Molecular Genetics of cortisol secretion in pigs

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© B. M. Babigumira1, S. Rousseau1, F. Salin2, S. Monllor2, P. Mormede1, E. E. Terenina1
1 University of Bordeaux, Laboratory for PsychoNeuroImmunology, Nutrition and Genetics, France
2 Plateforme Genome-Transcriptome, France
The hypothalamic-pituitary adrenocortical (HPA) axis exerts a large range of effects on metabolisms, the immune system, inflammatory processes, and brain functions. It is also the most important stress-responsive neuroendocrine system. Numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and we explore systematically the molecular mechanisms of HPA axis variation in pigs as a model species as well as for more efficient breeding. Genetic polymorphism can be found at each level of the axis, but hormone production by the adrenal cortices under stimulation by ACTH is a major source of individual differences and several candidate genes have been identified by genomic studies (Hazard et al. BMC Genomics 9: 101, 2008) of two highly divergent breeds of pigs, the Large White (LW) with a high production potential for lean meat and a low HPA axis activity, and the Meishan (MS) with low growth rate, fat carcasses — but giving large litters of highly viable piglets — and a high HPA axis activity. In the present experiment, we sequence a number of candidate genes for molecular polymorphisms and studied their association with neuroendocrine and metabolic traits in a genetically diverse population.
Candidate genes were chosen in the pathways of cortisol production and/or among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs (Hazard et al., 2008) such as ACTH receptor (MCR2), cholesterol suppliers (LDLR, SCARB1, STAR), regulatory factors (CREM), metabolic enzymes (CYP11A) and several genes with a currently unknown function in the adrenal glands (EIF1B, RNF2, PPAP2B). We studied of population of 100 female pigs from an advanced intercross between LW and MS breeders (F10-F12), which were extensively phenotyped in a previous project (Foury et al. Animal 1: 967, 2007). PCR primers were designed from the most recent pig genome database (http: //www. ensembl. org/Sus_scrofa/ Info/Index) and amplification products from animals with extreme phenotypes were sequenced to detect polymorphisms (SNP). The whole population was then genotyped with the best available technique (sequencing, high resolution melting) for association with available phenotypes (HPA axis parameters, metabolic and production traits). These studies open the way towards individualized medicine and more efficient marker-assisted selection in farm animal species.
том e/2010/1 обзоры по клинической фармакологии и лекарственной терапии I М29

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