Linked Life Data

16799961

Source:http://linkedlifedata.com/resource/pubmed/id/16799961

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-10-30
pubmed:abstractText
Inter-individual variation in quantitative traits as well as in disease susceptibility may be due to differences in the level and spatio-temporal pattern of gene expression. An evolutionary model of genetic variation in cis-regulatory regions may help identify loci of interest for the study of the genetic basis of complex diseases such as atherosclerotic cardiovascular disease (ASCVD). We studied the molecular evolution of 87 candidate genes for ASCVD to detect signatures of selection in 5' flanking regions. Resequenced data for these genes were available in 24 African-Americans, 23 European-Americans, and 1 chimpanzee (Pan troglodytes). Statistical tests of evolutionary neutrality (Tajima's D and Fay and Wu's H) were performed using coalescent simulations under a standard neutral model and a population structure model to differentiate selection from human demographic history. Evidence suggestive of selection was present in 5' flanking regions of 15 genes. A modified McDonald-Kreitman test was used to compare the ratio of putative functional and non-functional sites between and within species in 5' flanking regions. A significant excess or deficit of fixed changes over polymorphisms was noted in 16 genes. Of the 26 genes showing deviation from evolutionary neutrality based on the above two tests, 13 genes showed an unusual haplotype pattern in 5' flanking regions, providing supportive evidence of selection. These results indicate that selection may play a role in establishing variation in 5' flanking regions of a subset of candidate genes for ASCVD and motivate further studies of these loci in determining inter-individual susceptibility to ASCVD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0741-0395
pubmed:author
pubmed:copyrightInfo
(c) 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
557-69
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Molecular evolution of 5' flanking regions of 87 candidate genes for atherosclerotic cardiovascular disease.
pubmed:affiliation
Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural