色体的碱基位置为 96150k -96450k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 62400k - 62700k的窗口时, 其对应的第二类染色体窗口是第 4号染色体的碱基位置为 91050k -91350k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 62550k - 62850k的窗口时，其对应的笫二类染色体窗口是第 12号染色体的碱基位置为 72900k -73200k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 62700k - 63000k的窗口时, 其对应的第二类染色体窗口是笫 12号染色体的碱基位置为 73650k -73950k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 62850k - 63150k的窗口时，其对应的第二类染色体窗口是笫 2号染色体的碱基位置为 193200k -193500k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 63000k - 63300k的窗口时, 其对应的第二类染色体窗口是第 4号染色体的碱基位置为 181350k -181650k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 63150k - 63450k的窗口时, 其对应的第二类染色体窗口是第 ί2号染色体的碱基位置为 84150k -84450k的窗口；当第一类染色体的窗口是第 L8号染色体的碱基位置为 63300k - 63600k的窗口时，其对应的第二类染色体窗口是第 I号染色体的碱基位置为 157500k -157800k的窗口；当第一类染色体的窗口是第 ί8号染色体的碱基位置为 63450k - 63750k的窗口时, 其对应的第二类染色体窗口是第 i号染色体的碱基位置为 21750k -22050k的窗口；当第一类染色体的窗口是第 .8号染色体的碱基位置为 63600k - 63900k的窗口时，其对应的笫二类染色体窗口是第 '号染色体的碱基位置为 80850k -81150k的窗口；当第一类染色体的窗口是第 .8号染色体的碱基位置为 63750k - 64050k的窗口时，其对应的第二类染色体窗口是第 '号染色体的碱基位置为 110250k -110550k的窗口；当笫一类染色体的窗口是第 .8号染色体的碱基位置为 63900k - 64200k的窗口时，其对应的第二类染色体窗口是第 '号染色体的碱基位置为 110250k -110550k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 64050k - 64350k的窗口时，其对应的笫二类染色体窗口是第 2号染色体的碱基位置为 87150k -87450k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 64200k - 64500k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 12300k -12600k的窗口；当第一类染色体的窗口是笫 8号染色体的碱基位置为 64350k - 64650k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 111600k -111900k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 64500k - 64800k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 9900k -10200k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 64650k - 64950k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 85050k -85350k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 64800k - 65100k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 72600k -72900k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 64950k - 65250k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 92100k -92400k的窗口; 当第一类染色体的窗口是第 8号染色体的碱基位置为 65100k - 65400k的窗口时，其对应的第二类染色体窗口是第号染色体的碱基位置为 117450k -117750k的窗口；当第一类染色体的窗口是第 8号染色体的碱基位置为 65250k - 65550k的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 11 3400k -1 13700k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 65400k - 65700k的窗口时, 其对应的第二类染色体窗口是第 4号染色体的碱基位置为 181500k -181800k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 65700k - 66000k的窗口时, 其对应的第二类染色体窗口是第 5号染色体的碱基位置为 1 37100k -1 37400k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 65850k - 66150k的窗口时, 其对应的第二类染色体窗口是第 3号染色体的碱基位置为 1 74600k -174900k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 66450k - 66750k的窗口时, 其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 145800k -146100k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 66600k - 66900k的窗口时，其对应的第二类染色体窗口是笫 21号染色体的碱基位置为 27300k -27600k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 66750k - 67050k的窗口时，其对应的笫二类染色体窗口是第 6号染色体的碱基位置为 123300k -123600k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 66900k - 67200k的窗口时，其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 181950k -182250k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 67050k - 67350k的窗口时，其对应的第二类染色体窗口是第 8号染色体的碱基位置为 1 3800k - -14100k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 67200k - 67500k的窗口时, 其对应的第二类染色体窗口是第 4号染色体的碱基位置为 81 000k - -81300k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 67350k - 67650k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 162150k -162450k的窗口；当第一类染色体的窗口是笫 18号染色体的碱基位置为 67500k - 67800k的窗口时, 其对应的笫二类染色体窗口是笫 7号染色体的碱基位置为 85050k - -85350k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 67650k - 67950k的窗口时, 其对应的第二类染色体窗口是第 2号染色体的碱基位置为 52050k - -52350k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 67800k - 681 00k的窗口时, 其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 30900k - -31200k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 67950k - 68250k的窗口时, 其对应的第二类染色体窗口是第 12号染色体的碱基位置为 39450k -39750k的窗口；当第一类染色体的窗口是第 18号染色体的碱基位置为 68100k - 68400k的窗口时，其对应的第二类染色体窗口是第 4号染色体的碱基位置为 68400k -68700k的窗口；当笫一类染色体的窗口是第 18号染色体的碱基位置为 68550k - 68850的窗口时，其对应的第二类染色体窗口是第 5号染色体的碱基位置为 88350k -88650k的窗口； When the window of the first type of chromosome is a window with a base position of chromosome 18 of 2100k - 2400 k, the corresponding second type of chromosome window is a window with a base position of chromosome 12 of 32400 k -32700k; When the window of the first type of chromosome is a window with the base position of chromosome 18 being 2250 k - 2550 k, the corresponding second type of chromosome window is a window with the base position of chromosome 6 being 9600 k -9900 k When the window of the first type of chromosome is the window of the chromosome 18 with the base position of 2400k - 2700k, the corresponding second type of chromosome window is the base position of chromosome 5 is 1 30650 k -1 30950 k Window; when the window of the first type of chromosome is the window of chromosome 18 with a base position of 2550k - 2850k, The corresponding second type of chromosome window is a window with a base position of chromosome 4 of 48000 k -48300 k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 4200 k - 4500 k, The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 192450k -192750k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 4350k - 4650k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 