Investigation of the UTS2D Gene as a QTL for Ascites in Broilers

Idiopathic Pulmonary Arteriole Hypertension (IPAH) is a progressive disease in humans that causes a characteristic elevation in pulmonary arterial pressure eventually leading to right sided congestive heart failure and death. Lack of suitable animal models deters studies related to IPAH. Our group has been investigating chickens as an appropriate medical model for IPAH/PAH studies. Ascites, an industry term for PAH in chickens, is characterized by formation of plexiform arteriopathies, which are very closely related to the formation of plexiform lesions formed during human IPAH, supporting the suitability of chickens as a medical model for the disease. Our research group has developed broiler chicken lines with high heritabilities for IPAH susceptibility and resistance. We have identified several chromosomal segments that are associated with PAH in these lines including a region on chromosome 9 that contains the UTS2D (Urotensin 2 Domain Containing) gene. Since UTS2D is known to mediate vascular hypoxic responses in mammals, we hypothesize that it might play a role in the development of ascites in chickens. We have identified single nucleotide polymorphisms (SNPs) in the intronic and promoter regions of the gene.  These SNPs have been used to genotype a collection of DNAs from our research lines.  One particular SNP affects the IRF-2 RS (Interferon Regulatory Factor 2) binding site in the UTS2D upstream region. Genetic polymorphisms of the UTS2D gene associated with ascites in chickens will give a better insight into any role for this gene in the development of the disease, which in turn, will help us understand the appropriateness of chicken as a model for studying IPAH in humans.