Journal Article

Haplotypes in the <i>APOA1-C3-A4-A5</i> gene cluster affect plasma lipids in both humans and baboons

Qian-fei Wang, Xin Liu, Jeff O'Connell, Ze Peng, Ronald M. Krauss, David L. Rainwater, John L. VandeBerg, Edward. M. Rubin, Jan-Fang Cheng and Len A. Pennacchio

in Human Molecular Genetics

Volume 13, issue 10, pages 1049-1056
Published in print May 2004 | ISSN: 0964-6906
Published online March 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddh121
Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

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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.

Journal Article.  6172 words.  Illustrated.

Subjects: Genetics and Genomics

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