Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans
| العنوان: | Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans |
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| المؤلفون: | Merete Fredholm, Claus Jørgensen, Susanna Cirera, Emil V. R. Appel, Niels Grarup, Torben Hansen, Thierry Huby, Ehm A.A. Galjatovic, Mette Juul Jacobsen, Oluf Pedersen, Camilla S. Bruun, Philipppe Lesnik, Maryse Guerin, Sameer D. Pant, Thomas Mark, Peter Karlskov-Mortensen, Haja N. Kadarmideen, Lisette J. A. Kogelman, Theodorus Meuwissen |
| المساهمون: | HAL-UPMC, Gestionnaire, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), School of Animal and Veterinary Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institute of Animal and Agricultural Sciences, Norwegian University of Life Sciences (NMBU), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| المصدر: | PLoS ONE PLoS ONE, 2015, 10 (9), pp.e0137356. ⟨10.1371/journal.pone.0137356⟩ PLoS ONE, Public Library of Science, 2015, 10 (9), pp.e0137356. ⟨10.1371/journal.pone.0137356⟩ Pant, S D, Karlskov-Mortensen, P, Jacobsen, M J, Cirera Salicio, S, Kogelman, L, Bruun, C V S, Mark, T, Jørgensen, C B, Grarup, N, Appel, E V R, Galjatovic, E A A, Hansen, T, Pedersen, O B, Guerin, M, Huby, T, Lesnik, P, Meuwissen, T H E, Kadarmideen, H & Fredholm, M 2015, ' Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans ', PLOS ONE, vol. 10, no. 9, e0137356 . https://doi.org/10.1371/journal.pone.0137356Test PLoS ONE, Vol 10, Iss 9, p e0137356 (2015) |
| بيانات النشر: | HAL CCSD, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Genotype, Genetic Linkage, Population, Quantitative Trait Loci, Sus scrofa, lcsh:Medicine, Genome-wide association study, Context (language use), Quantitative trait locus, Biology, Breeding, Body Mass Index, Mice, Absorptiometry, Photon, Metabolic Diseases, Genetic linkage, Animals, Humans, Obesity, lcsh:Science, education, 2. Zero hunger, Genetics, education.field_of_study, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Genetic heterogeneity, lcsh:R, Chromosome Mapping, Phenotype, Genetic architecture, Disease Models, Animal, Body Composition, lcsh:Q, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Genome-Wide Association Study |
| الوصف: | International audience; 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8155a4ef0610008bdf5c211b1e2249b4Test https://hal.sorbonne-universite.fr/hal-01275896Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8155a4ef0610008bdf5c211b1e2249b4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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