Article

Localization of a long-range cis-regulatory element of IL13 by allelic transcript ratio mapping.

Department of Paediatrics, Oxford University, Oxford OX3 7BN, United Kingdom.
Genome Research (impact factor: 13.61). 02/2007; 17(1):82-7. DOI:10.1101/gr.5663007 pp.82-7
Source: PubMed

ABSTRACT It appears that, for many genes, the two alleles possessed by an individual may produce different amounts of transcript. When such allelic differences in transcription are observed for some individuals but not others, a plausible explanation is genetic variation in the cis-acting elements that regulate the gene in question. Here we describe a novel analytical approach that uses such observations, combined with genotyping data from the HapMap project, to define the genomic location of cis-acting regulatory elements. When applied to the human 5q31 chromosomal region, where complex regulatory mechanisms are known to exist, we demonstrate the sensitivity of this approach by locating a highly significant cis-regulatory element operating on IL13 at long range from a position 250 kb upstream from the gene (P = 2 x 10(-6)). As this method is unaffected by other sources of variation, such as environmental and trans-acting genetic factors, it provides a tractable approach for dissecting the complexities of genetic variation in gene regulation.

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Keywords

allelic differences
 
cis-acting elements
 
cis-acting regulatory elements
 
different amounts
 
dissecting
 
gene regulation
 
genes
 
genetic variation
 
genotyping data
 
HapMap project
 
human 5q31 chromosomal region
 
plausible explanation
 
position 250 kb upstream
 
significant cis-regulatory element
 
trans-acting genetic factors
 
transcript
 
transcription
 
two alleles