%0 Journal Article %J Nat Genet %D 2000 %T Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. %A Matsuura, T %A Yamagata, T %A Burgess, D L %A Rasmussen, A %A Grewal, R P %A Watase, K %A Khajavi, M %A McCall, A E %A Davis, C F %A Zu, L %A Achari, M %A Pulst, S M %A Alonso, E %A Noebels, J L %A Nelson, D L %A Zoghbi, H Y %A Ashizawa, T %K Animals %K Asian People %K Brain %K Chromosome Mapping %K Chromosomes, Human, Pair 22 %K DNA %K Epilepsy %K Female %K Humans %K Male %K Mexican Americans %K Mice %K Mice, Inbred C57BL %K Molecular Sequence Data %K Pedigree %K Polymorphism, Genetic %K Repetitive Sequences, Nucleic Acid %K Spinocerebellar Ataxias %K United States %K White People %X

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

%B Nat Genet %V 26 %P 191-4 %8 2000 Oct %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/11017075?dopt=Abstract %R 10.1038/79911 %0 Journal Article %J Genome Res %D 1999 %T Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication. %A Burgess, D L %A Davis, C F %A Gefrides, L A %A Noebels, J L %K Amino Acid Sequence %K Calcium Channels %K Chromosomes, Human, Pair 16 %K Chromosomes, Human, Pair 17 %K Evolution, Molecular %K Expressed Sequence Tags %K Gene Duplication %K Genetic Variation %K Humans %K Molecular Sequence Data %K Multigene Family %K Peptides %K Phylogeny %K Physical Chromosome Mapping %K Sequence Alignment %X

Gene duplication is believed to be an important evolutionary mechanism for generating functional diversity within genomes. The accumulated products of ancient duplication events can be readily observed among the genes encoding voltage-dependent Ca(2+) ion channels. Ten paralogous genes have been identified that encode isoforms of the alpha(1) subunit, four that encode beta subunits, and three that encode alpha(2)delta subunits. Until recently, only a single gene encoding a muscle-specific isoform of the Ca(2+) channel gamma subunit (CACNG1) was known. Expression of a distantly related gene in the brain was subsequently demonstrated upon isolation of the Cacng2 gene, which is mutated in the mouse neurological mutant stargazer (stg). In this study, we sought to identify additional genes that encoded gamma subunits. Because gene duplication often generates paralogs that remain in close syntenic proximity (tandem duplication) or are copied onto related daughter chromosomes (chromosome or whole-genome duplication), we hypothesized that the known positions of CACNG1 and CACNG2 could be used to predict the likely locations of additional gamma subunit genes. Low-stringency genomic sequence analysis of targeted regions led to the identification of three novel Ca(2+) channel gamma subunit genes, CACNG3, CACNG4, and CACNG5, on chromosomes 16 and 17. These results demonstrate the value of genome evolution models for the identification of distantly related members of gene families.

%B Genome Res %V 9 %P 1204-13 %8 1999 Dec %G eng %N 12 %1 https://www.ncbi.nlm.nih.gov/pubmed/10613843?dopt=Abstract %R 10.1101/gr.9.12.1204