Physical map and haplotype analysis of 16q-linked autosomal dominant cerebellar ataxia (ADCA) type III in Japan.
Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. We previously mapped a gene locus for ADCA with pure cerebellar syndrome (ADCA type III) to a 3-cM region in chromosome 16q, and found a common haplotype among affected individuals. This region was exactly within the locus for another ADCA, spinocerebellar ataxia type 4 (SCA4). To identify the gene causing 16q-linked ADCA type III, we constructed a contig with 38 bacterial artificial chromosome clones between D16S3043 and D16S3095. The size of this contig was estimated to be 4.8 Mb. We found more than 500 nucleotide tandem repeats, including 9 CAG/CTG repeats in this candidate region, although none of the 94 tandem repeats analyzed were expanded in affected individuals. However, we found 11 new polymorphic markers, giving 22 markers spanning the candidate region. By typing these markers on eight Japanese families with ADCA type III, including two new families, we found that a common "founder" haplotype is seen in a more restricted 3.8-Mb region, spanning markers GGAA05 and D16S3095. We present here a newly refined critical interval of 16q-ADCA type III/SCA4. Data of 11 new DNA markers on 16q22.1 would also be useful for other research of genes mapped to this region.
Li
Mingshun
M
Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Ishikawa
Kinya
K
Toru
Shuta
S
Tomimitsu
Hiroyuki
H
Takashima
Minoru
M
Goto
Jun
J
Takiyama
Yoshihisa
Y
Sasaki
Hidenao
H
Imoto
Issei
I
Inazawa
Johji
J
Toda
Tatsushi
T
Kanazawa
Ichiro
I
Mizusawa
Hidehiro
H
D002524:Cerebellar Ataxia / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D002885:Chromosomes, Human, Pair 16; D020451:Contig Mapping; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences
D005819:Genetic Markers