A cerebellar ataxia locus identified by DNA pooling to search for linkage disequilibrium in an isolated population from the Cayman Islands

Abstract

A non-progressive recessive cerebellar ataxia was identified in a highly inbred Cayman Island population. Cayman cerebellar ataxia is characterized by marked pyschomotor retardation, and prominent cerebellar dysfunction manifested by nystagmus, intention tremor, dysarthric speech, and an ataxic gait. In this study, we identify linkage to chromosome 19p13.3 using pooled DNA samples of affected individuals from an isolated population as PCR template for a genome wide screen with short tandem repeat markers. Our data demonstrate that the DNA pooling approach to identify disease gene loci is feasible using individuals from isolated populations in which kindred relationships are highly complex and exact relationships between all affected individuals are not known. Genetic fine mapping demonstrates that the genetic disease interval is approximately 9 cM, but contained within a small physical region. The existence of multiple individuals that are recombinant with flanking markers indicates that the disease interval can be further narrowed with additional markers.