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Identification of candidate genes regulating HDL cholesterol using a chromosomal region expression array
Laura A Cox1, Shifra Birnbaum, John L VandeBerg
1Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA. lcox@darwin.sfbr.org
Genome Research
|November 8, 2002
Summary
Researchers identified candidate genes for high-density lipoprotein cholesterol (HDL-C) regulation in baboons using a novel strategy. This approach integrates comparative mapping, bioinformatics, and expression arrays for complex trait gene discovery.
Area of Science:
- Genetics
- Bioinformatics
- Comparative Genomics
Background:
- Atherosclerosis risk factors are influenced by quantitative trait loci (QTLs).
- A specific QTL on chromosome 18q in baboons affects high-density lipoprotein cholesterol (HDL-C) levels.
- Previous candidate gene analysis in this region was limited.
Purpose of the Study:
- To develop and validate a novel strategy for identifying candidate genes underlying QTLs.
- To pinpoint genes regulating HDL-C phenotypes in baboons.
- To demonstrate the strategy's applicability in complex trait gene discovery.
Main Methods:
- Integrated comparative mapping, bioinformatics, and expression arrays.
- Developed a chromosomal region expression array (CREA) using baboon and human genome data.
- Screened CREA with liver cDNA from baboon sib-pairs with contrasting HDL-C phenotypes on different diets.
Main Results:
- Identified a list of candidate genes for the HDL-C regulating QTL on chromosome 18q.
- Expression profiles combined with phenotypic data prioritized candidate genes.
- Demonstrated the effectiveness of the integrated strategy.
Conclusions:
- The novel strategy successfully identifies candidate genes for QTLs in complex traits.
- This approach is valuable for model organisms and potentially human studies.
- Highlights the power of integrating multiple data types for gene discovery.