GENETIC-MAPPING OF THE SPINOCEREBELLAR ATAXIA TYPE-2 GENE ON HUMAN-CHROMOSOME-12

The dominant spinocerebellar ataxias are a genetically heterogeneous g roup of diseases leading to premature death of neurons in the cerebell um and other parts of the nervous system. The mutation causing SCA1 is on human chromosome (CHR) 6p and SCA3 is on CHR 14q. To refine the lo cation of the SCA2 gene on CHR 12q, we performed genetic linkage analy sis between the SCAB locus and nine loci (D12S58, D12S78, D12S317, D12 S330, D12S353, D12S84, D12S105, D12S79, and PLA2) in three SCA2 famili es. The highest pairwise lod scores were obtained between SCA2 and D12 S84/D12S105 and D12S79, We determined the best order and genetic dista nces among these loci in ten multigenerational families by multipoint linkage analysis and established the following order: 12S317-D12S330/D 12S353-D12S84/D12S105-D12S79-PLA2. Using this genetic map, multipoint linkage analysis placed SCA2 between D12S84/D12S105 and D12S79.