Date of Graduation
Master of Science in Cell & Molecular Biology (MS)
Second Committee Member
Biological sciences, Hypertension, Serotonin
Pulmonary Arterial Hypertension (PAH) is a sever disorder characterized by high pulmonary artery pressure and pulmonary vascular resistance along with specific histological changes. Idiopathic PAH is a human disease of unknown origin that showed common characteristics to PHS/ascites in chicken. PHS/ascites is a condition found in broilers causing right ventricular hypertrophy, valvular insufficiency, increased venous pressure, variable liver changes, accumulation of fluids in the abdominal cavity, and finally lung and heart failure. Currently, there is no acceptable animal model for human PAH. Our group has been validating the chicken as the medical animal model for human PAH, thus we have mapped chromosomal regions associated with susceptibility to ascites. The region on Gga9 contains the serotonin receptor (5HT2B) gene which showed linkage disequilibrium with respect to ascites susceptibility. Sequence data obtained from a previous research work for the 5HT2B gene from several SUS and RES lines identified a C/T SNP on the 3rd exon that result in a silent mutation and had no effect on protein production or structure. My research project was to extend our sequence analysis to the upstream promoter regions of 5HT2B to identify any sequence polymorphisms of several DNA samples from both SUS and RES lines. I identified 15 polymorphisms SNPs present in the 5HT2B promoter region. Three SNPs were found to be in a complete linkage defining alternative alleles and have a potential ability in affecting transcription factors binding sites. A TaqMan Assay was then developed for these particular SNPs used to SNPlotype a large collection of DNA samples from birds previously phenotyped for ascites susceptibility in the hypobaric chamber challenged. Statistical analyses of the SNPlotyped data support the association of particular genotypes/haplotypes of the 5HT2B gene with resistance to ascites especially in females. Identifying the underlining genetics of ascites syndrome will lead to genetic selection to reduce ascites incidence in chicken and further establish chicken as the medical animal model for human PAH.
Alzahrani, K. A. (2013). Genetic Analysis of the Promoter Region of the Serotonin Receptor 5HT2B and its Contribution to Pulmonary Hypertension Syndrome in Broiler-Type Chickens. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/754