Unraveling the Genomics of Obesity and Related Metabolic Diseases Using a Pig Model

Animal models of high comparative value are essential for unraveling the complex genetic architecture behind obesity.  We have established a 3-generation intercross pedigree by crossing Göttingen minipigs (prone to obesity) with production pigs (selected for leanness) to produce 454 F2’s.  A total of 36 obesity related traits have been recorded for all pigs (e.g. DEXA, slaughter values, growth, conformation traits), and in addition 25 metabolic parameters (e.g. triglycerides, cholesterol, phospholipids, fructosamine, creatinine) have been measured.  A biobank of tissues has been established comprising 24 different tissues from all animals. The entire pedigree has been genotyped using the Illumina Porcine 60k SNP Beadchip.

GWAS using the EIGENSTRAT method and LDLA based on LDMIP algorithms have been performed on the 36 obesity phenotypes. A total of 443 QTL representing more than one trait (53 with SNPs confirmed at conservative Bonferroni level) and 645 QTL representing single traits (36 with SNPs confirmed at conservative Bonferroni level) have been identified. Also, a global analysis of epigenetic differences has been performed in adipocytes to identify differentially methylated regions between obese and lean animals. To evaluate the accordance between our results and results of human obesity studies we investigated the coincidence of QTL identified in our pig population with genes found to be associated with obesity in human studies. Although the results obtained until now are very preliminary they demonstrate that we have established an animal model of high comparative value.