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

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

Agricultural, Environmental and Veterinary Sciences

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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 Gottingen 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 Gottingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Gottingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

Original language	English
Article number	e0178828
Pages (from-to)	1-13
Number of pages	13
Journal	PLoS One
Volume	12
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0178828
Publication status	Published - Jun 2017

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title = "Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals",

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 Gottingen 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 Gottingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Gottingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.",

keywords = "Haplotypes, Lipids, Obesity, Genome-wide association studies, Pig models, Cholesterol, Phenotypes, Quantitative trait loci",

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AU - Frederiksen, Simona D.

AU - Karlskov-Mortensen, Peter

AU - Pant, Sameer D.

AU - Guerin, Maryse

AU - Lesnik, Philippe

AU - Jørgensen, Claus B.

AU - Cirera, Susanna

AU - Bruun, Camilla S.

AU - Mark, Thomas

AU - Fredholm, Merete

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N2 - 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 Gottingen 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 Gottingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Gottingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

AB - 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 Gottingen 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 Gottingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Gottingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

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KW - Obesity

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KW - Pig models

KW - Cholesterol

KW - Phenotypes

KW - Quantitative trait loci

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

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