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Genetic Localization of the Ca 2+ Channel Gene CACNG2 Near SCA10 on Chromosome 22q13
Author(s) -
Burgess Daniel L.,
Matsuura Tohru,
Ashizawa Tetsuo,
Noebels Jeffrey L.
Publication year - 2000
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.2000.tb01500.x
Subject(s) - biology , locus (genetics) , genetics , spinocerebellar ataxia , ataxia , genetic linkage , cerebellar ataxia , microbiology and biotechnology , gene , neuroscience
Summary:Purpose : Voltage‐dependent calcium channel mutations have been associated with spinocerebellar ataxia in humans (SCA6) and with ataxia, progressive cerebellar degeneration, and epilepsy in mice (tottering, lethargic, and stargazer). A novel autosomal dominant spinocerebellar ataxia syndrome with epilepsy (SCA10) was recently mapped to chromosome 22q13. The human ortholog of the mouse stargazer locus, the calcium channel γ subunit gene CACNG2 , also is located in this region. Because the phenotypes of stargazer mice and SCA10 patients were similar, consisting of both cerebellar ataxia and seizures, we hypothesized that CACNG2 was a likely candidate for the SCA10 locus. Methods : Polymerase chain reaction (PCR) based assays were developed for two polymorphic microsatellite markers near CACNG2 . The location of CACNG2 was determined by linkage and haplotype analysis of the genotypes of 22 individuals from a human pedigree segregating SCA10. Results : SCA10 was previously localized distal to marker D22S1177 on chromosome 22q13. We determined that CACNG2 was linked to D22S283 and D22S1177 with the marker order: centromere‐ D22S283‐bcmDLB1 (CACNG2)–D22S1177‐D22S423 ‐telomere. Thus CACNG2 is located proximal to the SCA10 recombinant interval. Conclusions : Here we report the first genetic linkage of CACNG2 on chromosome 22q13 and exclude it as a candidate for SCA10. In addition, our data clarify the relation between the physical and genetic linkage maps of this region and will facilitate isolation of the SCA10 gene.