title: Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons.
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.
authors.affiliation: Genome Sciences Department, Lawrence Berkeley National Laboratory, CA 94720, USA.
authors.forename: Qian-fei
authors.initials: QF
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Jeff
authors.initials: J
authors.lastname: O'Connell
authors.forename: Ze
authors.initials: Z
authors.lastname: Peng
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: John L
authors.initials: JL
authors.lastname: VandeBerg
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Jan-Fang
authors.initials: JF
authors.lastname: Cheng
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
mesh_terms: D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D006239:Haplotypes; D006801:Humans; D008055:Lipids / Q000097:blood*; D005810:Multigene Family / Q000235:genetics*; D010215:Papio / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008076:Cholesterol, HDL; D008055:Lipids; D014280:Triglycerides