CN1865440A - Novel pathogenetic gene mutation of hypertrophic cardiomyopathy and use thereof - Google Patents
Novel pathogenetic gene mutation of hypertrophic cardiomyopathy and use thereof Download PDFInfo
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Abstract
The invention relates to several new mutations of pathogenic genes for hypertrophic cardiomyopathy, and their use in the treatment and diagnosis of hypertrophic cardiomyopathy.
Description
Technical field
The present invention relates to the new mutant of some hypertrophic cardiomyopathy Disease-causing genes, and their purposes aspect hypertrophic cardiomyopathy treatment and diagnosis.
Background technology
As far back as in the middle of the 19th century, Frenchman A.Vulpian just observes and has described hypertrophic cardiomyopathy under mirror, but up to later stage the 1950's, the clinical characters of hypertrophic cardiomyopathy uniqueness is just systematically discussed.It is a feature with an asymmetric left side and/or right ventricle plumpness usually, can involve the different sites of ventricle, is outstanding with the ventricular septum especially, and bulk of left ventricle can normally or reduce.Typical morphological change is the myofiber arrangement disorder.Clinically often show as expiratory dyspnea, stenocardia and faint irregular pulse, sudden death.Hypertrophic cardiomyopathy was considered to a kind of rare heart disease in the past, but the epidemiology survey that Maron etc. carry out shows, youthful sickness rate reaches 0.2% (Maron BJ, Gardin JM, Flack JM, et al.Prevalence ofhypertrophic cardiomyopathy in a general population of youngadults:echocardiographic analysis of 4111 s ubjects in theCARDIA study.Circulation.1995; 92:785-789).We check Chinese 8080 normal peoples' of nine provinces and cities ultrasonic heart doppler and show that the hypertrophic cardiomyopathy among the Chinese is also very common, the patient can reach 0.08% (Zou Y. etc., Am.J.Med.2004,116:14-18).It is autosomal dominant inheritance that hypertrophic cardiomyopathy has at least 60%-70% above, claims familial hypertrophic cardiomyopathy (FHC).Molecule genetics research is found, the transgenation of coding sarcomere structural protein is the basic cause of disease [Seidman JG, the Seidman C.The genetic basis for cardiomyopathy:from mutationidentification to mechanistic paradigms.Cell.2001 of familial hypertrophic cardiomyopathy; 104 (4): 557-67; Bonne, Carrier L, Richard P.Familialhypertrophic cardiomyopathy:from mutations to functionaldefects.Cir Res.1998; 83:580-593].
Sarcomere is the fundamental unit of myocardial contraction, mainly is made up of thick, thin filament two portions.Thick filament is mainly myosin (myosin) and cardiac myosin binding protein-C (MyBPC), and the former comprises two myoglobulin heavy chains (MHC) and two light chains---essential/alkaline light chain (MELC, MLC-1) and adjusting/phosphorylation light chain (MRLC, MLC-2).Thin filament comprise Actin muscle (actin), α-tropomyosin (α-Tm) and troponin complex body (and TnT, TnC, TnI).In addition, the sarcomere composition also has flesh to connect albumen (titin) etc.
1. familial hypertrophic cardiomyopathy Disease-causing gene
1. present, confirmed that more than 160 site mutation of 13 genes is relevant with the morbidity of FHC, wherein there are 10 kinds to be the gene of coding sarcomere structural protein, overwhelming majority sudden change is positioned at these genes (Marian AJ, Roberts R.The molecular menetic basis for hypertrophiccardiomyopathy.J Mol Cell Cardio.2001; 33:655670) (table 1).
The occurrence frequency and the mutation type of table 1. familial hypertrophic cardiomyopathy Disease-causing gene
| Albumen | Gene | Chromosomal localization | Frequency | Sudden change |
| β-MHC cMyBPC cTnT α-Tm cTnI MLC-1 MLC-2 Titin α-Actin α-MHC PKA potassium channel mitochondria | MYH7 ? MYBPC3 ? TNNT2 ? TPM1 TNNI3 MYL3 MYL2 TTN ACTC ? MYH6 PRKAG2 KCNQ4 MTTI | 14q11.2-q12 11p11.2 1q32 15q22 19p13.2-q13.2 3p21.2-p21.3 12q23-q24.3 2q24.1 11q 14q 7q22-q31.1 1p34 mitochondria | Be～50%～20%～15%～5%～5%＜5%＜5%＜5%＜5% rare? rare | 74 missense, 3 disappearances, 13 missense of a nonsense mutation, 12 splice sites, 12 missense of 8 insertion/deletion mutantions, 1 splice site, 7 missense of 6 missense mutation of 1 deletion mutantion, 7 missense of 2 missense mutation of 1 deletion mutantion, 1 missense of 5 missense mutation of 1 missense mutation of 1 nonsense mutation, 1 deletion mutantion of 1 missense mutation of a phase shift mutation (merging WPW) (merging deaf) Isoleucine, glycine tRNA sudden change |
Yet all genotype myocardial hypertrophy type Disease-causing gene sudden changes are not included in these sudden changes.
The objective of the invention is to find new sudden change, be convenient to the early diagnosis and the prevention of hypertrophic cardiomyopathy.
Summary of the invention
What the present invention is based on is to exist in the hypertrophic cardiomyopathy Disease-causing gene on this discovery basis of sudden change of not reporting as yet before some.The invention provides the isolating nucleic acid that contains such sudden change.The present invention also provides the oligonucleotide that can be used for detecting these sudden changes, and utilizes such oligonucleotide to detect the method for sudden change.The invention provides the method for utilizing such sudden change to carry out hypertrophic cardiomyopathy diagnosis or drug screening or assessment.The present invention relates to microarray in addition.
Embodiment
In the present invention, term " sample " is meant any biological sample that derives from the human individual, include but not limited to for example cell, tissue sample such as body soft tissue be osseous tissue, hair etc. for example, biological fluid such as lymph liquid, blood, saliva, urine and other body discharged liquid etc.Term " isolating " means the non-natural existence.The nucleic acid that 5 ' and/or 3 ' adjacent flanking sequence adjoins mutually in the genes of individuals group that " isolating nucleic acid " refers to not with it is originated.Therefore, " isolating nucleic acid " also comprises insertion year intravital nucleic acid, mixes the interior nucleic acid of genome of allos cell, perhaps the nucleic acid that exists with separate component.This term also comprises the recombinant nucleic acid that is connected with other nucleotide sequence.Such recombinant nucleic acid may be used to produce fusion rotein.
In the present invention, wild type gene refers to the normal gene corresponding with the hypertrophic cardiomyopathy Disease-causing gene.Their sequence is known in the prior art, for example is listed in the Genbank database.For example, the sequence of wild-type beta-mhc gene is open with Genbank accession number gi:M57965.1, represents with SEQ ID NO:1 in the present invention; The sequence of wild-type cMYBPC gene is open with Genbank accession number gi:Y10629, represents with SEQ IDNO:2 in the present invention; The sequence of wild-type cTnT gene is open with Genbank accession number gi:X90780, represents with SEQ ID NO:3 in the present invention.But, those of ordinary skills are fully aware of, owing to may have some mistakes in the order-checking process of gene, will cause the sequence of the sequence of wild type gene and the accession number indication that this paper lists different, perhaps the numbering of nucleotide residue changes to some extent.At this moment, will be as the criterion with the final sequence of determining.
The method for expressing of transgenation is as follows among the present invention:
" x nt1＞nt2 " is illustrated in the displacement that Nucleotide has taken place in the reference sequences.Wherein " x " phalangeal process becomes the site that takes place, and what it was followed is the nucleotide residue numbering of the wild type gene that corresponding accession number provides among the Genbank.Displacement has taken place in "＞" expression.Nucleotide before " nt1 " phalangeal process becomes, the i.e. nucleotide residue in corresponding site in the normal gene (wild type gene).Nucleotide residue after " nt2 " phalangeal process becomes.For example, " 4693C＞T " in the cTnT gene is illustrated in the cTnT gene replacement mutation taken place, and causes " C " of the 4693rd nucleotide residue site in the sequence of listing corresponding to Genbank accession number gi:X90780 (SEQ ID NO:3) to be substituted by " T ".
Disappearance has taken place to nucleotide site place of " x2 " position in " x1 " position that " x1-x2 del nt1...nt2 " is illustrated in reference sequences, thereby has lacked the nucleotide residue that " nt1 " arrives " nt2 ".For example, " 14262-14264delAAG " represents that the 14262nd to the 14264th Nucleotide " AAG " has been lacked.
Inserted " nt1...nt2 " nucleotide residue between " x1 " position that " x1^x2 ins nt1...nt2 " is illustrated in reference sequences and the nucleotide site of " x2 ".For example, " 18115^18116insGCAAG " is illustrated between the 18115th and the 18116th nucleotide site and inserted " GCAAG ".
In one embodiment, the invention provides a kind of β-mhc gene or its fragment of sudden change, it contains the one or more sudden changes that are selected from down group: 10353G＞A, 10429A＞C corresponding to the following position in the listed sequence of Genbank accession number gi:M57965.1 (SEQ ID NO:1), 10895A＞T, 11811A＞C, 13653A＞C, 14449T＞C, 14452G＞A, 14557G＞A.
In one embodiment, the invention provides a kind of cMYBPC gene or its fragment of sudden change, it contains the one or more sudden changes that are selected from down group: 4826G＞A, 8697G＞A corresponding to the following position in the listed sequence of Genbank accession number gi:Y10629 (SEQ ID NO:2), 8887G＞A, 12101G＞A, 13261G＞A, 14262-14264delAAG, 14364delG, 18115^18116insGCAAG.
In one embodiment, the invention provides a kind of cTnT gene or its fragment of sudden change, it contains the one or more sudden changes that are selected from down group: 4693C＞T, 4769G＞A corresponding to the following position in the listed sequence of Genbank accession number gi:X90780 (SE Q ID NO:3).
In further embodiment, also contain extra sudden change in mutator gene of the present invention or the fragment, comprise any known or sudden change or the nucleotide polymorphisms known in the future.
The invention still further relates to by said mutation gene or fragment deutero-mRNA or cDNA or encoded protein matter.
The invention still further relates to can be with above-mentioned arbitrary mutator gene or fragment or by its deutero-mRNA or cDNA or their complementary sequence specific hybrid, but can not with the nucleic acid of corresponding wild type gene order or its complementary sequence hybridization, oligonucleotide for example, they can be used as the said mutation that probe or primer are used for the specific detection human individual.Those of skill in the art are all clear, and probe generally has and the sequence complementation of purpose nucleic acid and the sequence of not hybridizing mutually with the nucleic acid with wild type gene sequence with the nucleic acid specificity hybridization that comprises sudden change to be detected.This oligonucleotide generally is positioned around the mutational site, and the existence of said mutation is whether in the test sample specifically.Preferably, contain above defined any one or a plurality of sudden change in described nucleic acid or its complementary sequence.As illustration, Oligonucleolide primers or probe can be designed to mutational site to be detected and be positioned at that it is 5 ' or 3 ' terminal or in the centre, and mutational site perhaps to be detected is positioned at complementary sequence 5 ' or 3 ' terminal or in the centre of this primer or probe.In the context of the present invention, term " specific detection " is meant that this oligonucleotide only hybridizes with the nucleic acid that comprises sudden change defined above or its complementary sequence, and does not hybridize with the nucleic acid that has wild type gene sequence or its complementary sequence respectively.
When the mutational site related to a plurality of Nucleotide, oligonucleotide probe or primer can be designed so that the nucleotide sequence in mutational site or be included in the nucleotide sequence of probe or primer with the whole of its complementary sequence or part.Like this, might utilize thus the oligonucleotide of preparation to make probe and whether measure the situation that exists of sudden change by the existence of hybridization or differential hybridization, perhaps as primer by amplification and detect the situation that exists that (by for example order-checking, restriction enzyme digestion etc.) suddenly change subsequently.
The general length of oligonucleotide probe or primer is greater than about 10bp, 10-100 Nucleotide for example, and preferably, its length is 15-75 Nucleotide, more preferably 18-50 Nucleotide especially is preferably 20-35 Nucleotide, most preferably is 23-30 Nucleotide.Those of skill in the art can be easy to design suitable oligonucleotide probe or primer, are used for the detection in mutational site.As for its preparation, then can be undertaken by method well known to those skilled in the art, include but not limited to for example chemical synthesis etc.Preferably, probe/primer is by detectable label, so that detect.Mark can be biological example element, fluorescence dye, radio isotope etc., but is not limited to this.They are well known in the prior art, and can be connected on probe/primer by ordinary method.This nucleic acid can be strand, also can be double-stranded.
Be well known in the art, can utilize primer to extend nucleotide sequence by adding free nucleotide.Hybridization refers under rigorous condition and nucleotide sequence generation selective binding.In this article, rigorous condition is only to allow primer and the nucleotide sequence or its complementary sequence hybridization that contain sudden change, and not with the condition of wild-type nucleic acid sequence or its complementary sequence hybridization.According to employed primer, those of ordinary skill can be determined corresponding rigorous hybridization conditions by normal experiment.There is numerous prior aries can be for reference in this respect, comprises for example Sambrook etc., molecular cloning laboratory manual, the 2nd edition, press of cold spring harbor laboratory, cold spring port, New York.
The invention still further relates to and utilize the detection that suddenlys change of the segmental primer be designed to after amplification, will to obtain to comprise sudden change to be detected.Described primer generally is positioned around the mutational site or its 5 ' or 3 ' direction 1000bp, preferred 500bp, more preferably 250bp, especially preferred 200bp, most preferably in the scope of 100bp, its length is generally greater than about 10bp, be preferably 15-100bp, 18-75bp more preferably, especially be preferably 20-50bp, most preferably be 25-40bp.
Can also be at oligonucleotide sequence 5 ' of the present invention and/or 3 ' terminal some extra nucleotide sequences that connect.Such oligonucleotide also within the scope of the invention.
Utilize such oligonucleotide,, whether can detect the existence that suddenlys change described in the described human individual by the genetic stocks from the human individual is increased and subsequent analysis.For example, amplified production can be carried out agarose gel electrophoresis, use ethidium bromide, SYBR green solution, dyeing like that subsequently, thereby detect amplified production with the form of band (dna fragmentation).Thus, can detect the gene fragment that comprises the mutational site with the form of dna fragmentation.Except agarose gel electrophoresis, also can carry out polyacrylamide gel electrophoresis or capillary electrophoresis.Further, can separate amplified production, whether the existence by order-checking or restricted enzyme cutting analysis sudden change subsequently.Also might use in advance and carry out PCR, and detect amplified production through primer such as material marks such as fluorescence dyes.Can also adopt does not need electrophoretic detection method; In this method, amplified production is attached to solid support such as on the minitype plate, and comes the testing goal dna fragmentation by fluorescence, enzyme reaction, means such as like that.
The invention provides the method that detects said mutation, comprise and use oligonucleotide probe mentioned above or the primer detection of biological product that imitate, perhaps Application Design one-tenth will obtain comprising the step of segmental primer to increasing this biological sample and detecting of this sudden change after amplification.In detection, use the biological sample of individuality to be measured usually, its blood for example, but be not limited to this.In one embodiment, directly using this biological sample detects.For example, utilize above-mentioned nucleic acid, comprise the fragment in mutational site to be detected by the amplification of PCR method as primer.In another embodiment, before detection, at first separate genetic stocks from this biological sample, genomic dna for example, but be not limited to this.Detection can be undertaken by for example method routines such as nucleic acid hybridization, PCR method, sequencing, restriction fragment length polymorphism assay method, but is not limited to these methods.Its condition is to it will be clear to those of skill in the art that or can determine easily.Preferably, the oligonucleotide that uses preparation as mentioned above comprises the dna fragmentation in mutational site to be detected as primer with the archaeal dna polymerase amplification coding.Perhaps, with the probe and the template DNA hybridization of preparation as mentioned above, thereby detect the DNA that those have sudden change interested.Can prepare template DNA according to ordinary method, as caesium chloride density gradient centrifugation, SDS cracking process or phenol/chloroform extracting.
The invention still further relates to a kind of microarray, wherein contain above-mentioned oligonucleotide probe or primer.This oligonucleotide can be fixed on the solid support.In one embodiment, described microarray is the form of DNA chip, gene chip, microchip, pearl battle array etc.The DNA chip is a variety of dna probes to be arranged and are fixed on substrate for example on the sheet glass, carry out the hybridization of marker DNA then in the above, detect coupling and Nucleotide mispairing fully by the marking signal on the detection probes separably, thus nucleic acid is detected.The conventional preparation method of chip is well known by persons skilled in the art.
The invention still further relates to the test kit that can be used for detecting said mutation, comprising one or more relevant diagnostic primer or probe and/or special Oligonucleolide primers of this mutator gene, for example previously described oligonucleotide probe or primer.Also can comprise container, working instructions, damping fluid, enzyme and/or other reacted constituent in the test kit.Preferably, wherein also comprise positive control and negative control, so that further confirm detected result.In one embodiment, test kit of the present invention comprises any and all the components enzyme or the composition that is used for predetermined assay method.The example of these compositions include but not limited to oligonucleotide, polysaccharase (as the Taq polysaccharase), damping fluid (as the Tris damping fluid), dNTP, contrast agents (as tissue sample, as the target oligonucleotide of the positive and negative control, etc.), mark and/or detection reagent (fluorescence dye such as VIC, FAM), solid support, specification sheets, exemplary chart and/or product information, inhibitor etc.Test kit of the present invention can be the part test kit that only comprises the essential composition of part.In this case, the user can provide all the other compositions.Test kit of the present invention can comprise two or more containers that separate, and each all comprises the part composition that will use.For example, in test kit, first container comprises enzyme, and second container comprises oligonucleotide.The specific examples of enzyme comprises the structure specificity nickase in suitable preservation damping fluid or the container.
The invention still further relates to the method for diagnosis hypertrophic cardiomyopathy or definite hypertrophic cardiomyopathy prognosis risk, comprise the step that the vitro samples of individuality is detected one or more sudden changes in following: the following sudden change in β-mhc gene: 10353G＞A, 10429A＞C, 10895A＞T, 11811A＞C, 13653A＞C, 14449T＞C, 14452G＞A, 14557G＞A; Following sudden change in the cMYBPC gene: 4826G＞A, 8697G＞A, 8887G＞A, 12101G＞A, 13261G＞A, 14262-14264delAAG, 14364delG, 18115-18116insGCAAG; The perhaps following sudden change in the cTnT gene: 4693C＞T, 4769G＞A.Preferably, detecting step carries out according to the described sudden change detection method of preamble.For example, use the oligonucleotide that is positioned at the mutational site upstream and downstream at first the nucleic acid fragment that comprises mutational site to be detected to be carried out pcr amplification.Detection can be undertaken by for example PCR method, sequencing, restriction fragment length polymorphism etc.
The invention still further relates to the method for said mutation gene of utilizing as target spot screening or assessment medicine, for example comprise and give one or more medicines cell, tissue, organ or the animal individual that carries described sudden change, and assess the index of its one or more indication hypertrophic cardiomyopathy situations, with indication amelioration of disease situation.Preferably, described cell, tissue, organ or animal individual are by gene knockout (gene knockout) or knock in (gene knockin) or transgenic method obtains.Gene knockout or knock in or transgenic method is well known to those skilled in the art, comprise for example design two with native gene homologous flanking fragment.Under the situation of gene knockout, comprise the predetermined sudden change that makes native gene inactivation in the body between two homologous fragments, thereby after in importing body, can be with corresponding native gene inactivation.Under the situation that gene is knocked in, comprise the predetermined nucleic acid that imports native gene place in the body between two homologous fragments, thereby after in importing body, purpose nucleic acid can be inserted predetermined site.Operand can be individual, for example mouse.Perhaps, operand also can be cell, for example people's myocardial cell.Like this, can on individuality or cell levels, screen or assess medicine.
In the mode of embodiment the present invention is made an explanation below.These embodiment are exemplary, and they limit scope of the present invention never in any form.
Embodiment
The extraction of embodiment 1 genomic dna
The selection of 1 research object
The hypertrophic cardiomyopathy patient of research object for going to a doctor or be in hospital in the clear and definite outpatient service of China Medical Sciences Academy Fu Wai Hospital diagnosis, totally 100 examples are through the family investigation consanguinity-less relation.Comprising hypertrophic cardiomyopathy family propositus 51 people, relevant 356 people of family member, Sporadic cases 49 people.Normal research contrast 120 examples are the healthy people of sex, age-matched.Those selected fills in " molecule genetics research case questionnaire ", content comprises: patient link mode, individual generalized case, clinical symptom, physical examination result, family history investigation, laboratory examination, electrocardiogram(ECG (Holter in case of necessity), the rabat report, ultrasonic cardiogram report (needing cardiac MRI or left chamber and coronary artery radiography result in case of necessity).Set up document data base.
Hypertrophic cardiomyopathy Case definition (WHO/ISFC announced in 1996)
(1) primary standard: the agnogenic heart left chamber wall thickness of ultrasonic cardiogram diagnosis is more than or equal to 13mm; Or apical hypertrophy or right ventricular hypertrophy.
(2) reference standard: the high-voltage performance of chamber, an electrocardiogram(ECG left side, accompany/do not accompany II, III, avF, avL and V
4V
5The pathologic of leading Q involves ST-T and changes.
(3) exclusion standard: long-term hypertension, ischemic cardiomyopathy and other can cause the primary disease of ventricular hypertrophy.
(4) familial hypertrophic cardiomyopathy settles the standard: myocardiac familial inheritance tendency is arranged, many people's morbidities are promptly arranged in patient (propositus) family, and meet the autosomal dominant inheritance characteristics.
The separation of 2 genomic dnas
Get patient's ulnar vein blood 5ml, EDTA (0.5M) anti-freezing, the centrifugal 10min of 2500rpm.The careful upper plasma of drawing is with the Eppendorf pipe packing of 1.5ML.Hemolysate (the NH that in hemocyte, adds 3 times of volumes
4Cl 8.29g, KHCO
31.0g, EDTA-Na
20.03734g, add bi-distilled water to 1000ml, regulating PH is 7.4), shake up ice bath 15min.The centrifugal 10min of 2500rpm abandons supernatant.In cell precipitation, add the 10ml hemolysate, shake up ice bath 15min.The centrifugal 10min of 3000rpm abandons supernatant, obtains white corpuscle, is directly used in the extraction genomic dna, and is perhaps frozen standby in-80 ℃.
Following extraction genomic dna: get white corpuscle, add 4.5ml SE (NaCl 4.383g, EDTA-Na
29.306g add bi-distilled water to 1000ml, regulating pH value is 8.0), piping and druming with strength, mixing.10%SDS along tube wall adding 0.5ml adds proteolytic enzyme E (100mg/ml, MilliQ water) 50 μ l then, head and the tail jog 10min, and mixing spends the night in 37 ℃ of water-baths then.Took out in second day, and added the saturated NaCl of 3ml along tube wall, rapid hand 15s separates out protein denaturation, then in the centrifugal 10min of 4000rpm.Get supernatant, change in another pipe, add isopyknic trichloromethane, shake 10min, mixing.The centrifugal 10min of 2500rpm.Get supernatant, change in another pipe, add isopyknic trichloromethane, shake 10min, mixing.The centrifugal 10min of 2500rpm gets supernatant, changes in the 50ml pipe, add 3 times of volume dehydrated alcohols after, the head and the tail jog sees that the DNA flocks separates out.DNA is chosen to tube wall, with 75% washing with alcohol 2 times.DNA is chosen to the 0.5ml pipe freeze-drying.Add TE (10mM Tris-HCl, 1mM EDTA, regulating PH is 8.0) 300 μ l at last, make the DNA dissolving, it is quantitative that ultraviolet spectrophotometer is surveyed the OD value, 4 ℃ of preservations.
Sudden change in embodiment 2 PCR methods screening β-myoglobulin heavy chain (B-MHC) gene
The primer and amplification condition (genome sequence is from Genebankdatabase, and the number of landing is M57965) as shown in table 1 below:
Table 1
| Exon | The PCR fragment length | Primer | The PCR reaction conditions |
| Exon3 ? Exon4 ? Exon5 ? Exon6 ? Exon7 ? Exon8 ? Exon9 ? Exon10 ? Exon11 ? Exon12 ? Exon13 ? Exon14 ? Exon15 ? Exon16 ? Exon17 ? Exon18 ? Exon19 ? Exon20 ? Exon21 ? Exon22 ? Exon23 ? Exon24 ? Exon25 ? Exon26 ? Exon27 ? | 245bp ? 248bp ? 200bp ? 146bp ? 244bp ? 240bp ? 223bp ? 226bp ? 229bp ? 398bp ? 267bp ? 213bp ? 232bp ? 438bp ? 180bp ? 474bp ? 271bp ? 298bp ? 285bp ? 300bp ? 400bp ? 282bp ? 221bp ? 151bp ? 420bp ? | ?F?5’act?cca?ggc?aca?gcc?atg?gg?3’ R?5’gtg?gac?tct?cac?atc?agc?ct?3’ F?5’gaa?agc?cca?ggc?tga?cag?ga3’ R?5’ggg?tgg?aca?tgg?atg?gag?ca?3’ F?5’gca?act?ggc?aag?tca?ctg?ct?3’ R?5’ctc?tca?cct?gtc?agc?atg?ta?3’ F?5’gag?aag?ccc?cac?gag?agc?at?3’ R?5’tgg?agg?ctg?ggg?atc?agg?gag?3’ F?5’ctg?att?tga?ggc?ttg?ctg?gt?3’ R?5’aag?aag?gag?gca?ggt?gag?ag?3’ F?5’cgc?aga?agg?gag?gga?gaa?ga?3’ R?5’agt?ggt?gat?gag?ttg?ggg?ga?3’ F?5’gga?ctt?gga?ctg?gtg?gag?ga?3’ R?5’ggg?gag?aga?gag?aga?gga?ca?3’ F?5’att?aat?ttt?cct?tgt?gcc?ca?3’ R?5’caa?gca?gag?ggg?acc?agg?tt?3’ F?5’cct?cca?tga?gag?ccg?ggg?gc?3’ R?5’ctg?ctt?ttg?gac?ccc?tgt?tt?3’ F?5’gga?tct?cac?tta?ccc?atc?at?3’ R?5’ggg?agg?ctg?agg?cag?gag?a?3’ F?5’tta?cag?gca?tga?acc?aca?cac?c?3’ R?5’gtg?aac?ttg?aaa?act?ctc?atc?cc?3’ F?5’gtc?tct?cct?cca?cct?tgc?ag?3’ R?5’cga?gtg?agt?gat?tgt?tct?cc?3’ F?5’acc?cac?ttt?ctg?act?gct?cc?3’ R?5’tgg?taa?ggc?caa?aga?ggc?ac?3’ F?5’ttg?acc?ata?gag?cag?aat?cc?3’ R?5’ctc?aga?acc?ttg?gga?gaa?tc?3’ F?5’gct?gtg?atc?tta?ctc?aca?cc?3’ R?5’tgg?gca?gat?ggg?gag?cca?ag?3’ F?5’tct?ctc?ctc?ttt?ccc?ttc?tgt?ctc?3’ R?5’tgc?ctt?aca?cat?cac?cct?cat?tac?3’ F?5’aat?cag?tga?caa?agc?cag?ga?3’ R?5’gca?gat?ccc?att?ccc?atc?ag?3’ F?5’cct?gat?ggg?aat?ggg?atc?tg?3’ R?5’atg?att?aca?aca?gga?aaa?gc?3’ F?5’tcc?taa?ggt?aat?ccc?cac?ca?3’ R?5’ctt?ttt?ttc?ctg?aca?ctg?cc?3’ F?5’gca?gag?gct?cag?cac?tcc?tt?3’ R?5’gcc?tca?ccg?cct?gca?ctt?gg?3’ F?5’ccc?tcc?tat?ttg?agt?gat?gtg?c?3’ R?5’ggt?cag?tat?ggt?ctg?aga?gtc?c?3’ F?5’aca?gat?ggc?acc?aag?ctg?gt?3’ R?5’gat?aga?cat?ggc?ata?tca?ag?3’ F?5’ggc?tcc?ttc?tct?cta?cca?gc?3’ R?5’tgc?ttg?tac?tgt?tat?ggg?ct?3’ F?5’acg?agt?ctc?cct?tac?ctc?ac?3’ R?5’cgt?ggg?tgt?cca?gac?ctc?ac?3’ F?5’gtg?tct?gac?cag?gca?ctc?at?3’ R?5’agg?ccg?agc?aga?gcc?tac?ct?3’ | 95℃5’，94℃30”，61.5℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，58℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，56℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，59.2℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，55℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，64℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，53℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，55℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，63℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，68℃30”，72℃ 50”(45cycles)；72℃7’ 95℃5’，94℃30”，57℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，55℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，58℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃1’，59.5℃40”，70℃1’ (35cycles)；70℃10’ 95℃5’，94℃30”，57.4℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60.6℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，62℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ |
Be prepared as follows PCR reactive group body series (50 μ l):
Primer (concentration 20pmol/ μ l) 1 μ l
10×buffer 5μl
TaqDNA polysaccharase (2u/ μ l) 1 μ l
dNTP(10mM) 1μl
Human gene group DNA 1 μ l
ddH
2O 41μl
According to the PCR condition in the table 1 genomic dna of each patient or contrast is carried out pcr amplification, and by following step to the PCR reaction product preceding purification step that checks order:
(1) dehydrated alcohol of 50 μ l PCR reaction product with its 6 times of volumes mixed with 5M Ammoniom-Acetate (5: 1) mixing solutions, place-80 ℃ more than 30 minutes.
