Linked Life Data

19506001

Source:http://linkedlifedata.com/resource/pubmed/id/19506001

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-8-14
pubmed:abstractText
Variation in gene expression is an important contributor to phenotypic diversity within and between species. Although this variation often has a genetic component, identification of the genetic variants driving this relationship remains challenging. In particular, measurements of gene expression usually do not reveal whether the genetic basis for any observed variation lies in cis or in trans to the gene, a distinction that has direct relevance to the physical location of the underlying genetic variant, and which may also impact its evolutionary trajectory. Allelic imbalance measurements identify cis-acting genetic effects by assaying the relative contribution of the two alleles of a cis-regulatory region to gene expression within individuals. Identification of patterns that predict commonly imbalanced genes could therefore serve as a useful tool and also shed light on the evolution of cis-regulatory variation itself. Here, we show that sequence motifs, polymorphism levels, and divergence levels around a gene can be used to predict commonly imbalanced genes in a human data set. Reduction of this feature set to four factors revealed that only one factor significantly differentiated between commonly imbalanced and nonimbalanced genes. We demonstrate that these results are consistent between the original data set and a second published data set in humans obtained using different technical and statistical methods. Finally, we show that variation in the single allelic imbalance-associated factor is partially explained by the density of genes in the region of a target gene (allelic imbalance is less probable for genes in gene-dense regions), and, to a lesser extent, the evenness of expression of the gene across tissues and the magnitude of negative selection on putative regulatory regions of the gene. These results suggest that the genomic distribution of functional cis-regulatory variants in the human genome is nonrandom, perhaps due to local differences in evolutionary constraint.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1537-1719
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2047-59
pubmed:dateRevised
2010-9-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Genomic features that predict allelic imbalance in humans suggest patterns of constraint on gene expression variation.
pubmed:affiliation
Department of Biology, Duke University, Durham, NC, USA. jt5@duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural