Huntington disease: No evidence for locus heterogeneity

Abstract

A total of 63 families with Huntington disease (HD) were examined for linkage between HD and G8 (D4S10). The families included 57 Caucasian, four Black American, and two Japanese. The combined maximum lod score was 87.69 at theta = 0.04 (99% confidence interval 0.018-0.071). The maximum frequency of recombination was 0.03 in males and 0.05 in females. Fifty-seven families gave positive lod scores; five small families gave mildly negative lod scores. The maximum likelihood estimate of alpha, the proportion of linked loci, was 1.0 with a lower 99% confidence interval of 0.88. These data suggest that there is only one HD locus, although a second rare locus cannot be ruled out.

The evaluation of the `stages of change' model for use in counselling client's undergoing predictive testing for Huntington's disease

“…1983 ). This discovery allowed some individuals at risk of Huntington's disease to discover whether they carried the gene for the disorder with varying degrees of certainty ( Conneally et al . 1989 ).…”

“…Huntington's disease was the ®rst condition in which linked deoxyribonucleic acid (DNA) markers were discovered (Gusella et al 1983). This discovery allowed some individuals at risk of Huntington's disease to discover whether they carried the gene for the disorder with varying degrees of certainty (Conneally et al 1989). More recently, the isolation of the Huntington's disease gene (The Huntington's Disease Collaborative Research Group 1993) has provided a de®nitive test for any person at risk of the disorder.…”

Genetic linkage between Huntington disease and the D4S10 locus in South African families: further evidence against non-allelic heterogeneity

“…Initially, no recombination events between G8 and HD were reported but several have now been detected, placing G8 approximately 4 centimorgans (cM) from the HD gene locus. By 1989, a total of 63 families worldwide had been examined for linkage with G8 and a combined lod score of 87.69 at 0 = 0.04 (95% confidence interval 0.018-0.071) had been calculated, indicating that there is not evidence for non-allelic heterogeneity at the disease locus (Conneally et al 1989). Two recent publications describe further linkage studies confirming genetic linkage of HD in Italy, and reporting allele frequencies at the marker loci in different Western European countries (Fontali et al 1990), and in Japan, where the results provide evidence that the Japanese HD gene is identical with the Western European gene (Kanazawa et al 1990).…”

Genetic analysis of Huntington disease in Italy

“…The populations so far tested include, aside from the large Venezuelan pedigrees [Gusella et al, 19831, North Americans and northern Europeans [Conneally et al, 1989;Skraastad et al, 19891. No reports have demonstrated heterogeneity for this disease [Conneally et al, 19891, and the linkage between the available markers and the disease was always confirmed, except for among a Finnish population [Ikonen et al, 19901. No data on linkage analysis or heterogeneity in Italy have been described.…”