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: 14.63). 02/2007; 17(1):82-7. DOI: 10.1101/gr.5663007
Source: PubMed


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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Available from: Susana Campino, Sep 06, 2015
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    • "Many attempts have been made to connect AEI with a cis-factor [46, 47]. On the basis of human IL13 allelic ratio a cis-factor responsible for the allelic ratio skew has been indicated 250 kb upstream of the gene [19]. "
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    • "Since the overall experimental variability was very low, being little influenced by variations in cell culture or other experimental techniques, these results strongly suggest that the allelic imbalances observed in the six individuals studied here represent a true biological phenomenon. As the allelic imbalance data observed was bidirectional, i.e. showing over-expression of different alleles among the cell lines, the cis-acting variant is likely to be in low LD with the transcript SNP [15,27]. "
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