Abstract
BackgroundEnvironmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the VE of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in VE of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower VE of LS were found to be more resilient to infections than animals with a higher VE of LS.ResultsBy using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with VE of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3′UTR region of the HUNK gene that was fixed in the low VE line and absent in the high VE line.ConclusionsThis is the first study that combines GWAS and WGS analyses to study the genetic basis of VE. The new candidate genes and functional mutations identified in this study suggest that the VE of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous VE of litter size.
Highlights
Environmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience
Genomic regions associated with VE of litter size (LS) genome-wide association study (GWAS) identified SNPs associated with VE of LS using two approaches, single-marker regression (SMR) and Bayesian multiple-marker regression (BMMR)
With BMMR, we identified 60 SNPs on several chromosomes that had a Bayes factor ( BF ) higher than 10 (Fig. 1b), including all the SNPs that were identified by SMR (Table 1)
Summary
Environmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. We combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS These lines differ in terms of biomarkers of immune response and mortality. We performed a GWAS and a whole-genome sequencing (WGS) analysis using data from two rabbit lines that have been divergently selected for high and low VE of LS [9] These lines show a remarkable difference in VE of LS (4.5% of the mean of the base population), as well as differences in mortality, in biomarkers of immune response (plasma cortisol, leukocytes and acute-phase protein levels), and in plasma concentrations of cholesterol and triglycerides [20]. The line with a low VE of LS was found to cope better with environmental stressors such as infections than the line with a high VE of LS, which suggests that the homogeneous line is more resilient
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