Linkage disequilibrium studies of dentatorubral-pallidoluysian atrophy (DRPLA) in Japan
- Univ. of California, San Francisco, CA (United States)
- Univ. of California, San Francisco, CA (United States); and others
Dentatorbral-pallidolluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder which is almost unknown outside of Japan. The molecular basis of this disorder was recently demonstrated to be an expansion of a CAG repeat, within a previously unknown gene. This genetic mechanism, trinucleotide repeat expansion, has now been shown to be the basis of several neurological diseases. For many of these disorders, population studies have indicated that individuals with predisposition to expansion demonstrate conservation of haplotypes for polymorphic markers which flank the trinucleotide repeat, suggesting that predisposing mutations occurred on a small number of founding chromosomes. For most of the disorders associated with unstable repeats, prevalence is not mainly limited to a single population, and therefore it is unlikely that a single region can be identified which is completely conserved in all patients. However, for DRPLA, the Japanese predominance suggests that investigating patterns of linkage disequilibrium and haplotype conservation may be especially instructive. We have collected a sample consisting of 8 unrelated Japanese DRPLA patients and 74 unrelated members of the general Japanese population, and have genotyped these individuals for the DRPLA trinucleotide repeat; all of the patients demonstrate the expansion. In addition, 6 individuals from the general population have CAG repeat numbers in the high normal/predisposing size range. By typing 8 microsatellite markers from a 7 cM region between D12S99 and D12S77, we have identified a haplotype, consisting of four markers, which appears to be partially conserved in the DRPLA patients. Future work will focus on more complete reconstruction of the predisposing haplotype with additional markers.
- OSTI ID:
- 133907
- 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
Similar Records
Isolation and characterization of a full length cDNA for dentatorubral-pallidoluysian atrophy (DRPLA) gene
Normal CAG repeat variation at the DRPLA locus in world populations