Linkage disequilibrium at the SCA2 locus
- Olivier Didierjeana,
- Géraldine Cancela,
- Giovanni Stevanina,
- Alexandra Dürra,
- Katrin Bürkb,
- Ali Benomarc,
- Agnès Lezind,
- Samir Belale,
- Myriem Abada-Bendidf,
- Thomas Klockgetherb,
- Alexis Bricea
- aINSERM U289, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France, bDepartement of Neurology, University of Tübingen, D-72076 Tübingen, Germany, cService de Neurologie (Pr T Chkili), Hôpital des Spécialités, Rabat, Morocco, dLaboratoire de Biologie Moléculaire, CTS-Hôpital Perre Zobda-Quitman, Fort-de-France, Martinique, eInstitut National de Neurologie, La Rabta, 1001 Tunisia, fService de Neurologie, Hôpital de Ben-Aknoum, CHU Alger-ouest, Algiers, Algeria
- Professor Brice.
- Received 22 July 1998
- Revised 22 October 1998
Abstract
Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.
