title: Haplotype study in Dutch SCA3 and SCA6 families: evidence for common founder mutations.
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.
authors.affiliation: Department of Medical Genetics, University Medical Center, Stratenum, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. D.S.Verbeek@med.uu.nl
authors.forename: Dineke S
authors.initials: DS
authors.lastname: Verbeek
authors.forename: Sytse J
authors.initials: SJ
authors.lastname: Piersma
authors.forename: Eric F A M
authors.initials: EF
authors.lastname: Hennekam
authors.forename: Elly F
authors.initials: EF
authors.lastname: Ippel
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pearson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
mesh_terms: D000067699:Ataxin-3; D015220:Calcium Channels / Q000235:genetics*; D005190:Family; D005260:Female; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D017827:Machado-Joseph Disease / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009426:Netherlands; D009687:Nuclear Proteins; D010865:Pilot Projects; D012097:Repressor Proteins; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D020864:Calcium Channels, N-Type
chemical_list: D000067699:Ataxin-3; D015220:Calcium Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C026742:plastin; C092341:ATXN3 protein, human