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 locus of spinocerebellar ataxia type 4 (SCA4). In this study, we extended our research to refine the gene locus of the disease by applying linkage disequilibrium with 20 microsatellite DNA markers. With 9 markers flanked by D16S3031 and D16S3107, we found that the affected individuals in six families had a common haplotype on their disease chromosomes. Furthermore, linkage disequilibrium was demonstrated with 5 informative markers: D16S3019 (P = 0.013), D16S3067 (P = 0.008), D16S3141 (P = 0.011), D16S496 (P = 0.032), and D16S3107 (P = 0.000). These results indicate that the disease could have originated from a common ancestor harboring a mutation within a less than 3-cM region between D16S3043 and D16S3095. The founder alleles were also observed in other patients with ADCA type III unrelated to the six families.
Takashima
M
M
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Japan.
Ishikawa
K
K
Nagaoka
U
U
Shoji
S
S
Mizusawa
H
H
D000368:Aged; D016022:Case-Control Studies; D002524:Cerebellar Ataxia / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005192:Family Health; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008875:Middle Aged; D005810:Multigene Family; D010375:Pedigree; D020161:Physical Chromosome Mapping
D005819:Genetic Markers