Haplotype study in Dutch SCA3 and SCA6 families: evidence for common founder mutations.

• 影响指数: 5.351
• 发表时间: Jun 2004
• 来源期刊: Eur J Hum Genet
• DOI: 10.1038/sj.ejhg.5201167
• PMID: 15026782
• 文章类型: Comparative Study
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Verbeek DS,Piersma SJ,Hennekam EF,Ippel EF,Pearson PL,Sinke RJ

Mesh: Ataxin-3; Calcium Channels / genetics; Family; Female; Founder Effect; Haplotypes / genetics; Humans; Linkage Disequilibrium; Machado-Joseph Disease / genetics; Male; Membrane Glycoproteins; Microfilament Proteins; Mutation / genetics; Nerve Tissue Proteins / genetics; Netherlands; Nuclear Proteins; Pilot Projects; Repressor Proteins; Spinocerebellar Ataxias / genetics; Trinucleotide Repeat Expansion / genetics

Abstract

This pilot study was initiated to show the existence of founder effects in the Dutch autosomal dominant cerebellar ataxia (ADCA) population. The ADCAs comprise a clinically heterogeneous group of neurodegenerative disorders and the estimated prevalence in the Netherlands is approximately 3:100 000 individuals. Here, we focused on the SCA3 and SCA6 genes because mutations in these genes occur most frequently in the Netherlands. We were able to determine a common origin of the CAG repeat expansions in the majority of Dutch SCA3 and SCA6 families. Haplotype analysis and linkage disequilibrium studies with polymorphic markers revealed shared haplotypes surrounding the SCA3 and SCA6 genes. These results strongly suggest that ADCA families can be traced back to common ancestors in particular parts of the Netherlands.