145800k - 146100 k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 4650k - 4950k, its corresponding The second type of chromosome window is a window with the base position of chromosome 4 being 1 07550k -107850 k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 4800k - 5100k, its corresponding The second type of chromosome window is a window with a base position of 笫12 chromosome of 38100k - 38400 k; when the window of the first type chromosome is a window of the chromosome 18 with a base position of 4950k - 5250k, The corresponding second type of chromosome window is a window with a base position of chromosome 2 of 39000k - 39300 k; when the window of the first type chromosome is a window with a base position of chromosome 5 of 5100k - 5400k, the corresponding The second type of chromosome window is the window with the base position of chromosome 6 being 164550k -164850 k; when the window of the chromosome of the first chromosome is the window with the base position of chromosome 18 being 9000k - 9300k, its corresponding The second type of chromosome window is a window with a base position of chromosome 8 of 91050k -91 350 k; when the window of the first type of chromosome is a window with a base position of chromosome 18 of 16800k - 171 00k, the corresponding The second type of chromosome window is a window with a base position of chromosome 12 of 39150k -39450k; when the window of a chromosome of the first chromosome is a window with a base position of chromosome 18 of 16950k - 17250k, the corresponding The second type of chromosome window is a window with a base position of 3281 1 chromosome of 32850k -33150k; when the window of the first type of chromosome is a window with a base position of chromosome 18 of 17100k - 17400k, The corresponding second type of chromosome window is a window with the base position of chromosome 9 being 19950k-20250k; when the window of the chromosome of the first chromosome is the window of the base of chromosome 18 of 17250k - 17550k, the corresponding The second type of chromosome window is a window with a base position of chromosome 2 of 39600k -39900k; when the window of the first type of chromosome is a window with a base position of chromosome 18 of 17400k - 17700k, the corresponding second The chromosome-like window is the window of the chromosome 6 with the base position of 80850k -81150k; when the window of the first chromosome is the window of the 18th chromosome with the base position of 18450k - 18750k, the corresponding second chromosome The window is a window with the base position of chromosome 17 being 64350k -64650k; when the window of the chromosome of the first chromosome is the window with the base position of chromosome 18 being 18600k - 18900k, The corresponding second type of chromosome window is a window with a base position of chromosome 3 of 19500k -19800k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 21750k - 22050k, the corresponding The second type of chromosome window is a window with a base position of 1484 chromosome of 148350k -148650k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 21900k - 22200k, the corresponding The second type of chromosome window is a window with a base position of chromosome 2 of 1 3800k -14100k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 22800k - 23100k, the corresponding second The chromosome-like window is a window with a base position of chromosome 7 of 120150k - 120450k; when the window of the first chromosome is a window with a base position of chromosome 18 of 23250k - 23550k, the corresponding second chromosome The window is a window with the base position of chromosome 2 being 153450k - 153750k; when the window of the first chromosome is the window with the base position of chromosome 18 being 23550k - 23850k, The corresponding 笫 second-class chromosome window is a window with a base position of 笫12 chromosome of 15450k -15750k; when the window of the first chromosome is a window with a base position of chromosome 18 of 24000k - 24300k, the corresponding The second type of chromosome window is a window with a base position of chromosome 4 of 125700k -126000k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 24150k - 2450k, the corresponding The second type of chromosome window is a window with a base position of 笫12 chromosome of 80100k -80400k; when the window of the first type of chromosome is a window with a base position of 笫18 chromosome of 24300k - 24600k, the corresponding second type The chromosome window is a window with a base position of chromosome 17 of 48150k - 48450k; when the window of the first chromosome is a window with a base position of chromosome 24 of 24450k - 24750k, the corresponding second type of chromosome window Is the window of the chromosome 11 with a base position of 26250k -26550k; when the window of the chromosome of the first chromosome is the window of the chromosome 18 with a base position of 24600k - 24900k, The corresponding second type of chromosome window is a window with a base position of chromosome 6 of 62550k - 62850k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 24750k - 25050k, the corresponding The second type of chromosome window is a window with the base position of chromosome 12 being 47550k - 47850k; when the window of the first chromosome is the window of the chromosome 18 with the base position of 24900k - 25200k, the