(2) 14000rpm, 4 ℃ centrifugal 15 minutes, suct clearly and discard.
(3) add 75% alcohol of 200 μ l, 14000rpm, 4 ℃ centrifugal 5 minutes, suct clearly and discard.
(4) after room temperature or the lyophilize, add 20 μ l TE dissolving.
(5) inhale 2 μ l point samples, quantitatively.
The following sequencing reaction that carries out:
(1) reaction system (20 μ l)
BigDye
TM 4μl
BigDye
TM?Buffer 2μl
Primer (with the pcr amplification primer) 10pmol/ μ l
(2) reaction conditions (annealing temperature according to primer is decided):
(3) purifying of order-checking product:
Add 25 μ l ammonium acetates and 125 μ l ethanol in the 20 μ l products, put-70 ℃ 1 hour, 14, centrifugal 10 minutes of 000rpm abandons supernatant, adds 75% ethanol 100 μ l, 14, centrifugal 5 minutes of 000rpm abandons supernatant, dries in 1 minute for 95 ℃, add 2 μ l loading buffer, mixing, 94 ℃ of sex change 5 minutes place on ice rapidly then.
(4) the sequencing reaction product behind the purifying is checked order on ABI PRISM377 automatic sequencer.
(5) with GeneJockey, AssemblyLIGN
TM, Sequencing Analysis 3.4 softwares are read and check sequencer map, and with compare with the gene order of announcing.The transgenation that screens is thus listed in the table 5.
Sudden change in embodiment 3 PCR methods screening cardiac troponin T (cTnT) gene
The primer and amplification condition (genome sequence is from Genebankdatabase, and the number of landing is AY044273) as shown in table 2 below:
Table 2
| Exon | The PCR fragment length | Primer | The PCR reaction conditions |
| Exon2 ? Exon3，4 ? Exon5，6 ? Exon7 ? Exon8，9 ? Exon10，11 ? Exon12，13 ? Exon14 ? Exon15，16 ? | 203bp ? 272bp ? 596bp ? 292bp ? 682bp ? 1357 bp 743bp ? 315bp ? 667bp ? | ?F?5’tcg?ctg?atc?tct?gta?caa?cgg?ggg-3’ R?5’ggt?gtc?agg?gca?gcg?gcg?g-3’ F?5’atg?tgt?gtg?cag?gcg?tgt?gtg?ttt-3’ R?5’cca?ggg?ctc?cca?gga?ttt?cca-3’ F?5’tct?ctg?ctc?tgg?gtt?ctg?cct?gat?a-3’ R?5’att?ctc?ctc?caa?agc?tgc?tgt?ga-3’ F?5’gcc?ccc?gct?gcc?ttc?att?c-3’ R?5’cac?cat?act?gca?ccc?tgt?tcc?atc?a-3 ?F?5’ggg?cag?tgc?tgg?aag?att?ctc?tag?g-3’ R?5’gag?gaa?ggc?tgt?ctg?gag?gag?gt-3’ F?5’gtc?cgt?gga?gct?ggt?tga?aag?tg-3’ R?5’aat?ctc?ttc?ctg?gga?cct?gac?cta?aa-3’ F?5’ctt?tgt?ctt?cct?gcc?ttc?tct?ctg?tgt-3’ R?5’cag?aaa?gga?gtt?ggc?ccg?acc-3’ F?5’gga?agg?agg?gct?ggg?atg?ctg-3’ R?5’ctg?aag?ggg?gct?gtt?ggg?ga-3’ F?5’cac?tca?gcc?ccc?ttc?tcc?cca-3’ R?5’cca?gct?ccc?cat?ttc?caa?aca-3’ | 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃10’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃10’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃10’ 95℃5’，94℃30”，63℃30”，72 ℃30”(35cycles)；72℃10’ 95℃5’，94℃30”，63℃30”，72 ℃1’(35cycles)；72℃10’ 95℃5’，94℃30”，61℃30”，72 ℃1’(35cycles)；72℃10’ 95℃5’，94℃30”，61℃30”，72 ℃1’(35cycles)；72℃10’ 95℃5’，94℃30”，61℃30”，72 ℃30”(35cycles)；72℃10’ 95℃5’，94℃30”，63℃30”，72 ℃1’(35cycles)；72℃10’ |
Prepare the PCR reactive group body series (50 μ l) similar basically, just use the primer of this embodiment instead to embodiment 2.
According to the PCR condition in the table 2 genomic dna of each patient or contrast is carried out pcr amplification, separate amplified production and to its order-checking through conventional method.The transgenation that screens is thus listed in the table 5.
Sudden change in the embodiment 4 PCR methods screening cardiac troponin I gene
The primer and amplification condition (genome sequence is from Genebankdatabase, and the number of landing is X90780) as shown in table 3 below:
Table 3
| Exon | The PCR fragment length | Primer | The PCR reaction conditions |
| Exon3 ? Exon4 ? Exon5 ? Exon6 ? Exon7 ? Exon8 ? | 128bp ? 163bp ? 239bp ? 251bp ? 287bp ? 239bp ? | ?F?5’ggg?tcc?cca?ctc?ctc?cta-3’ R?5’tcc?ggc?gcc?tgt?act?ctg-3’ F?5’tgc?tgg?ggg?tgt?ctt?gag?gt-3’ R?5’cac?ctg?cct?gct?ctt?tcc?ca-3’ F?5’gag?ggt?tta?gaa?ggg?cag?agg-3’ R?5’ccg?gga?cta?gaa?acc?tcg?ca-3’ F?5’ggt?ctc?cct?gtt?ttt?ggt?tcc?c-3’ R?5’tgg?gtc?tcc?tgg?gat?gtg?ca-3 ?F?5’atg?gag?gag?ttg?ggt?gtg?cg-3’ R?5’aca?gcc?ctt?ccc?ctc?agc?at-3’ F?5’aga?ctg?gag?agg?aag?aag?aga?ccc-3’ R?5’tcc?tgc?cta?agc?cct?ggg?taa?t-3’ | 94℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 94℃5’，94℃30”，63℃30”，72 ℃30”(35cycles)；72℃7’ 94℃5’，94℃30”，60℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72℃ 30”(35cycles)；72℃10’ 95℃5’，94℃30”，64℃30”，72 ℃1’(35cycles)；72℃10’ 95℃5’，94℃30”，60℃30”，72 ℃1’(35cycles)；72℃10’ |
Prepare the PCR reactive group body series (50 μ l) similar basically, just use the primer of this embodiment instead to embodiment 2.
According to the PCR condition in the table 3 genomic dna of each patient or contrast is carried out pcr amplification, and separate amplified production and to its order-checking according to the method for embodiment 2.The transgenation that screens is thus listed in the table 5.
The pcr amplification of embodiment 5 cardiac myosin binding protein C genes (cMYBPC)
The primer and amplification condition (genome sequence is from Genebankdatabase, and the number of landing is Y10629) as shown in table 4 below:
Table 4
| Exon | The PCR fragment length | Primer | The PCR reaction conditions |
| Exon1 ? Exon2 ? Exon3-5 ? Exon6 ? Exon7-9 ? Exon11.12 ? exon13 ? exon 14-17 exon18 ? exon19.20 ? exon21.22 ? exon23 ? exon24.25 ? exon26 ? exon27 ? exon28.29 ? exon30-.32 ? exon33.34 ? | 145bp ? 550bp ? 1016bp ? 344bp ? 674bp ? 594bp ? 315bp ? 915bp ? 537bp ? 537bp ? 623bp ? 525bp ? 619bp ? 567bp ? 275bp ? 770bp ? 996bp ? 605bp ? | ?F?5’atg?gtg?agt?agc?ctg?gtg?tga?c?3’ R?5’ccc?cct?caa?gaa?ctc?ctc?ct?3’ F?5’tgt?cct?cct?ctg?aga?aat?gaa?cag?3’ R?5’cag?caa?agg?caa?gaa?agt?gtg?a?3’ F?5’gtg?gag?ggg?tct?ctg?gtt?agt?3’ R?5’tct?gtg?tgc?ctt?gtg?cct?tct3’ F?5’ggg?tgc?gga?gcc?ttg?tct3’ R?5’gcc?ttg?ggg?ttt?ctc?tca?cac3’ F?5’cag?ggc?agg?gct?tct?caa?a3’ R?5’gac?aga?caa?gga?aac?caa?ctc?aga3’ F?5’ggg?tgg?ggt?cca?ggt?ctt?t3’ R?5’atg?ccc?tct?cct?ctc?ctg?tgt3’ F?5’gcg?gca?cag?agg?gga?ttg3’ R?5’ggg?cag?gag?gca?agg?cta?t3’ F?5’tct?cgg?ggc?tca?ctt?cct?c3’ R?5’gtc?acc?tca?gca?tcg?tca?ttt?tag3’ ?F?5’cag?cct?aaa?cct?cat?cct?tct?ca3’ R?5’tgt?ttc?ctg?tgt?ctc?tct?ctg?t3’ F?5’cac?ttt?tac?gct?gcc?tac?ctc?tg3’ R?5’atc?ctt?gct?ttt?ccc?tct?gtg?a3’ F?5[‘tgg?ctc?tcc?cgt?ttc?tct?ga3’ R?5’agc?aac?aca?ccc?gac?caa?gt3’ F?5’agt?cgg?tgc?cca?gag?atg?aat3’ R?5’cag?cag?tgt?cgc?agg?aaa?tct3’ F?5’ctg?tgg?cgg?tta?gtt?gga?gtg3’ R?5’agg?atg?aaa?gga?gac?tgt3’ F?5’act?tga?act?cgg?gag?gca?gaa3’ R?5’ccc?tct?ctg?cac?ttt?ttc?cct?a3’ F?5’cag?tgg?gag?tgg?ggt?gtc?ag3’ R?5’ggt?gtc?aat?ggc?ggg?tct?t3’ F?5’agg?gag?gtt?gga?gct?gtg?ga3’ R?5’tgg?gga?gga?ctt?ggc?ttg?t3’ F?5’gga?ccc?aac?cca?cag?ctc?ac3’ R?5’agg?ctg?ggg?aga?gga?ctg?c3’ F?5’gga?ccc?ccc?gag?tag?aaa?ca3’ R?5’gcc?cct?aca?gcc?tcc?cat?tt3’ | 95℃5’，94℃30”，58℃30”，72 ℃30”(38cycles)；72℃7’ 95℃5’，94℃30”，62℃30”，72 ℃40”(38cycles)；72℃7’ 95℃5’，94℃30”，62℃30”，72 ℃40”(35cycles)；72℃7’ 95℃5’，94℃30”，62℃30”，72 ℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，63.9℃30”， 72℃40”(35cycles)；72℃7’ 95℃5’，94℃30”，62.5℃30”， 72℃40”(39cycles)；72℃7’ 95℃5’，94℃30”，56℃30”，72 ℃30”(38cycles)；72℃7’ 95℃5’，94℃30”，63℃30”，72 ℃90”(35cycles)；72℃7’ 95℃5’，94℃30”，58℃30”，72 ℃40”(36cycles)；72℃7’ 95℃5’，94℃30”，58℃30”，72 ℃40”(38cycles)；72℃7’ 95℃5’，94℃30”，56℃30”，72 ℃40”(35cycles)；72℃7’ 95℃5’，94℃30”，53℃30”，72 ℃50”(36cycles)；72℃7’ 95℃5’，94℃30”，58℃30”，72 ℃40”(38cycles)；72℃7’ 95℃5’，94℃30”，55.5℃30”， 72℃30”(35cycles)；72℃7’ 95℃5’，94℃30”，60℃30”，72 ℃40”(40cycles)；72℃7’ 95℃5’，94℃30”，62℃30”，72 ℃50”(40cycles)；72℃7’ 95℃5’，94℃30”，66.5℃30”， 72℃120”(40cycles)；72℃7’ 95℃5’，94℃30”，56.3℃30”， 72℃50”(35cycles)；72℃7’ |
Prepare the PCR reactive group body series (50 μ l) similar basically, just use the primer of this embodiment instead to embodiment 2.
According to the PCR condition in the table 4 genomic dna of each patient or contrast is carried out pcr amplification, and separate amplified production and to its order-checking according to the method for embodiment 2.The transgenation that screens is thus listed in the table 5.
Embodiment 6 restriction fragment length polypeptide (RFLP) detect
Sequence change because of the gene position, destroyed or set up the specificity restriction enzyme site of being limited property restriction endonuclease identification, after this sample is handled by the specificity restriction enzyme, because of its endonuclease bamhi length with normal specimens different, when gel electrophoresis, can show different travelling speeies.With this principle, can carry out the gene mutation for screening of the patient family member in known mutations site.Use Promega company enzyme to cut test kit during this detects, and carry out according to appended product description.
Table 5 100 routine hypertrophic cardiomyopathy patient β-MHC, cMYBPC, cTnT and cTnI gene mutation for screening result:
| Disease-causing gene | Position in the gene | Nucleotide changes | Amino acid change | Transcript changes | Frequency | Patient's per-cent (%) |
| MYH7 (β-MHC) gi：M57965.1 | exon?3 exon?5 exon?14 exon?14 exon?15 exon?16 exon?18 exon?18 exon?19 exon?20 exon?20 exon?22 exon?22 exon?22 exon?23 exon?23 | 5797?C＞T 6739?G＞A 10353?G＞A 10429?A＞C 10895?A＞T 11811?A＞C 10600?C＞T 10601?G＞A 13463?G＞A 13653?A＞C 13673?G＞C 14449?T＞C 14452?G＞A 14557?G＞A 15373?G＞A 15391?G＞A | A26V R143Q G425R K450T I511F K615Q R663C R663H R719Q Q734P G741R M822T G823E R858H E924K E930K | Missense missense missense missense missense missense missense missense missense, the missense missense, the missense missense, the missense missense, missense | 4 2 1 1 1 1 1 4 1 1 1 1 1 1 2 1 | 24 |
| MYBPC3 (cMYBPC) gi：Y10629 | ? exon?6 exon?7 exon?15 intron?15 exon?21 exon?23 exon?25 ? exon?25 exon?29 | ? 4295?G＞A 4826?G＞A 8697?G＞A 8887?G＞A 12101?G＞A 13261?G＞A 14262-14264 delAAG 14364delG 18115^18116 insGCAAG | ? E258K G263R G416S ? R668H G758D ? ? ? ? ? | Missense missense missense montage missense missense codom disappearance is moved the frame of frameing shift | ? 2 1 1 1 1 1 1 ? 1 1 | 13 |
| TNNI?3(cTnT) gi：X90780 TNNT2(cTnI)gi： AY044273 | exon?7 exon?7 exon?10 | 4693?C＞T 4769?G＞A 14035?T＞C | R145W R170Q R130C | Missense missense missense | 2 1 1 | 3 ? 1 |
Annotate: what band was focused on look all is new mutant, totally 19.
2.MHC:G425R, Q734P, M822T, G823E; CMYBPC:G263R, 8887 G＞A (intron15), R668H, G758D, 18115^18116 insGCAAG (exon 29); Sudden changes such as cTnT:R145W find in the family patient, are with hypertrophic cardiomyopathy to be divided into from trend.
3.120 do not find above site mutation in the routine normal control.
The foregoing description is just in order to illustrate rather than limit the present invention.Those skilled in the relevant art know clearly, can do other suitable modification and variation to content as herein described, and can carry out this modification and variation in the scope of the present invention or its any embodiment.Such modification and variation all fall into protection scope of the present invention.
Sequence table
＜110〉China Medical Sciences Academy Fu Wai Hospital
＜120〉new mutant of hypertrophic cardiomyopathy Disease-causing gene and uses thereof
<130>idc040150
<160>4
<170>PatentIn?version?3.2
<210>1
<211>28438
<212>DNA
＜213〉β-mhc gene
<220>
<221>misc_feature
<222>(11380)..(11380)
<223>n?is?a，c，g，or?t
<400>1
gatctatctg?gtccagacca?tcctttgaac?caagtggact?tagtggggct?gaaggaggtg 60
tggggacaaa?gaacctatgg?cagggcaacc?ggccctcctg?tctgcagcct?ggcttcctca 120
attttgtgtt?cctaacctaa?gagctgccat?tcagtgaggg?cccacagtgt?gtctgctgtg 180
tgtagactct?gcttgtgcaa?tctctaatgg?cctgagtagc?cctggaaaca?aaatgtggct 240
atccccatgt?tacagatgac?aaaactggct?caaagcaatt?atatgactga?cgtagaccac 300
acagctagaa?aatggaatca?ctgggtttca?aagtggattt?ttgtgactga?ctccaaagct 360
gaccagagtg?ctcatcctgt?atgcttctga?ggcctctggc?cctccagacc?ggtcactccc 420
cacaaagtct?cccttttggt?gagttgtgtc?cctccaaaca?ctccctgaag?gcaagatcaa 480
cctgccctaa?ctaccccaaa?gtgaactagg?ccagccccaa?gcctgtctcc?ggccctccat 540
ctctctcttt?gttcacatcc?atcagaaagc?agagacctag?agtagggaat?gagagggggt 600
gcacaagtac?aaaagatttt?gaagcagcag?gaagacgaaa?gaagtacaag?aaggagcagc 660
tgtttgtaaa?agggaaaatc?tgagacaggc?agaaagctca?gctccctaat?cctaggctcg 720
tgtggagcca?gggcagggtc?ccccaaggtc?agggattctg?ggggcaggcg?gatgggagag 780
tcagcctcca?ctcctgggtg?gctcccctct?gccctgtgca?caaacaacga?gtgcctcatt 840
cctcccctgc?accaagtgcc?ctgcctcttc?ctgccccgtt?tcttccttcc?ctttgggtac 900
cggatctttt?ttctgattcc?cctctctcca?tgctgacatc?gcttctaatt?cgccctggtg 960
tctccctccc?tcacaattac?tgggagtaat?tttagcaact?tttcctctga?actaccgctg 1020
gcgtgttcac?agcaaatggc?ccctgttttg?gcttgacact?tgatcagggt?ggtgacagag 1080
tgcagacaaa?gccggcacaa?tgcggggagg?ggaggaccgg?ggcagatcac?cttcctttca 1140
cttcagggcc?ttatttggtc?taccttgccg?aagcggccct?ccttccagcc?tctctttatt 1200
tatagcattt?tgcttgctct?cctttatctt?gctatcactt?gtagcacact?ctgcacaatc 1260
cccacccacc?ccagcatggt?ggggcccctg?gctcactctc?cccacaagga?atgtgcatgt 1320
gtgcaaaggg?taggcctgga?tgccatttct?acaaacagtt?gactaaagca?gtccagagca 1380
gggatctttc?tttgggtcat?tgttatgtcc?ttattgacca?gaataatgcc?tggcacatag 1440
taggcactca?ataaatactt?gttgaatgga?ggaatctgca?aagctgctca?gtcttcagac 1500
agcagcaagc?agcaggaaga?gaatcatgat?gtaaccaaga?gcaggtgctg?gaggagctag 1560
ggagtgagtg?gggatcttta?aggacagcag?gccctctgat?ctgtctgagc?gtgtgagcaa 1620
agcctagtta?gggaggtgag?ttctatctgc?aatgagaggg?ggcatgggtg?gagacagata 1680
acaccaacac?caacagacca?gacctcccaa?acccgaaagg?agagacaaag?tgtgattgat 1740
ttcccaaatg?cagaaaagac?tacccaagtc?cccagccaag?aagaatcgct?ggcctgtgga 1800
tgaagacact?ggctttgaaa?tggctcaact?acgtcccaag?caccctttgt?gcatcttaat 1860
tgccctggga?aatcagggag?gggtggcagt?ttggagcttg?gaaagctgga?aggtggggac 1920
gaaaggagtt?tttgcccctc?atcgccaatc?cttgaggttc?ctacagggaa?cctcagacaa 1980
cagctgtctt?aggggtttcc?ttccagctcc?aagcagctgt?attatctata?gctttgagag 2040
ggtctgtctc?tgtcaatggg?gctgattcct?cagcacctgg?cagggcctgg?gggggactgc 2100
cagagtctgt?tctgccgggc?atgttagtag?cacagactac?tgggataacc?tcagcaactg 2160
tataccttag?cactgcagag?ctgcggtgtt?gtcagacaca?ggcccttgca?gttcgtggtc 2220
tacccccact?tgcctgcacc?ccccttatag?ctgctcaatg?tcctcagact?gtaccttagt 2280
gccttggtta?ccaagcaacc?cccacagagg?ccctcctcct?ggattttccc?ttccctgcta 2340
tgcccacccc?accttcaaaa?tgtacctgct?gcacccatcc?cccaggcctg?cctcactcct 2400
tccaagctga?cagctaatca?gatggactaa?tcgcatgcgc?ggaagagctg?tgctcgggaa 2460
gaagggggag?atttcacacc?aaatcgtgca?gtggttgcct?agacacggag?ccagtcaagc 2520
ttgcatgccc?cgttgctaga?agagcatggc?atcggttgtg?ttctgtgctc?gtaggctggg 2580
ccccagctcc?ctttcctccc?ctcctttgtg?gctgttcctc?aggcctgcag?aggggaagat 2640
ttttcctgtc?ctgttactct?gcctcacttg?ccagaacact?agtcgcctcc?agctctggat 2700
aaagctgagg?ctgggtgggc?cagacaacag?ctgtcttagg?ggtctccttc?cagctccaag 2760
tagttgtatt?atctatagct?ctgagagggt?ctgtctctgg?gctcaggcct?ttagtacctg 2820
tggggcagag?ccaggaacgt?gagtcaggca?aaccgctcca?aactaggacc?aatgcagctg 2880
ggtcctgctc?tctgcgcata?gggggtcccc?acatctttgg?aatcccagcc?cacctttcca 2940
ggctaccctc?cacaggccgg?gctccactcc?catctgctga?ggtttcccac?cttgaatcct 3000
gctgccccga?ttagctgtat?aaccttaaag?aatgcactgt?ccctctccat?taaatgaagt 3060
gcttggatgg?attgctaaag?gcctgtctgg?ctcggaggct?tggtgcctca?acacattgcc 3120
tgctggtcca?aggaaatcag?tgcctgagcc?agagtcccca?tctctaagct?ccatggttat 3180
tgttcttgcc?acctggctag?gaaatgtcct?tccagctgcc?ccagtctagc?tgcctcaccc 3240
tggggccatg?ccccaactct?gtcctaccct?tctctgctgc?tgacactcag?ccccttccca 3300
gcttccagtt?ggatacagga?cctgggccag?gagagcaggg?aggacactgt?ggaaatgcgg 3360
ccaggccatc?aggggcctcg?cagcagggga?ctggaggggg?agcagtgtcc?agggccagaa 3420
gtgccctgcg?ggagagccag?gacattggct?gcctgtggtc?ttggtggtcg?tggtcagttc 3480
cctctcctgc?cagctgtgga?atgtgaggcc?tggcctggga?gatatttttg?ctgcactttg 3540
agccaccccg?ccccctggaa?ctcagaccct?gcacagtcca?tgccataaca?atgacgacca 3600
cttccaattg?tttcctagct?ggagaggcgg?ggaggggagc?actgtttggg?aaggggggga 3660
gcctggggga?aatgcttcta?gtgacaacag?ccctttctaa?atccggctag?ggactgggtg 3720
ccgttggggg?tgggggtgcc?ctgctgcccc?atatatacag?cccctgagac?caggtctggc 3780
tccacagctc?tgtcctgctc?tgtgtctttc?cctgctgctc?tcaggtagga?gcgggagctg 3840
gaggctttac?tctgggataa?gggggctcca?ggcttaggaa?gggattcctc?ttggaatagc 3900
aagcttcatg?caggacttca?tgcagagtac?caggtccagt?cactgggcac?acatgtgcag 3960
gtctaaacat?gggcgtatgt?gccacaggag?ttccataggg?gcagatatct?gcatctgagc 4020
atatgggacc?aatatgcatt?acagggtgtg?tgtgtgtgtg?tgtgtgtgtg?tgtgtgtgga 4080
caagcctgca?tagtctgaat?gtgagaaagg?gtatgtacct?cactgactga?tacagaaata 4140
tcaagtggga?gatgtgggtg?tatgatcacg?tctgtgaacg?aggaggttcc?tttgcaggga 4200
gggagaaaga?atggtggaga?aggattctag?gaagtgtgta?tgccttcatg?tgattctgtg 4260
aggcctggaa?tgtgtagcta?cccctgtcca?tgcatgcaga?ggttcttgtc?tatgcctcca 4320
cgagtaatga?ctgttatagt?atctgtaccc?tctgcagaag?gaactcacag?gcacgggggt 4380
gtaggatgtt?ccaggtcttt?gtgtactgaa?gaacacgcag?atgtgatcta?cttacgtggc 4440
acacatcctc?aaatgtgcac?atttgctgtt?gaggcatata?tggcaccctg?gggttggggt 4500
gcggattgag?gtatgggaag?gaagcctgtc?ctcatgtgag?aggcatgccc?aagcagcagg 4560
catgagtgtt?catcagaggg?cttgtggagg?gtgtttggct?atgtgatggg?tgtgtctgtg 4620
agaggaagcc?cacagtgtct?tctctctgag?aatgtccaca?aagtctgaca?acaaaatggg 4680
gacaggatgg?aaaagaagtc?tctttagagt?catcagactt?gcattcaagt?cttggctctc 4740
ccacttgttg?tcatgggctc?ttggccaagc?aagccattta?acctcgattt?cctcatctgt 4800
caaatggggt?gaagactgag?taggagaaag?tgcattgaag?tgcttttaga?ctggaaagtg 4860
ccgaacaaat?gtgaccatta?gttgtctctc?agatggctca?aagaaaggta?ccactagatg 4920
ggtacaggca?ggggtgggac?catctcgcag?gagtgaagag?gattagggtt?caggttgagt 4980
tgacacagga?agctgttaga?actagttctt?gaggaaaaag?ggaatagggt?ttgaaaaaca 5040
agaaggatgg?gttgggccag?agaagctgac?caccctttcc?accttgtttt?ggaagagggt 5100
ggatgctgaa?gaacagagcc?agggagaagc?aggaaggtgg?gactggtcag?gtgggcacag 5160
cctgccctga?cacagcctct?tccctctctc?caggtcccct?gcaggccttg?gcccctttcc 5220
tcatctgtag?acacacttga?gtagcccagg?taagaaaagc?tgaagctaga?gcgttgaaaa 5280
tctagtaaga?ctgggcatta?gagccccaaa?gccagcctat?ggaactctag?tttctgccat 5340
gtgctggaga?gaatatcttg?gctatcaaga?gctacttacc?tgtgaccagg?gggtccaggg 5400
atagatgagg?gtcagagatg?gaaatagtta?gatttctgct?cctacagggg?acctgcaggg 5460
agctcagaat?gctcttcctt?cccctaggag?agccccagct?tgaacaatag?ttagttgttc 5520
cttttaccct?ggcaggtttg?ctaggctgct?cctctggtta?aggggtaacc?tcaaaaggaa 5580
gggactcact?ggtaactcct?cttgactctt?gagcatggtg?ctaggttttg?gggctcccac 5640
tgaaggggag?agcccaggga?gggaagggaa?gaatgggcag?atgggagggc?agccagcttc 5700
tgctcactcc?aggcacagcc?atgggagatt?cggagatggc?agtctttggg?gctgccgccc 5760
cctacctgcg?caagtcagag?aaggagcggc?tagaagcgca?gaccaggcct?tttgacctca 5820
agaaggatgt?cttcgtgcct?gatgacaaac?aggagtttgt?caaggccaag?atcgtgtctc 5880
gagagggtgg?caaagtcact?gccgagactg?agtatggcaa?ggtgggtgtc?aggctgatgt 5940
gagagtccac?cctggccacc?tgtacacctg?ggtggacaga?gaggggtaca?cccatgcccc 6000
atgcccatgc?agacctgagg?atggtcccat?tctccttccc?tttgggaaga?atccagaccc 6060
tccaaagagc?cctctccttc?ccaatatccc?ttctgtcttc?cctgtgagat?cctggttcct 6120
tctctcttga?gcactattgc?cctgtcactc?accaactcct?aaccctcttg?aggaaggagg 6180
gaaagcccag?gctgacagga?gggcttgggt?gggggctctt?gcagacagtg?accgtgaagg 6240
aggaccaggt?gatgcagcag?aacccaccca?agttcgacaa?aatcgaggac?atggccatgc 6300
tgaccttcct?gcatgagccc?gcggtgctct?acaacctcaa?ggatcgctac?ggctcctgga 6360
tgatctacgt?gagtgctgca?cctggcccta?cgttgggatc?tctgttcttg?ctccatccat 6420
gtccacccca?ggagccaaga?gtgtcttctg?tttgtgtcta?ggcagggtta?cactctaacc 6480
tcgtcccaac?atccttggtt?caattccaac?actctgggga?ctggcattac?tcagattgag 6540
tgcatgcaga?ggttttcctt?tctcttcttt?ctctcctggg?atctttctct?aactcccaaa 6600
atcaccagcc?ctcccccttc?gcaactggca?agtcactgct?ccttttctat?ccccagacct 6660
actcgggcct?cttctgtgtc?accgtcaacc?cttacaagtg?gctgccggtg?tacactcctg 6720
aggtggtggc?tgcctaccgg?ggcaagaaga?ggagcgaggc?cccgccccac?atcttctcca 6780
tctccgacaa?cgcctatcag?tacatgctga?caggtgagag?gccctggaag?gtcttcctga 6840
agggaactgg?gataggccgg?gagggagagg?gagaaggaag?ggagaagccc?cacgagagca 6900
tcctgtgcag?ctcctgacct?ttcctcccca?ccctctcccc?acagacagag?aaaaccagtc 6960
catcctgatc?acgtgagtgt?agctgctact?gtattccctt?tcagaatctc?cctgatccca 7020
gcctccagcc?ccatcaggtg?tcccaggccc?cgaggcatag?actcagcctc?tttcccccca 7080
acctcgtgcc?catctccttc?ttctctgacc?attaccctga?cccctctctt?tgctctccct 7140
cttcctttct?gctttccatc?cccttcatgt?ttttcctctc?ccacctcctt?cacccactct 7200
ccaactcatc?acgcgtttat?ccagaagctc?attatcgcca?tgtcttcacc?tctgcatttt 7260
ctttcccttc?agaaacattt?cccattcttc?cagccctacc?aacttttccc?aaaacagccc 7320
aggcccatct?cccctgttta?ctttgcccag?ccaagcacag?gtcagcctgc?ccaaaccagt 7380
gccttctggt?ggcatccttc?ctggtgccag?ccctgacctc?tgtgcatcag?aagacagttg 7440
tggattttgg?gtgtagataa?cctggcagct?tcttgcccag?ggctcctact?ctcgggtagg 7500
cccaggcatt?ctctcctgat?ttgaggcttg?ctggtctcca?gtagtattgt?tcactgccca 7560
ataagcccct?gtcttcacag?cggagaatcc?ggagcaggga?agacagtcaa?caccaagagg 7620
gtcatccagt?actttgctgt?tattgcagcc?attggggacc?gcagcaagaa?ggaccagagc 7680
ccgggcaagg?taggcctgct?gccctccaag?gtcctgtacc?gcagaaggga?gggagaagag 7740
ctctcacctg?cctccttctt?ggcctctgca?gggcaccctg?gaggaccaga?tcatccaggc 7800
caaccctgct?ctggaggcct?ttggcaatgc?caagaccgtc?cggaacgaca?actcctcccg 7860
cttcgtgagt?ggtccctgac?cttggccttg?ggacttggac?tggtggagga?atggtctcag 7920
atatgagcct?tcccccaact?catcaccact?ctcttccatc?tctccagggg?aaattcattc 7980
gaattcattt?tggggcaaca?ggaaagttgg?catctgcaga?catagagacc?tgtgagtgcc 8040
atgaatctgc?taggctcagc?ctaagctcac?ccttgctcta?gaccatctgg?tcttgacctc 8100
tctctctctc?ccctccctcc?ctctgttttt?ctcctcttta?agtctctgtc?tgtaggtgtc 8160
tctgtcttca?ggtctacata?tctgtctctc?tctgagactt?cctctgcatc?tttctccatt 8220
tctgtctctg?catggctagg?tgtctttctc?tgggatttct?ctctgagact?atttctctcc 8280
ttctgggtct?ctgtttccat?ctctctgtgt?gatctctttg?tgtctgtcca?actagtctct 8340
ctggctcttc?ccttccctct?gccttttgct?tgctacattt?atcattaatt?ttccttgtgc 8400
ccaaacccta?acttttcttt?ctctccttct?tctccccacc?tgttcacaga?tcttctggaa 8460
aaatccagag?ttattttcca?gctgaaagca?gagagagatt?atcacatttt?ctaccaaatc 8520
ctgtctaaca?aaaagcctga?gctgctgggt?gagtcagagc?caccgactga?gaccaactat 8580
ctccatggca?acctggtccc?ctctgcttgt?ggctggactc?agctggcatg?ccctgggttt 8640
catggcactg?ctggattcaa?ttcagctggg?atgtggggcc?aagccaagcc?ctgtcctgtg 8700
ctgcttcctc?aggccatgtg?ctgtggcgag?cagcctccat?gagagccggg?ggcttgtgtc 8760
ccaccctaac?catgtttttt?cccctagaca?tgctgctgat?caccaacaac?ccctacgatt 8820
atgcattcat?ctcccaagga?gagaccaccg?tggcctccat?tgatgacgct?gaggagctca 8880
tggccactga?tgtgagtgtg?tgaggaccca?gccagggggt?gggaggattg?gcagtgaggg 8940
gcaaacaggg?gtccaaaagc?agagctaaga?ctctggccat?tggttgttta?aagtggtatg 9000
gacctcctga?gagccagaat?gtgccctgtg?atcagggtgt?actggggaat?ggatgaggtg 9060
agacaggact?ggccagtatc?tggtgttcta?tcaaaccagg?aagagctgaa?agccatgaga 9120
cagagagaca?cacaagccaa?gaaacaagca?tcaccgaggg?agcaggacga?ggagggaagg 9180
ccatgcagac?ggcatggggc?tggaggggct?gttaggtgaa?cagatgcaga?caggtatgga 9240
aggccaggca?ggaagcaagt?gtagggccag?gaagcataag?tgggtaactc?agaaaagctg 9300
tggccactga?cactggggct?gcggccaact?gacgtctgct?ctgctcttgc?atcttacatc 9360
ctttgttttg?gagttccctg?catcttacat?cctttgtttt?ggagctcccc?actgggtatg 9420
ggagtctcag?aacccacagg?gattaaggag?acaagttttc?tctccaactt?acaagggatc 9480
tcacttaccc?atcatacttc?tttttctggg?gtccgccaat?atggggcctc?cctacagaac 9540
gcttttgatg?tgctgggctt?cacttcagag?gagaaaaact?ccatgtataa?gctgacaggc 9600
gccatcatgc?actttggaaa?catgaagttc?aagctgaagc?agcgggagga?gcaggcggag 9660
ccagacggca?ctgaaggtgg?gaggcaggat?tcttggggca?gctgtaagtc?atgaggcagt 9720
ctgctcagca?gtatctctct?tctcttttct?tttttttttt?ttttttgaga?tggagtcttg 9780
ctctgttgcc?caggctggag?cgcagtggca?cgatcttggc?tcactgccac?ctccacatcc 9840
tgggttcaag?tgattctcct?gcctcagcct?cccgagtagc?tggaattaca?ggcatgcacc 9900
accatgcctg?gctaattttt?gtatttttag?tagagatggg?gtttcatcat?gttggccagg 9960
ttggtctcaa?actcctgacc?tcaagtgatc?cgcctgcctt?ggcctcccaa?agtgctggga 10020
ttacaggcat?gaaccaccac?acctggccag?cagtcatctc?tttaccaact?ttgctacttg 10080
ccttttcctt?ccagaggctg?acaagtctgc?ctacctcatg?gggctgaact?cagccgacct 10140
gctcaagggg?ctgtgccacc?ctcgggtgaa?agtgggcaat?gagtacgtca?ccaaggggca 10200
gaatgtccag?caggtgggtc?catcttcaga?tgataatggg?tgggcagggt?agggagactg 10260
gcatggtggg?atgagagttt?tcaagttcac?tcttcccaac?aaccctgctc?aatatgggtc 10320
tctcctccac?cttgcaggtg?atatatgcca?ctggggcact?ggccaaggca?gtgtatgaga 10380
ggatgttcaa?ctggatggtg?acgcgcatca?atgccaccct?ggagaccaag?cagccacgcc 10440
agtacttcat?aggagtcctg?gacatcgctg?gcttcgagat?cttcgatgtg?agttgggacc 10500
cctgggagtg?ggagaacaat?cactcactcg?ctcccacatt?caacagctat?ttgcttagag 10560
ccagctgtgg?accagacatg?ggaaggcagt?ggggactgtg?tggtgacaga?ggcagtcatt 10620
ttctctgtct?tcaggggaag?ccctccttca?ctgccttgac?atggagggga?ccagccacgc 10680
cctgctgggc?tcaggcacag?tggacgggca?cagccccaat?ggccactcac?acccactttc 10740
tgactgctcc?cacccctcat?gccccctgca?gttcaacagc?tttgagcagc?tctgcatcaa 10800
cttcaccaac?gagaagctgc?agcagttctt?caaccaccac?atgtttgtgc?tggagcagga 10860
ggagtacaag?aaggagggca?tcgagtggac?attcattgac?tttggcatgg?acctgcaggc 10920
ctgcattgac?ctcatcgaga?aggtgcctct?ttggccttac?cacctgaatt?ctccctgcac 10980
acccaacaag?aacaccatag?acaaaatagc?agcccctctc?ccttctgggg?aatataaaaa 11040
tagaaggggc?tgaaggatcc?gagcccttgg?ttccagagcc?tatgttgtgc?tgagcaccca 11100
ggacagggtg?gcaccaggga?cagctgattt?cccaggggct?tgaaagtgga?cacatggagg 11160
atgggcacct?gcatgatgac?ctcccacacc?tgcatgttta?ttgggcctgg?tttatgcatc 11220
caaggatcag?gaagtgtgag?ggtggtgtag?gggatcataa?gagtgcacct?attttcaacc 11280
ctagcatctc?aggcatctgg?gtcgtggagt?ggtgtgtaca?gcatcgatag?aatccatatt 11340
cccagacttt?cacaaagtcc?ttctgtcatc?agacaaaatn?ctccaccttg?aaccggttcc 11400
agtcagtaga?taactgtact?cagagctgag?cctactacct?taacacccaa?catggcacct 11460
ccacgagcaa?gtatattgac?catagagcag?aatccatgtc?cacctgtgtg?aaggacactc 11520
agtgatgctc?tctcctgctt?cctcagccca?tgggcatcat?gtccatcctg?gaagaggagt 11580
gcatgttccc?caaggccacc?gacatgacct?tcaaggccaa?gctgtttgac?aaccacctgg 11640
gcaaatccgc?caacttccag?aagccacgca?atatcaaggg?gaagcctgaa?gcccacttct 11700
ccctgatcca?ctatgccggc?atcgtggact?acaacatcat?tggctggctg?cagaagaaca 11760
aggatcctct?caatgagact?gtcgtgggct?tgtatcagaa?gtcttccctc?aagctgctca 11820
gcaccctgtt?tgccaactat?gctggggctg?atgcgcgtaa?gtagggactg?aggctcccgg 11880
tacagaggag?cagggattct?gccaaggttc?tgagccaggt?caattgctac?accccaccac 11940
ttcaatgtca?ggttgtaccc?caaggtttac?agactcagtg?ggatggaact?gggtgaagaa 12000
actgaggcag?ccacattgaa?ggcctaccag?gggcaaatgc?cagcaaggat?gtaaagaggg 12060
gctgtgatct?tactcacacc?ctacctcccc?acactgatgc?ttcttttgtt?gactctcctt 12120
cctgcagcta?ttgagaaggg?caaaggcaag?gccaagaaag?gctcgtcctt?tcagactgtg 12180
tcagctctgc?acagggtgag?tgggacacag?ccccagccaa?cttggctccc?catctgccca 12240
accccaccca?gccccaccct?tccctgcctt?gttcatcccc?tactcctccc?gttccctgtc 12300
tccttggtgc?attcgggacc?attttcactc?tgtcttctct?tcccgtcatc?tcctggcctc 12360
ttcacttatt?tacttcccat?ctcccttctc?tcctctttcc?cttctgtctc?ccaccctctc 12420
tccttatccc?tgtctccccc?agggcccctt?catctctgtg?acttctcgaa?ttctctccat 12480
ctctcttttc?cttccttctt?ctcctctctt?cttcctgcat?ctctttctgg?cattttcttt 12540
acttttctct?attgcatttt?tggccacagg?aaaatctgaa?caagctgatg?accaacttgc 12600
gctccaccca?tccccacttt?gtacgttgta?tcatccctaa?tgagacaaag?tctccaggtg 12660
aggccacaaa?ctagggccaa?cccactgctg?ggcatacacc?gccctgggaa?caggacctcc 12720
taggacatct?ccctacctac?caccacagtg?gtttccaaac?cacattcttc?tcctcccatc 12780
ccgcatgagg?cctcccaggg?tacctccctc?tcagcgctac?cttgcacttg?cagtgtgtaa 12840
tgagggtgat?gtgtaaggca?ctctgatgga?cattacctca?tcagtggccc?tacaaccccc 12900
tggatagctg?gttgtccaag?acagaatctt?agttcaactt?taaatttacc?tgcagaacca 12960
cttaagcccc?caatgagaca?tattcaaatt?gttaatccat?ttttggctaa?ttaggagaca 13020
gaggctcagg?gacctgggtt?caagacctgg?ctctgttctt?gatcagctta?gtgaacttgg 13080
cctgtcccgt?aacccctctg?ggcttaattt?actcatctag?aacattggat?atatctgttc 13140
tggctaccac?ctatgataat?aggtgtgaat?catataaaaa?aggaatgtga?aagcctttta 13200
gttaaaaatg?tggctagaag?aaaatgaaac?aaatgattat?tactaactga?cttgctaaga 13260
ttacaagcta?atcagtgaca?aagccaggat?cagaacccag?aacttcagtc?cagtgttctc 13320
acagactcct?cctacttcct?tcttgccaca?ggcgtgatgg?acaaccccct?ggtcatgcac 13380
cagctgcgct?gcaatggtgt?gctggagggc?atccgcatct?gcaggaaagg?cttccccaac 13440
cgcatcctct?acggggactt?ccggcagagg?tgggtatgag?ggtgcaccag?agctcataga 13500
acagggggag?ccaggctgcc?ctgatgggaa?tgggatctgc?aggtgaccct?agaattctat 13560
gggcagagca?gatcactgca?gagcatgggt?gactctggac?acttccctcc?tcaggtatcg 13620
catcctgaac?ccagcggcca?tccctgaggg?acagttcatt?gatagcagga?agggggcaga 13680
gaagctgctc?agctccctgg?acattgatca?caaccagtac?aagtttggcc?acaccaaggt 13740
gaggaaagga?gactaattaa?ttaaaggaag?acatctcttt?tccattgact?cctctgatgc 13800
ttttcctgtt?gtaatcatct?tagcaaaatc?tcttacctgt?atgctacccc?tcccagtgga 13860
acatctagca?ccactcccct?catcccagct?ccagctgcca?ttgacctcct?ccctgcaatc 13920
cttttctagg?ctgttaccct?tcctaaggta?atccccacca?tctctttccc?tcgtacccct 13980
ccctagtcat?ggccaacaca?caccttgcct?gcaggtgttc?ttcaaggccg?ggctgctggg 14040
gctgctggag?gaaatgaggg?acgagaggct?gagccgcatc?atcacgcgta?tccaggccca 14100
gtcccgaggt?gtgctcgcca?gaatggagta?caaaaagctg?ctggaacgta?ggtgagagat 14160
ctcaagagga?ggtttcccgc?ttctctgagg?cccaggctgg?ttcaggggca?gtgtcaggaa 14220
aaaaagctca?gcagatcttc?aaacacagag?acctgcagga?ggggctcata?tgaacacact 14280
gcagtcacag?ggtcagaggc?ctcaggaagg?gtgggaggga?tgaaggaaat?gggatattcc 14340
caaggtttca?ggacctcagg?taggaaggag?gcagaggctc?agcactcctt?tcaatgggcc 14400
cctgcagaga?ctccctgctg?gtaatccagt?ggaacattcg?ggccttcatg?ggggtcaaga 14460
attggccctg?gatgaagctc?tacttcaaga?tcaagccgct?gctgaagagt?gcagaaagag 14520
agaaggagat?ggcctccatg?aaggaggagt?tcacacgcct?caaagaggcg?ctagagaagt 14580
ccgaggctcg?ccgcaaggag?ctggaggaga?agatggtgtc?cctgctgcag?gagaagaatg 14640
acctgcagct?ccaagtgcag?gcggtgaggc?tcctgggcta?ctgttggctc?ttccaccctg 14700
ctctgccttc?acttcccaca?accctgcacc?tccctgcaca?ggggctcact?gtcttgttcc 14760
ttcagtcaga?ggactctggg?atcaacactt?ctaaagacct?ccaaagaggt?ccctcaggag 14820
gaggaaaggg?cagagggaaa?agagctgact?tttaaaagca?caggctttct?acttgggttc 14880
aacctagata?cacagcttaa?ttattttgtg?accttgggca?gaccatgcat?catctttgag 14940
cctcaatttc?ctctagacag?ggaataaagc?tgtccatttc?attaagccat?catacataag 15000
tgcttggcat?cagcaaatgc?aattcccacc?cttcgatgga?ggagaccaga?ggaagaggtc 15060
cagatgaaga?tttctggttc?ctttcctctc?tgctcccctc?cccagtgttc?ccaagttata 15120
ctatcctgaa?actcttcccc?tccccatact?tctgaagctc?ttgccaagtg?gggatatcct 15180
agagttaccc?tcctatttga?gtgatgtgcc?tctccttccc?tctacctgca?agaatgagga 15240
ccttaccccc?tgaacagcct?cccctctgtt?cctcaccttc?aggaacaaga?caacctggca 15300
gatgctgagg?agcgctgtga?tcagctgatc?aaaaacaaga?ttcagctgga?ggctaaggtg 15360
aaggagatga?acgagaggct?ggaggatgag?gaggagatga?atgctgagct?cactgccaag 15420
aagcgcaagt?tggaagatga?gtgctcagag?ctcaaaaggg?acatcgatga?tctggagctg 15480
acactggcca?aagtggagaa?ggagaaacac?gcaacagaga?acaaggtaag?ggcagctccc 15540
tttggctcca?gcccgggtct?catcaggact?ctcagaccat?actgaccttg?acccaggcta 15600
gccactcgca?tccagagagc?agcatggacc?ttgatcatgg?agctccccac?agatggcacc 15660
aagctggtga?cctttgaccc?taaaggagat?gggattcttg?gtcggcaggt?gaaaaacctg 15720
acagaggaga?tggctgggct?ggatgagatc?attgccaagc?tgaccaagga?gaagaaagct 15780
ctgcaagagg?cccaccaaca?ggctctggat?gaccttcagg?ccgaggagga?caaggtcaac 15840
accctgacta?aggccaaagt?caagctggag?cagcaagtgg?atgatgtgag?tagattgaga 15900
gttgtggggc?ctagatatgc?catgtctatc?tgtgcccaga?gctctgtgtg?tgtgtgtgtg 15960
tgtgtgtgtg?tgtgtgtgtg?tgtgtgtgtg?tttgtgttta?tgtttagagg?ggggtagggt 16020
tagaggatgt?taacttttct?gatatctttc?tagaaaggag?ctggggaatg?aaaagtcaga 16080
ggtggtgatc?aattctgaat?tatgtatcta?atctcactgg?tatgatcaat?aatagagatg 16140
agttttctta?tttaatttaa?gtgcaatccc?atatatctct?gcctttgaca?caagatttag 16200
agggtcatct?cataagaaca?tgataaattt?ctttggaaat?tttgtgaggc?tccccaagta 16260
gaatttttga?aattccaata?tttaaggcag?aatctgatca?ttgttccctc?tgatgcacat 16320
atgtctgttg?actcacttat?cactctgtat?tttaattatt?taagcttcta?tctcagccat 16380
aagactacaa?gcttccttta?gataggaact?tagatctatt?caatttgggg?actgcagtgc 16440
ttagcaagag?cctgatgccc?agtaggtgtt?tataggatgc?tgaaagaatg?aatacgcgcg 16500
gccagccggt?ggctcacacc?tgtaatccca?gcactttggg?aggccaaggc?gggtggatca 16560
cgaggtcaag?agatcgagac?catcctggcc?aatatggtga?aaccccatct?ctactaaaaa 16620
tacaaaaatt?agctggatgt?ggtggcgtgc?gcctgtagtc?ccagctactc?aggaggctga 16680
ggcagaataa?tcccttgaac?cagggaggcg?gaggttgcag?tgagccgaga?tcgcgccact 16740
gcactccagc?ctggcgacag?agtgagactc?cataaaaaaa?aaaaaaaaaa?aaaggaggaa 16800
ggaaggaagg?aaggagagaa?agaaaggaga?gaaagaaaga?aagaaagaaa?gggaaagaaa 16860
gaaagaatac?ggctttgggg?tttcatccca?cagtcattta?ttcctttatc?tataaaatat 16920
tgattcagca?tcccctatat?ctaggcaatc?tcacagtccc?ctaataacat?ttggcccact 16980
ctggggaagg?tttcccaagt?cctgaacaca?aagatttacc?aagtcctgag?gtaactgaac 17040
aacaaaatca?ccaagtcagg?atgctttgcc?tcactgggcc?tggctccttc?tctctaccag 17100
ctggaaggat?ccctggagca?agagaagaag?gtgcgcatgg?acctggagcg?agcgaagcgg 17160
aagctggagg?gcgacctgaa?gctgacccag?gagagcatca?tggacctgga?gaatgacaag 17220
cagcagctgg?atgagcggct?gaaaaagtac?tgtgtcccct?ccctgctgcc?cttcctcctc 17280
cccagcccat?aacagtacaa?gcagacccaa?gacagccatc?ctctgaggca?acaacctcac 17340
gcagcctcca?caagtggagg?cgcaaaccat?gggaaaaggc?ctcccaggca?agggctttcc 17400
tcccctagtc?ccagatatca?gggttagtta?gatggtcctc?cctggcaaaa?agtccattgt 17460
atcccatgag?acctttcttc?ttgttaggca?ctcagtggga?atgaaaataa?cagccttccc 17520
ccttcataca?catctctctt?tggagaccag?ttccttgaca?tggaggaagg?ctccacatga 17580
gagcctctta?ggaaagtccc?tttgtggctt?ttcacagaga?gcccacaggg?caccaagaaa 17640
tgccctcaca?ttaaagaagt?caggggatca?gggccatttc?tttgttttgc?ttaacttgtg 17700
gttccaattc?ttagtgtaag?ttcttccaaa?atgtatagac?tttccagact?tggtaaacag 17760
tgagcttgca?gaacatattt?tgataattga?aggtcttatg?gtgtttcagg?ctcaggactt 17820
tgaaaggctt?tgagaatcat?cataatctac?atcctcatca?agtttgtgtt?tgcacaggaa 17880
tcttcatacc?ttcccaggca?cagaatgtgt?tgaataaatg?aataaataca?cgatcctatt 17940
tgattctcaa?aacacctttt?aaggatggta?tctttaattt?cactttacca?aagaggaaaa 18000
taagtttcag?aaaggttagc?tgagttaccc?aaagcaatag?tgacaaaatt?aaagaccatc 18060
agagctaaaa?aggacctttg?aaacaatcta?gtccgacccc?ctcattttac?attatgagaa 18120
aacaaggacc?aaagatggga?atgtcctgta?gagcccaggc?cccatcaccc?tgtctacagc 18180
actcctccca?ttacattctt?gttggatttc?aatctaccgc?aggtgttaca?cttccaggga 18240
tcctacatca?cccccagaag?ctgtttttct?aatgaaatcc?tactctttac?ctgtatcatt 18300
