Autosomal dominant ataxia : genetic evidence for locus heterogeneity from a cuban founder-effect population

• Published in: American journal of human genetics Vol. 46; no. 6; pp. 1163 - 1177
• Main Authors: AUBURGER, G, OROZCO DIAZ, G, HEREDERO BAUTE, L, FERREIRA CAPOTE, R, GISPER SANCHEZ, S, PARADOA PEREZ, M, EDSTRADA DEL CUETO, M, GARCIA MENESES, M, FARRALL, M, WILLIAMSON, R, CHAMBERLAIN, S
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01-06-1990
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 6; Cuba; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Genes, Dominant; Genetic Linkage; HLA Antigens - genetics; Humans; loci; Lod Score; Male; Medical sciences; Mutation; Neurology; Original; Pedigree; Polymorphism, Restriction Fragment Length; Spinocerebellar Degenerations - genetics; Cuba; Genetic mapping; Human; Central America; Nervous system diseases; Linkage; Genetic marker; Family study; West Indies; Inheritance; HLA»-System; Genetic disease; Cuba; Autosomal character; America; Ataxia; Genetics; Dominant character; C6-Chromosome; Degenerative disease; Molecular biology
• ISSN: 0002-9297; 1537-6605

The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1-HLA-GLO1-MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease.