GEOGRAPHICAL-DISTRIBUTION OF HAPLOTYPES IN SWEDISH FAMILIES WITH HUNTINGTONS-DISEASE

This study was planned to determine the number of origins of the mutat ion underlying Huntington's disease (HD) in Sweden. Haplotypes were co nstructed for 23 different HD families, using six different polymorphi sms [(CCG)(n), GT70, 674, BS1, E2 and 4.2], including two within the g ene. In addition, extensive genealogical investigations were performed , and the geographical origin of the haplotypes was studied. Ten diffe rent haplotypes were observed suggesting multiple origins for the HD m utation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least th ree origins for the HD mutation in Sweden. One of these haplotypes (7/ A) accounts for 89% of the families, suggesting that the majority of t he Swedish HD families are related through a single HD mutation of anc ient origin. Furthermore, three of the families that were previously c onsidered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.