Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals

Simona D Frederiksen; Peter Karlskov-Mortensen; Sameer D Pant; Maryse Guerin; Philippe Lesnik; Claus B Jørgensen; Susanna Cirera; Camilla S Bruun; Thomas Mark; Merete Fredholm

doi:10.1371/journal.pone.0178828

Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals

PLoS One. 2017 Jun 1;12(6):e0178828. doi: 10.1371/journal.pone.0178828. eCollection 2017.

Affiliations

¹ Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, Australia.
³ INSERM UMR_S1166, Integrative Biology of Atherosclerosis Team, Paris, France.
⁴ Novo Nordisk, Scandinavia AB, Region Denmark, Maaloev, Denmark.

Abstract

We have established a pig resource population specifically designed to elucidate the genetics involved in development of obesity and obesity related co-morbidities by crossing the obesity prone Göttingen Minipig breed with two lean production pig breeds. In this study we have performed genome wide association (GWA) to identify loci with effect on blood lipid levels. The most significantly associated single nucleotide polymorphisms (SNPs) were used for linkage disequilibrium (LD) and haplotype analyses. Three separate haploblocks which influence the ratio between high density lipoprotein cholesterol and total cholesterol (HDL-C/CT), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels respectively were identified on Sus Scrofa chromosome 3 (SSC3). Large additive genetic effects were found for the HDL-C/CT and LDL-C haplotypes. Haplotypes segregating from Göttingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Göttingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

MeSH terms

Animals
Chromosome Mapping*
Genome-Wide Association Study
Haplotypes*
Obesity / genetics*
Obesity / metabolism
Polymorphism, Single Nucleotide
Swine / genetics*
Swine, Miniature

Grants and funding

The authors acknowledge the financial support by The Danish Independent Research Council Grant Number DFF 1335-00127. The coauthor Thomas Mark is presently employed by Novo Nordisk, however, at the time when the research generating the data presented in this manuscript was conducted, he was employed as Associate Professor at University of Copenhagen. Novo Nordisk has not contributed any funding to the research presented in this manuscript. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.