CA2338250A1 - Lafora's disease gene - Google Patents

Lafora's disease gene Download PDF

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Publication number
CA2338250A1
CA2338250A1 CA002338250A CA2338250A CA2338250A1 CA 2338250 A1 CA2338250 A1 CA 2338250A1 CA 002338250 A CA002338250 A CA 002338250A CA 2338250 A CA2338250 A CA 2338250A CA 2338250 A1 CA2338250 A1 CA 2338250A1
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CA
Canada
Prior art keywords
sequence
nucleic acid
detecting
lafora
disease
Prior art date
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Granted
Application number
CA002338250A
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French (fr)
Other versions
CA2338250C (en
Inventor
Stephen W. Scherer
Berge A. Minassian
Antonio Delgado-Escueta
Guy Rouleau
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
McGill University
Hospital for Sick Children HSC
University of California
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Individual
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Publication of CA2338250A1 publication Critical patent/CA2338250A1/en
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Publication of CA2338250C publication Critical patent/CA2338250C/en
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/172—Haplotypes

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

A novel gene (EPM2A) that is deleted or mutated in people with Lafora's disease is described. The EPM2A gene encodes a protein having an active catalytic site of a protein tyrosine phosphatase. Many different sequence mutations as well as several microdeletions in EPM2A have been found that co - segregate with Lafora's disease.

Claims (19)

1. An isolated nucleic acid molecule containing a sequence encoding a protein tyrosine phosphatase which is associated with Lafora's disease.
2. A nucleic acid according to claim 1 having a sequence as shown in SEQ.ID.NO.:1 or Figure 13.
3. An isolated nucleic acid molecule according to claim 1 comprising (a) a nucleic acid sequence as shown in SEQ.ID.N0.:1 or Figure 13, wherein T
can also be U;
(b) nucleic acid sequences complementary to (a);
(c) nucleic acid sequences which are homologous to (a) or (b);
(d) a fragment of (a) to (c) that is at least 15 bases, preferably 20 to 30 bases, and which will hybridize to (a) to (d) under stringent hybridization conditions; or (e) a nucleic acid molecule differing from any of the nucleic acids of (a) to (c) in codon sequences due to the degeneracy of the genetic code.
4. An isolated nucleic acid molecule according to claim 1 having a sequence as shown in Figure 4A.
5. An isolated nucleic acid molecule according to claim 1 having a sequence as shown in Figure 7.
6. An isolated nucleic acid molecule according to claim 1 having a sequence as shown in Figure 9.
7. A method of detecting Lafora's disease comprising detecting a mutation or deletion in a nucleic acid sequence according to any one of claims 1 to 6 in a sample from an animal.
8. A method according to claim 7 comprising detecting a mutation or deletion in a region of the nucleic sequence between markers DS61003 and DS61042.
9. A method according to claim 7 comprising detecting a C to T change in nucelotide number 721 of the sequence shown in SEQ.ID.NO.:1 or Figure 13.
10. A method according to claim 9 wherein the C to T change is detected by a method comprising:

(a) amplifying the nucleic acid sequences in the sample with primers H1F
(5'-GAATGCTCTTTCCACTTTGC-3) and PTPR (5'-GGCTCCTTAGGGAAATCAG-3') in a polymerase chain reaction;

(b) digesting the amplified sequences with the restriction endonuclease HaeIII; and (c) determining the size of the digested sequences wherein the presence of a fragment of approximately 199bp indicates the sample is from an animal with Lafora's disease or an animal that is a carrier of Lafora's disease.
11. A method according to claim 7 comprising detecting a G to A mutation of nucelotide number 836 of the sequence shown in SEQ.ID.NO.:1 or Figure 13.
12. A method according to claim 11 wherein the G to A change is detected by a method comprising:
(a) amplifying the nucleic acid sequences in the sample with primers H1F
(5'-GAATGCTCTTTCCACTTTGC-3) and PTPR (5'-GGCTCCTTAGGGAAATCAG-3') in a polymerise chain reaction;

(b) digesting the amplified sequences with the restriction endonuclease Pst1;
and (c) determining the size of the digested sequences wherein the presence of at least one fragment of approximately 520bp indicates that the sample is from an animal that does not have Lafora's disease or an animal that is a carrier of Lafora's disease.
13. A method according to claim 7 comprising detecting a deletion of 75 kb in the sequence of EPM2A shown in SEQ.ID.NO.:1 or Figure 4A.
14. A method according to claim 7 comprising detecting a deletion of 25 kb in the sequence of EPM2A shown in SEQ.ID.NO.:1 or Figure 4A.
15. A method of according to claim 13 or 14 comprising:
(a) amplifying the nucleic acid sequences in the sample with primers JRGXBF ( 5'-TCCATTGTGCTAATGCTATCTC-3') a nd J RGXBR
(5'-TCAGCTTGCTTTGAGGATATTT-3') in a polymerise chain reaction; and (b) detecting amplified sequence wherein the absence of an amplified sequence indicates that the sample is from an animal with Lafora's disease.
16. A method according to claim 7 comprising detecting a mutation or deletion as specified in Table 3 in a sample from an animal.
17. An isolated protein containing a tyrosine phosphatase domain which is associated with Lafora's disease.
18. A protein according to claim 17 having the amino acid sequence as shown in SEQ.ID.N0.:2 or Figure 14.
19. A method for detecting Lafora's disease comprising detecting a deletion or mutation in a protein according to any one of claims 17 or 18.
CA2338250A 1998-07-20 1999-07-20 Lafora's disease gene Expired - Lifetime CA2338250C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US9349598P 1998-07-20 1998-07-20
US60/093,495 1998-07-20
US13026999P 1999-04-21 1999-04-21
US60/130,269 1999-04-21
PCT/CA1999/000646 WO2000005405A2 (en) 1998-07-20 1999-07-20 Lafora's disease gene

Publications (2)

Publication Number Publication Date
CA2338250A1 true CA2338250A1 (en) 2000-02-03
CA2338250C CA2338250C (en) 2012-02-21

Family

ID=26787605

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2338250A Expired - Lifetime CA2338250C (en) 1998-07-20 1999-07-20 Lafora's disease gene

Country Status (3)

Country Link
AU (1) AU4765599A (en)
CA (1) CA2338250C (en)
WO (1) WO2000005405A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6825328B1 (en) 1998-07-20 2004-11-30 Stephen W. Scherer Lafora's disease gene
WO2005012526A1 (en) 2003-08-04 2005-02-10 The Hospital For Sick Children Lafora's disease gene

Also Published As

Publication number Publication date
WO2000005405A3 (en) 2000-05-11
CA2338250C (en) 2012-02-21
AU4765599A (en) 2000-02-14
WO2000005405A2 (en) 2000-02-03

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