The overall objective of this research is to determine the genetic linkage relationships of autosomal dominantly inherited spinocerebellar ataxia. We are currently studying several kindreds, one particularly large kindred having been shown to be due to a gene at a locus on human chromosome 6 in close linkage with the HLA histocompatibility complex. In addition to HLA, Glyoxalase 1 and Pepsinogen 5, both possibly within measurable linkage distance on human chromosome 6, are currently being studied. Preliminary evidence shows linkage for Glyoxalase 1. Three smaller kindreds are also under investigation. Linkage has not yet been demonstrated for these three additional families. Additional studies should yield information of value both for mapping chromosome 6 in man and for establishing linkage relationships of a disorder roughly equivalent in social impact to Huntington's chorea. Thus more precise genetic counseling can be provided in this large kindred and possibly other families.