BABOON MODEL FOR THE GENETICS OF CHAGAS DISEASE

描述（申请人提供）：恰加斯病是一种人畜共患疾病 遍布中美洲和南美洲。 原生动物寄生虫T.克鲁兹， 南美锥虫病的病原体，估计感染1600 - 1800万人 约有1亿人面临感染风险。 南美锥虫 疾病是拉丁美洲心脏病的主要原因-大约30-40%的 感染者最终会有一定程度的心脏受累。 那里 没有疫苗，也没有安全有效的预防或治疗药物。 据估计，至少有10万感染者居住在美国， 对血液和组织安全提出公共卫生关切的国家 银行的 查加斯病研究的一个关键问题是缺乏一个 模拟人类疾病过程的合适模式生物。 在 西南地区灵长类动物研究中心（SRPRC）是一个大型的纯种群体， 很多狒狒都是自然感染T. cruzi提供了一个 理想的模型系统，用于研究遗传易感性， 感染猫弓首蛔虫克鲁兹 有人建议把狒狒培养成灵长类动物 研究人类恰加斯病遗传学的模型。 的影响 环境和遗传因素在确定T.克鲁济因 将对狒狒的纯种群体进行定量。 遗传效应是如何 与主机环境的各个方面交互，例如共享的Sire环境， 将确定共同的笼舍环境和笼舍同居史。 年龄和性别特异性T. cruzi在笼子里， 将在同一宏观环境中对圈养狒狒进行对比， 如果这些笼子的做法影响到罕见的感染。 基因组连锁扫描 将进行识别狒狒基因组的区域， 对T.血清转化证实了克氏病。 最后，一种新的方法将用于关节连杆和连杆 不平衡分析，以精细绘制连锁区域并确定特定的 影响T.克鲁兹

DESCRIPTION (provided by applicant): Chagas' disease is a zoonotic disease found throughout Central and South America. The protozoan parasite T. cruzi, the causative agent of Chagas' disease, is estimated to infect 16-18 million people, and approximately 100 million are at risk of infection. Chagas' disease is the leading cause of heart disease in Latin America-about 30-40% of those infected will ultimately have some degree of cardiac involvement. There are no vaccines and no safe and effective drugs for prophylaxis or therapy. It is estimated that at least 100,00 infected persons reside in the United States raising public health concerns regarding the safety of blood and tissue banks. A critical problem for research on Chagas' disease is the lack of a suitable model organism that mimics the disease process in humans. At the Southwest Regional Primate Research Center (SRPRC) a large, pedigreed colony of baboons, many of which are naturally infected with T. cruzi, provides an ideal model system for investigating the genetics of susceptibility to infection with T. cruzi. It is proposed to develop the baboon as a primate model for studying the genetics of Chagas' disease in humans. The effect of environmental and genetic factors in determining seropositivity to T. cruzi in the pedigreed colony of baboons will be quantified. How genetic effects interact with aspects of the host environment such as shared sire environment, common cage environment, and cage cohabitation history will be determined. Age- and sex-specific prevalence of seropositivity to T. cruzi in caged and corralled baboons in the same macroenvironment will be contrasted to determine if these caging practices affect the rare infection. A genome linkage scan will be performed to identify regions of the baboon genome that effect susceptibility to infection by T. cruzi as evidenced by seroconversion. Finally, a novel method will be used for joint linkage and linkage disequilibrium analysis to fine-map linkage regions and identify specific candidate genes that affect infection with T. cruzi.