accattttca?accactggtg?gaccctcctg?aggccccacg?agtctccctt?acctcaccat 18360
ccctccttcc?ccacagaaaa?gactttgagc?tgaatgctct?caacgcaagg?attgaggatg 18420
aacaggccct?cggcagccag?ctgcagaaga?agctcaagga?gcttcaggtg?aggtctggac 18480
acccacgcgg?gatgctgagt?ccctgggctg?gttctgtttc?ccctgccccc?tcctctaggg 18540
tgtcctgttc?acagcattac?aggaactgat?tatgtgtcca?tggaggcagg?cacgcagcta 18600
tcacagtgtg?cccatggata?catccaaaag?gggtcaggtg?atccacagag?accctgaaaa 18660
ggtgcacagg?cctggagggc?agaattcctg?gcttcctgtc?tcagctctgc?cttagttggg 18720
tgacctctgg?gagcccactc?cagatctctg?ggtctccatg?ccctcccctg?ttacatggag 18780
gtttttaaga?gtccttcgac?tctgatggca?tgactttcct?ccttactcta?gagcagaagc 18840
tgtgttaggt?ctttagttgt?ctggtcagac?aaatacggct?ctctcatttt?caacttttgt 18900
tattttttta?tgactaaact?gcttaaaata?tccccagaac?acaggtctct?ttgtccatct 18960
ttaagagcaa?gtttcaacca?ctttccttcc?aataaagagc?catgtagact?gtcaggccct 19020
cgcctaaagg?aaggctcttc?aaactatctt?ccccaaatcc?tttaattccc?acctctccag 19080
tggaagagct?aaactgactt?gctgttccag?agaagccgag?agccttttag?agccgggggg 19140
attccagtgg?aggggtccag?gcggtgggtc?tgagcccttt?gtgtctgacc?aggcacgcat 19200
cgaggagctg?gaggaggagc?tggagtccga?gcgcaccgcc?agggctaagg?tggagaagct 19260
gcgctcagac?ctgtctcggg?agctggagga?gatcagcgag?cggctggaag?aggccggcgg 19320
ggccacgtcc?gtgcagatcg?agatgaacaa?gaagcgcgag?gccgagttcc?agaagatgcg 19380
gcgggacctg?gaggaggcca?cgctgcagca?cgaggccact?gccgcggccc?tgcgcaagaa 19440
gcacgccgac?agcgtggccg?agctgggcga?gcagatcgac?aacctgcagc?gggtgaagca 19500
gaagctggag?aaggagaaga?gcgagttcaa?gctggagctg?gatgacgtca?cctccaacat 19560
ggagcagatc?atcaaggcca?aggcaggctc?tgctcggcct?cccctcctcc?aacttcctcc 19620
tcccacctcc?cctttctgtc?catgtagtgt?ctcttccttc?atggttcatt?ttcccacttc 19680
ccttcctctg?cctggttctc?agatcccctc?cttcttttca?caccttccct?cttcttttct 19740
ccttcagttg?cacctcttac?accccttcat?tccccccgcc?cccaacatcc?atcatataac 19800
tctccttccc?ttctcaggct?aacctggaga?agatgtgccg?gaccttggaa?gaccagatga 19860
atgagcaccg?gagcaaggcg?gaggagaccc?agcgttctgt?caacgacctc?accagccagc 19920
gggccaagtt?gcaaaccgag?aatggtgagc?ctagagcagg?ggctccatgg?ttcccaccac 19980
agtctcccca?acctcctgag?ccactccagc?ctcgggcaca?agccaataca?cgcacacaca 20040
gacacagagt?ctctccagaa?aatggggcct?gagggctaga?ggaggaggtg?gggatagaga 20100
ggagtgctga?tctagaatgg?tgcttcccca?ggtgagctgt?cccggcagct?ggatgagaag 20160
gaggcactga?tctcccagct?gacccgaggc?aagctcacct?acacccagca?gctggaggac 20220
ctcaagaggc?agctggagga?ggaggttaag?gtaagggcta?gactcgggcc?acctggccca 20280
agcaaggagc?acactgacta?gccttgcatc?aaatcacttc?ccttcccagc?aataaggctg 20340
gctgtggacc?aacagttctc?caagaattct?aaaaagaaat?cacagcccaa?accctgccac 20400
atgccatcta?ctccccaggc?tgaggccctc?tgcttctgct?gcatccctgg?acgggaggca 20460
gggtgtgaga?aggaggagag?aaaatgaact?agggaggcac?gagatggcct?tgcccgggca 20520
cggctagggg?atgtagggac?tgcacaaatg?ggtcctggat?tgctagggcc?accctgaaaa 20580
ctggagaaag?aaattcaact?ggagcctatt?cctagcactt?tgctggactc?atgaaaaagg 20640
agaaagaaca?tgatttttaa?aaaactccag?ggttcatact?aacctgcctc?ttatagctca 20700
gtgatcttag?gttagggaag?tcccctaacc?tttctgagcc?tgtttccctc?tccccagcca 20760
ggtaaaatgg?cggtgatgat?gaccatgtct?ggtgtgggga?ggagctcagg?gccaatggcc 20820
atgaagcttt?tcttaaatag?ttcactgctg?tattggcatt?ctttgttatc?agcaaacagt 20880
aaaccatgac?aggtccactg?ggggtttgga?catagatgag?gccaagggat?gatgttgaga 20940
ttggggtgag?gagaagggca?agggtggggt?tgctttatgg?agaaagctga?acccacctcc 21000
tggtgcccac?ccctccccag?gcgaagaacg?ccctggccca?cgcactgcag?tcggcccggc 21060
atgactgcga?cctgctgcgg?gagcagtacg?aggaggagac?ggaggccaag?gccgagctgc 21120
agcgcgtcct?ttccaaggcc?aactcggagg?tggcccagtg?gaggaccaag?tatgagacgg 21180
acgccattca?gcggactgag?gagctcgagg?aggccaagtg?agttctgagc?agcctgactt 21240
ctggctgagg?cccctttgca?ggcaggactc?agcccagccc?cagcctcagc?agatcccaca 21300
caggcgatgc?ttagctagtg?tttgacaaca?caggaggact?ctgccccggc?cccacctcct 21360
tctcctctca?gggaagcttt?ttgctcgaat?tatgtttctg?atccgaatat?aagacgaaca 21420
aaaggtttgt?ctgagggcag?agtgcttccg?tctggggcag?ggcactgtgg?cagggaaagg 21480
cagtggggag?ggctgcagaa?gcccatacct?cctcaatgtc?catagcgcag?aggctgggcc 21540
agggtcagag?ggtgcctggg?tctccacgcc?ctgctgggat?cctctgcctg?atgttctcgg 21600
cccctgggac?ctgtcctcag?gcttctccag?ctacacttct?gaggtttcaa?ggattgtctt 21660
tgagaaggtt?catgttgttt?acctcttgtc?cccatccaca?ccctccatcc?tccccaccct 21720
ctgccacctc?ccctgggcag?gaagaagctg?gcccagcggc?tgcaggaagc?tgaggaggcc 21780
gtggaggctg?ttaatgccaa?gtgctcctcg?ctggagaaga?ccaagcaccg?gctacagaat 21840
gagatcgagg?acttgatggt?ggacgtagag?cgctccaatg?ctgctgctgc?agccctggac 21900
aagaagcaga?ggaacttcga?caaggtgggc?cctgggtggg?ggccgcagcc?agcatgcagg 21960
gcaagggggc?atgaggggtt?cagtgagagg?ccagagccat?cctccttgga?ggtgggggag 22020
gagggctgag?cccaggcagg?tcctgagaca?gaccctggac?atggggctga?ggctgggggg 22080
ctgaagagtg?agccttgtcc?ccgggcagat?cctggccgag?tggaagcaga?agtatgagga 22140
gtcgcagtcg?gagctggagt?cctcgcagaa?ggaggctcgc?tccctcagca?cagagctctt 22200
caaactcaag?aacgcctatg?aggagtccct?ggaacatctg?gagaccttca?agcgggagaa 22260
caaaaacctg?cagggtgtgc?tgggggccca?agaggctggg?gaggggctgc?actggcagtg 22320
ttcccatatg?gtgccaccca?agggctccaa?gaggcgtctg?ggcaaagagg?cgtgtccctc 22380
caactccact?ggacctcagc?agccctcaac?cgagttaccg?tgttccccac?acagaggaga 22440
tctccgactt?gactgagcag?ttgggttcca?gcggaaagac?tatccatgag?ctggagaagg 22500
tccgaaagca?gctggaggcc?gagaagatgg?agctgcagtc?agccctggag?gaggccgagg 22560
tgtgtgtgtg?tgcagggcac?ggggtgcagg?gagctgagct?ccaggatttt?ggctccctgt 22620
tctcatcccc?cgctttgtcg?ttttgttcac?tgtcccatcc?ccagagccta?ggacagagcc 22680
tggcacatag?taggcattca?gtgaagattt?gtggagtgaa?tgaatgacca?gtcactgaac 22740
tctcttcaca?taggcatttt?acccattgca?tcttagctga?gcttcccatt?tccacatacc 22800
tcccggttcc?cacctctgcc?tccctctgtt?ttcttttata?ctctatacct?gattgcctct 22860
gtttccttgg?caacactttt?ttcttcattt?tcctccttat?cttcatagct?ggctctcccc 22920
tgtgagggcc?tgaatcactt?tctcttaggc?ttatttttat?tttctcttag?attctctttt 22980
cctccacctt?ctgcttcttt?gaaccactta?caccactctt?gaagtcactt?cgtatccatg 23040
attagtgagc?aggcccccac?cctgccctgt?gccctgactg?tctgcctgca?tcccctcccc 23100
caaccccttc?ccaggcctcc?ctggagcacg?aggagggcaa?gatcctccgg?gcccagctgg 23160
agttcaacca?gatcaaggca?gagatcgagc?ggaagctggc?agagaaggac?gaggagatgg 23220
aacaggccaa?gcgcaaccac?ctgcgggtgg?tggactcgct?gcagacctcc?ctggacgcag 23280
agacacgcag?ccgcaacgag?gccctgaggg?tgaagaagaa?gatggaagga?gacctcaatg 23340
agatggagat?ccagctcagc?cacgccaacc?gcatggccgc?cgaggcccag?aagcaagtca 23400
agagcctcca?gagcttgttg?aaggtactca?cccagagggg?actggcctcc?acgtggcctg 23460
gcgaagcagt?agtgtcttga?tacaggcacc?agattcctcc?tgcccctagg?ttactgcagg 23520
gacctctgac?aggtgccttt?agtgaaggga?accgaggctg?gctccctgct?catgcccact 23580
ctcctgatcc?tcaggacacc?cagattcagc?tggacgatgc?agtccgtgcc?aacgacgacc 23640
tgaaggagaa?catcgccatc?gtggagcggc?gcaacaacct?gctgcaggct?gagctggagg 23700
agttgcgtgc?cgtggtggag?cagacagagc?ggtcccggaa?gctggcggag?caggagctga 23760
ttgagactag?tgagcgggtg?cagctgctgc?attcccaggt?gagcagctcc?cctgctcatt 23820
cctgaaggga?gcacaggctg?gggctcagca?agcaaggctt?gagagctatg?catagatgct 23880
caatgctttt?cctgctctgc?ccaaccctcc?cccaacccag?aacaccagcc?tcatcaacca 23940
gaagaagaag?atggatgctg?acctgtccca?gctccagact?gaagtggagg?aggcagtgca 24000
ggagtgcagg?aatgctgagg?agaaggccaa?gaaggccatc?acggatgtaa?gtcccccact 24060
ccaccgaccc?gatccagacc?agtgtctctc?cgtgggctgg?gcagcaagtg?tgtgaggact 24120
tgaccagacc?atgtgccacc?tctctcctgc?acacaggccg?ccatgatggc?agaggagctg 24180
aagaaggagc?aggacaccag?cgcccacctg?gagcgcatga?agaagaacat?ggaacagacc 24240
attaaggacc?tgcagcaccg?gctggacgaa?gccgagcaga?tcgccctcaa?gggcggcaag 24300
aagcagctgc?agaagctgga?agcgcgggtg?cgggagctgg?agaatgagct?ggaggccgag 24360
cagaagcgca?acgcagagtc?ggtgaagggc?atgaggaaga?gcgagcggcg?catcaaggag 24420
ctcacctacc?aggtgcgacg?ggcggtgact?ccaggcagag?ccctggcacc?atagccacag 24480
tgacaaccag?ctgaggagaa?tgaagagttt?gctcttagcc?tcttccaggg?cgaggatggg 24540
aatgcagccc?ccgtttaaac?tttgcctagc?cctgccccac?tctgaatgtc?ccctagctca 24600
gaggtcagtc?tctgagcctc?ctggcctggg?agctccatct?caacacccac?tcttagccca 24660
tgcgccaggg?gacacacaca?gaattccaga?caaagctcac?ccagtacagc?tcaccagaaa 24720
gcaaatatgt?agccagggtc?acccccaaaa?gacaccaaaa?acacacccat?cccattcaaa 24780
caagcataaa?aactttttca?ttgcccaggg?cagtgtggac?tctagctttc?tgaggtgttt 24840
tctagaatca?gactctgaat?tagaatttgt?ttcttttcca?atccaggatg?tcactatctc 24900
tctaagcaca?ctttgtcctt?aacttagatt?aagtcagtgt?tttcctggcc?tgcattgcag 24960
cccaggaaat?tccatcacac?tcatagcccc?aaagtcactc?ccagcatgtg?ccgaggtcca 25020
gagcagggga?cttcatcccg?catggggtcc?ccggaccctg?aaaaacctgc?tccctggagc 25080
actgcacaca?cacaattttg?tgcataattt?caggagtccc?actagttctt?tggactcttt 25140
cctggtacag?atcatttaaa?atatttacac?atatttggta?agaaattata?aggagaattc 25200
aagtgtttag?tgaggatcag?aaagtagaat?tgggtcagga?tatcagatga?agcagggcag 25260
ggcggagggg?atgctacctt?ctatgactgt?gccatcttca?ccccctgcct?accctctggc 25320
ccccagacgg?aggaggacag?gaaaaacctg?ctgcggctgc?aggacctggt?agacaagctg 25380
cagctaaagg?tcaaggccta?caagcgccag?gccgaggagg?cggtgagtga?ccctgctggg 25440
gactaggccc?aggggaggca?taggagagct?cgtcccccaa?gccaggagtc?tgagaaccca 25500
ggccccctct?cacctcatgc?tcccacctcc?cgcaggagga?gcaagccaac?accaacctgt 25560
ccaagttccg?caaggtgcag?cacgagctgg?atgaggcaga?ggagcgggcg?gacatcgccg 25620
agtcccaggt?caacaagctg?cgggccaaga?gccgtgacat?tggcacgaag?gtgggtccct 25680
cttttgggct?ttgctagtca?cccccacagc?aggcataccc?agacagagca?ccctcaaacc 25740
cgggatgctt?ccttttcatt?tattccacac?acttgagcca?catggcccca?gaggccaagg 25800
taatgcagtt?ctctgtgatt?tcaaggattc?ttccagctct?aacttttttt?tttttttttt 25860
ttgagacggt?gtctcactct?gccgcccagg?ctggagtgca?gtggcacaat?ctcagctcac 25920
tgcaacctct?gcctcctggg?ttctcctgcc?tcagcctccc?aagtagctgg?gattataggc 25980
atgtgctacc?atgtctagct?aatttttata?ttttagtaga?gatgcggttt?caccatgttg 26040
gccaggctgg?tcttgaactc?ctgaccttgt?gatccactcg?cctcagcctc?ccaaagtacg 26100
ggattacagg?cgtggagcac?cactcccagc?tcagctctaa?gtttcagtgg?ttctgggaat 26160
ttcagcgtta?gggaggggtg?ccacctagaa?gaccctaatt?tatatacaac?cagtatatcc 26220
cagtttcccc?ccaactgcta?gtttccagtt?cccttccacc?taattttgtc?ctgcaatcat 26280
tgtaactaaa?acctaaaatg?gacatcccag?agaacccggg?cctggctttg?ttctcgccca 26340
ggcaacttcc?ctctgaccaa?ccccagaacc?ctaccctcca?gaacttgccc?cccgaccatc 26400
gatccctgga?aacacatgtg?ctgctgccac?aggggcttcc?acctgcccac?aaagcaggcc 26460
ccccaccatc?agacccctct?cacctttgtt?cccatgccct?gtccctgccc?aataccatct 26520
ctccaaggac?tgattggact?ttgtttcctt?tcaaaagggc?ttgaatgagg?agtagctttg 26580
ccacatcttg?atctgctcag?ccctggaggt?gccagcaaag?ccccatgctg?gagcctgtgt 26640
aacagctcct?tgggaggaag?cagaataaag?caattttcct?tgaagccgag?atcctgactc 26700
cagactcttc?ttcactgccc?tgaggacccg?gggatggggt?ctggcatagg?ggaggtggaa 26760
atgcacggga?gtgggggcaa?attcaaaggc?ctggcctagg?aggccttcgt?ggagcagcac 26820
tgaaaacccc?tttcacttcc?cccaaaccag?ccaaatgcag?tagaggcgac?acctctcctc 26880
ccagccttct?ccctggtcca?gccaggattt?aaaggagatt?tagggagacc?cctaaagttc 26940
acctagagca?ccctgagccc?atctactgtg?gacctgcacc?ccagcttccg?tcaaccctgc 27000
cccacccacc?accatggata?ctgcccaggg?ctgggcaaag?ggcagcggtt?cggggtgtgg 27060
gtgctggcca?gtgccctttc?tgagcccgga?gaagttgtga?accactgggc?caggtgaggc 27120
aatggctgcc?taagtgccag?tcccaggcga?gtctctgaga?gtacacaagg?attcacagct 27180
gtagcctgca?tcccctttta?aatagagcca?ccaccctctc?cagccaccgc?cagaagccag 27240
cataccccct?gcccaccaca?ggtggagaaa?cacaccctca?gcccacctgc?cgtcctcctc 27300
agctcctcct?ggtgccgagc?ccccttggcc?cagggtgctc?ccttcttccc?actcatttct 27360
tcccattgta?attcccatta?ccaagccctt?tgtcctctgg?gcttgtggga?agatggggtt 27420
ctcctggccc?atttatggca?agccattctt?gaggggaggc?agacagatga?ggggctgggg 27480
aaggttatgt?gtgaacagga?ctctggggag?agggagggaa?gggatggctc?ccgagagggc 27540
caggaggtgg?aggaaagagt?aagtctcctc?caactaaaca?agttcagccc?ctttggagtt 27600
cctgccacag?ctggattgct?taggcaggcc?tggtactgtg?ggccacagag?gtcaggggct 27660
tgaaaggcac?tggggctgtc?ggaccccact?gggaacctgg?gaaggagtgg?ttcaaccctg 27720
gactggatct?cccccaaccc?accaaccata?cccactcgga?gcccactcct?gctctctacc 27780
cagctctgag?ctctgaggac?tgcggcagca?gagccaaggg?cctaagccgg?agaaggagaa 27840
acactactgg?acaatagcag?gtgacagcag?aggagaaaaa?gggggtaggg?aggggacaag 27900
gaaagaacct?gagggggtgg?cagtggacaa?agagattgag?caaccacagg?acaaggtaac 27960
cagaggaaac?agagacaagg?aaaaaagatg?caggaaatga?ggaggcccca?gaaagatccg 28020
cagcgccgcc?acctttctcc?tcatagccac?ctccattctc?cttccctagg?ccaacccaga 28080
cagagctcct?caaaacaggg?atgcttcctt?ttcatttatc?cagctcaatt?gaaccacaca 28140
gccccagagg?ccaaggtaat?tcagtatctc?tgtgatttct?aggattcttt?cagtcctttt 28200
tgtttttgtt?tttgtttttg?tgacggagtc?tcactctgct?gcccaggctg?gagtgcagtg 28260
gcacaacctc?ggcttgggcc?gagatcccta?gggccattcc?tctggctagg?aacagacttg 28320
gacagcaatg?caagagataa?ctagaaacaa?aggagagaac?ccttgaaaag?ggagctatgc 28380
agagagaccc?agggcaccta?agcaaccaga?gcaagagaga?ccgcaagaga?tacagatc 28438
<210>2
<211>20662
<212>DNA
＜213〉cMYBPC gene
<220>
<221>misc_feature
<222>(7506)..(7516)
<223>n?is?a，c，g，or?t
<400>2
catggtgagt?agcctggtgt?gacgtctctc?aggatgcctg?agccggggaa?gaagccaggt 60
agctttagga?ctggggttgg?gtctaagtgt?gggagcatgg?gggtgtctac?aattggggag 120
caggctagga?ggagttcttg?agggggttga?cgaggacgtg?gcctctgagc?cccaggacag 180
gggcagccag?tcctccaggg?tccttttttg?attctcggtt?tctttttccc?atccctctga 240
tgagaggtga?aggtaaaccc?aaggtcaggg?acgcagagag?gggacacagc?caagacagga 300
aagcacccgg?ggtcaaccca?ttctgagaat?gcaaagggac?cccttccctg?tcccattgcc 360
ttcaccttcc?acagcaaggt?tccccgcgga?cagaacccac?gtttagtatg?gagctgagcc 420
aggctcacgg?catgccttca?gaccagtctc?tacccactat?gggtctcagt?ctcccaacct 480
ggggtgccgg?gggtggtggt?ggcattgggt?tggttcctcc?tggctgtgac?attatctgct 540
tcatgagcct?gtacggtgtg?gcccccatgt?tgagggtgac?acagcccctc?ttctctgaga 600
gaggacagtc?aggagcccct?gaacccaggc?caagggcagg?gaaaatcaca?gcccagggac 660
ctgggcctgg?gctgtgccct?tatgaaggtt?gtccagggca?gagatccagg?tcccatcccc 720
cagcgccctc?ccaggccagc?tttatctcag?ttgctgatac?ccagcctgag?gtccttggag 780
gacaaatttg?gccacattcc?aagtaggcag?acttccccgc?cccctgccaa?gggcccgaaa 840
tggttggggg?aaagggagct?gggttcatca?cgggtgtctc?caagcaggga?aagtggacac 900
atgcagaaaa?agtcttgttg?ggaggtcagg?accacagccc?tggctctccc?gactgctagc 960
tgtgtgatct?tggaggagcc?gcttagcttc?tctgagcctc?agtgtcctcc?tctgagaaat 1020
gaacagaata?actgcaacta?cctcagagaa?ctggtagagt?attacgtgag?gggatgcata 1080
gaaagtgcta?gcacagtatt?tactgagagg?ggctgcaggg?gcggggtgca?cgctccaacc 1140
aggggccgct?gtagcctcca?cctggccctt?cagtctcagc?ctttagcaag?aagccacggt 1200
cagtggaagt?ggccgcaggc?agccctgccg?tgttcgaggc?cgagacagag?cgggcaggag 1260
tgaaggtgcg?ctggcagcgc?ggaggcagtg?acatcagcgc?cagcaacaag?tacggcctgg 1320
ccacagaggg?cacacggcat?acgctgacag?tgcgggaagt?gggccctgcc?gaccagggat 1380
cttacgcagt?cattgctggc?tcctccaagg?tcaagttcga?cctcaaggtc?atagaggcag 1440
gtaagatcct?gatcagcctt?ccctgagttt?gggctgctgg?gggagggcag?cccagcgact 1500
ctccatccat?ccagggaaca?ggaggtgctt?tcacactttc?ttgcctttgc?tgtggctgtg 1560
ccccccgcca?ggaacgccct?ttcccccttt?tctgcacatg?acctctctga?tacccccatg 1620
tgccatcctg?gcttgttcca?gccatggggt?agtgggagag?atgaacaaga?cacaacccca 1680
ctctccccct?gcagacctcc?ctggggagat?gacctgcaca?gacggccggg?aagccccagg 1740
agctgtggat?gaggggagtg?cagcccagtc?tgaggggctg?ctctaaggct?ggggcagagc 1800
agggatggac?ctggagctgt?tcagggcaga?tgcagaggac?atgggaagtg?atggcctggg 1860
acggggagga?gaatgtgaga?ggcaggctgg?ctctccagct?cagcatgagc?tgcctctgag 1920
gggcccaggc?agcgggagga?cagccatggc?agactttcct?catccacagc?gggctcatgg 1980
gtccaatgct?caggagagag?agggtggagg?ggtctctggt?tagtggctgc?accacgactc 2040
ccatctgatc?ccctccagag?aaggcagagc?ccatgctggc?ccctgcccct?gcccctgctg 2100
aggccactgg?agcccctgga?gaagccccgg?ccccagccgc?tgagctggga?gaaagtgccc 2160
caagtcccaa?aggtgagagg?ggctgggcag?ggaggggcag?gatccgtggg?tagggcgtgt 2220
ccagggcagg?tctcaaaagc?ctttgctggg?ccaggtgcgg?tggctcaggc?ctataatccc 2280
cagtactttg?ggaggccgag?gtgggcggat?catgaggtca?ggagattgag?accatcctgg 2340
ctaacatgat?gaaaccccat?ctctactaaa?aatacaaaaa?attagccggg?cgtggtggcg 2400
ggcacctgcg?gtcccagcta?acttgggagg?ctgaggcagg?agaatggtgt?gaacctggga 2460
ggcggagctt?gcagtgagcc?gagattgtgc?ctctgcactc?cagcctgggt?gacagagcaa 2520
gactccatct?caaacaaaca?gaaaaagcct?ttgctcacag?ggtcaagctc?agcagctctc 2580
aatggtccta?cccctggagc?ccccgatgac?cccattggcc?tcttcgtgat?gcggccacag 2640
gatggcgagg?tgaccgtggg?tgagtgtgag?ctgctgtgcc?cagcattggg?gtgggaaggg 2700
ggggcagcag?gacactcccc?aagccgggcc?tgtcgccctg?cctttgcagg?tggcagcatc 2760
accttctcag?cccgcgtggc?cggcgccagc?ctcctgaagc?cgcctgtggt?caagtggttc 2820
aagggcaaat?gggtggacct?gagcagcaag?gtgggccagc?acctgcagct?gcacgacagc 2880
tacgaccgcg?ccagcaaggt?gggccagcac?ctgcagctgc?acgacagcta?cgaccgcgcc 2940
agcaaggtgg?gtccaccggg?gtcgtggaga?cacggagaga?ggggacatgg?agagccctag 3000
aaggcacaag?gcacacagag?ggcaccatga?gacccagagg?cacacacgag?ctgcaagcaa 3060
ggggtgtggg?gaatctggga?ggcaggtgga?ggggccaggg?gcccacaggg?agatcccgga 3120
ggcctggggg?ccagggagtg?catgaggctc?atgggagcac?tgtcggggac?ctgggagact 3180
tggtggacat?gatcacctca?agggggcacc?taataaggtt?tggccggggg?tgggggggcg 3240
cccagggtgg?tcaggaagcc?tggaggacac?tgtgaagcat?gggggcacca?gctagtgggg 3300
ttgtaaagcc?ccgggatggg?tgagtatcag?ggctaagggc?tcaagggact?ctcagggatt 3360
aaccagaaca?attcctcatt?atacagacac?ggaaaccaaa?gcttgagagg?ttaagtggct 3420
gctccaaggt?cacttagaca?taggcctaga?accttaagcc?ttcgtttttt?gtgttttgtt 3480
tttttccgcc?ctgcccacca?gaaccttaag?gcttaagtcc?ccttgtttgt?tcactccaag 3540