corresponding second The chromosome-like window is a window with the base position of chromosome 9 being 1 0050k -10350k; when the window of the first chromosome is the window with the base position of chromosome 18 being 25050k - 25350k, the corresponding second class The chromosome window is a window with a base position of chromosome 3 of 84300k - 84600k; when the window of the first chromosome is a window with a base position of chromosome 18 of 25200k - 25500k, The corresponding second type of chromosome window is a window with a base position of the nickname chromosome of 70800k - 71100k; when the window of the first type chromosome is a window of the chromosome 8 with a base position of 25350k - 25650k, the corresponding The second type of chromosome window is a window with the base position of the first chromosome being 119100k -119400k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 25500k - 25800k, the corresponding second type The chromosome window is a window with the base position of the first chromosome being 119100k -119400k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 25650k - 25950k, the corresponding second type of chromosome window is The base position of the first chromosome is a window of 51300k - 51600k; when the window of the first type of chromosome is a window with a base position of chromosome 8 of 25800k - 26100k, the corresponding second type of chromosome window is the first chromosome The base position of the window is 145200k -145500k; when the window of the first chromosome is the window of the chromosome 8 of 25950k - 26250k, the corresponding The chromosome-like window is a window with a base position of the first chromosome of 125550k -125850k; when the window of the first chromosome is a window with a base position of 26100k - 26400k, the corresponding second type of chromosome window Is the window of chromosome 1 with a base position of 16500k -16800k; when the window of the first chromosome is the window of chromosome 8 with a base position of 26250k - 26550k, the corresponding second type of chromosome window is the first The base position of the chromosome is 6000k - 96300k; when the window of the first chromosome is the window of chromosome 8 with the base position of 26400k - 26700k, the corresponding second type of chromosome window is the chromosome The base position is a window of 95850k -96150k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 26550k - 26850k, the corresponding second type of chromosome window is the base position of the chromosome a window of 61350k -61650k; when the window of the first chromosome is the window of chromosome 8 with a base position of 26700k - 27000k, the corresponding second chromosome The mouth is the window of the chromosome 3 with the base position of 92850k -93150k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 26850k - 27150k, the corresponding chromosome 2 window is The base position of the first chromosome is a window of 89700k -90000k; when the window of the first type of chromosome is a window of the base of chromosome 8 of 27000k - 27300k, the corresponding second type of chromosome window is 笫7 The base position of the chromosome is a window of 25050k - 25350k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 27150k - 27450k, the corresponding second type of chromosome window is the chromosome 2 The base position is a window of 88050k - 88350k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 28650k - 28950k, The corresponding second type of chromosome window is a window with a base position of chromosome 6 of 92400k ■ -92700k; when the window of a chromosome of the first chromosome is a window with a base position of 28800k - 29100k of chromosome 18, The corresponding second type of chromosome window is a window with the base position of chromosome 2 being 52050k - 52350k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 28950k - 29250k, the corresponding The second type of chromosome window is a window with a base position of chromosome 138300k -138600k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 29100k - 29400k, the corresponding The second type of chromosome window is a window with the base position of chromosome 7 being 144450k - 144750k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 29250k - 29550k, the corresponding second type The chromosome window is a window with a base position of chromosome 11 of 115200k -115500k; when the window of the first chromosome is a window with a base position of chromosome 18 of 29550k - 29850k, The corresponding second type of chromosome window is a window with the base position of chromosome 6 being 92250k - -92550k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 29700k - 30000k, the corresponding The second type of chromosome window is a window with the base position of chromosome 4 being 62250k - -62550k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 29850k - 30150k, the corresponding The second type of chromosome window is a window with the base position of chromosome 8 being 84900k - -85200k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 30000k - 30300k, the corresponding The second type of chromosome window is the window of the chromosome 7 with the base position of 82650k - -82950k; when the window of the first type chromosome is the window of the 18th chromosome with the base position of 30150k - 30450k, the corresponding second The