title: Association analyses between type 2 diabetes genes and obesity traits in pigs.
abstract: To investigate candidate genes involved in human type 2 diabetes (T2D) for obesity-related phenotypes in pigs. Statistical association analyses of genes with fat deposition were realized in a pig reference family constructed by two breeds, Berkshire and Yorkshire. Extensive sequencing was then attempted to discover the causative polymorphism. Genes implied in human T2D development, TCF7L2, WFS1, FTO, SLC30A8, and GCKR, were mapped on Sus scrofa chromosomes 14, 8, 6, 4, and 3, respectively. Only TCF7L2 was significantly associated with five fat traits in pigs. Further investigation demonstrated that one haplotype (HapB), but not the HapA (homologous to the region for human T2D susceptibility where single-nucleotide polymorphism (SNP) rs7903146 is located), is significantly associated with the fat-related traits. In HapB, two SNPs in TCF7L2 exon 8 and intron 10 are significantly associated with five fat traits, and may be in linkage disequilibrium with the causative variant with additive effects on all four backfat traits, and the total lipid percentage. Pigs of genotype TT for the SNP in exon 8 have only one transcript isoform (the one without exon 4), and lower backfat depth. Candidate gene analyses could provide novel ideas about how these genes function in T2D susceptibility in human, and support that the pig can be a suitable model for human obesity and T2D research. Further replication of this research in other pig populations should be considered, so that the possibility of utilizing these genetic markers in pig breeding or in animal model research can be explored.
authors.affiliation: Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, Iowa, USA.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Du
authors.forename: Bin
authors.initials: B
authors.lastname: Fan
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Randy
authors.initials: R
authors.lastname: Amoako
authors.forename: Max F
authors.initials: MF
authors.lastname: Rothschild
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D013552:Swine / Q000235:genetics*; D013553:Swine Diseases / Q000235:genetics*; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D000075703:Zinc Transporter 8
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D027682:Cation Transport Proteins; C485100:GCKR protein, human; D008565:Membrane Proteins; D011506:Proteins; C492522:SLC30A8 protein, human; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D000075703:Zinc Transporter 8; C114987:wolframin protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human