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 Huntington's disease chromosomes in the Scottish population.
The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and have found very strong evidence for disequilibrium in this population. For the 131 families where phase was unambiguously determined, 130 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal population distribution where 31% of people have an allele of 185 bp. The evidence for and against a possible founder effect in the Scottish HD population is discussed. We propose the hypothesis that we may have identified a region of the IT15 gene that is critical in Huntington's disease.
Barron
L H
LH
Molecular Genetics Service, University of Edinburgh, Western General Hospital, UK.
Rae
A
A
Holloway
S
S
Brock
D J
DJ
Warner
J P
JP
D000483:Alleles; D001482:Base Composition; D001483:Base Sequence; D002877:Chromosomes, Human; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis; D003710:Demography; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D012606:Scotland
D017931:DNA Primers; D018076:DNA, Complementary; D004247:DNA