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Use of the G8 probe in predicting risk of Huntington disease.

Discovery of the linkage between the G8 probe and the gene for Huntington disease (HD) in families of varying ethnic origin, age-of-onset characteristics, and neurological symptomatology, makes it possible to use the G8 marker for presymptomatic testing of at-risk individuals. Risk estimates for such situations were calculated, using the program LIPED, with different G8 haplotype frequencies, different age-of-onset distributions, and varying amounts of family information. In the presence of untyped relatives, the resulting risk estimates can be extremely sensitive to G8 haplotype frequencies, and the higher risk was seen in individuals carrying rare haplotypes. Including haplotype information on distant relatives can also lead to greater variation in risk estimates. Changing the age-of-onset distribution had only a minimal effect on estimated risks; the largest effect was seen when informative at-risk sibs of the consultand were in their forties.