Date of Award
Doctor of Philosophy
Max F. Rothschild
This dissertation reports on studies of the pig genome as a model to identify obesity-related genes. Pig geneticists have sought to reduce fat in their pigs through selective breeding, and these efforts ultimately improved the genetic potential in the pig for higher growth, increased efficiency of conversion of food into body weight and lower fat percentage in the body. Therefore, the genetic information obtained from lean growth in the pig can be applicable to studying the genetic basis of human obesity and other related health problems. A three-generation pig family and several commercial lines of pigs were used to study porcine obesity quantitative trait loci (QTL), and genes for the relevant phenotypes to human growth and obesity. Several candidate genes were successfully localized within the porcine obesity QTL and the comparative locations of these QTL and candidate genes were discussed in the present study. Furthermore, the relationships between DNA polymorphisms of the candidate genes and a variety of phenotypic measurements were studied. These results provide important insights into the role of biological candidate genes in obesity and other related metabolic disorders. The functional properties of a naturally occurring variant of porcine melanocortin-4 receptor ( MC4R) gene were comparatively characterized to determine functionally important structural amino acid residues in the MC4R sequences. This research also discovered a unique imprinting phenotype in the porcine delta-like 1 (DLK1) locus. The imprinting phenotype was first found in the callipyge locus in sheep and called 'polar overdominance'. However, further identification has been elusive in other mammals. The results of the porcine DLK1 locus indicate that the inheritance mechanism of polar overdominance for callipyge sheep might have a conserved role for growth and fat deposition phenotypes in pigs and the DLK1 gene might be an important player for the imprinting phenotypes. This dissertation demonstrates the useful value of comparative genomic study of pigs as a model organism to investigate genes of interest for human health, especially obesity, and the results also have implications for the development of improved genetic selection programs for the targeted traits of interest in pig production systems.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Kim, Kwan-Suk, "Comparative genome analysis in the pig as a model for understanding human obesity " (2003). Retrospective Theses and Dissertations. 3044.