cctctgcttt?tcccaacctt?ccccagtcct?gggctaggca?agggggcctc?tagcaagaga 3600
ggccaacatg?ttctgctgtg?cggggctgtg?cattgcacaa?aagcctgtat?ttcaccacaa 3660
ccgtgtgcca?gcagatggca?atcatgggtt?tcgagatagt?cccctttctc?tgtacaaaaa 3720
ctctgtatgg?gttaactaaa?gcctgagggt?gcgaagatcg?atgagcattt?gtcactccca 3780
gcctccttta?aatatatata?tatatatata?atttgagaca?gggtctcgct?ctgtcgctca 3840
ggctggagtg?cagtggctca?atctcggctc?actgcaacct?ccacctcctg?ggttcaagcg 3900
attctcccac?ctcagcctcc?cgagtagctg?aaactagagg?tgtgcaccac?catacttggc 3960
taattttcgt?tatttttagt?agagacggaa?tttcaccacg?ttggccaggc?tggtctggag 4020
ctcctggtct?tatgtgatcc?gcccgcctca?gcctcccaaa?gtggggatta?caggcctgag 4080
ccaccgcgcc?cggccactcc?cagtctcctt?taagggtgcg?gagccttgtc?tcccggcccc 4140
tggtgtcccc?tgacgccccg?tccctccatg?cacacaggtc?tatctgttcg?agctgcacat 4200
caccgatgcc?cagcctgcct?tcactggcag?ctaccgctgt?gaggtgtcca?ccaaggacaa 4260
atttgaatgc?tccaacttca?atctcactgt?ccacggtgag?ggggccctgg?tgtctgtcct 4320
gggctcgggc?tccccatggg?tcctggtctc?ctacctcctt?ttcccaacac?taaggaggat 4380
gcctcgtccc?atccagacat?gagtgctggc?cacgtgccca?gtgctgcaca?cacagggtgt 4440
gagagaaacc?ccaaggcttg?cagggtaggc?gtgggggctt?agggctgaat?ccgggtctca 4500
tctgggtggg?actctgtttt?atcatcttgg?tgtcacggct?cctggcccac?ggcctggcac 4560
tgtctgaatg?tttgggcgat?gggtgaaggt?gagttgagag?atgggtggga?attggggaca 4620
ataaaccgtc?ccacctgctg?gtaccttgac?cctgggaaag?gctgggaagg?tgagatcctg 4680
gggcagatgc?ccagcctcat?ggggtcatga?atgggcaagt?ctgtgaatac?tcagaggccg 4740
cccccagggc?agggcttctc?aaacggcccc?tctgaagccc?cttcccccat?ctctccaccc 4800
tttgaaccca?gaggccatgg?gcaccggaga?cctggacctc?ctatcagcct?tccgccgcac 4860
gtgagtggcc?atcctcaggg?cctgggggag?ccagtgctgg?agtctgaggc?ccttcagggt 4920
ctcgactggg?ggtcagggct?ggggatgatt?tgcggggcgg?aactgaagtc?agtgggggct 4980
gcaggggaga?gcaagcttcc?caggcaggtg?aggatactga?gtctaacccc?cacaggagcc 5040
tggctggagg?tggtcggcgg?atcaggtacc?cctgccccag?gccctacctg?caccatccgc 5100
agacccccag?gggtctgaga?cgggtgggag?cccaatctgg?ctagtgtccc?tttctccctc 5160
cccactccac?tcccatcctg?ctcctaatcc?ctttccagtc?cctcactgca?gcctcactgg 5220
gggtccctct?ccatagtgat?agccatgagg?acactgggat?tctggacttc?agctcactgc 5280
tgaaaaagag?gtgagtcctg?ggtggcagtt?cctggggcat?ctggtgaggc?ctggctccaa 5340
atcccagcac?tgtggtttgc?cagctgtgtg?accctgagca?caacactgca?cctctctgag 5400
ttggtttcct?tgtctgtcga?ggggatgatc?ccagtgtgga?aggagttaaa?gggctctgca 5460
gacattatgt?cccgtcaaca?gtcatcctca?cagtgtcccc?cacggccact?ccacacttga 5520
ggctgcaaaa?gctccctccg?taaactccgg?ggacccagaa?ggaacagaga?gagggtcccc 5580
agagctgcag?ggtctaccag?gtcggcccaa?ctgacttatg?ttctctctgc?cctctctctc 5640
cctctccccc?ggcccctcca?ttatggctgc?tgctgctgtg?gcccagagag?taagaatcgg 5700
ggtctgggtg?tttgggggcg?gcagggcgct?ggtgggtgca?gaggggattc?ccgtcccctc 5760
tctgagaggc?tgtggtgaga?gactcagagc?agggtgcggc?tccccacgga?caggggtgag 5820
tctctgtgcc?ttgggcttct?cctgccaccc?acctatctgt?cagagcttag?gagggataag 5880
aaaaagtaat?gcacacagga?ggtcctgcca?gagcctccgg?agcagcatgg?gtgccccaca 5940
acacagggag?tgcaagtgcg?gaaaataggg?aggaagtaaa?ggcccatggg?tggggtccag 6000
gtctttgagg?gaaggtggcc?atacctctca?tgtgccacct?accctttctc?ccacccccac 6060
ccctggagca?gcagtttccg?gaccccgagg?tgagtgccca?acatagcaca?gcaccctcat 6120
cacccctaat?tctgccagga?gcccctccag?atccccagcc?cctcttcagc?tcccttggcc 6180
cccagtcctg?cctggcctgg?gacccagagc?agctccagct?gccccaccag?aagggaaggg 6240
gcagagggac?aggggtggct?acagctcctt?ggtcctgggc?ccaggaagcc?ccgcccaggg 6300
ggctgcagtc?ttgcccccgg?ccacagccta?gactgcggga?cacagggact?cgaagctgga 6360
ggcaccagca?gaggaggacg?tgtgggagat?cctacggcag?gcacccccat?ctgagtacga 6420
gcgcatcgcc?ttccagtacg?gcgtcactga?cctgcgcggc?atgctaaaga?ggctcaaggg 6480
catgaggcgc?gatgagaaga?agagcacagg?ttagcccttc?ctcagaggga?gaggaagagg 6540
gcacaggcta?gcccttccct?acacaggaga?ggagagggca?taggttagcc?cttccccaca 6600
ggggagagga?gagggcacag?gttagccccc?cacctcgtcc?acatacatgg?aaagagcgga 6660
gtccggcttt?agcacagaga?ctcacaggaa?acaagagccc?aggttaaccc?ctccttgtgt 6720
agaaaaagcc?aagaatgccc?aggttagccc?cttaccacag?agatagaaga?gaagagcaaa 6780
agttaggcca?ggacagccac?aaggaaaagg?acagagctca?ggttaaccct?cctcaccaag 6840
gaaaaatcag?gctacacttt?ctttctctac?cctcttctga?aaagaaatga?agcccggtta 6900
accctctcca?cacccaaaag?aaaagggaag?aggcccgcta?agcctggaga?gccacacaca 6960
ggcaaagaac?agagcctggc?taatctttct?ctcaggcaaa?caaagcagga?tggcttgggt 7020
taactaccct?cacccccagg?cagatggaaa?gaggagagcc?caggaatagc?ccttctccac 7080
tgaggggttg?acagggcggg?tgtgaccggg?aaagcagggg?tctcacatgc?cttctcccca 7140
ccatgtctgg?gtctagcaca?gggcctggca?cacacctcga?gcgctctata?aacaccgact 7200
gaatggaggg?gtcagcttcc?atgcaggata?tgggagacaa?gcccctccca?aagcacacac 7260
acaaaacaca?cacgatcatg?gggacgggga?gaggagctgg?ttagtccctc?cctgctgacc 7320
tcccccaggc?cccttatccc?tctgccctgc?ctccctgttg?tctcagcctc?actgggtttc 7380
ccatcacccc?atcgctaggt?ggcctggccc?ttaccggcac?gtggcccatt?taagccaggg 7440
atcccctgaa?tgccacaact?gtctctggta?ctcctgaact?gctgagccca?gaagggcaca 7500
agccannnnn?nnnnnntggg?caacagaggt?gctagtggag?cgctgggaag?gagtacacac 7560
aactcagggt?gctgagagaa?gagaaggcac?agcgtcccag?ccccagttct?ctgacaagtt 7620
ctttctttct?ggaagcccta?acccatcctg?agctgagcag?gtggagagga?ccccaaggaa 7680
gacagaagga?caagtcagac?agacagagac?aaggaggtgg?gttgacacat?agacacagat 7740
aaagaaatga?agacaccatg?cctgtaatcc?cagcactttg?ggaggctgag?gcgggcgcat 7800
cacctgaggt?caggatttca?agaccagccc?ggccaacatg?gtaaaacccc?gtctctacta 7860
aaaatacaaa?aattagctgg?gcgtggtggc?acatgcctgt?aatcccagct?atcgggaggc 7920
cgaggcagga?gaatcacttg?aacctgggag?gcagaggttg?cagtgagcca?agatggcggc 7980
cattgcatcc?agcctggccc?acagagcaag?atttgtccga?aaacaaccaa?cagacacacc 8040
aaccaaccta?aagaaataga?gacacagaga?agtggaagcg?gggcggcaca?gaggggattg 8100
gaggggggga?cctgggcccc?agccacagcc?acagtagctt?ggcctggggg?agcagggtgc 8160
gggcggtggg?gtggccgggg?ctgaggggtg?gtgctcagcc?tttcagaaga?agctggagcc 8220
ggcctaccag?gtgagcaaag?gccacaagat?ccggctgacc?gtggaactgg?ctgaccatga 8280
cgctgaggtc?aaatggctca?agaatggcca?ggagatccag?atgagcggca?ggtgcagcct 8340
ggggtgggga?gggggctcgg?gtggaggtgg?ggacccccat?agccttgcct?cctgcccctc 8400
tccacatgcg?tatctctgac?tcggtgtggc?tctcagcccc?atctctctgg?gcctaatttc 8460
ccatcctttt?gctcctgccg?gtccctctct?ctctctcctt?ttgtctcggg?gctcacttcc 8520
tcccgtcggg?aacacttcaa?cggccccttc?tgttctacag?caagtaagtt?cccctctgga 8580
tggcttgggg?tggggggcac?agggattatc?acggggcgca?ctgggcccgg?aggggtgtcc 8640
gcagctttcc?tgccacttcc?ctgcggcccc?cacccaggta?catctttgag?tccatcggtg 8700
ccaagcgtac?cctgaccatc?agccagtgct?cattggcgga?cgacgcagcc?taccagtgcg 8760
tggtgggtgg?cgagaagtgt?agcacggagc?tctttgtgaa?aggtgggcct?gggacctgag 8820
gatgtgggaa?cctggggagg?agatggcctc?aggggagcca?accctcatgc?tcaccctgcc 8880
tggacagagc?cccctgtgct?catcacgcgc?cccttggagg?accagctggt?gatggtgggg 8940
cagcgggtgg?agtttgagtg?tgaagtatcg?gaggaggggg?cgcaagtcaa?atggtgagtt 9000
ccagaagcac?ggggcatggg?tgttgggggc?atctgcccag?aagaggccac?agcacttgcc 9060
acccacccac?ccggctaggc?tgaaggacgg?ggtggagctg?acccgggagg?agaccttcaa 9120
ataccggttc?aagaaggacg?ggcagagaca?ccacctgatc?atcaacgagg?ccatgctgga 9180
ggacgcgggg?cactatgcac?tgtgcactag?cgggggccag?gcgctggctg?agctcattgt 9240
gcagggtgag?cctggctggg?ggggcacatg?aggctttagg?gcttggaccc?ctcagccccc 9300
accccaccta?gccctgtagg?ggagcaggca?aacctgggct?caaggcctct?gtgaccttgg 9360
gcctttgaca?gcctaaacct?catccttctc?atctctaaaa?tgacgatgct?gaggtgaccg 9420
ctccagaggg?tactgagagg?gtcatacggg?cctggtgagc?atcaccaccc?ctcagacact 9480
tgaggttcct?tatgtgcact?gcaccatcac?aggcaaacat?ggcacacaca?ggcacacgtg 9540
ttttcacatg?cccacatgca?cccagacacg?tgcgcaccag?cgcccatggg?cccacacgcc 9600
ctccacaggg?attcacgcca?cacccacaca?ccctcccgag?ctcaatggct?ctgccctgcc 9660
ctgcagaaaa?gaagctggag?gtgtaccaga?gcatcgcaga?cctgatggtg?ggcgcaaagg 9720
accaggcggt?gttcaaatgt?gaggtctcag?atgagaatgt?tcggggtgtg?tggctgaaga 9780
atgggaagga?gctggtgccc?gacagccgca?taaaggtgtc?ccacatcggg?cggtgagtgt 9840
gcagggcagg?tggatgggac?aggtggagac?tgagatggag?acagagagag?acacagggag 9900
aaacagagag?agagagataa?agacaggtgg?acagagaggc?agatgcacag?agacaggaca 9960
gagactgaga?cagagaccca?cagagaggga?gaaacagaca?gacccaaaaa?gacaaagaga 10020
cagaaagaca?gaaatagttc?tatagagaca?gaaagatatg?cacagggagg?cacacacata 10080
ggagagttcg?tcagagacag?agaagaacag?agggacagag?acaaagaggc?agcaggggag 10140
agacacggac?ggggtcgaga?gctccccagc?accctccccc?agcttgtgac?cagggcaggg 10200
caggaggcca?ccaaggaggc?cggctctggc?cagaggccct?cactgcctct?cccgccctct 10260
tgctcatccc?tggagcaact?gggctggcct?gctgggccca?agttcacaga?gattaatgag 10320
acccagcccc?tgcccagtct?ccaagggccc?agccaaggag?atgctttgat?gtagaaatca 10380
cttttacgct?gcctacctct?gaaggcacat?taaaaagctg?gaaaattaga?taatatagaa 10440
aaaaaaaggc?atttttaaaa?atcagaatac?caacaagcca?ggacaaggtg?agggcctcct 10500
gggaccctgg?ctggggtatc?tggcaaggcc?aggggtgtgt?ggcccagtgg?ggtcccctga 10560
gccactgctc?ccctgcaggg?tccacaaact?gaccattgac?gacgtcacac?ctgccgacga 10620
ggctgactac?agctttgtgc?ccgagggctt?cgcctgcaac?ctgtcagcca?agctccactt 10680
catgggtgag?cctgctccag?ggtagggtgg?gtcggggcag?tggggccagg?agcccctgtc 10740
actgggccct?gcctttgccc?ccgtgctact?tgctcttcct?tctcttgcag?aggtcaagat 10800
tgacttcgta?cccaggcagg?gtaagtcttg?gggcccctga?gtcttggttc?tgctcacttt 10860
cccgcaaccc?acccacgcag?gcctcccctc?cactcacaga?gggaaaagca?aggatcaaaa 10920
ttgggggtcc?tggggcccag?ctccagcttt?gccactcatg?accatgggtc?aattataatc 10980
tctgtgagcc?tcagtttcct?cttctctaaa?atgggaaccc?tgatagtgcc?acctcatagg 11040
atagttataa?agatgaggtg?acatgatgta?tcagacctgt?caagtgctgt?cacactgtga 11100
ctgttattat?tacatctttt?cttcttcttc?cttttttttt?atttttattt?tttttgagac 11160
ggattctccc?tctgtcgccc?acgctggaga?gaagtggcgc?gatctcggct?cactgcaagc 11220
tccgcctccc?aggttcacac?cactctcctg?cctcagcctc?ctgagtagct?gggactacag 11280
gcgcccgcca?ccatgcccag?ctaattattt?tttgtatttt?tagtagagac?ggggtttcac 11340
catgttagcc?aggatggttt?cgatctcctg?atctcatgat?ctgcctgcct?cggcctccca 11400
aagtgctggg?attacaggcg?tgagccactg?cgtccagact?gctttgcttt?gtttaactga 11460
gggcagattc?ttgatttatt?tggccaggga?acccttttaa?tgtgtgcatg?tgtgcgtgca 11520
tgtgtgcgcg?cgtgcgtgtg?tgtgcatgtg?tctgtgtgtg?tatgtatata?tgtgtgtctg 11580
tgtctgtgtg?tgtgcgtgta?tgtatgtgta?tttgtgtctg?tgtgcatgtg?tgtgtctgtg 11640
tgtgcatgtg?tgtatgtgta?tgtgtgtctg?tgtgtatgtg?tatatgcgtg?tgtgtgtgtg 11700
tattgtgtgt?gtgtgtatgt?gtgtggcaag?acactgatgt?tcccccagtt?ttcaaaatgc 11760
tatgctaggt?gacctgacct?gaatattaca?agcctcccag?ccaacgtcct?ggggtgatgg 11820
gaatgttcca?gatcttggtt?ggattaataa?ttgcatgggt?gtattcatct?gtcagaactc 11880
agcctactgt?cagatctgag?cataaactat?acctcaatac?aaatctaaaa?aaccaataac 11940
caggggccca?ggctcttgag?cagccccgcc?ccagtgacct?gtgctcctcc?tggctctccc 12000
gtttctctga?actacattgt?gtcttctgca?gaacctccca?agatccacct?ggactgccca 12060
ggccgcatac?cagacaccat?tgtggttgta?gctggaaata?agctacgtct?ggacgtccct 12120
atctctgggg?accctgctcc?cactgtgatc?tggcagaagg?ctatcacgca?ggtactgtgg 12180
gtccctcctc?agtctcccca?tctataagat?gggtgtgtgg?aaccagccaa?gtgctaggac 12240
ctgctgcaca?ccccacccac?atgtgcacgc?cctgctgttg?gctaccccat?gggagagact 12300
ggtcaggggg?caggcaaggt?gggcagtgtg?ggtcaggggg?tggaagaatc?agcagagggc 12360
cgcttccagg?ctgagtcagc?tcctctgctc?cctacttccc?tcctgccctg?ttcccagggg 12420
aataaggccc?cagccaggcc?agccccagat?gccccagagg?acacaggtga?cagcgatgag 12480
tgggtgtttg?acaagaaggt?gagtgagact?gaggtcagga?ggaggatcgt?ttgtctttca 12540
tcactttcta?cctacgtggt?gccggccctt?ggagaagtct?ccataggtgc?cacacttggt 12600
cgggtgtgtt?gctgccccca?gcagggctcc?ctgtgggacc?ctcacacctc?agccagaggg 12660
tctctgttga?agttgctgat?gcccatcaca?aggatgtgga?caccctctca?ttaccaggaa 12720
cccctcatga?ctgggctgct?ccctggctcc?cttcatccta?agctgaccat?gaccttgacc 12780
ttgtgctccc?tctcaactca?ggagtagttt?ctgagacact?tttctgccag?tgtagctgcc 12840
ggggtcttgc?tcctgcctgg?cactgttggt?tcttctgaag?gctggggtct?tgaggggtcc 12900
tcatgatagc?tcacctgaga?ggaacaggtg?gttcccccag?gtcccgtgcc?aaatcaagaa 12960
aggcgagccc?ctgccttcag?tcggtgccca?gagatgaatt?gtactagaat?attgtggatt 13020
cagtcttccc?acagactgtg?ttccccccat?ggacccccgg?gacatctggc?tgttgggagg 13080
ctgcaaggac?ctcctgggtc?tgacttggat?ctcaccccaa?ctctgcaccc?ccccagctgc 13140
tgtgtgagac?cgagggccgg?gtccgcgtgg?agaccaccaa?ggaccgcagc?atcttcacgg 13200
tcgagggggc?agagaaggaa?gatgagggcg?tctacacggt?cacagtgaag?aaccctgtgg 13260
gcgaggacca?ggtcaacctc?acagtcaagg?tcatcggtga?ggccggccgg?ggtccaagct 13320
ggagaacaca?gaggggcagc?cccaaggagg?gcccatccgt?tcgctcattc?agccactcga 13380
caaacatcac?gggcatgctc?cctgagccga?gcggcaacag?gacaggtttt?tctgcccaaa 13440
aggagccccg?ctctggggga?gatggaggca?gatgcatcca?gcagatttcc?tgcgacactg 13500
ctgtacatga?gccatgtcca?gagtgccgtg?ggagcactga?gcagagagcc?atccctgtgc 13560
ctgggggtga?tgcctttagg?aggctgagaa?gatggtgagg?aaaggcatcc?caggcagagg 13620
aaactgtgta?caaaggggtg?gaggagggaa?agggcctttt?gggtgtggag?aatgaatgaa 13680
acatgtcagg?agaggactgg?gtggggttgg?gaggatcaga?gccaggacag?gggtgaatat 13740
gggcagtgag?aagccttaaa?gggttgacgg?agggctggcg?acatgatcag?aaatgcatcc 13800
tgttggagac?cagcctggac?aacacagtgg?agactccata?tcactaaaaa?aaaaaaaaaa 13860
aaggaaaaga?agaaagaaat?gcattctaga?aagatctctt?tggatctggg?ggtggtgggg 13920
gcagcctgtg?gcggttagtt?ggagtgggaa?ggggacgagc?aacgttactc?aaggccctga 13980
gcggggcagg?gctgatgtgg?gtccatccca?ccccatccag?acgtgccaga?cgcacctgcg 14040
gcccccaaga?tcagcaacgt?gggagaggac?tcctgcacag?tacagtggga?gccgcctgcc 14100
tacgatggcg?ggcagcccat?cctgggtgag?tgcaagggca?ccggatggag?gtgtgagggc 14160
gccaaacaga?tccgagggaa?ggtggtgtgg?ggatgcctgg?gttccagacc?agagctgcca 14220
cctcccctga?gccaggctac?atcctggagc?gcaagaagaa?gaagagctac?cggtggatgc 14280
agctgaactt?cgacctgatt?caggagctga?gtcatgaagc?gcggcgcatg?atcgagggcg 14340
tggtgtacga?gatgcgcgtc?tacgcggtca?acgccatcgg?catgtccagg?cccagccctg 14400
cctcccagcc?cttcatgcct?atcggtgagc?ctgcctggcc?tggtcctgcc?ccccgccccc 14460
tccccagtta?aaaacctcca?ataatagcag?gtgctctgca?ggcagccatg?ctagacactc 14520
acatccacag?tctcctttca?tcctcgactg?gggatactca?gccgcatttt?acagatgagg 14580
aaacaggctc?caagcagtta?aatgacctgc?ttgagatctc?ccagctggtt?ggggtggagc 14640
tgactctcac?actacgccga?cccctagttc?acgtttcaag?cctctctttc?catgtctaca 14700
aaatgggaat?aatgacactg?cctatctcag?agagctgtta?ggatgatatg?ggatgaccag 14760
gcaggccatc?tggcatctaa?caggtgctca?ataaatgttc?attgtcccct?gttctccaca 14820
cccttcaacc?cagggttttc?acctatggga?tggggcaagg?gctgtagtta?gtggaggggt 14880
ctcaggggca?tctgtctgtg?gaaagagtcc?tggaccaaga?ctcagagatg?gcagaggcag 14940
ctccatggtc?cccggggggc?caactggagt?catccctccc?tgaagcctca?gcttcctcat 15000
ctgtataatg?gggtctgagt?gggcagaaca?gtgttgagac?tgtgcaggct?cagagacacc 15060
tgtcccacta?ggtggtgatc?ggggcagctg?ctgtgcaggc?agcagacctg?gccagatggg 15120
cacacttgga?gatgcagatc?ggctgtggga?gaggtcagct?ctcttttagt?tttttttttt 15180
ttttttttgg?agatggagtc?tcgctctgtc?acccagactg?gagtgcagtc?ctggcgcgat 15240
ctggggtcac?tgtaaccttc?acctcccagg?ttcaagcaat?tctcccacct?cagccttctg 15300
agtagctggg?attacaggca?tccaccacca?tgcccagcta?atttttgtat?ttttgtagag 15360
acggagtttc?accatgttgg?ccaggctggt?cttgaactcc?tgacctcagg?tgatcctccc 15420
acctcggcct?cccaaagtgc?tgggattaca?ggcgtgagcc?accgtgcctg?gctgctgttg 15480
ctgtttgttt?ttaagccaat?ttacagacat?gtcttgtaac?agggacaaaa?tattccttaa 15540
agtggccaaa?agccagctga?acaggaagtg?ccccctatgt?gaccagtggg?cagttcagag 15600
tctagggcat?ggatctccag?cttccccagg?cttgctcaga?cccctctctg?acctctcctc 15660
tgcccaggtc?cccccagcga?acccacccac?ctggcagtag?aggacgtctc?tgacaccacg 15720
gtctccctca?agtggcggcc?cccagagcgc?gtgggagcag?gaggcctgga?tggctacagc 15780
gtggagtact?gcccagaggg?ctgtgagtgt?ccccgccccc?aacccccctc?cccaaaggaa 15840
gaacatgctc?accttgccat?tgagcagatt?cacctgtagt?caagtttttt?aggcccactt 15900
ttgccgaaag?ttgaggacac?ccagagaaat?atctgtcctg?ttttcagaag?taaaaaagct 15960
tgcctagtga?aaaacaaatg?cagagtaaag?ctgactgtaa?cacttctttg?agcagtgcga 16020
aatcagcaac?tacattttaa?aaacatattt?aaggccaggc?gcgatggctt?acgcctgtaa 16080
tcccagcact?ttgggaggcc?aaggtgggcg?gatcacctga?ggtcgggagt?tcgagaccag 16140
tctgaccaac?gtggagaaac?cccgtctcta?ctaaaaatac?aaaattagcc?gggtgtggtg 16200
gtgggcacct?gtgatcccag?ctacgcggga?ggctgaggca?ggagaatcac?ttgaactcgg 16260
gaggcagaag?ttgcggtgag?ccaagatcat?gccattgcac?tccagcctgg?gagacaagag 16320
cgaaactcca?tctcaaaaat?aaataaacaa?ataaaaattt?aaaaaaacat?atttaaatcc 16380
tggagattcc?tatcagagga?gtgggcagtg?ggagtggggt?gtcagtggtg?acacagcctg 16440
tggccttgcc?tccccctccc?cacccccagg?ctcagagtgg?gtggctgccc?tgcaggggct 16500
gacagagcac?acatcgatac?tggtgaagga?cctgcccacg?ggggcccggc?tgcttttccg 16560
agtgcgggca?cacaatatgg?cagggcctgg?agcccctgtt?accaccacgg?agccggtgac 16620
agtgcaggag?atcctgcgtg?agtgcccctt?tgtgcagtca?caagacccgc?cattgacacc 16680
ccaggccctt?ggtgtccagt?ggaggtgggg?acagttgggg?aggcccagaa?tgctctgccc 16740
agaacgctgg?gcagagacag?gaggggttgg?agccatcgtc?catgcgctag?gcctagggaa 16800
aaagtgcaga?gagggtggcc?aggcacagtg?gctcaagcct?gtaatcccag?cactttagga 16860
ggccaaggca?ggcagatcac?ttgaggtcag?gagtttgaga?ccagcctggc?caacatagtg 16920
aaaccctgtc?tctactaaaa?atacaaaaac?tagccaggtg?tggtggcgcg?tgcctgtatt 16980
ccctcaacta?cttggggagc?tgaggcagaa?gaatcgcttg?gacccgggag?gtggcagttg 17040
caatgagctg?agatcacact?attgcactcc?agtctgggtg?acagagtgag?acaacgtctc 17100
aaaaaaaaaa?aagtgcagaa?agggctctct?tggtgtatgt?cagtccctta?gttctggaac 17160
agggaaagta?aaagccacag?tacccaagct?ctcttccagg?agtgtctcag?ctccaacagg 17220
taaatattgt?ctatgtagtc?agattggtcc?ctctgggatc?cacttcccat?tcctttgttc 17280
cttgtcccaa?caaagggtcc?atcttttgta?aggattggtt?ctcaaagctg?gaacgaggca 17340
