Haplotypes in the APOA1-C3-A4-A5 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, Len A. Pennacchio

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1049-1056
Number of pages8
JournalHuman Molecular Genetics
Volume13
Issue number10
DOIs
StatePublished - May 15 2004
Externally publishedYes

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Papio
Multigene Family
Haplotypes
Lipids
Primates
HDL Cholesterol
Single Nucleotide Polymorphism
Triglycerides
Phenotype
Apolipoproteins
Quantitative Trait Loci
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Wang, Q. F., Liu, X., O'Connell, J., Peng, Z., Krauss, R. M., Rainwater, D. L., ... Pennacchio, L. A. (2004). Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. Human Molecular Genetics, 13(10), 1049-1056. https://doi.org/10.1093/hmg/ddh121

Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. / Wang, Qian Fei; Liu, Xin; O'Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, john L.; Rubin, Edward M.; Cheng, Jan Fang; Pennacchio, Len A.

In: Human Molecular Genetics, Vol. 13, No. 10, 15.05.2004, p. 1049-1056.

Research output: Contribution to journalArticle

Wang, QF, Liu, X, O'Connell, J, Peng, Z, Krauss, RM, Rainwater, DL, VandeBerg, JL, Rubin, EM, Cheng, JF & Pennacchio, LA 2004, 'Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons', Human Molecular Genetics, vol. 13, no. 10, pp. 1049-1056. https://doi.org/10.1093/hmg/ddh121
Wang QF, Liu X, O'Connell J, Peng Z, Krauss RM, Rainwater DL et al. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. Human Molecular Genetics. 2004 May 15;13(10):1049-1056. https://doi.org/10.1093/hmg/ddh121
Wang, Qian Fei ; Liu, Xin ; O'Connell, Jeff ; Peng, Ze ; Krauss, Ronald M. ; Rainwater, David L. ; VandeBerg, john L. ; Rubin, Edward M. ; Cheng, Jan Fang ; Pennacchio, Len A. / Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. In: Human Molecular Genetics. 2004 ; Vol. 13, No. 10. pp. 1049-1056.
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