chromosome-like window is a window whose base position of chromosome 7 is 93600k - -93900k; when the window of the first chromosome is the window of the chromosome 18 with a base position of 30300k - 30600k, The second type of chromosome window should be the window of the chromosome 2 with the base position of 103950k -104250k; when the window of the first chromosome is the window of the chromosome 18 with the base position of 32700k - 33000k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 77100k - -77400k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 33900k - 34200k, the corresponding The second type of chromosome window is a window with a base position of chromosome 9 of 76200k - -76500k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 34800k - 35100k, the corresponding second The chromosome-like window is a window with a base position of chromosome 8 of 106350k - 106650k; when the window of the first chromosome is a window with the base position of chromosome 18 being 35550k - 35850k, The corresponding second type of chromosome window is a window with a base position of chromosome 5 of 35400k - 35700k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 36450k - 36750k, the corresponding The second type of chromosome window is a window with a base position of the first chromosome of 145050k - 145350k; when the window of the first type of chromosome is a window with a base position of chromosome 8 of 36600k - 36900k, the corresponding first. The second type of chromosome window is a window whose base position of chromosome 3 is 103050k - 103350k; when the window of the first type chromosome is a window with the base position of chromosome 8 being 36750k - 37050k, the corresponding second class The chromosome window is a window with a base position of the first chromosome of 83250k -83550k; when the window of the first chromosome is a window with the base position of chromosome 8 being 36900k - 37200k, the corresponding second type of chromosome window is The base position of the first chromosome is a window of 34650k -34950k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 37800k - 38100k, its corresponding The second type of chromosome window is a window with a base position of the first chromosome of 93300k -93600k; when the window of the first type of chromosome is a window with a base position of the chromosome 8 of 38400k - 38700k, the corresponding second class The chromosome window is a window with a base position of the first chromosome of 50100k - 50400k; when the window of the first chromosome is a window with a base position of 3850k - 38850k, the corresponding second type of chromosome window is The base position of chromosome 2 is a window of 83100k - 83400k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 38700k - 39000k, the corresponding chromosome window of the second type is the nickname The base position of the chromosome is 106350k -106650k; when the window of the first chromosome is the window of the chromosome 8 of 38850k - 39150k, the corresponding second type of chromosome window is the base of the chromosome The base position is a window of 141000k -141300k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 39000k - 39300k, the corresponding second type of dye The color body window is a window with a base position of the nickname chromosome of 64050k -64350k; when the window of the first type chromosome is a window with a base position of chromosome 8 of 39150k - 39450k, the corresponding second type chromosome window Is the window of the chromosome 1 with a base position of 69450k -69750k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 39300k - 39600k, the corresponding second type of chromosome window is the number The base position of the chromosome is a window of 105150k -105450k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 39450k - 39750k, the corresponding second type of chromosome window is the chromosome 1 a base position of 29400k -29700k; when the window of a genus of chromosomes is a window with a base position of chromosome 8 of 39600k - 39900k, The corresponding second type of chromosome window is a window with a base position of the first chromosome of 88950k - 89250k; when the window of the first type chromosome is a window with a base position of the chromosome 8 of 39750k - 40050k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 71550k -71850k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 39900k - 40200k, the corresponding second The chromosome-like window is a window with a base position of the first chromosome of 163200k -163500k; when the window of the first chromosome is a window with a base position of the chromosome 8 of 44850k - 45150k, the corresponding second type of chromosome window Is the window of the first chromosome of 112955k -113250k; when the window of the first chromosome is the window of the chromosome 8 of 45000k - 45300k, the corresponding second chromosome window is the first The base position of the chromosome is a window of 32850k -33150k; when the window of the first chromosome is the window of the chromosome 8 of 48600k - 48900k, the corresponding The second type of chromosome window is a window with a base position of the first chromosome of 76800k -77100k; when the window of the first type of chromosome is a window with the base position of the eighth chromosome being 48750k - 49050k, the corresponding second type of