Human Molecular Genetics Advance Access originally published online on March 25, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 10 1049-1056
DOI: 10.1093/hmg/ddh121
Human Molecular Genetics, Vol. 13, No. 10 © Oxford University Press 2004; all rights reserved
Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons
1Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA, 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA, 4Children's Hospital Oakland Research Institute, Oakland, CA, USA, 5Department of Genetics and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, USA and 6USA Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, USA
Received January 16, 2004; Accepted March 15, 2004
Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well-established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well-characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL-cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human quantitative trait loci genes in a highly controlled non-human primate model.
* To whom correspondence should be addressed at: Department of Genome Sciences, MS 84-171, One Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Tel: +1 5104867498; Fax: +1 5104864229; Email: lapennacchio{at}lbl.gov
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