gcaaactcag?gtggtaacaa?cacagggcat?agggtgtcaa?agcccaggct?tacaccctgg 17400
tctatgactt?actagctgtg?tgacttcagt?caagttgctt?accctctctg?atccctgcct 17460
tttgaagtgg?tgaggctcgg?ggaagccagc?tgggcttggg?cagcctggag?ttgctgtgtt 17520
agcaggagct?aaaggaggcg?cagggcccag?caggcagctt?ttttcttagc?tgcagctctc 17580
tgggccttgt?ctcaagggag?gttggagctg?tggagcccct?cagagctgtg?gcgggccctc 17640
acttagctac?ccactttata?cccacagaac?ggccacggct?tcagctgccc?aggcacctgc 17700
gccagaccat?tcagaagaag?gtcggggagc?ctgtgaacct?tctcatccct?ttccaggtgg 17760
gactggcccc?cttccctgtc?ccccagggga?gagaggctat?agtgtgttgt?tcccatccag 17820
tggactgatg?tctcagggct?ggcctgatct?gaggtaccag?aggctggggt?ggcggccggc 17880
ccttggagtg?atccaggttc?agggttaagc?ttttcctccc?ctcagggcaa?gccccggcct 17940
caggtgacct?ggaccaaaga?ggggcagccc?ctggcaggcg?aggaggtgag?catccgcaac 18000
agccccacag?acaccatcct?gttcatccgg?gccgctcgcc?gcgtgcattc?aggcacttac 18060
caggtgacgg?tgcgcattga?gaacatggag?gacaaggcca?cgctggtgct?gcaggttgtt 18120
ggtgcgtggc?caaggcctcc?ttgagccccc?ttgtttccct?tccctgggct?gggctgctgg 18180
ggccaagggt?ggggccacgg?ggacccaacc?cacagctcac?attttccagt?ccactgcccc 18240
agcaggcctg?gccctggttg?gcaggggtgg?ggtggtccct?ggagccagtg?accccctgct 18300
cactgtcagg?aggcgtggtg?acccaactgg?gtctgtctcc?cgcagacaag?ccaagtcctc 18360
cccaggatct?ccgggtgact?gacgcctggg?gtcttaatgt?ggctctggag?tggaagccac 18420
cccaggatgt?cggcaacacg?gaactctggg?ggtacacagt?gcagaaagcc?gacaagaaga 18480
ccatggtgag?cccagggtct?ggggtcccca?cgtgcaccct?gcctaggccc?ggcagaccca 18540
ggccgcagct?acccttcact?gtcctcaccg?tggacccctc?accctccctc?tgctgatctg 18600
aatccctcca?tagtaggggt?ggagatgcca?agggcaccca?ggagaggctc?tcggcatcag 18660
gaagggcctg?gcccagagat?gcctcccctc?cctccctgcc?cccaggagtg?gttcaccgtc 18720
ttggagcatt?accgccgcac?ccactgcgtg?gtgccagagc?tcatcattgg?caatggctac 18780
tacttccgcg?tcttcagcca?gaatatggtt?ggctttagtg?acagagcggc?caccaccaag 18840
gagcccgtct?ttatccccag?accaggtgct?gtaccctcat?tcttccaacc?aggggctggg 18900
gcagggaggc?tgtgggaaca?gggagagggg?cctagctttg?tgtggccctc?tcggtaccaa 18960
gtcctgtcac?caacaggcat?cacctatgag?ccacccaact?ataaggccct?ggacttctcc 19020
gaggccccaa?gcttcaccca?gcccctggtg?aaccgctcgg?tcatcgcggg?ctacactgct 19080
atgctctgct?gtgctgtccg?gggtagcccc?aaggtaggga?actttaggcg?ctggtccagg 19140
ccgaccagga?ggcagggctc?acaggccccg?acgttgagca?gtcctctccc?cagcctgtct 19200
cccctgcttt?ctctccacct?tggggtgtat?ggaccgggtt?cctccccctg?ggcagggcca 19260
tggtactcac?tcttggttcc?atgtttgttt?ccagccttgg?gcatagtcag?ggactctcgt 19320
gggacccccc?gagtagaaac?acagatgtgt?ctccctgggt?ccctgccagg?tcccctctca 19380
gcctggatgg?cttccctccc?tctctttacc?ttatttatag?cccaagattt?cctggttcaa 19440
gaatggcctg?gacctgggag?aagacgcccg?cttccgcatg?ttcagcaagc?agggagtgtt 19500
gactctggag?attagaaagc?cctgcccctt?tgacgggggc?atctatgtct?gcagggccac 19560
caacttacag?ggcgaggcac?ggtgtgagtg?ccgcctggag?gtgcgaggtg?aggaccctcg 19620
gggccagggc?ctgggagatg?ggaagagcgg?gcggcagtgg?ggaccctggg?ctttgctccg 19680
ttgtcctcgg?ccaagcacct?gccctggctg?caagggcacg?gaccctgcca?cgcccagatg 19740
ggcaatagct?tccagaaggc?tgggaggaca?cagtgacatg?gcctcctctt?ctgcagtgcc 19800
tcagtgacca?ggctggctcc?tggggatggc?caggtatgtc?cacccgacac?ccagggcaca 19860
agtcagtggc?tgagccctgg?cccttggtcc?tggggcagcc?atcagtaaat?gggaggctgt 19920
aggggccctc?cattcactcg?taagataacc?tgtgttgcag?gtacaaccgg?atgccagccc 19980
cgtgccagga?gcctggaggg?aagttgggga?aacccctccc?tactgttgga?tgtatgtgtg 20040
acaagtgtgt?ctcctgtgct?gcgatggggg?atcagcaggg?cagttgtcgg?gcagtcctga 20100
gtgggtgttg?cacagactgg?tccacagggc?tcctgaagga?agcccctgga?tctttggggt 20160
aaaaggaggg?tggcctcaag?aaacaatgtc?tggggacagg?cctttctggc?ctgctatgtc 20220
ttcccaatgt?ttattgggca?ataaaagata?agtgcagtca?cagagaactc?actcttcatc 20280
acctgagctc?accatagtct?aatagaaaac?aaccgaaacc?aaataattca?agcactgctt 20340
attacaattt?tactgggtct?ctattttacc?ctcctacaag?cctcagagta?cttcgagtct 20400
cccttcacca?tttccgacgg?catctacggc?tcaacatttt?ttgtagccac?aggcttccac 20460
ggacttcacg?tcattattgg?ctcaactttc?ctcactatct?gcttcatccg?ccaactaata 20520
tttcacttta?catccaaaca?tcactttggc?ttcgaagccg?ccgcctgata?ctggcatttt 20580
gtagatgtgg?tttgactatt?tctgtatgtc?tccatctatt?gatgagggtc?ttaaaaaaaa 20640
aaaaaaaaaa?aaggaattct?cg 20662
<210>3
<211>6592
<212>DNA
＜213〉cTnT gene
<400>3
gaattccaaa?ttccacttct?gaggctctaa?tgccagccta?ggatctgaca?ctgagtctca 60
gggccttgac?tttggccccc?tgttcccagg?caccctgtgg?ctgactaggg?ctggggtgtc 120
tcctcaggag?ggcctcagca?cccagaggat?ggttcaagta?agcaagttgt?gtccaccctt 180
ctgtgtgtcc?aagcgtcttt?cctgtcctat?gtccgtctcc?agggctggga?gagaaaggcc 240
caggagtgct?ggacagagga?ggccagaaac?cagattcctg?ggtttccaag?tggacgaggg 300
atggatttcc?cagtgctatt?gactgagagc?tagccccgag?cacagctgca?tcctcaaatt 360
aatcaacaac?atttattgag?tggcctggac?tcctgggtct?gaggggagag?ggattggggt 420
cctggactcc?tcggtctgag?gggagaggga?ttggggtcct?ggactcctgg?tctgagggag 480
gaggagctga?gggtgcagac?tcttgagtct?gagagaggaa?gtgtgctggg?ggcctgcctg 540
gactcccttg?tctgagggag?gggctggggg?cctggacccc?tgggtctgag?ggaggagggg 600
ctgggggcct?ggactcctgg?gtctgaggga?ggaggggctg?gggcctggac?tcttgggtct 660
gagggaggag?gggctggggc?ctggactctt?gggtctgagg?gaagaggagc?tgggggcctg 720
gactcttggg?tctgagggag?gaggggctgg?gggcctggac?tcttgggtct?gagggaagag 780
gagctggggg?cccagacact?tgagtctgag?ggaaaagggg?gctgggggcc?tggactcctt 840
gtgtgaggga?gtggccaggg?tctcccaggg?tcctgggact?gagggaggag?gaggttggga 900
ggtcgggcat?tctctgggtc?tgagggagga?ggggtctagg?actccaggat?cagagggagg 960
gtccggattc?ctgtgcccgg?aggtggctgg?tgatccagct?ggagcagggc?ccaccccgcc 1020
cctcacgcgc?ccccgttatc?tggcatagtg?ggcaggggga?ggaggaggtg?acagtatatt 1080
tagtctgtgt?cctcgccctt?tatctcagtg?tcctcgggga?gtctcaagca?gcccggagga 1140
gactgacggt?ccctgggacc?ctgaaggtca?cccgggcggc?cccctcactg?accctccaaa 1200
cgcccctgtc?ctcgccctgc?ctcctgccat?tcccggcctg?agtctcagca?tggcggatgg 1260
gtgagtgatg?ccccaaggca?gtggggagtt?gggggcgacc?tcccgggttc?ccaagagggg 1320
tcgcagctga?gaggctggac?ccaaggcctg?cgaggatggc?gtagggactc?ttccctgaag 1380
agaggaagtg?ggtttgcgag?tcagactcct?ggaacccaag?gaaggggaag?ctcggtcccc 1440
cgacctcttg?ttcatagggg?actccagggg?tcccttagga?gacaggacac?agcccaccac 1500
taacccccct?ccttggtttc?tctccttcca?ggagcagcga?tgcggtgaga?gcagcgggct 1560
aaggcgtggc?tgggaccccc?aggtccaggg?tgggccctgc?agtgaggggt?ctgggtcggg 1620
aggctgcagc?ctagcagagg?gtgcggtacg?gtaagggctg?ggtggggtct?tggtggtcat 1680
ggggtcccca?ctcctcctaa?cccaggctag?ggaacctcgc?cctgcaccag?ccccaatcag 1740
acgccgctcc?tccaactacc?gcgcttatgc?cacggagccg?cacgccaagg?tgggacgggg 1800
cttcctgggg?gcagagtaca?ggcgccggag?ggatccaaga?ccctgggagt?ggggggagga 1860
gccagggctg?cgaagggggc?ggggactacg?cggaggggct?tcaggggcgg?agttttgcag 1920
agggtcatgc?tcggattggt?gacagcagcc?tgcgggcgga?actccgttgc?cctcggactt 1980
gcttagggat?agatgggaag?tgcctatcca?aaggaagaga?cccagattgg?tggatgggaa 2040
tgaggggcgg?ggcctcccgt?agactcaggg?ctcaagttgg?acgtgggccc?aaatctggac 2100
cggctgggtt?tgctgggggt?gtcttgaggt?cccctccacc?gtcgtctccg?aatccccctc 2160
catgatcctt?ccttgctcca?tctcaccctg?gcagaaaaaa?tctaagatct?ccgcctcgag 2220
aaaattgcag?ctgaaggtga?ggacgggcgg?gactgggaaa?gagcaggcag?gtgctcaggg 2280
ggcggacgtt?gagaatgggt?ggggctttcg?gggtaggtgg?gcggaagtgg?gcggggtttg 2340
gccgctcggg?gcgtggcttt?agcggggagt?actgctcggg?gtgggacggg?gccttggaac 2400
agtggagacc?aaactggagg?gtttagaagg?gcagaggcgg?ttccccacgc?ctggtcttta 2460
tcctgaagcc?ccgggtggcg?tgcgcttccc?tcccacccct?ctgcagactc?tgctgctgca 2520
gattgcaaag?caagagctgg?agcgagaggc?ggaggagcgg?cgcggagaga?aggggcgcgc 2580
tctgagcacc?cgctgccagc?cgctggagtt?ggccgggctg?ggcttcgcgg?agctgcaggt 2640
accggctccc?aaggatgcga?ggtttctagt?cccggaattc?agcagtacag?cctctatccc 2700
ctcttctgct?cgggacccag?gcgtccaata?tggctgtcct?tacccaatta?tatatggttc 2760
gtgggactcc?tggcccctaa?caccctttgt?gtgcaggtct?gtggagtctt?ggctccaacc 2820
tactccttca?ggaccatgtg?gccctcctat?cccagacaga?agcccaagcc?ccagcccctc 2880
ctccctcaga?ccctggagtc?caggccccag?cccctcctcc?ctcagaccca?ggagtccagt 2940
ccccagcccc?tcctccctga?gaccctgaag?tccaggcccc?agcccctcct?ccctcagacc 3000
ctggagtcca?ggccccagcc?cctcctccct?cagaccctgg?agtccaggcc?ccagcccctc 3060
ctccctcaga?ccctggagtc?caggccccca?gcccctcctc?cctcagaccc?tggagtccag 3120
gccccagccc?ctcctccctc?agacccagga?gtccagtccc?cagcccctcc?tccctcagac 3180
cctggaatcg?aggccctcag?cccctcctcc?ctcagaccct?gaagtccagg?ccccagcccc 3240
tcctccctca?gaccctgaag?tccaggcccc?agcccctcct?ccctcagacc?ctgaagtcca 3300
ggccccagcc?cctcctccct?cagacccagg?agtccagtcc?ccagcccctc?ctccctcaga 3360
ccctggagtc?caggccccag?cccctcctcc?ctcagaccct?ggagtcgagg?ccccagcctc 3420
tcctccctga?gaccctggag?tccaggcccc?agcctctcct?ccctcagacc?ctggagtcca 3480
ggccccagcc?cctcctccct?cagaccctgg?agtccaggcc?ccagctcctc?ctccctcaga 3540
ccctggagtc?caggccccag?cccctcctcc?ctcagaccct?ggagtccagg?ccccagcccc 3600
tcctccctca?gacccaggag?tccagtcccc?agcccctcct?ccctcagacc?ctgaagtcca 3660
ggccccagcc?cctcctccct?cagacccagg?agtccagtcc?ccagcccctc?ctccctcaga 3720
cccaggagtc?cagtccccag?cccctcctcc?ctcagaccct?ggaatcgagg?ccctcagccc 3780
ctcctccctc?agacccagga?gtccaggccc?ccagcccctt?ctcctccctc?aaacccagga 3840
gtccaggccc?ccaactcctc?cctcagaccc?aggagtccag?gcccccagcc?ccttctcctc 3900
cctcagaccc?aggagtccag?gccccgagcc?ccttctccct?cagacccagg?agtccaggtc 3960
tccctgtttt?tggttccccc?aacaacacac?accacgttcc?tcctccagga?cttgtgccga 4020
cagctccacg?cccgtgtgga?caaggtggat?gaagagagat?acgacataga?ggcaaaagtc 4080
accaagaaca?tcacggaggt?gggacgcatg?ggcagctcgg?gtaccttcgg?ggtagggtga 4140
gatggctggg?acttggtctc?tgcctgaccc?cttgcagctg?cttttggctg?cacatcccag 4200
gagacccagg?acaactgtga?gcctggcagg?gctggggcag?aaggatgagt?acaatatagt 4260
caaggaaagc?tgttctaggc?agagggaaca?gcacatgcaa?ggccatgggt?tgggaaacag 4320
aaaataagtt?agtgaacatg?ctcagggcat?cacatgttgg?taaattagct?caggcactgg 4380
ccagggaatt?gtgatttgca?tgtagctgga?ccaggttatg?ccagtggttt?tgagaggtga 4440
ggctggagca?tatgaggagg?gggattcagt?tccaggatta?gaagcctaga?ctgggagcct 4500
aagccgggaa?gagactggta?aggcctcggt?actggaagac?gagataagga?gaataaaaaa 4560
ggagtgtagg?atggaggagt?tgggtgtgcg?ggaaatggaa?ggagaagtac?ccaccccctc 4620
gtgtgccccc?agattgcaga?tctgactcag?aagatctttg?accttcgagg?caagtttaag 4680
cggcccaccc?tgcggagagt?gaggatctct?gcagatgcca?tgatgcaggc?gctgctgggg 4740
gcccgggcta?aggagtccct?ggacctgcgg?gcccacctca?agcaggtgaa?gaaggaggac 4800
accgagaagg?tgagtgtggg?ctaaggccag?gaaagaggat?gctgagggga?agggctgtgg 4860
gtgccaacaa?ccctaggcct?gagggcagat?ggtgcttgga?gttggaggta?gaagcagcta 4920
gtaaggggtc?ctcagaaatg?caagaggaag?acaggaagta?gaaggggaag?acaggaagtg 4980
cattagggct?acaggaagtc?catgtaagag?caaagaggta?catgaaggtc?caggtgcagt 5040
ggcttatgcc?tgtaatcttt?gaggtttaaa?aaaaattttt?tttaaatttc?cttttttttt 5100
tttttgagat?ggagtctctg?ctgtccaggt?gcagttgctt?atgcctgtaa?tctttgaggt 5160
ttaaaaaaaa?ttttttttta?atttcctttt?tttttttttt?ttgcgatgga?gtctctgctg 5220
cccaggctgg?agtgcaatga?caccatctcg?gttgctggag?tgcagtgaca?ccatctcggc 5280
tcactgcaac?ctctgcctcc?caggatcaag?tgattctcat?gcctcagcct?cccgagtagc 5340
tgggactaca?ggtgcacacc?accatgttgt?tgttttaatt?tctacaaatt?tcttttttaa 5400
attagccagt?cacggtggtg?gcatgcagct?tctcaggagg?ctgaggcagg?aaaatcgctt 5460
gagcccatga?gatcgagggt?gcagtgagct?atgactgcac?cactgcactc?cagcccaggc 5520
aacactggga?gactccatct?caaaacaaaa?caaaacagaa?caaaagttag?ctgggcatgg 5580
tggcacacac?ctgtggtccc?agctcctcag?gagtctgagg?tgagaggatg?gcttgagccc 5640
aggaagttga?ggctgcagtg?agccgagatt?gcacgactgc?actccagctt?ggatgaggca 5700
gccagaccct?gtctcaaata?ataataataa?taaaatagaa?caattataac?agattgtaat 5760
aaaactcatg?aatgtggtct?ctttctcaaa?atatcttata?gcactgtaat?cacccttctt 5820
ttccttgtga?tgtaaaatga?cagtgcctat?gtgctgagat?gaggtgaggt?ggatgacata 5880
ggcattatga?cctggcgtta?ggctactatt?gacctgagaa?tccatcaaac?ttatgaattg 5940
tttatttctg?gaattttcca?tttaatattt?ttgggccatg?gtttacctca?ggtaactgaa 6000
accacacaaa?gtaaaattgc?agaaaaggag?ggactactat?aataagaaga?gaaggaagga 6060
gacaggaagg?gcataaggca?gacaggaagt?ggaggggaaa?gataggaagt?gcaggaagga 6120
gacaggaagt?ggaggggaaa?gacaggaagt?gcatgaggga?gacaggaagt?ggatggggaa 6180
agacagaaag?tacatgaggg?agacaggaag?tgctggggaa?agacaggaag?tgcatgaggg 6240
ggacaggaag?tgcatgaggg?agacaggaag?tgcatgggga?aaattggcag?ggattatctt 6300
gaaaagacag?gaagtgctcc?agaactagat?acttaggcat?ccagggtaga?gtggccccac 6360
aggctggagg?gaagacaggg?attcttgaga?gactggagac?caagaagaga?ccctaacctc 6420
tgactcatcg?ccatcctcca?ggaaaaccgg?gaggtgggag?actggcgcaa?gaacatcgat 6480
gcactgagtg?gaatggaggg?ccgcaagaaa?aagtttgaga?gctgagcctt?cctgcctact 6540
gcccctgccc?tgaggagggc?cctgaggaat?aaagcttctc?tctgagctga?aa 6592
<210>4
<211>26875
<212>DNA
＜213〉cTnI gene
<400>4
attttaaagc?cgttagggga?tgacctttga?cagtccgcat?cacccctctc?acacaacgag 60
cgcctgttca?aggttcttga?ctggaagttc?taccttgtat?ctggcctcct?gtagcagttt 120
cagtccattc?cctgtgagga?gggtgtgcca?catggctttg?ggggtcatgg?agaagaccca 180
ccttgcagat?gtcctcactg?gggctggcag?agccggcaac?ctgcctaagg?ctgctcagtc 240
cattaggagc?cagtagcctg?gaagatgtct?ttacccccag?catcagttca?agtggagcag 300
cacataactc?ttgccctctg?ccttccaaga?ttctggtgct?gagacttatg?gagtgtcttg 360
gaggttgcct?tctgcccccc?aaccctgctc?ccagctggcc?ctcccaggcc?tgggttgctg 420
gcctctgctt?tatcaggatt?ctcaagaggg?acagctggtt?tatgttgcat?gactgttccc 480
tgcatatctg?ctctggtttt?aaatagctta?tctgagcagc?tggaggacca?catgggctta 540
tatggcgtgg?ggtacatgtt?cctgtagcct?tgtccctggc?acctgccaaa?atagcagcca 600
acacccccca?cccccaccgc?catccccctg?ccccacccgt?cccctgtcgc?acattcctcc 660
ctccgcaggg?ctggctcacc?aggccccagc?ccacatgcct?gcttaaagcc?ctctccatcc 720
tctgcctcac?ccagtccccg?ctgagactga?gcagacgcct?ccaggatctg?tcggcagctg 780
ctgttctgag?gtaaggctcg?ggcagggctc?tggggaagag?gagagcagag?aatggacggg 840
gagatgtgag?ggtcttgggc?cctggcatat?ttacccagag?tctgcctgtg?tccgcagaag 900
tccatggccc?ctcctggtgg?aggccacact?tcagaggaca?ggttgccagg?tctgggctcc 960
aagattggta?caatagagca?gagagaaaga?gagaatccca?tggtagccat?tggagactag 1020
ggttggagtc?ctggacctgc?cactaaagat?gtagagttta?aactcttgga?tgagtcactt 1080
tccctcccca?ggcctcagtt?ttctcatctg?tagagtgggc?taaatatttg?ctaggcctct 1140
gcctgctcta?aatacaatga?ggctctaacc?aacagagact?cccctaaatt?gcttgttcca 1200
ggccgagggt?cacctatacc?tttccagtca?ggtccttctt?gagtcccagg?gagcagagcg 1260
agactgcagc?cctgtcagtc?aagtgagtct?cctggtcata?ttctcaaggc?taggaactca 1320
gaaactgtcc?tggaagtact?gagaacgacc?agatgtgcag?ggtcctctgc?agcgcctctc 1380
caggccaacg?cgggaattcc?atttgatgcc?gctgactcag?tgccattccc?tcccagagct 1440
gagctgagct?cccagaccct?gagctgagct?gcacttgggg?ggcagatggg?gaaaggcccc 1500
actgggagaa?cctgtccttg?ggtgtgagcc?cagctggttg?gcattaaagg?gtttaacctg 1560
ggcccccgta?agtgtaaccc?ttgtcccatc?ccaccccaac?accccatctt?gggacaagcc 1620
ttgctctgtg?cccaggagtg?gtagagaaag?attcccttgg?tttctagttt?ctcctgggca 1680
ggctgaggac?tattcaggga?gggggttgcc?tggtgtgtaa?ggaatttcag?agcacattcc 1740
tggcctgctg?tagccgggaa?gctacctgcc?ctcccaaatt?ccttttctga?cccatgtctt 1800
agagggcgaa?tcttccttct?ctctgcaaaa?gtggaatctg?agaggatcag?gttgctggct 1860
gcctcctatt?tctgaccccc?acttccactc?ttcctgccct?ctccccatcc?ccttaccccc 1920
gctctcctgg?tgggctaaca?gctgttggct?taggaaaatc?ccattcgagt?gctggggaca 1980
aggactgagg?ggtggggcct?gtgtttctca?gaaactcgga?gactgtttct?acagggacag 2040
aactcaaggc?tctcctgctt?tgtagttggt?taactgaagt?cagagaggct?aggtgactta 2100
aataaggcca?cacagcaaaa?tctgggtttt?aagcccagat?tttttgaccc?caaggtcagt 2160
atgccttatg?ccttctattg?tctttgcttt?actccccaag?aaaggtgacc?ctgtgaacgt 2220
gttaggcttc?caacacgtgt?tggctatgaa?tgcattaggc?tagaaagctg?cctgtggaag 2280
tgggtgggac?ttgggtgtga?ggacacaggt?gtttcaggac?attctggttc?cttgccctgc 2340
caggttcttg?actctctccc?attctgcagc?ccccagtctc?agcccacctc?tttcccctgc 2400
atcaggtcct?gcctttgagc?cactggcatg?gtggtgtcct?ctgggctggc?tgaaagccct 2460
cctccatcct?gcatgtctgc?atgctatttt?tgggagctgg?atggtgcccc?caggaacagg 2520
gagaggagtc?caagctgctc?tgtcctcctg?tgaggcccca?gcaccatgcc?cagtggctct 2580
gaactggtgg?aagggcagag?taggagagga?gagagaaagc?tagaagctat?gcgcccaggc 2640
tggccatgca?cggttcctct?gagaattttc?tccctcccac?tgagggacaa?gcttctcctg 2700
gggctcaggt?aggagctcct?caagttctca?agtcactagt?tctggccgct?cccctggggc 2760
tttgggtaac?aattgtcagc?cccacccatc?ctagggttag?gaaggctatt?ctctttggcc 2820
actctcatcc?taagacctat?ttggagaacc?tctggggttt?gagtcttttt?ttcagcagaa 2880
tgaggcttga?tcccgcatta?tagcacctcg?cacatttgat?gtctcttctt?ctcacccact 2940
caccccaccc?tgggggttgg?ggcaaaaaag?tggctcagag?ctgcggttca?gagctccttg 3000
taaacaaggc?tcctccctca?ctgtcctcac?cctgctccag?cagagggagc?agcggaagga 3060
ccactctgct?gcagccatgc?ttgtttctaa?cccagcagaa?ctggacataa?tgggaacagg 3120
gtctgaagac?aatcaatcca?ggctgcagtg?ggtgctgagt?ctggggaagc?ctccacctgg 3180
aggggcagct?gggcagtggc?agctcccttg?gaatggctca?gcctctggac?atcaccccac 3240
ccaaccagag?ccctggctct?tgctggatgt?ccacagatga?gtgcctggga?ttggtctcag 3300
ccactatggg?ggggatgtgc?agggagaggt?gatgagggag?tgagcaggac?tgtctatgtg 3360
cctctgtcct?catcctgagg?cttgggtctg?aaattggtgc?tgcagcactg?gcacgcgtga 3420
gtggggcagg?aggtgggcag?caggggagga?gcattggagg?gtggtcctga?gcatcatttg 3480
gattcttctc?ccgcctcact?ttagcctcac?tctcacataa?ccctgtccat?tctctccctt 3540
ggaagccaac?atcaggaagg?ctgtggagct?ggcatattgc?actataacag?aggctgctgt 3600
tcacgtttca?aacaacgtga?ttgtgtccct?ggagcagtgc?actgtcatgg?ccccggaggg 3660
ttgggtcata?gtagttatta?gctgaatgcc?tacacttcac?actacctctg?ttcctcacac 3720
ctacccaaga?agagcagtaa?tttcacagca?aagagagctg?agatgtgggg?aggttaagtg 3780
accttgccaa?ggtcgcaggc?aaacgcatgc?tggagccagc?attcaaaacg?agattagtct 3840
cacactcaag?tgcttgctct?ctgccccctc?cctgtgatta?cacgcgcact?gtaacacctg 3900
acgttgccta?atgccttccc?cttttgttaa?tgtcaactgg?agcctcgtaa?agaccctgag 3960
tagccaggat?gtgtacactt?tatctccatg?agacagagaa?aggactgagg?tttggagatg 4020
ttaaaaagac?tcgcctaaac?accctcggca?agctaatgga?agaggatctg?aatctagatt 4080
atctgttccc?agtgcagtga?gaagatgatc?tcagaatgag?ttccctgggg?gaacattttt 4140
ttaatcggaa?ttttcattga?cataattaaa?gactagtaca?cagttgtctt?taataacgag 4200
cgtttacaca?cggtgcctag?tttctcccga?gggcaacatt?tgcaaaatta?gtactatatc 4260
aaaaccaaga?ttggacatca?atacaatcaa?tctatgatct?tattcagatt?tgcccacaat 4320
tgcaccatgt?gtatgtgaaa?ctctaaacaa?ctttaacctg?tggaggttca?cgtatccatc 4380
accacagtct?acatactgaa?aagatcccaa?accacaagga?tcccccctgt?gtgctttgat 4440
ttatttattt?agagacaagt?tctcactcat?ttgtccaggc?cagtctcttg?gggtgcccaa 4500
agaccttttg?tccaggtctc?acttttgtcc?agcacacatg?gaatgggtgc?ggtggctcac 4560
gcctgtaatc?tcagcacttc?gagaggctga?ggcaggagga?tcccttgagc?ctgggagttc 4620
gaaacagcct?gggcaatgtg?gcaaaatccc?agctttacta?aaaatacaaa?aattagtcgg 4680
gcatggtggt?gcacaactat?agtcccagca?actcaggagg?ctgaggtggg?agaatcgctt 4740
gagcccagaa?ggttgaggct?gcagtgaggc?tttgtgcagt?gaagatttgt?acagtgctga 4800
acagatcctg?tggagtgggg?gtgggcagag?tggatggaaa?ggttgagaaa?ctgcagacat 4860
tgtcttgagt?gtcacaaatg?gaaatgcagc?atcccaggca?gtattgcctg?ttcaggggca 4920
aggaacgaag?tggacatcag?caggtggcct?tgctgccatg?tgggtgtcac?tatctccccc 4980
agcaggggag?aaaacaggct?ttttgttgca?ggtcacacag?ctcatgaggg?gtggaactag 5040
attcacccta?ggcctcgctg?atctctgtac?aacgggggcc?agagctcttc?tgaggaaggc 5100
aggcttccct?ttgtacctgc?actgactttt?ttctcctttt?ggagggagag?cagagaccat 5160
gtctgacata?gaagaggtgg?tggaagagta?cgaggaggag?tgagtatctg?gagcatcttg 5220
cctgagtggg?gtcctctccc?gccgctgccc?tgacacctgg?tccaggagcc?tcccagctgt 5280
ccctcggatt?ctgggtagaa?gtagctgtgt?gtgttttggg?caccccgagg?agagatatag 5340
ccatttcctt?tccactcctg?tacccctggg?ttgtagatcc?caggcagagc?acaggccgag 5400
agacttcggg?aagcacagag?gttcagctcc?agggtcatca?gtgtccttgg?ccagtcttgg 5460
ctaggggcca?tgaacagaga?agctgagatg?ttgggtctcc?tgaaactgac?tgaggaaggt 5520
tcagtgactc?tccagaggca?cagagctgat?tatgcccccc?aaaccccagc?tcagaaccca 5580
gtgttatcac?cctgtcttgg?atccctactc?tctcatgaca?gtgccctgcc?cacagtccta 5640
tcccagaggg?aaaccagggg?gtgggacaca?gccaatccaa?taactacaga?ggatagtggt 5700
caccagggag?gagacagagg?tataggcacg?gctactgccc?tcacagaact?tactcttgtt 5760
gagatgttaa?gacataaact?gggagaagaa?attagcaact?gggggcctgg?tgtggagggc 5820
gggctgttgg?tagtgtagga?gttctgagga?gagggagatc?aggggctgga?atagtcaggg 5880
ggctgtgtgg?agaaggcagg?tcttacctgt?gtagaatttg?gaaagataag?agatttggga 5940
gagggcagga?ctttctagaa?aggggtacag?cttgggcaaa?gatggaaaga?gtaagtgagc 6000
agaacgctgg?tgagaccaag?ctggctgggg?cggaggcttg?cggaggatgg?taggaggcag 6060
ccctgcatga?gaacggcagg?ccaggctagt?gggtgtcatt?gcaaggtggg?cagggcagcg 6120
tggactccac?taggcaacaa?gggaaaagaa?agggggatta?tctttgggga?aaggccagtg 6180
tgtgcatgtg?tgtgcaggcg?tgtgtgtttg?catgtgcttg?tgtgcgagct?actgacagtg 6240
tttcctgttg?ctctcaggga?gcaggaaggt?aagcgtaaac?gtgtgtactc?atttggatca 6300
aagacagcct?ggttcgaaac?tgacccacct?cttctctctt?ctcttgctgc?ctggacttct 6360
cttctgagca?gaagcagctg?ttgaaggtat?gtgcctcagg?caggtggaga?gccagaaagg 6420
ggcaggctca?gcaatgtgga?aatcctggga?gccctgggaa?agcagctcat?ctgtccctgc 6480
tcctcactct?cagctgagca?agatcctcca?acaacagtgc?cttctaaaat?gggaatcagt 6540
cctacctggg?ttgctcgggt?cttgaggcaa?acgatttaaa?cctgtctctt?ctgtctgcca 6600
tttgcttcaa?acacactgat?cacttttccc?aatttttttt?gcttcttctc?ccttttatca 6660
tgggaaattt?taaatgcaca?taaaggtagc?aataataata?ataatggccc?cccctgccca 6720
aggtacccat?taccagcttc?aacaatcatc?atcttagggc?cagtcttctt?tcctctatac 6780
tccaccttcc?accagttatt?ttggagcaga?catccaaaat?tgttcccagg?caccatgtca 6840
gttcacgctt?caagatttcg?ctacaccgta?tctctaagag?ataagcacta?cttaaaaacc 6900
ataaccacaa?tgccatgata?tgccccaaaa?gattccattt?agtaatttct?caaatgcgat 6960
tgtgagtatg?aaattgctca?gtgatctgag?acgtcttatc?tcggcatgaa?gatttgtcat 7020
gattctgagc?ttgcagaggc?ccctcttgct?gctcctatgc?tgatcggtta?acccatcgcc 7080
ctcctcagct?gtgggtccca?catctccctg?aaagaacgcc?ctcaccttcc?cttcttcctg 7140
agagcttggc?acatggaaat?gactcagagg?cttcactcca?gtcctccccc?tgcaccccag 7200
gcaggtggac?cctgcctttt?agtggctcag?gtatcacttc?agcatgtggc?atgtagatat 7260
taggagaagg?gtctctatga?aggtccaagg?ggggagccag?gtggccccgc?ccttgctccc 7320
catggctcct?agggaaaatg?gggaccctcc?tgcacattta?gggctgttcc?agggctgtct 7380
ggccaaagag?gagacagaag?agaaattcac?aggagaaact?gaaagaggcc?acaggcgtct 7440
tttttggttt?ttaaggaaca?ccagatactt?cagaagctat?cagaaatata?tttttgaata 7500
aaaaatctaa?ctggctccaa?attctgctgt?gttccctgaa?cagactcttg?atatgatatc 7560
ccttcctttg?ttttggagga?ttttccactt?ccttataaca?ggtttagggt?ggtggagttt 7620
gagacataga?tctctggatt?tgggaccaat?ctgcctgcca?cacacagtag?aatttggctg 7680
tgagttagca?gagtcattct?ccactgtgct?ggggcctgag?ccgtgtagca?tctgccttgc 7740
ttgccatgaa?tagacgagac?ttgcctccca?cacagttgag?gatctggctg?caaatgatca 7800
agagagagca?acgtctagat?gggtgtccac?taagcctgca?ggatagataa?tgccaggtgt 7860
ccttcttcca?ggagaggaat?tgttccactt?gctggaactg?tttttttggg?cagatatttg 7920
tacgtagaac?aactgttgta?gatgcagcct?ctttccttag?atttataatg?ctggaccctt 7980
cttagatggg?gcagcatcct?cccaacaggc?cgggcaaatc?tcccctgggg?ccaggctctc 8040
caatgaggct?ttctaaagtg?tgactcctgg?aaactggaca?tagtttgcag?gatacccaag 8100
agcctcattc?agagcaggaa?catgggcagg?ctcgttgagg?gcaggaaatt?tgatggaaga 8160
gaattgtccc?ccactctctg?ctctttaggg?gcctctgtct?tagtaagaag?gaggccaagg 8220
ctctgtcgtc?tagaggcatt?gcagttacca?cagatcgcat?gctcctcttg?tgccaggcac 8280
ctgctgggcg?ctctatgcac?gctaggtcat?tcagtcctca?ccacggctga?gaagtgagta 8340
gaatgattcc?cattttactg?atgaggcacc?tgaggctcag?ggaagtaact?gagagttgcc 8400
cctgttgctg?gaaagtagtg?gcttgggaat?tggaatgccg?gcctaactcc?aaagcccaca 8460
ctcttaaaac?cactgcgctg?ggtggctgct?cctgccgcgg?gctctctgct?cccagactaa 8520
cctgtctcgc?ttttcccctc?cgctgcggcc?actccctgaa?cctcagaaga?ggaggactgg 8580
agagaggacg?aagacggtag?tacagccttt?ccttctgtgg?tgctttctgc?tgcctgctgt 8640
cccaagtgca?gcctccttgt?ccaggggccc?tgttctgggg?gctggggggt?gtgagtaggc 8700
ggcagggacg?gagtgggtca?gtcgtttcct?cccctgcctc?ccaggggcca?ggatcacagt 8760
tccaagctga?tcatcatgcc?tgaacttcag?ggccactggc?tcctcttcct?ggttcctgga 8820
tccttcccct?gggttgggtg?gtgggaggga?ccaaggctag?ctggtctccc?aagctgctcc 8880
aaatgtggcc?atagagggga?cctggcacct?ggaagacagc?agcgccaccc?tgcccccgcg 8940
cacaccccag?tgttccatgc?tgggccctcc?ttaggagctg?gacagcacca?agcagggtgg 9000
ccaggtgttg?gttggggggt?ctggggacag?agtcctctgg?agagcagcca?gggagactgg 9060
aaatagccag?agcaggaagg?acatgacgtc?agccttcaga?tgcgccctgc?tgatggggag 9120
cacaggacca?aggcaaggga?gtgagaccag?ggcttaattt?tagaaagtgc?gttctgacag 9180
ctatatctca?agatgcagta?ggtgggttgg?ggaggcagta?agctccccat?ccttgggatg 9240
ttgcatggcc?actgggtggg?ctggggtata?ttatatagag?aaatgacacg?tcagatgagg 9300
tggcagaggt?gtgaacaaga?tggcctaaag?gtagacccca?caatggccat?gtccttcctc 9360
gctagccctc?tgctttcaca?ctttctagaa?ggatcatttt?gaggtaagac?tcctgcaggg 9420
atcaaataaa?aggcatctcc?aggcttcaga?gaggactcag?acctgggaag?ggaggacaga 9480
gggaatgaag?gccaaccctt?ctcccacgat?ggtgtcttcc?tcctgtctga?ggtttttctt 9540
ctccctctgc?caagaggcac?ccacttccca?gtgcatcagt?gaacaggcat?cacagaacac 9600
ttcctacagg?cacagcccag?gccaggcggc?atcctgtctc?ccttatctgt?ttgtctgtct 9660
gtctacacca?agtgcctgag?tgagatgggg?gccacatcct?gccaaacaaa?tagatgaaaa 9720
tagaaaaatc?ctgcccactt?tctggatagt?acgaagatcc?agatattgag?tgtgccatcc 9780
agccacacag?tcgtactctt?ttggtttctt?tgagatgtgg?attgagggtg?tctagagtca 9840
ctaggttcag?gacaggagct?tctggacacc?tcggcttaag?cagagcatgt?tctgtggtgc 9900
cagacacggg?tgaaacttct?gggctggaaa?gttgggaatg?aggtggagtc?ccatcatcag 9960
ggagtttgcc?gggatgagtg?gggctaagct?gggtggcggg?aggtagccga?cagtcaaaac 10020
caagaatggc?agccccccag?cacgttgttg?cccccaaatt?catctggacc?tagacgtctt 10080
gacccccatc?cccactcccc?gctgcccatt?ctctgctctg?ggttctgcct?gatagcatga 10140
gtggggcctg?cttcttcact?ctgtctgctt?cacttctcca?gagcaggagg?aggcagcgga 10200
agaggatgct?gaagcagagg?ctgagaccga?ggagaccagg?gcagaaggta?agtctctggt 10260
tgagggtgca?ggggcctcag?ggggtggcga?gagcccctgg?agccattcct?gaggcagtaa 10320
gaaacccccc?agaacaggct?ttcccatgtg?cacctgactc tcctattgac?taagattcaa 10380
ccattgattg?cccaatcaac?aaacgttgac?ccagcgcttc?tcttgtgtca?ggcagtcttg 10440
ggtccagggg?aatgtgtgtg?tgagagacag?ctctgtaacc?ccaaaaacca?acagagtgca 10500
tcttggctag?ggcttatctg?tggggaaggc?tcttgctggt?ggcggagggg?gggacttgag 10560
ctcagaacaa?ggaccttgat?tgatttctcg?tgtttcattt?agaagatgaa?gaagaagagg 10620
aagcaaagga?ggctgaaggt?aaggatatca?ggagagaggt?acaagggagg?caaaggaacc 10680
cctcacagca?gctttggagg?agaatgccca?cagtgctctt?tccagggaag?tggatgtgca 10740
ctgagagggt?ttgggagagg?agaggacaga?acttggtggc?acttccaaag?ttttagatgt 10800
tgagctttca?actttgcccc?ttctcccaga?gaagttgcat?tggtggcacc?cagtgggaga 10860
ggggaccatt?gtccagcccc?ctggtctgga?cagagcaatg?ggacccagaa?gtcatatcca 10920
cacatgaagc?tcctagagct?taggtgaaat?cacttgtagg?atgtggtgtc?cgtaggatga 10980
aatcccaatg?catagatggt?catggtgggt?cattgctgca?gtcatcgtca?tgctgcagcc 11040
ttcaccaggg?ttctaagtgg?tcccagtcac?ttctccaaag?gggaggggac?aaccagctgg 11100
ggcttggaat?catgtcatca?gcttctgccc?tgtggccacc?gggaagtcca?aggggtaaca 11160
aagaaggcaa?agacctggga?ggggattcta?gggccaggac?ccttggggac?ctttccaaag 11220
gccttgtcac?tgtgaagcac?aagagaagca?aaattgcttt?gcccagaact?ggtgagtgag 11280
agaaggcttt?gtgtgaagtt?ccacactgcg?tgagtgtgtg?ccctgcagaa?ctctatggga 11340
gggggagtgt?ggcatctgca?gcccccgctg?ccttcattct?cctggatgct?tctggaatca 11400
gggctcccca?gtgccgggag?ggactcactg?tgcagatggg?gaaatggaaa?tccacaggga 11460
tctagctcat?cgagggcgga?gttgggacca?cttctggggc?ccctgaccca?tggctgtgtg 11520
cttctatctc?ctccagatgg?cccaatggag?gagtccaaac?caaagcccag?gtgagtgggg 11580
aggcacctgg?gtagagccgg?gagcagaggc?tcagggagag?aggatgatga?tggaacaggg 11640
tgcagtatgg?tgcagtggac?acgggctggg?ggtttggtgg?gcacagagca?ccacagtaca 11700
gttgtacaag?ttgtgtactg?cacaagcgtc?tcttcctaag?ggagtgagtg?agggctgaat 11760
tccacccaac?actccatcac?caatcgtgca?ccctagcagg?gatggggcta?tgttcttcta 11820
gaggaagggc?cctgaacgga?cactctcctc?tctcacagta?tggccagaac?accctcctcc 11880
atggccgagg?tgggaccttg?ggattaaggg?aagcaaattg?tggggagcca?aacaatgaaa 11940
ccgtgccagc?ataggcatgg?cggcttcaga?gagctgagag?agggcaggac?ggcttggtgc 12000
cacacacgtg?aagcccacct?gaaggtggtg?tgtgctgggg?ggggctgggg?gatagggagc 12060
atttcccttt?ttatgatgcc?aaccctgcca?gcagaggttg?acccatggca?cctctgccca 12120
ctcacaggct?cttcccattt?cagtggggcc?ttctgaaacc?agcccaagac?atcccagatc 12180
catttatttg?cccagtgcct?tcccccttcc?tggcctcttg?tgcactgcgg?tatctcattt 12240
cagctccaca?cacctgaggg?cagatgggga?catgaagaat?cagagaaccc?ctgggtctca 12300
gtatgtgttg?ggaccaggac?caaactgcaa?gactcccagg?ttcatggcca?gtttctgcgg 12360
ggtccaccag?gggatttgaa?gtccaagaag?catggcatct?tgtcacagct?tctttgattc 12420
caagttgtgt?ggctttgagc?aagtcattct?acctccctga?gcctcagttc?tcctaagtga 12480
gattaacggt?acccacttca?tgggcatatc?atgagcatga?agtgaaatag?catatgtgaa 12540
agagctttgt?gtattcccag?gtgctgagca?aggctgagga?ctgccattgt?tgacgtcagt 12600
gttactatca?ttgctgtggt?tggtcggggc?agtgctggaa?gattctctag?gaaggatcag 12660
gccctgcctg?tcctggacac?cctcagtccc?tgggtccaga?atggggctga?tgctgactat 12720
tcctctctcc?aacaggtcgt?tcatgcccaa?cttggtgcct?cccaagatcc?ccgatggaga 12780
gagagtggac?tttgatgtaa?gcggtggctg?tgggttgagt?aggcctgggc?tggggatagt 12840
cccaagggcc?ctcagtgaca?gagattttgt?gaccttgggc?tggggtagag?cataggtggg 12900
atggggtgca?gcacagccag?gctgggtgcc?catccatgag?cgtggtcctg?ggttcaggcc 12960
acagttaccc?cttccctggc?caggcgccat?gccctgccag?aggtcttttg?cactgcgttg 13020
ggggtgtcta?gcccacccat?ctctcctctg?gactctttgg?agtggcagcc?tctgagccgc 13080
agcggtccac?ccacaggaca?tccaccggaa?gcgcatggag?aaggacctga?atgagttgca 13140
ggcgctgatc?gaggctcact?ttgagaacag?gaagaaagag?gaggaggagc?tcgtttctct 13200
caaagacagg?atcgtaggtg?tccagtctgc?ccacctaaca?ttctctgatg?gcccagtctg 13260
tcctccatcc?cttttgtgag?gccccacctc?ctccagacag?ccttcctcgg?cgcctcaaac 13320
ccagctaggt?gtgaggtctc?cttcagaggc?cctccagcat?tctgcacagc?tcctgcagcc 13380
ctgactggtt?tctcgggtcc?ctgccttccc?tccccatcct?actggatgct?ccttgactgc 13440
cagagctgag?tctgatctgt?ttcaggcctc?ccccagggcc?taattcaggc?ccgggctgtg 13500
gactgattgg?tcacaggcct?gctgcgccac?ccctgccctt?gcctcctctt?cccccgcaga 13560
tgaaggggag?tgtgacctgc?agaatcccac?atccttctcc?tgcagagcgt?ggaggctgct 13620
ttgattgctt?ttgtttctcc?ccatcaaact?tgccttccca?cagacatgct?gctctggctg 13680
gagcaatgac?ttggccatct?atccaagcat?atggcacaga?gcagctgcca?gggcagggtg 13740
ggatggaggt?gggggggcag?cccagaagga?gcctgcctga?tgtctcccag?ttgtggaggg 13800
cagtctcacc?atgaggaatg?ttggaggtgg?gtcactgcag?gtaccctggt?gtgcacgtcc 13860
gtggagctgg?ttgaaagtgg?aggcccttgg?aggccgggca?ccattgcttc?aagactctgg 13920
aaggaaccct?cccccaggaa?ttcccttgcc?accccatgca?ggtttctgta?cctgcgatgt 13980
caccttctcc?ctatgcacac?ctgggtgggc?tttgcctctt?ctccttagga?gaaacgtcgg 14040
gcagagcggg?ccgagcagca?gcgcatccgg?aatgagcggg?agaaggagcg?gcagaaccgc 14100
ctggctgtga?gtgaccccta?gcccaggccc?atggaggccc?cccatgctcc?cagctcctgc 14160
tgggccccca?ggcccctctc?tattcatcaa?catgaatgaa?atcagtcaag?agacaatatt 14220
ggccgggtgc?ggtggctcac?gcctgtaatc?ccagcacttt?gggaggccaa?ggcgggtaga 14280
tcacttgagg?ttgggagttc?gagaccatcc?tgaccaacgg?agaaaccctg?tctctactaa 14340
aaatacaaaa?ttagccaggc?gtggtggcac?atgccggtca?tcctagctac?tcaggaggct 14400
gaggcaggag?aatcgcttga?acccaggagg?caaggttgca?gtgagccgag?gtcatgccat 14460
tgcactctag?cctgggcaac?aagagtgaaa?ctccaactca?aaaaaaaaaa?aaaaggaaaa 14520
aaaagagaca?atatcaatat?caacctagga?agtgctgggc?attgtcttgg?ctctgataat 14580
acatcagcaa?acaagacaga?aatgcctgcg?tccttatgaa?cgtgttattt?tataagactc 14640
tccagccctc?atcccttccc?cagtgcagac?ttcgtgggaa?ccgaaggccc?cgtagctctc 14700
ttcctgtgca?gctgctgaag?gcatttccag?agcaacaggt?cttccagggg?cactcccagc 14760
ttaaggggat?gacgagacct?cacatttggg?aatcaggacc?tcattcaatc?acgcagtcat 14820
ttctcagtca?gtggactcct?gtgggccagc?actgtgctgg?gagctaccct?ctcagaaagc 14880
tccttgctga?gcggagagaa?agctgaactc?acccataaag?accacaagct?tcagcccaga 14940
atcagggttt?ccaatccttt?cccctaattt?gctttcttcc?tccctgctgt?aaatcaggaa 15000
gagagggctc?gacgagagga?ggaggagaac?aggaggaagg?ctgaggatga?ggcccggaag 15060
aagaaggctt?tgtccaacat?gatgcatttt?gggggttaca?tccagaaggt?aggtagggag 15120
cagcaggggt?tgccaggaga?tcctagtata?gccctgagga?atgaggtgtc?cactgcagca 15180
ggtagacttt?aggtcaggtc?ccaggaagag?attcccagct?gctgtgggtg?gaagactgag 15240
gtctcctcat?gcccagccct?gagctggttt?tcagcctgac?cgcggcttgc?actaggaggg 15300
gcttgctggg?gtagggggct?acaggcagag?cctggggcac?caatggtgcc?ccccatgcct 15360
ggctccagca?gtgctcagga?gcccccaagg?aggctgggtg?cagctggaag?agccttgtgc 15420
ctagagtcag?agctctagtt?ggagacccag?ctctgccaca?tacagttgtg?tgaccttttg 15480
caacctctga?gcctcggttt?cctcaactgg?cactcatatt?gcctgccttg?atgctttgag 15540
aagctcaaat?gagctaccat?ggaaagtgtc?tatgtgccac?acagatgtga?ggttgtttgt 15600
tcctggaaac?tcactctcga?tccctaactt?ttgtgcccca?ttcctcctag?gtcctccatt 15660
ctcgagggag?gagggatatg?tgaaattgat?tttctctagg?tagtgaagga?atcaaaacat 15720
tttcttagat?ttccagctta?gtccctagct?caggactagg?ccaccccctg?cctctgcccc 15780
catggtgacc?acaccagcca?agactttggc?atcaaagtct?tcatgctacc?gaacagcccc 15840
tgctgtaacc?ctcagaccca?cgtcctagta?aacccggctg?actacagcga?gtatctgaat 15900
cttctcttcc?atgtctctcc?ttgcctttgt?cttcctgcct?tctctctgtg?tctctgttgc 15960
cgtcttggtc?tttttctatg?ggcctctctc?tcatggtttc?ccggtttagc?aggcccaggt 16020
gggtaccaaa?aacctcaagc?cttcttcctc?cccatagttt?tggagagctc?cctgggaggg 16080
gaaggcgcct?tgctggaggg?gaggagtgaa?gagattgggc?tggctgggga?ggggggaagc 16140
tggtgagagg?tgaaagagat?tagttaggca?aagaaggaag?agactgacgt?gatccttctt 16200
gcccctacct?cagtttccct?agggaataca?tgtagttggt?agttgggggg?tgtggcagga 16260
agaagagcat?aagaacctgg?ccctcctgca?ggccttgctc?cacccccagg?gggtttgggg 16320
agggttaggg?gacagggagg?gggcaatctg?gccagtttac?tctgcttccc?acaccctcca 16380
gacagagcgg?aaaagtggga?agaggcagac?tgagcgggaa?aagaagaaga?agattctggc 16440
tgagaggagg?aaggtgctgg?ccattgacca?cctgaatgaa?gatcagctga?ggtgggggct 16500
gggaggaatg?gtcctggggc?actgcccgca?tctgctctgg?gaggggtcgg?gccaagggca 16560
cttcttgctg?tgagccacca?gagggcagga?ctgcctcaca?tattttccca?tggcaagttt 16620
ggtgggacca?gagctgggcc?ccagcaggtc?gggccaactc?ctttctgggc?tttgctgatg 16680
gggaaagaga?actgagcagg?tgccccaccc?ctctgagctt?cacctaccca?cctgcacacg 16740
ggtgtcagga?caggggattg?aactagatgc?tctcctgcgc?cagaagggct?tctcctgctc 16800
cccgcttgtt?cttggaactt?tgccctggca?gtccctggtg?tccgttcctg?agcactgggt 16860
gctgccgtct?ggtccccagg?ctgggtcagg?cccagggggt?gggctggggt?acccttggca 16920
ggcctggagg?tgggaaggag?ggctgggatg?ctgggggctg?ggccgggacc?aggacggagg 16980
cccaggaggg?ccctttctta?ctggacctcc?ccattctcac?ccttgcccgt?gcagggagaa 17040
ggccaaggag?ctgtggcaga?cgatctataa?cttggaggca?gagaagttcg?acctgcagga 17100
gaagttcaag?cagcagaaat?atgaggtggg?ccgccatgct?gtccccgccc?agcatctcca 17160
tctcacactc?ctcctggttc?actgggtccg?gtaatactgc?tgcaggtccc?tgggtccctg 17220
tccctattcc?ccaacagccc?ccttcagctc?ctgcatctgc?ccctgctgcc?tggccttcag 17280
cagtgttcca?tgtccaccgc?attgacgact?gcttgctgga?agtgtctgag?agctcgctgg 17340
ggctgagcag?agacactttc?ctggtgttcc?aaccctgggg?gtctccaaca?cgttgaggca 17400
gcagctcagt?gatctgagct?ggttacaagg?accaggatgc?accaagccag?gacccccagt 17460
ggaaggggag?tgctgccaac?agagaggtgc?ttctccccac?atacacccaa?ggtcctggtg 17520
tgggcacaat?taggctgagc?ctcaagctca?cagtctttcg?gagtcctatg?tgcactaatg 17580
agggtcttag?gtgaacagac?accaggcaag?gaaatggctt?agaggacact?gatgctgcat 17640
accggagctt?agacctgggc?gccagtcctt?ccttacccac?cacccccgag?ccccggtccc 17700
