Positive selection of a pre-expansion CAG repeat of the human SCA2 gene

A region of approximately one megabase of human Chromosome 12 shows extensive linkage disequilibrium in Utah residents with ancestry from northern and western Europe. This strikingly large linkage disequilibrium block was analyzed with statistical and experimental methods to determine whether natura...

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Bibliographic Details
Published in:PLoS genetics 2005-09, Vol.1 (3), p.e41-e41
Main Authors: Yu, Fuli, Sabeti, Pardis C, Hardenbol, Paul, Fu, Qing, Fry, Ben, Lu, Xiuhua, Ghose, Sy, Vega, Richard, Perez, Ag, Pasternak, Shiran, Leal, Suzanne M, Willis, Thomas D, Nelson, David L, Belmont, John, Gibbs, Richard A
Format: Article
Language:English
Subjects:
Ataxia
Ataxins
Base Sequence
Bioinformatics - Computational Biology
Chromosome Mapping
Chromosomes, Human, Pair 12
Disease
Europe - ethnology
European Continental Ancestry Group - genetics
Evolution
Exons
Expansion
Frequency distribution
Gene Frequency
Genealogy
Genes
Genetics
Genetics/Functional Genomics
Genetics/Genetics of Disease
Genetics/Genomics
Genetics/Population Genetics
Genomes
Haplotypes
Homo (Human)
Humans
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Polymorphism, Single Nucleotide
Selection, Genetic
Spinocerebellar Degenerations - genetics
Trinucleotide Repeats
Utah
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Summary:A region of approximately one megabase of human Chromosome 12 shows extensive linkage disequilibrium in Utah residents with ancestry from northern and western Europe. This strikingly large linkage disequilibrium block was analyzed with statistical and experimental methods to determine whether natural selection could be implicated in shaping the current genome structure. Extended Haplotype Homozygosity and Relative Extended Haplotype Homozygosity analyses on this region mapped a core region of the strongest conserved haplotype to the exon 1 of the Spinocerebellar ataxia type 2 gene (SCA2). Direct DNA sequencing of this region of the SCA2 gene revealed a significant association between a pre-expanded allele [(CAG)8CAA(CAG)4CAA(CAG)8] of CAG repeats within exon 1 and the selected haplotype of the SCA2 gene. A significantly negative Tajima's D value (-2.20, p < 0.01) on this site consistently suggested selection on the CAG repeat. This region was also investigated in the three other populations, none of which showed signs of selection. These results suggest that a recent positive selection of the pre-expansion SCA2 CAG repeat has occurred in Utah residents with European ancestry.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.0010041