Whole-Genome Sequencing Identifies Multiple Protein Function Affecting Variants Within QTL Regions for Pulmonary Hypertension Syndrome in Chicken

The recent advances in next generation sequencing technologies have enabled rapid and cost-effective detection of genetic variants within a genome, thereby facilitating the identification of causal variants underlying quantitative trait loci (QTL). We combined a SNP based genome-wide association study with whole-genome re-sequencing to identify causal variants involved in the susceptibility or resistance to the pulmonary hypertension syndrome (PHS) in chicken. PHS is a metabolic disease that has been linked to intense selection on growth rate and feed conversion ratio in modern broilers (meat-type chicken). PHS has become one of the most frequent causes of mortality within the broiler industry and leads to substantial economic losses and reduced animal welfare. In total, 15 QTL regions were identified in a genome-wide association study based on ~900 individuals genotyped for ~18k SNPs. In order to detect potential causal variants underlying these QTL regions, we re-sequenced the genomes of 16 individuals at an average coverage of 10X using the Illumina HiSeq2000 platform. To maximize the detection of causal variants we selected the individuals based on their extreme phenotypes for PHS. Within the 15 QTL regions, 92 variants (78 non-synonymous SNPs and 14 deletions) were identified that were predicted to affect protein function. These variants are located within 60 genes. Additional analyses are ongoing to validate these variants and to examine their possible involvement in the susceptibility or resistance to PHS.