Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

被引：16

作者：

Pant, Sameer D. ^{[1
]}

Karlskov-Mortensen, Peter ^{[1
]}

Jacobsen, Mette J. ^{[1
]}

Cirera, Susanna ^{[1
]}

Kogelman, Lisette J. A. ^{[1
]}

Bruun, Camilla S. ^{[1
]}

Mark, Thomas ^{[1
]}

Jorgensen, Claus B. ^{[1
]}

Grarup, Niels ^{[2
]}

Appel, Emil V. R. ^{[2
]}

Galjatovic, Ehm A. A. ^{[2
]}

Hansen, Torben ^{[2
]}

Pedersen, Oluf ^{[2
]}

Guerin, Maryse ^{[3
,4
,5
]}

Huby, Thierry ^{[3
,4
,5
]}

Lesnik, Philipppe ^{[3
,4
,5
]}

Meuwissen, Theo H. E. ^{[6
]}

Kadarmideen, Haja N. ^{[1
]}

Fredholm, Merete ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet Clin & Anim Sci, Copenhagen, Denmark

[2] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[3] Integrat Biol Atherosclerosis Team, INSERM, UMR S 1166, F-75013 Paris, France

[4] Univ Paris 06, Sorbonne Univ, Integrat Biol Atherosclerosis Team, UMR S 1166, F-75013 Paris, France

[5] Hop La Pitie Salpetriere, Inst Cardiometab & Nutr ICAN, Paris, France

[6] Norwegian Univ Life Sci, Inst Anim & Agr Sci, As, Norway

来源：

PLOS ONE | 2015年 / 10卷 / 09期

基金：

欧盟第七框架计划;

关键词：

GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; LINKAGE DISEQUILIBRIUM; ADIPOSE-TISSUE; CHOLESTEROL; GENE; RECEPTOR; ALPHA; LOCI; EXPRESSION;

D O I：

10.1371/journal.pone.0137356

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 +/- 48 days), including body composition determined at about two months of age (63 +/- 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity-and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity.

引用

页数：22

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