Quantitative genetics of gene expression and methylation in the chicken

Abstract: In quantitative genetics the relationship between genetic and phenotypic variation is investigated. The identification of these variants can bring improvements to selective breeding, allow for transgenic techniques to be applied in agricultural settings and assess the risk of polygenic diseases. To locate these variants, a linkage-­‐based quantitative trait locus (QTL) approach can be applied. In this thesis, a chicken intercross population between wild and domestic birds have been used for QTL mapping of phenotypes such as comb, body and brain size, bone density and anxiety behaviour. Gene expression QTL (eQTL) mapping was also done for tissues such as comb base, medullar bone, liver and brain. By overlapping eQTL and QTL, regions were identified associated with both the gene expression levels and the phenotypes simultaneously. In this way, a number of candidate genes, underlying variation in the above-­‐mentioned phenotypes, were identified. Additionally, DNA methylation QTL (mQTL) mapping was done in the brain and the methylation landscape was assessed which indicated a decrease in methylation in the domestic breed. A small number of regions were identified which affected DNA methylation levels throughout the whole genome, so-­‐called trans hotspots. Finally, DNA methylation levels were correlated with eQTL to assess the degree to which gene expression is affected by methylation, and with gene expression in general to assess the relationship between the transcriptome and methylome. Taken together, these studies link the differences observed in various phenotypes between two populations of chicken to genetic variants coupled with gene expression correlations suggesting candidate genes. DNA methylation levels were influential in regulating variation in gene expression, both positively and negatively, but gene expression was also influential in regulating the methylation level. Epi-­‐alleles were identified which indicated genetic variants regulating methylation levels and gene expression levels either as the causal variant or in close linkage.