chromosome The window is a window with a base position of chromosome 1 of 40800k -41100k; when the window of the first chromosome is a window with a base position of chromosome 4 of 49350k - 49650k, the corresponding second type of chromosome window is The base position of chromosome 2 is a window of 38850k - 39150k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 49650k - 49950k, the corresponding second type of chromosome window is an apostrophe The base position of the chromosome is a window of 39900k - 40200k; when the window of the chromosome of the first chromosome is the window of the chromosome 8 with a base position of 49800k - 50100k, the corresponding chromosome of the second chromosome is the base of the chromosome a window with a base position of 130350k - 130650k; when the window of the first chromosome is a window with a base position of chromosome 4 of 49950k - 50250k, the corresponding second type of dye The body window is a window with a base position of the chromosomal chromosome of 106350k -106650k; when the window of the first type of chromosome is a window with a base position of chromosome 8 of 50100k - 50400k, the corresponding second type of chromosome window is The base position of the chromosome 1 is a window of 87150k - 87450k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 50250k - 50550k, the corresponding second type of chromosome window is No. 2 The base position of the chromosome is a window of 79350k -79650k; when the window of the first type chromosome is a window with the base position of chromosome 8 being 52350k - 52650k, the corresponding second type of chromosome window is the chromosome 6 The base position is a window of 70950k - 71250k; when the window of the first type chromosome is a window of the chromosome 8 with a base position of 55950k - 56250k, The corresponding second type of chromosome window is a window whose base position of chromosome 3 is 103800k - 104100k; when the window of the first type chromosome is a window with the base position of chromosome 8 being 56100k - 56400k, the corresponding The second type of chromosome window is a window with a base position of the first chromosome of 172650k - 172950k; when the window of the first type of chromosome is a window with a base position of the chromosome 8 of 56250k - 56550k, the corresponding second The chromosome-like window is a window with a base position of the first chromosome of 10050k - 10350k; when the window of the first chromosome is a window with a base position of chromosome 8 of 56400k - 56700k, the corresponding second type of chromosome window Is the window of the nickname chromosome with a base position of 90150k - 90450k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 56550k - 56850k, the corresponding 笫 second chromosome window is the number The base position of the chromosome is a window of 126750k -127050k; when the window of the chromosome of the first chromosome is a window with the base position of chromosome 8 being 57750k - 58050k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 79350k -79650k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 57900k - 58200k, the corresponding 笫2 The chromosome-like window is a window with a base position of the first chromosome of 101700k -102000k; when the window of the first type of chromosome is a window with a base position of the chromosome 8 of 60000k - 60300k, the corresponding second type of chromosome window Is the window of the chromosome 3 with a base position of 77700k -78000k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 60150k - 60450k, the corresponding second type of chromosome window is the first The base position of the chromosome is 126450k -126750k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 60300k - 60600k, the corresponding second type of chromosome window is the chromosome The base position is a window of 167100k -167400k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 60450k - 60750k, the corresponding second The chromosome window is a window with a base position of the nickname chromosome of 123300k -123600k; when the window of the first chromosome is a window with a base position of chromosome 8 of 60600k - 60900k, the corresponding second type of chromosome window is The base position of the chromosomal chromosome is 34800k -35100k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 60750k - 61050k, the corresponding second chromosome window is the chromosome The base position of the chromosome is 145950k -146250k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 60900k - 61200k, the corresponding second type of chromosome window is the base of the chromosome a window with a position of 93900k -94200k; when the window of the first type of chromosome is a window with a base position of chromosome 8 of 61050k - 61350k, The corresponding second type of chromosome window is a window with a base position of 5508 chromosome of 116550k -116850k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 61200k - 61500k, the corresponding The second type of chromosome window is a window with a base position of chromosome 12 of 27000k -27300k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 61 350k - 61650k, the corresponding The second type of chromosome window is a window with the base position of chromosome 3 being 85950k -86250k; when the window of the first chromosome is the window of the chromosome 18 with a