QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl

Abstract

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 F 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 trans-acting 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 NR0B1, 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.

The potential of shifting recombination hotspots to increase genetic gain in livestock breeding

“…Although information of QTN at the nucleotide level is largely unknown, cruder measures derived from classical quantitative trait locus (QTL) mapping, regional heritability mapping (e.g. [37–42]) or functional genome annotation [43] are available and could be used to crudely identify regions of the genome that may be suitable for introducing recombination hotspots. We believe that much of the benefit of shifting recombination hotspots would likely be obtained with crude knowledge of regions of the genome that harbour QTN rather than very refined knowledge of the precise location and effect of each QTN.…”

Harnessing genomic information for livestock improvement

“…In pigs, eQTL studies have been conducted in skeletal muscle, lung, adipose tissue and liver [46][47][48][49][50][51][52][53][54][55][56][57] . In poultry, genome-wide eQTL analyses have been reported for liver, bone, adrenal gland and hypothalamus [58][59][60][61] . The time seems right for the animal genomics community to take advantage of working with livestock species to collaboratively generate large, multi-omic, multi-tissue data sets similar to the human Genotype-Tissue Expression (GTEx) data set 62 .…”

A Novel Targeted Analysis of Peripheral Steroids by Ultra-Performance Supercritical Fluid Chromatography Hyphenated to Tandem Mass Spectrometry

“…The results will be reported separately. Furthermore, we have already published some more applications based on this method in peer-reviewed journals showing its applicability in biological samples 27 , 28 .…”

“…Sample preparation commences with liquid-liquid extraction (LLE). A slightly modified method of steroid extraction was used 28 . Briefly, 50 µL of plasma was mixed with the mixture of IS.…”