Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene

Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene

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Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene

dc.contributor.author	Yu, Fuli
dc.contributor.author	Hardenbol, Paul
dc.contributor.author	Fu, Qing
dc.contributor.author	Fry, Ben
dc.contributor.author	Lu, Xiuhua
dc.contributor.author	Ghose, Sy
dc.contributor.author	Vega, Richard
dc.contributor.author	Perez, Ag
dc.contributor.author	Pasternak, Shiran
dc.contributor.author	Leal, Suzanne M.
dc.contributor.author	Willis, Thomas D.
dc.contributor.author	Belmont, John
dc.contributor.author	Gibbs, Richard A.
dc.contributor.author	Sabeti, Pardis Christine
dc.contributor.author	Nelson, David L.
dc.date.accessioned	2010-10-25T14:54:46Z
dc.date.issued	2005
dc.identifier.citation	Yu, Fuli, Pardis Christine Sabeti, Paul Hardenbol, Qing Fu, Ben Fry, Xiuhua Lu, Sy Ghose, et al. 2005. Positive selection of a pre-expansion CAG repeat of the human SCA2 gene. PLoS Genetics 1(3): e41.	en_US
dc.identifier.issn	1553-7390	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:4506285
dc.description.abstract	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.	en_US
dc.description.sponsorship	Organismic and Evolutionary Biology	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi:10.1371/journal.pgen.0010041	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1239938/	en_US
dash.license	LAA
dc.title	Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS Genetics	en_US
dash.depositing.author	Sabeti, Pardis Christine
dc.date.available	2010-10-25T14:54:46Z