Mapping Ascites QTLs In Broilers

Our group has been investigating the underlying physiology, histopathology, and genetics of Idiopathic Pulmonary Arterial Hypertension (IPAH) or ascites in the chicken.   Under IPAH inducing conditions we have determined that the lungs of susceptible chickens contain complex vascular lesions.  We have mapped chicken QTLs affecting susceptibility to two regions on Gga9 and one on Gga27 containing candidate genes ACE, 5HTR2B, UTS2D, and AGTR1.    Association studies in humans have linked mutations affecting ACE, 5HT2B and AGTR1 with various forms of hypertension or PAH, while UTS2D is associated with vascular response to hypoxia.  IPAH in the chicken and some human cases respond to treatment with serotonin antagonists.  Humans and chickens develop complex vascular lesions (plexiform lesions) in their lungs, which distinguishes them from the hypertensive dog or fawn-hooded rat.  Therefore, the ascitic chicken appears to be similar for genetics and histopathology for some forms of human hypertension.  We have identified SNPs in ACE, 5HT2B, UTS2D, and AGTR1, and developed qPCR assays for SNPlotyping and expression analyses of these genes in different tissues.  Our genetic analyses have demonstrated a gender specific effect for some regions, association of some regions with ascites in commercial broiler lines, and a possible association with production traits.  Current work is focused on determining how particular candidate gene mutations correlate with expression levels to dissect the physiological, cellular and vascular responses associated with the disease.