A SINGLE ALLELE FROM THE POLYMORPHIC CCG RICH SEQUENCE IMMEDIATELY 3'TO THE UNSTABLE CAG TRINUCLEOTIDE IN THE IT15 CDNA SHOWS ALMOST COMPLETE DISEQUILIBRIUM WITH HUNTINGTONS-DISEASE CHROMOSOMES IN THE SCOTTISH POPULATION

The CCG rich sequence immediately 3' to the CAG repeat that is expande d in Huntington's disease (HD) has recently been shown to be polymorph ic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 1 80 HD families resident in Scotland and have found very strong evidenc e for disequilibrium in this population. For the 131 families where ph ase was unambiguously determined, 130 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observatio n is significantly different to the normal population distribution whe re 31% of people have an allele of 185 bp. The evidence for and agains t a possible founder effect in the Scottish HD population is discussed . We propose the hypothesis that we may have identified a region of th e IT15 gene that is critical in Huntington's disease.