agggcctctt?tgctacctaa?gggaagaatt?cagcttcccc?tggaaggtct?cctttgctgc 17760
tcctgccaaa?ccactcctcc?ctgggcaaga?agcccctcgc?tgggcaggct?caggctgcag 17820
tggctacagg?gtactcccac?ctcccaatac?ggagagaggc?tgtattgcct?ggtgacagtg 17880
gcatggactt?tggagccata?atgcctgggt?tgaatttcta?cctgtgcccc?tcactggctg 17940
tgtgacattg?ggtgagttag?tccactgttc?cttgcctcca?tttccacagg?taacactaca 18000
atatacttca?gagggtgatt?gtgagggtta?cagagataat?actaattgtt?attattgcta 18060
tagtgttcca?accactgttc?caagcatgtc?ccatgtatta?acttactatg?ccctcatagc 18120
agccctatgg?gttcatatct?gggaaggtgc?tcaggacaga?gcctggcacc?cactaaatgc 18180
tcagcaggtg?tcagccattg?ttatggcctc?tctagtcctg?tgccttccac?ttttttctct 18240
ttttttggtt?ccacactgaa?ctctgcaccg?gccaacagga?cacagatttg?ccaaactttg 18300
gggcagcacc?ctgcaggggt?ggtgcatggg?gatgctactg?ctcaaagggc?acagcttccg 18360
ggatggtggg?cagctgggca?ggggtgcccc?agaggggtct?ggggctgggc?tgctaggagg 18420
gctccatgac?acagcctcca?gctttgtgcc?cagctctcag?aggcccttct?tatgggactc 18480
tcatatcctg?aacctattat?ggccctggga?ccccacagtg?ggaggcccat?gaggcatcct 18540
ggaagcttct?ccttggcttc?tgcctgtggt?acacgggccc?ctcctgaccc?ttaactatcc 18600
taacccctcc?tactcttcca?tgctcctcct?tctcctcctg?cactgctgca?ctcagccccc 18660
ttctccccat?ccccaggcca?cctgggacct?gagccagtca?gctccagcgt?tgctctttgt 18720
ccttcccact?tttcttgcag?atcaatgttc?tccgaaacag?gatcaacgat?aaccagaaag 18780
tgtaagtgtc?tgaggtcatt?ctcgcctagc?cctccccctg?ccccctcctt?ccctaccttc 18840
cagctatccc?attcctcctt?ggagggcccc?aggctcccag?cccttcctcc?tctgcttcag 18900
cccacaggtt?tccttctctg?gctcctccgg?ggcctcgtgc?ttctctccct?gtggcctctg 18960
cttgctggtg?ggggtgaaat?gtggggcgga?gaagcttccc?tccagcctca?ggctgctgtc 19020
ctattctgcc?cctggaggca?gctccagcct?gctcctctcc?cctttggcac?cccagtccta 19080
ccccagccgc?atggtgacct?actaccctgc?ctgtgtctcc?atgtcactgc?gtcctgcttc 19140
ccctgcagct?ccaagacccg?cgggaaggct?aaagtcaccg?ggcgctggaa?atagagcctg 19200
gcctccttca?ccaaagatct?gctcctcgct?cgcacctgcc?tccggcctgc?actcccccag 19260
ttcccgggcc?ctcctgggca?ccccaggcag?ctcctgtttg?gaaatgggga?gctggcctag 19320
gtgggagcca?ccactcctgc?ctgcccccac?acccactcca?caccagtaat?aaaaagccac 19380
cacacactga?ctggcatttc?tgtcacgtcc?ccttcagaga?gagagagaaa?ctgaggcgag 19440
accctgctct?cacaggtccc?cggtgtctgc?caagctctaa?ggagctttcc?cctgtctggt 19500
ctccctgctt?gcctctagct?ggggagaggg?tggagggccc?agggtgcagc?ccaggaggca 19560
ggagcagtgg?aaagggcttc?agatcattgc?tcctgggagt?caccaaaaca?gcacatggga 19620
aaagtgctgt?tgagggggac?agagtgttcc?ctgcatgagt?cactcactgg?agaacaatgc 19680
aggactcttc?ggatggttcc?cgttctcttt?ctcctcctag?ccagggccct?aggaaccagg 19740
tgtctgaggg?acagggagct?cttgaggaag?gaaggaaggc?cagttttatt?gggcagctat 19800
tcaggcctga?gttgttgaga?ggtgtgggtt?agtctgggtg?cctcagtttc?cccctcccat 19860
gatctgcaca?tcctcgaggg?cttaagtcac?agggtcctga?gctgaagagg?acagcttggt 19920
ggcatggatt?tcagttggca?gaaagacaag?gaaacgatga?gagggcacca?tcctcctctc 19980
cagaggagag?cctgagacga?cacattctct?tgaccctcca?ttcctttgtc?aggcgtggaa 20040
tttcccccaa?ttcctgattc?cttcccttgg?ctccccactt?gccatccatc?agcaagtgcc 20100
tcatgagctg?tgtctggaaa?ggcttcctgt?ggtctcccag?ccagagcaaa?tccatttctg 20160
cttgctagag?catgtgctgt?cacagctatg?ccatccaatg?ccacactctg?ttagacgggt 20220
ctcttcctgc?aggcgtggct?ctcatgctcc?caggagacaa?tgcagacatg?ttatcctgtg 20280
ctgtatgcca?agcactggga?tccatgtagt?gagagatgaa?gaggaaatgg?tccttgggcc 20340
acagggaggg?gcttagcctg?gggtctcggc?ctcatttctt?attcattcat?tcgttcagtc 20400
attcaaatac?ctcctgagca?ccaactatgt?gctagacact?gtgttgggtg?tggggtgctg 20460
tgatttaagc?cagcacatcg?ctcatggagc?tcacagagct?cacatccagc?agcagggaga 20520
cagcaagcag?aggtcccagc?cctgggtgac?aggggcgggt?ggggggtgcg?atgctgggga 20580
gaggcatagc?cacgcaccac?acctggccct?ggcaggtggg?aaggctttct?ggaggaaaga 20640
gtgtctaggc?cgagtaccag?agggtgagga?gggggaagtc?aaggggaaga?ggttgggggt 20700
ggggctggga?acggcacata?gaaagtttga?gaagcaagag?ccagcatggt?gtgtttgaag 20760
agatatagtt?attagcagaa?tccaagcatc?ttctggtggg?gacaagaagg?ctccatcata 20820
aatgccccca?aaatggacag?ggaggcagga?cgcaggcctc?aggcccaagg?agggctgtca 20880
ccacgggctc?tgggagaccc?actggcagct?cctggcacgc?accagcccta?ctatctcagt 20940
ttgccggata?ggacagctgg?ggcagtgccc?tagcccctct?ccccataaag?gggcactgca 21000
cctctacccc?cacctgccgc?cttggctcca?ccgcctatgc?ctcagtgtct?ccttggtgca 21060
acaagaggtc?atgatgggcc?gtgtgtctgg?ggccctgtct?cctgctcccc?ctctcccagc 21120
agggtccttg?tgaccatttc?tctagtacag?cggtccccaa?cctttttggc?accaaggacc 21180
agtttcttgg?aagactattt?ttccatggac?aggggtgggg?tggggaagaa?aagtaggggt 21240
gggtgggtgg?gggtggtttc?aggatgaaac?tattccactt?cagatcgtca?ggcaatagat 21300
tctcgtaagg?agtatgcacc?ctagatccct?cgcatgcaca?gttcacaata?ggtttcacac 21360
tcctatgaga?atctaatgct?gctggctgct?gatctgacaa?gaggtggagc?tcaggccgtc 21420
atgctcgccc?acccacagct?cacctgctgt?gcagcctggt?tcataacagg?ctatagactg 21480
gtagagtctg?gtccacggtg?cagaggttgg?ggacccctgc?tctagtagat?gtggtctctc 21540
ttttaaaaat?tgtgcccagg?ccgagcgcgg?tggctcatgc?ctgtaatccc?agcactttgc 21600
gaggccgagg?caggcacatc?atgaggtcag?gagatcaagg?ccatcctggg?caacatggtg 21660
aaaccctgtc?tttactgcac?tccagcctgg?caacagaacg?agactccgtc?tcaaaaaaaa 21720
aattagctgg?gcatggtggc?gcgtgcctgt?agtagggctc?gggaggctga?ggcaggggaa 21780
tcgctcaaaa?aaaaaaaaca?actgtgccca?gaggtgggca?cagaagacac?ccttgccctc 21840
cgactctgaa?aagcccctaa?gaccagatcc?cacttaatct?cttttctcct?aaggtcacct 21900
ggtgttcagg?aaagaacttc?ggagtgtccc?aggcgctgcc?cccatggggg?cctcacccag 21960
ttgaggtccc?catcccatca?tcttaagagg?aacaccacag?gttaacccaa?gcgctgcctc 22020
taggcaggag?atctgcagac?acctggtctg?catggaacct?ggagcactaa?tccataagtg 22080
gagcctggga?aggggacctt?gtcctatccc?aggacagagg?agaaagcaag?tgagtgtcag 22140
ggtgcagggg?cacacctggt?ccatcagccc?agtgcaggga?gtcctgccaa?tttcaaaagg 22200
caagggtggg?ggcttcagac?caagtggtcc?tgtgctctcc?ccataatatt?gctagggaac 22260
agaaagatca?tggatgtgtg?cacagaacac?actgagatag?cttcacagat?agggcctcca 22320
cacaccctcc?tcagttcacc?caccacttcc?atcattcttg?tgcttatgat?ggtcctgaac 22380
caaacgttga?aggtgcagca?gtggccaaga?gctgtcctgg?gcctcctgac?aactgaggag 22440
ctggatgcag?cggggtgagt?tgacgcccac?ccagacactc?tgacccccac?tgtccccact 22500
gtcccctgca?gggacctccc?tctatgcctc?tcagatccca?tctcactgta?ctttcgatcc 22560
atgacccatt?gcctcatggg?cctctcagca?ccctgtgtac?accaaatgct?cagggaaaat 22620
tacttgcagg?ctcttctcag?ccctgagtca?gaggtgaaga?ctcttccgcc?atcctgtcat 22680
cagattcgtt?ctcctaacaa?gctcgcatcc?tgggcagagc?ttgttcgtgt?gatgcccact 22740
ttagaggtag?agctgggaga?gaacaaggtg?ttcccccagg?gctccttcgc?ctgggaatcc 22800
agctcctcca?gctggagccc?cgatgctctg?aagctagagc?ctcactttct?cccatcaaac 22860
tctggctctg?ccccttccca?gctctgggat?tttggtcaaa?ttccttgcct?tctctgtgct 22920
gaagttcccc?tatctaaaca?atggggattg?ttatgaaggc?taaatgaaat?aaacatgcag 22980
caactagcac?agtgcttagt?gcatagtgtg?taatcagcac?gagccactgc?tactgccttt 23040
tggatgaaaa?cacgttatta?gcctttctca?agggctcaag?gtctgcagaa?gaagagttca 23100
cccatgctgg?gtctgggctg?gctcctcctt?gcctgtgtgg?ttttagggaa?cccttcaatg 23160
gctcctcttt?cctcctggat?tccacggcct?ggtcttctcc?ctcaccagat?aggccaccag 23220
gggttggggg?tgggtgggat?ttgctgctac?ggactgtccc?tcctggcacg?tggttcagcg 23280
tgtgccactg?tctggatgga?ggtgccagaa?cttgttccca?ggccaggctc?cactccctac 23340
tctgcagctt?gatttctggg?aaaggtgggg?cagggcctga?gcttccaggg?aacctgccct 23400
ggttggggga?aatagctggg?ctcagggata?ggtctcaggg?ccaggctctc?taataggctc 23460
ctgttgggta?tggggcaggc?tgggggtgca?ggggagacca?ggctggaccc?catgttccca 23520
cagtgtagcc?acgggcactc?acttgcttct?ctgggcttgg?cttctcctct?gaaagtccag 23580
tctgccctgt?catccctacc?aggaggaaga?ctaagtgtga?atttggggaa?aatgctgctg 23640
atctgggtca?gctcgtcttc?tccccctgca?cacataccct?tcatgtgttt?ctcgctctgc 23700
gccccccacg?caggcactgg?gccagctact?ttacatatgt?tctctccagc?caaccatcca 23760
cagtccccag?atcacaccgc?atgttgcaga?tgaggaaact?gaggtacaga?gagtttaggc 23820
aacatgccaa?gggccattca?gttagtaagt?ggcaaagctg?ggatttgaac?ccaggtctat 23880
gtgacgccag?agccaggatt?cttcctaaca?tgtggatctt?gtagattgag?gagcatccca 23940
aatctcccca?gattgcagtg?cttgggccag?aatcagagcc?tcccgtgggc?tgacttgggg 24000
tgagggcaca?gggcaggagt?ccaggagctt?gaccctctct?gctgccctcc?agctgcccac 24060
ctgggacctg?acaggaggag?atgtgctatg?tctagcacat?ggaggcggcc?tctggaggga 24120
acagtagagg?tggggttgag?tggggctcta?cccagggtgc?aagagaatca?ttggccagcc 24180
tcctccttct?tgggagtaat?tataccccat?acctgtgtcc?cagagtagtt?ggggggatct 24240
gtgggtcatg?gaagcacctg?tcattacctt?gtctgtgggt?tacccctcga?ctctgcaaag 24300
atagtgagta?aacctcaggg?tgggcagaat?cctgggtcta?gatgccagca?gggcctatct 24360
ggctgttgtt?gggggtggca?gaggtgcttt?agggaccctc?tgcagtctac?ctccagcctt 24420
acttttcagc?caaatggagc?tagctacttt?tgtttctcca?gcatgtccta?tgctctccca 24480
cctctgcatg?gctttttctt?gcccttcttt?ctgtctctgc?ctatccaact?gccctccgcc 24540
ttcctcaggg?cctcgatgaa?gtccctgttt?ctccaagaag?cctttgggac?tccctcctga 24600
gcacctgggg?cttcctgagc?accagcgatg?cctctggtga?tgccttaaga?gccgcacatt 24660
gaaggcccat?tcactctggg?cctcctgtgg?ttcacagaaa?ccaggactgg?gtgcccagcc 24720
cagacctccc?tgcctggcac?tgttcccagg?gcttcagccc?cacccacctg?ctcatcccag 24780
gttctcagct?cccaccccag?catctacagg?aatttaaatt?gctctcaaat?gaagactcag 24840
gagaaaaatg?tttccatact?tgtgcagagc?gccctgacct?ggggcggggg?ttgggggaag 24900
tagccccagc?tccgccctgt?ggccctgccc?tcagtgctgg?ccttggccac?actggccaca 24960
cctgcagcac?gccccaatcc?caaagcagtt?ttccccgtaa?agccaggcct?gagcaatgca 25020
aacctgaaga?agcctggggc?taggctgggg?ctgctcttca?ggaacgcagt?gggcggggtg 25080
ggagaggtgg?tgtgattccc?aggctgagag?gtgctgagat?tgtgctgggt?ttgctaaatg 25140
tgggacaggg?agacctgttt?aggatgagct?gcctcacccc?gtcctctccc?cacccatccg 25200
taccctgcca?attcccagaa?gatgatgcca?gctaggaatg?caggttgatg?aagataaagg 25260
cagaaggtca?cttcacttct?acctgggggc?aatagacaaa?gcagtgtttc?cctctgaact 25320
tcacacagag?actcctctgg?ccccacatct?cccacctgtt?caggcccagg?tgatgtggtg 25380
agcagtggtt?tctgctggga?gacacttggc?ataatttgta?agccagctac?atgataatac 25440
taacaaatga?tatttgcctc?catatattag?gcacctatcg?tgtgccatat?actatgttac 25500
gtaatttatg?tccactctct?aattacagta?acatgcaaaa?ttaggtccta?tataataact 25560
ccattttata?cacaaggaaa?ctgaggctca?gagaagttag?gtgactcatc?caaggtcata 25620
cagggcagga?tcctgattac?tgtattttta?ttacaatgtt?aaaattattt?gaatggtaca 25680
cttcctacca?aatcaagtca?ggcatctgat?agaaacaaag?aaaagcatat?tttcaagaag 25740
tcccttctgt?attttagcca?acaaatattt?gaataatttc?tgattatata?atgcaaagta 25800
cgagtgcatc?gatccttatc?atagaaaaac?ttgtgtgaaa?taatgttcaa?atttgtctat 25860
tgcaaaaatt?tgatcactca?cctgggaaat?ctggaattag?gaatgtaaga?tcttaccact 25920
gcctcttgct?catataaagt?ggcttgtgaa?ttcacctagc?cctcatccca?ctcagttgcg 25980
gttggtggtt?tcctcatctc?tcccctacat?ctagcctggg?cacttcctgg?gacctggggt 26040
cctgggttgt?tcatccgtag?atcccagtgg?cctccatgca?tgggaatgaa?tacaggagaa 26100
aaatcattct?caaattagat?gatcttgttt?aaggtttgat?cttttaaata?tcaaatatca 26160
gagagggaaa?atatggcaaa?ctaatcacat?tagagttgca?ttgtctttca?cagttgtcaa 26220
agcactgtaa?caagtccata?ggatagtaac?tttagaaaaa?gaagaccttt?gatcttggaa 26280
gggtcatacg?tttacctcgc?tcacatcata?tcgatgcaag?cattaaatct?gcttgataac 26340
caatgtttct?attagaaaat?aggggtcact?gacacattgg?ttcagtcatt?gtgtaaatcc 26400
aacacatatt?tattaaacac?atactctatt?ctaggtactg?gctagttatc?agggttatac 26460
ctgaggacag?accaagactg?tttcctacct?tcataaacaa?gaggagaaaa?gtattaaaca 26520
gacattagat?cactggatag?atagatagat?gatagataga?tagatagata?gatagataga 26580
tagatagata?gatagatagg?agatagagat?aggtgacaga?tggatagatg?gatagataga 26640
tagcagatag?aaaagagata?ggtagataga?tgggaggaag?gtagatagat?agagataggt 26700
ggatacatac?atgcatatat?gcatagacac?agacacatgt?atgtacagat?atagatatac 26760
atatgcagtg?cctgggtctc?aaattgtaaa?aagagaaacc?cagaggaaaa?cagcagtgtg 26820
ctgtgaaaga?gaacaggttg?acataactta?aacggagttt?ggatgaggaa?gcgtc 26875
Claims (10)
1. an isolating sudden change β-mhc gene or its fragment, its following position in the sequence of listing corresponding to Genbank accession number gi:M57965.1 (SEQ ID NO:1), contain the one or more sudden changes that are selected from down group: 10353G＞A, 10429A＞C, 10895A＞T, 11811A＞C, 13653A＞C, 14449T＞C, 14452G＞A, 14557G＞A.
2. an isolating sudden change cMYBPC gene or its fragment, its following position in the sequence of listing corresponding to Genbank accession number gi:Y10629 (SEQ ID NO:2), contain the one or more sudden changes that are selected from down group: 4826G＞A, 8697G＞A, 8887G＞A, 12101G＞A, 13261G＞A, 14262-14264de1AAG, 14364de1G, 18115-18116insGCAAG.
3. an isolating sudden change cTnT gene or its fragment, the one or more sudden changes that are selected from down group are contained: 4693C＞T, 4769G＞A in its following position in the sequence of listing corresponding to Genbank accession number gi:X90780 (SEQ ID NO:3).
4. each mutator gene or fragment among the claim 1-3 wherein also comprise extra sudden change or nucleotide polymorphisms.
By claim 1-4 each mutator gene or the protein of fragment coding.
6. nucleic acid, its can with each mutator gene or fragment or its complementary sequence specific hybrid among the claim 1-4, but can not with the nucleic acid hybridization of corresponding wild type gene or its complementary sequence.
7. a test kit wherein comprises the described nucleic acid of claim 6, and working instructions.
8. a test right requires the method for the sudden change that each limited among the 1-3, comprise that application rights requires 6 described nucleic acid as probe or the primer detection of biological product that imitate, perhaps Application Design becomes will obtain comprising the step of segmental primer to increasing this biological sample and detecting of this sudden change after amplification.
9. a microarray wherein comprises the defined nucleic acid of claim 6.
One kind the screening or the assessment medicine method, comprise that cell, tissue, organ or animal individual to carrying each described mutator gene among the claim 1-4 give one or more medicines, and assess the index of its one or more indication hypertrophic cardiomyopathy situations, with indication amelioration of disease situation.
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| CN 200410104647 CN1865440A (en) | 2004-12-31 | 2004-12-31 | Novel pathogenetic gene mutation of hypertrophic cardiomyopathy and use thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105695606A (en) * | 2016-04-07 | 2016-06-22 | 昆明理工大学 | Non-treatment-purpose method for screening mutation of pathogenic genes relevant with hypertrophic cardiac myopathy |
| CN106868175A (en) * | 2017-03-28 | 2017-06-20 | 昆明理工大学 | A kind of Primer composition and its application |
| CN107287317A (en) * | 2017-07-10 | 2017-10-24 | 中国人民解放军第四军医大学 | MYH7 A934V mutators are used for the application for preparing Diagnosis of Hypertrophic Cardiomyopathy kit |
| CN108642155A (en) * | 2018-06-15 | 2018-10-12 | 合肥艾迪康临床检验所有限公司 | Detect method, oligonucleotides and its application of MYH7 gene mutations |
| CN111974985A (en) * | 2020-09-16 | 2020-11-24 | 南京大学 | Nano particle cluster assembling method using micro magnetic beads as growth template and DNA frame as guide carrier |
| CN112941175A (en) * | 2021-04-14 | 2021-06-11 | 大理大学 | Primer probe composition for detecting MYH7 gene mutation and application thereof |
| CN113684216A (en) * | 2021-09-26 | 2021-11-23 | 百世诺(北京)医学检验实验室有限公司 | MyBPC3 gene hypertrophic cardiomyopathy detection kit based on mutation |
| CN115873862A (en) * | 2022-11-24 | 2023-03-31 | 百世诺（北京）医疗科技有限公司 | Hypertrophic cardiomyopathy variant gene MYH7 and application thereof |
-
2004
- 2004-12-31 CN CN 200410104647 patent/CN1865440A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105695606A (en) * | 2016-04-07 | 2016-06-22 | 昆明理工大学 | Non-treatment-purpose method for screening mutation of pathogenic genes relevant with hypertrophic cardiac myopathy |
| CN105695606B (en) * | 2016-04-07 | 2020-08-28 | 昆明理工大学 | Screening method for hypertrophic cardiomyopathy related pathogenic gene mutation for non-therapeutic purpose |
| CN106868175A (en) * | 2017-03-28 | 2017-06-20 | 昆明理工大学 | A kind of Primer composition and its application |
| CN107287317A (en) * | 2017-07-10 | 2017-10-24 | 中国人民解放军第四军医大学 | MYH7 A934V mutators are used for the application for preparing Diagnosis of Hypertrophic Cardiomyopathy kit |
| CN108642155A (en) * | 2018-06-15 | 2018-10-12 | 合肥艾迪康临床检验所有限公司 | Detect method, oligonucleotides and its application of MYH7 gene mutations |
| CN111974985A (en) * | 2020-09-16 | 2020-11-24 | 南京大学 | Nano particle cluster assembling method using micro magnetic beads as growth template and DNA frame as guide carrier |
| CN112941175A (en) * | 2021-04-14 | 2021-06-11 | 大理大学 | Primer probe composition for detecting MYH7 gene mutation and application thereof |
| CN112941175B (en) * | 2021-04-14 | 2022-06-17 | 大理大学 | Primer probe composition for detecting MYH7 gene mutation and application thereof |
| CN113684216A (en) * | 2021-09-26 | 2021-11-23 | 百世诺(北京)医学检验实验室有限公司 | MyBPC3 gene hypertrophic cardiomyopathy detection kit based on mutation |
| CN115873862A (en) * | 2022-11-24 | 2023-03-31 | 百世诺（北京）医疗科技有限公司 | Hypertrophic cardiomyopathy variant gene MYH7 and application thereof |
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