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Cis-acting expression quantitative trait loci in mice.

Sudheer Doss1, Eric E Schadt, Thomas A Drake

  • 1Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Genome Research
|April 20, 2005
PubMed
Summary

This study validates expression quantitative trait loci (eQTL) in mice, confirming over 64% of cis-acting eQTL are true positives. Integrating genetic and gene expression data aids in identifying positional candidates for complex traits.

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Area of Science:

  • Genomics
  • Systems Biology
  • Quantitative Genetics

Background:

  • Genome-wide expression profiles and diabetes traits were analyzed in a mouse cross (C57BL/6J x DBA/2J).
  • Thousands of expression quantitative trait loci (eQTL) with LOD score >4.3 were identified by treating transcript levels as quantitative traits.

Purpose of the Study:

  • To experimentally estimate the fraction of false-positive eQTL under cis-acting regulation.
  • To validate the reliability of identified eQTL using a cis-trans test.

Main Methods:

  • Utilized a classic cis-trans test in (B6 x DBA)F(1) mice to compare relative transcript levels from parental alleles.
  • Analyzed correlation structures between genotypes, gene expression, and phenotypic traits.

Main Results:

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  • At least 64% of cis-acting eQTL with LOD >4.3 were confirmed as true positives.
  • 36% of apparent cis-acting eQTL could not be confirmed as truly cis-acting.
  • >96% of apparent cis-acting eQTL were found in regions without shared SNP haplotypes.

Conclusions:

  • Cis-acting eQTL are a valuable resource for identifying positional candidates in mouse quantitative trait loci (QTL) studies.
  • Integration of genetic and gene expression data offers insights into cis-acting gene regulation and its impact on phenotypic traits.