Huntington disease in Finland: linkage disequilibrium of chromosome 4 RFLP haplotypes and exclusion of a tight linkage between the disease and D4S43 locus.

The question about heterogeneity of Huntington disease (HD) at the DNA level can be approached by analyzing the RFLP haplotypes formed by several RFLP loci of the diseased chromosome in different populations. In genetically isolated populations such as Finland, it is further possible to use this approach to test the hypothesis of a single mutation enriched in this population demonstrating an exceptionally low prevalence of HD. In this study covering 70% of all diagnosed HD cases in Finland, linkage disequilibrium of RFLP haplotypes of D4S10 and D4S43 loci polymorphisms was found. This phenomenon, not so far reported in any other population, could support the hypothesis of one ancestor HD mutation in the Finnish population. Despite the lower heterozygosity obtained with some RFLP markers, the proportion of individuals receiving informative DNA test results did not significantly differ from that reported in more mixed populations. In one HD family we established a recombination event between HD and the D4S43 locus, an event which can be highly useful in the more precise mapping of the HD gene.