University of Arkansas, Fayetteville
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Abstract

Our multidisciplinary group at the University of Arkansas has been investigating the suitability of the chicken as a medical model for pulmonary arterial hypertension (PAH) in humans. There are several forms of PAH in humans arising from elevated pulmonary arterial pressure and pulmonary vascular resistance. Spontaneous cases of PAH are known as idiopathic PAH (IPAH), where the exact physiological causes are not known. IPAH patients that do not respond to standard treatments have a prognosis of only a few years. Currently, there is no acceptable animal model for IPAH. As part of our effort to pursue the chicken as model for IPAH, we have mapped chromosomal regions associated with susceptibility to ascites, an industry term for PAH in chickens. One region identified contains the angiotensin II type 1 receptor gene (AGTR1), a gene known to be associated with particular forms of PAH in humans. My project was to sequence the exonic regions of AGTR1 from chickens selected for susceptibility and resistance to ascites. I identified a total of 15 single nucleotide polymorphisms (SNPs) in intronic regions and 9 affecting exonic sequences that distinguish resistant and susceptible birds. One of the SNPs alters the encoded protein, but more sequencing data is needed to confirm the presence of this SNP. The 24 SNPs have become the basis for further genotypic efforts using quantitative polymerase chain reaction high-resolution melt (qPCR-HRM) assays to determine the association of alternative alleles of AGTR1 with PAH in the chicken. This knowledge will help the poultry industry in genetic selection to reduce incidence of ascites. Characterization of the genetic determinants of ascites in the chicken will also identify specific gene networks and further our understanding of PAH in humans.

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