Identification of candidate genes regulating HDL cholesterol using a chromosomal region expression array

Laura A. Cox, Shifra Birnbaum, John L. VandeBerg

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

To identify candidate genes encoding QTLs in baboons, we have developed a novel strategy that integrates comparative mapping, bioinformatics, and expression arrays. A genome-wide scan, performed previously on pedigreed baboons to localize QTLs for phenotypes that are known risk factors for atherosclerosis, revealed a QTL on chromosome 18q that influences high-density lipoprotein cholesterol (HDL-C) phenotypes. After ruling out the only two biologically relevant positional candidate genes in this chromosomal region, we combined information from baboon pedigrees and HDL-C phenotypes with a baboon microsatellite marker map, human microsatellite marker maps, and human genome maps to develop a chromosomal region expression array (CREA). The CREA was screened with heterologous liver cDNA from sib-pairs of contrasting HDL-C phenotypes on two different diets, and genes were prioritized for further study by expression profiles. Analysis of gene expression in this restricted chromosomal region, combined with HDL-C phenotypic information, yielded a list of candidate genes for the QTL regulating HDL-C in baboons. Our data demonstrate the power of this strategy for identifying candidate genes encoding QTLs for multigenic traits. This strategy is applicable to many species that serve as models for human diseases and can even be used with human subjects.

Original languageEnglish (US)
Pages (from-to)1693-1702
Number of pages10
JournalGenome Research
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Papio
Genetic Association Studies
HDL Cholesterol
Phenotype
Genes
Microsatellite Repeats
Human Genome
Pedigree
Computational Biology
Atherosclerosis
Complementary DNA
Chromosomes
Genome
Diet
Gene Expression
Liver

ASJC Scopus subject areas

  • Genetics

Cite this

Identification of candidate genes regulating HDL cholesterol using a chromosomal region expression array. / Cox, Laura A.; Birnbaum, Shifra; VandeBerg, John L.

In: Genome Research, Vol. 12, No. 11, 01.11.2002, p. 1693-1702.

Research output: Contribution to journalArticle

Cox, Laura A. ; Birnbaum, Shifra ; VandeBerg, John L. / Identification of candidate genes regulating HDL cholesterol using a chromosomal region expression array. In: Genome Research. 2002 ; Vol. 12, No. 11. pp. 1693-1702.
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