A linkage disequilibrium at the candidate gene locus for 16q-linked autosomal dominant cerebellar ataxia type III in Japan

We previously mapped the gene responsible for autosomal dominant cerebellar ataxia (ADCA) type III to a 10.9-cM interval between D16S3089 and D16S515 on chromosome 16q. This region, however, was identical to the candidate loc us of spinocerebellar ataxia type 4 (SCA4). In this study, we extended our research to refine the gene locus of the disease by applying linkage disequ ilibrium with 20 microsatellite DNA markers. With 9 markers flanked by D16S 3031 and D16S3107, we found that the affected individuals in six families h ad a common haplotype on their disease chromosomes. Furthermore, linkage di sequilibrium was demonstrated with 5 informative markers: D16S3019 (P = 0.0 13), D16S3067 (P = 0.008), D16S3141(P = 0.011), D16S496 (P = 0.032), and D1 6S3107 (P = 0.000). These results indicate that the disease could have orig inated from a common ancestor harboring a mutation within a less than 3-cM region between D16S3043 and D16S3095. The founder alleles were also observe d in other patients with ADCA type III unrelated to the six families.