Linked Life Data

15906097

Source:http://linkedlifedata.com/resource/pubmed/id/15906097

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2005-6-20
pubmed:abstractText
It has been proposed that variation in calpain 10 (CAPN10) contributes to the risk of type 2 diabetes (T2D). A previous survey of CAPN10 in ethnically diverse populations revealed an intronic region with a significant excess of polymorphism levels relative to inter-species sequence divergence, suggesting that this region was the target of long-standing balancing selection. Based on the thrifty genotype hypothesis, variation that increases risk to T2D in contemporary humans at one time conferred a survival advantage in ancestral populations. Thus, the signature of positive natural selection in a T2D candidate gene could identify a genomic region containing variation that influences disease susceptibility. Here, we investigate this hypothesis by re-sequencing the CAPN10 region with unusual polymorphism levels in T2D cases and controls (n=91) from a Mexican American (MA) population, and by using networks to infer the evolutionary relationships between the major haplotypes. Haplotype tag SNPs (htSNPs) were then selected in each population sample and in MA cases and controls. By placing the htSNPs on the haplotype network, we investigate how cross-population differences in CAPN10 genetic architecture may affect the detection of the disease association. Interestingly, despite the small scale of our case-control study, we observe a nearly significant signal of association between T2D and variation in the putative target of balancing selection. Finally, we use phylogenetic shadowing across 10 primate species to search for conserved non-coding elements that may affect the expression and function of CAPN10. These elements are postulated to be the targets of long-standing balancing selection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0340-6717
pubmed:author
pubmed:issnType
Print
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
258-66
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Haplotype structure and phylogenetic shadowing of a hypervariable region in the CAPN10 gene.
pubmed:affiliation
Department of Human Genetics, University of Chicago, 507F CLSC, 920 E. 58th Street, Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural