Demonstration by sequence analysis of a linkage disequilibrium between polymorphic CCG repeat and the CAG expansion in HD gene
- Universite Rene Descartes-Paris (France); and others
Huntington disease (HD) is a progressive neurodegenerative disorder with autosomal dominant inheritance. It has been recently found that HD is associated with an expansion of a CAG triplet repeat (37 to 140) in the 5{prime} coding region of the IT15 gene. The CAG repeat region is also polymorphic in normal alleles (11 to 34 repeats). The PCR assay previously described for estimating the number of CAG repeats involved primers which encompass the CAG repeat region but also a 3{prime} adjacent CCG repeat region. The number of CAG triplet repeats is then calculated from the size of the PCR product by comparison to an M13 sequencing ladder on a 6% denaturing polyacrylamide gel. A polymorphism in the number of CCG triplet repeats would interfere with the estimation of the number of CAG triplet repeats. We sequenced the CCG triplet repeat region of normal and HD alleles from 50 unrelated heterozygous HD patients. After PCR, the two alleles were purified on a 1.5% low melting agarose gel and directly sequenced. In normal chromosomes we found: 50% of (CCG){sub 7}(CCT){sub 2}, 48% with (CCG){sub 10}(CCT){sub 2} and 2% with (CCG){sub 7}(CCT){sub 3}. In contrast, in the HD chromsomes the (CCG){sub 7}(CCT){sub 2} allele was found in 85% of cases showing significant linkage disequilibrium ({chi}{sup 2}=16.6). It has been reported previously in Canada and in Wales, but not assessed by sequence analysis. This indicates that systematic determination of the CAG repeat is warranted when the suspected HD allele is between 30 to 40.
- OSTI ID:
- 134274
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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