a substitution in the ligand binding domain of the porcine glucocorticoid receptor affects activity of the adrenal gland一个替换的配体结合域猪的肾上腺糖皮质激素受体影响活动.pdfVIP

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a substitution in the ligand binding domain of the porcine glucocorticoid receptor affects activity of the adrenal gland一个替换的配体结合域猪的肾上腺糖皮质激素受体影响活动.pdf

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a substitution in the ligand binding domain of the porcine glucocorticoid receptor affects activity of the adrenal gland一个替换的配体结合域猪的肾上腺糖皮质激素受体影响活动

A Substitution in the Ligand Binding Domain of the Porcine Glucocorticoid Receptor Affects Activity of the Adrenal Gland 1. 1. 2 1 1 Eduard Murani , Henry Reyer , Siriluck Ponsuksili , Stephan Fritschka , Klaus Wimmers * 1 Research Unit Molecular Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany, 2 Research Group Functional Genome Analysis, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany Abstract Glucocorticoids produced in the adrenal cortex under the control of the hypothalamic-pituitary axis play a vital role in the maintenance of basal and stress-related homeostasis and influence health and well-being. To identify loci affecting regulation of the hypothalamic-pituitary-adrenal (HPA) axis in the pig we performed a genome-wide association study for two parameters of acute and long-term adrenal activity: plasma cortisol level and adrenal weight. We detected a major quantitative trait locus at the position of the glucocorticoid receptor gene (NR3C1) – a key regulator of HPA axis activity. To determine the causal variant(s), we resequenced the coding region of NR3C1 and found three missense single nucleotide polymorphisms (SNPs). SNP c.1829C.T, leading to a p.Ala610Val substitution in the ligand binding domain, showed large (about 0.6 6and 1.2 6 phenotypic standard deviations for cortisol level and adrenal weight, respectively), and highly significant (2.1E-39#log10(1/p)#1.7E+0) negative effects on both traits. We were able to replicate the association in three commercial pig populations with different breed origins. We analyzed effects of the p.Ala610Val substitution o