base position of 61500k - 61800k, the corresponding second The chromosome-like window is the window of the chromosome 7 with a base position of 81600k -81900k; when the window of the first chromosome is the window of the chromosome 18 with the base position of 61650k - 61950k, the corresponding chromosome II The window is a window whose base position of chromosome 11 is 89,700k - 90,000k; when the window of the first type of chromosome is a window with a base position of 6118 chromosome of 61800k - 621 00k, The corresponding second type of chromosome window is a window whose base position of chromosome 2 is 83700k-84000k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 61950k-62250k, the corresponding The second type of chromosome window is a window with a base position of 6001 3 chromosome of 81600k -81900k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 62100k - 62400k, the corresponding The second type of chromosome window is the window of the chromosome 8 with the base position of 78450k -78750k; when the window of the first chromosome is the window of the chromosome 18 with the base position of 62250k - 62550k, the corresponding second type The chromosome window is a window with the base position of chromosome 3 being 96150k -96450k; when the window of the first chromosome is the window with the base position of chromosome 18 being 62400k - 62700k, its corresponding second type of chromosome window Is the window of the chromosome 4 with a base position of 91050k -91350k; when the window of the chromosome of the first chromosome is a window with the base position of the chromosome 18 of 62550k - 62850k, the corresponding The second type of chromosome window is the window of the chromosome 12 with a base position of 72900k -73200k; when the window of the first type chromosome is the window of the chromosome 18 with a base position of 62700k - 63000k, the corresponding second The chromosome-like window is a window with a base position of 73612 chromosome of 73650k -73950k; when the window of the first chromosome is the window of the chromosome 18 with a base position of 62850k - 63150k, the corresponding second chromosome The window is a window with a base position of 1932 chromosome of 193200k -193500k; when the window of the first chromosome is a window with a base position of chromosome 18 of 63000k - 63300k, the corresponding second type of chromosome window is The base position of chromosome 4 is a window of 181350k -181650k; when the window of the first type of chromosome is a window with a base position of chromosome 18 of 63150k - 63450k, The corresponding second type of chromosome window is a window with a base position of 8450k -84450k on the chromosome ί2; when the window of the first chromosome is a window with a base position of the L8 chromosome of 63300k - 63600k, the corresponding The second type of chromosome window is a window with a base position of chromosome 157500k -157800k; when the window of the first chromosome is a window with a base position of 63350k - 63750k, the corresponding The second type of chromosome window is a window with a base position of the i chromosome of 21750k - 22050k; when the window of the first type chromosome is a window with a base position of the chromosome 8 of 63600k - 63900k, the corresponding two The chromosome-like window is a window with the base position of the chromosome '808 is 80850k -81150k; when the window of the first chromosome is the window with the base position of chromosome 8 of 63750k - 64050k, the corresponding second class The chromosome window is a window with a base position of the chromosome '110' from 110250k to 110550k; when the window of the chromosome of the first chromosome is a window with a base position of the chromosome 8 of 63900k - 64200k, The corresponding second type of chromosome window is a window with a base position of the chromosome '110' from 110250k to 110550k; when the window of the first chromosome is a window with a base position of the chromosome 8 of 64050k - 64350k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 87150k - 87450k; when the window of the first type chromosome is a window with the base position of chromosome 8 being 64200k - 64500k, the corresponding The second type of chromosome window is a window with a base position of the first chromosome of 12300k -12600k; when the window of the first type chromosome is a window of the base position of the chromosome 8 of 64350k - 64650k, the corresponding second type chromosome The window is a window with a base position of the first chromosome of 111600k -111900k; when the window of the first chromosome is a window with a base position of the chromosome 8 of 64500k - 64800k, the corresponding second type of chromosome window is the first The base position of the chromosome is 9900k - 10200k; when the window of the first chromosome is the window of the chromosome 8 of 64650k - 64950k, the corresponding The second type of chromosome window is a window with a base position of the first chromosome of 85050k - 85350k; when the window of the first type chromosome is a window with a base position of the chromosome 8 of 64800k - 65100k, the corresponding second type The chromosome window is a window whose base position of the chromosome is 72600k -72900k; when the window of the first chromosome is the window of the chromosome 8 with the base position of 64950k - 65250k, the