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QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl
Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.ORCID iD: 0000-0002-7167-5473
Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
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2017 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 446, no C, p. 52-58Article in journal (Refereed) Published
Abstract [en]

Domestication of animals is associated with numerous alterations in physiology, morphology, and behavior. Lower reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and reduced fearfulness is seen in most studied domesticates, including chickens. Previously we have shown that the physiological stress response as well as expression levels of hundreds of genes in the hypothalamus and adrenal glands are different between domesticated White Leghorn and the progenitor of modern chickens, the Red Junglefowl. To map genetic loci associated with the transcription levels of genes involved in the physiological stress response, we conducted an eQTL analysis in the F12 generation of an inter-cross between White Leghorn and Red Junglefowl. We selected genes for further studies based on their known function in the regulation of the HPA axis or sympathoadrenal (SA) system, and measured their expression levels in the hypothalamus and the adrenal glands after a brief stress exposure (physical restraint). The expression values were treated as quantitative traits for the eQTL mapping. The plasma levels of corticosterone were also assessed. We analyzed the correlation between gene expression and corticosterone levels and mapped eQTL and their potential effects on corticosterone levels. The effects on gene transcription of a previously found QTL for corticosterone response were also investigated. The expression levels of the glucocorticoid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. We found several cis- and transacting eQTL for stress-related genes in both hypothalamus and adrenal. In the hypothalamus, one eQTL for c-FOS and one QTL for expression of GR were found. In the adrenal tissue, we identified eQTL for the genes NROB1, RGS4, DBH, MAOA, GRIN1, GABRB2, GABRB3, and HSF1. None of the found eQTL were significant predictors of corticosterone levels. The previously found QTL for corticosterone was associated with GR expression in hypothalamus. Our data suggests that domestication related modification in the stress response is driven by changes in the transcription levels of several modulators of the HPA and SA systems in hypothalamus and adrenal glands and not by changes in the expression of the steroidogenic genes. The presence of eQTL for GR in hypothalamus combined with the negative correlation between GR expression and corticosterone response suggests GR as a candidate for further functional studies regarding modification of stress response during chicken domestication.

Place, publisher, year, edition, pages
2017. Vol. 446, no C, p. 52-58
Keywords [en]
Animal domestication, Stress response, HPA axis, QTL, eQTL
National Category
Medical Genetics Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-322082DOI: 10.1016/j.mce.2017.02.010ISI: 000399509600006OAI: oai:DiVA.org:uu-322082DiVA, id: diva2:1096605
Funder
Swedish Research Council, 621-2011-4731Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 221-2011-1088EU, European Research Council, Genewell 322206Available from: 2017-05-18 Created: 2017-05-18 Last updated: 2018-08-24Bibliographically approved
In thesis
1. Mass spectrometry based analysis of endogenous sterols and hormones
Open this publication in new window or tab >>Mass spectrometry based analysis of endogenous sterols and hormones
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bioanalytical applications using supercritical fluid chromatography (SFC) as analytical technique are of increasing interest. In essence, bioanalysis involves measurement of bioactive or endogenous compounds in biological matrices. SFC has emerged as an excellent choice for bioanalytical analysis, attributable to its speed, selectivity and efficiency compared with high performance liquid chromatography. Moreover, coupling of SFC with mass spectrometry (MS) provides the additional benefits of specificity and sensitivity.

The aim of this thesis was to exploit these features by developing methods for the analysis of endogenous steroids, cholesterol oxidation products (COPs) and thyroid hormones (THs) by using ultra-performance supercritical fluid chromatography–tandem mass spectrometry (UPSFC–MS/MS) as analytical technique.

Endogenous steroids control many physiological processes, including reproduction, maturation, gene expression and neurological functions in humans and animals. In the first study, three steroids were measured in domesticated White Leghorn (WL) chickens and ancestral Red Junglefowl (RJF) birds. Restraining stress caused a significantly larger increase in corticosterone levels in RJF than in WL, indicating a blunted hypothalamic–pituitary–adrenal (HPA) axis activity in domesticated chickens. The second study was a continuation of the first study and corticosterone levels from the F12 generation of an intercross between WL and RJF birds were measured before and after physical restraint stress. The expression levels of the glucocorticoid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. In the third study, the measurement of steroids was extended to assess more endogenous steroids from the four major classes, i.e. estrogens, androgens, progestogens and corticosterone.

Endogenous COPs are of interest in pathophysiology. COPs are more readily disposed by cells than cholesterol. Therefore, cholesterol is oxidised to the more polar COPs and are generally more bioactive than cholesterol. Moreover, if their production in cells and tissues and/or their introduction with dietary animal fat are excessive, COPs could indeed contribute to the pathogenesis of various disease processes. Fourteen COPs were included in the fourth study and a novel method for their separation was developed.

The last study in this thesis, involved the analysis of five THs. These hormones are vital for growth, developmental and metabolic processes of vertebrate life and play an important role in energy homeostasis. Measurements of circulating thyroid hormone levels are used in thyroid disorder diagnoses or treatment status monitoring. Two rapid methods for the separation of five THs were developed.

In summary, the work in this thesis demonstrates the applicability of UPSFC–MS/MS as an analytical technique in bioanalysis of endogenous compounds.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1698
Keywords
mass spectrometry, supercritical fluid chromatography, UPSFC–MS/MS, bioanalysis, steroids, oxysterols, thyroid hormones
National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-356767 (URN)978-91-513-0396-3 (ISBN)
Public defence
2018-09-19, B7:101a, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-08-30 Created: 2018-08-06 Last updated: 2018-09-10

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de Kock, NeilUbhayasekera, S. J. Kumari A.Bergquist, Jonas

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