title: Linkage disequilibrium and modification of risk for Huntington disease.
abstract: The major limitation in performing predictive testing for Huntington disease (HD) is the unavailability of DNA from crucial family members. In our program approximately 20% (36/183) of persons have been excluded from predictive testing because of this reason. The major aim of this study was to examine whether data derived from linkage disequilibrium could modify risk analysis for persons at risk for HD. As a first step, we assessed whether the previously reported linkage disequilibrium between alleles recognized by probe pBS674E-D at locus D4S95 remained significant in a much larger data set. A total of 1,150 chromosomes from 622 individuals--200 affected and 422 unaffected--from 118 families were assessed. Significant haplotype association was detected with AccI and MboI RFLPs at the locus D4S95, with all the families (P = .00003), as well as for a subset from the United Kingdom (P = .0037). Data derived from linkage disequilibrium studies using D4S95 modifies the risk for HD, especially in persons of U.K. descent. Utilization of this approach for risk modification of HD awaits both validation of these data and additional information concerning ethnic-specific alleles at the D4S95 locus.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Adam
authors.forename: J
authors.initials: J
authors.lastname: Theilmann
authors.forename: K
authors.initials: K
authors.lastname: Buetow
authors.forename: A
authors.initials: A
authors.lastname: Hedrick
authors.forename: C
authors.initials: C
authors.lastname: Collins
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: M
authors.initials: M
authors.lastname: Huggins
authors.forename: M
authors.initials: M
authors.lastname: Hayden
mesh_terms: D000328:Adult; D000483:Alleles; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015252:Deoxyribonucleases, Type II Site-Specific; C024405:GATC-specific type II deoxyribonucleases; C067488:GTMKAC-specific type II deoxyribonucleases