corresponding second type of chromosome window is The base position of the first chromosome is a window of 92100k - 92400k; when the window of the first type of chromosome is a window with the base position of chromosome 8 being 65100k - 65400k, the corresponding second type of chromosome window is the first chromosome The base position is a window of 117450k -117750k; when the window of the first chromosome is the window of the chromosome 8 with a base position of 65250k - 65550k, The corresponding second type of chromosome window is a window with a base position of chromosome 6 of 11 3400 k -1 13700 k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 65400 k - 65700 k, The corresponding second type of chromosome window is a window with a base position of chromosome 4 of 181500k -181800k; when the window of the first type chromosome is a window with a base position of chromosome 18 of 65700k - 66000k, the corresponding The second type of chromosome window is a window with the base position of chromosome 5 being 1 37100k -1 37400k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 65850k - 66150k, the corresponding The second type of chromosome window is a window with a base position of chromosome 3 of 1 74600k -174900k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 66450k - 66750k, the corresponding The second type of chromosome window is a window with the base position of chromosome 4 being 145800k - 146100k; when the window of the first type of chromosome is the window with the base position of chromosome 18 being 66600k - 66900k The corresponding second type of chromosome window is a window with a base position of 笫21 chromosome of 27300k -27600k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 66750k - 67050k, the corresponding The second type of chromosome window is a window with the base position of chromosome 6 being 123300k -123600k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 66900k - 67200k, the corresponding 笫The second type of chromosome window is a window with the base position of chromosome 4 being 181950k -182250k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 67050k - 67350k, the corresponding second type The chromosome window is a window with a base position of chromosome 8 of 1 3800k - -14100k; when the window of the first chromosome is a window with a base position of chromosome 18 of 67200k - 67500k, the corresponding second type The chromosome window is the window with the base position of chromosome 4 being 81 000k - -81300k; when the window of the first chromosome is the window with the base position of chromosome 18 being 67350k - 67650k The corresponding second type of chromosome window is a window with a base position of chromosome 162150k - 162450k; when the window of the first type chromosome is a window with a base position of 67500k - 67800k of chromosome 18, The corresponding 笫2 chromosome window is a window with the base position of 笫7 chromosome of 85050k - -85350k; when the window of the first chromosome is the window of the chromosome 18 with the base position of 67650k - 67950k, the corresponding The second type of chromosome window is a window with the base position of chromosome 2 being 52050k - 52350k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 67800k - 681 00k, the corresponding The second type of chromosome window is a window with a base position of chromosome 4 of 30900k - -31200k; when the window of the first type of chromosome is a window with a base position of chromosome 18 of 67950k - 68250k, The corresponding second type of chromosome window is a window with the base position of chromosome 12 being 39450k -39750k; when the window of the first type chromosome is a window with the base position of chromosome 18 being 68100k - 68400k, the corresponding The second type of chromosome window is a window with a base position of chromosome 4 of 68400k -68700k; when the window of a chromosome of the first chromosome is a window with the base position of chromosome 18 being 68550k - 68850, the corresponding The second type of chromosome window is a window with the base position of chromosome 5 being 88350k -88650k;

当笫一类染色体的窗口是第 18号染色体的碱基位置为 68700k - 69000的窗口时，其对应的笫二类染色体窗口是第 4号染色体的碱基位置为 87300k -87600k的窗口； When the window of a genus of chromosomes is a window with a base position of chromosome 68 of 68700k - 69000, the corresponding 笫-type chromosome window is a window with a base position of chromosome 87 of 87300k - 87600k;

当第一类染色体的窗口是笫 18号染色体的碱基位置为 68850k - 69150的窗口时，其对应的第二类染色体窗口是第 6号染色体的碱基位置为 70350k -70650k的窗口； When the window of the first type of chromosome is a window of the base position of chromosome 18 of 68850k - 69150, the corresponding second type of chromosome window is a window with a base position of chromosome 6 of 70350k - 70650k;

当第一类染色体的窗口是第 18号染色体的碱基位置为 69000k - 69300的窗口时，其对应的第二类染色体窗口是第 7号染色体的碱基位置为 85950k -86250k的窗口。 When the window of the first type of chromosome is a window with the base position of chromosome 18 being 69000k - 69300, the corresponding second type of chromosome window is a window with the base position of chromosome 7 being 85950k - 86250k.

20.权利要求 19中的有极强相关性窗口组合在建立用于染色体非整倍性的检测计算函数式中的用途，或者是在制备用于染色体非整倍性的检测试剂盒中的用途。 20. Use of a strongly correlated window combination according to claim 19 for establishing a test calculation function for chromosomal aneuploidy, or for use in preparing a test kit for chromosomal aneuploidy .