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Obesity/diabetes‐associated gene screening in rhesus monkeys
Author(s) -
Hansen Barbara C,
Shamekh Rania,
Budagov Temuri,
Linden Ellen,
Pessin Jeffrey,
Atzmon Gil
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.859.4
Subject(s) - single nucleotide polymorphism , biology , candidate gene , genome wide association study , genetics , genotyping , snp , snp genotyping , type 2 diabetes , obesity , genotype , gene , type 2 diabetes mellitus , genetic association , diabetes mellitus , endocrinology
We examined the genetic basis of naturally occurring obesity and type 2 diabetes mellitus (T2DM), in rhesus monkeys (Macaca mulatta, N=81) longitudinally studied under constant environmental and dietary conditions and fully phenotyped. An initial genome wide association study (GWAS) was conducted using Affymetrix 6.0 gene chip arrays. The successful call rate on all chip assays averaged 91.9% with high heterozygosity (60%), demonstrating the applicability of genotyping the monkey using the human platform. Principal component analysis classified the groups accurately. Five SNPs passed the test for multiple comparison correction and were of complete homology between the rhesus and human. We resequenced 4 of those SNPs, revealing one variant that clearly defined the obese/T2DM animals. Nine out of 18 SNPs selected on the basis of candidate human genome sequence polymorphisms associated with obesity/T2DM resulted in a measurable genotype. Muscle (vastus lateralis) expression levels of the four candidate genes with the most significant associated SNPs demonstrated differences in expression compared to normal animals. These data demonstrate the successful use of human SNP platforms to identify genetic variants associated with obesity/T2DM in rhesus monkeys. This research was supported by NIH/NIA HHSN263200800022C and NIA NO1AG3 1012 and by the Einstein Diabetes Research Training Center award DK020541.