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病 遍布中美洲和南美洲。原生动物寄生虫T.ruzi， 恰加斯病的病原体估计有1600万至1800万人感染 约有1亿人面临感染风险。Chagas‘ 疾病是拉丁美洲心脏病的主要原因--约30%-40% 那些被感染的人最终会有一定程度的心脏损害。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10万名感染者居住在美国 各国对血液和组织的安全提出公共卫生关切 银行。Chagas病研究的一个关键问题是缺乏 模拟人类疾病过程的合适的模式生物。在 西南地区灵长类动物研究中心(SRPRC)一个庞大的血统聚居地 其中许多是自然感染克氏锥虫的，提供了一种 研究易感基因的理想模式系统 感染克鲁兹毛滴虫。有人建议将狒狒发展为灵长类动物。 研究人类恰加斯病遗传学的模型。的影响 环境和遗传因素对克氏毛滴虫血清学检测的影响 这种纯正的狒狒种群将会被量化。遗传效应如何 与主机环境的各方面交互，例如共享SIRE环境， 将确定共同的网箱环境和网箱同居历史。 笼养和笼养人群克氏毛滴虫血清阳性率的年龄和性别特征 将圈养在同一大环境中的狒狒进行对比，以确定 如果这些关在笼子里的做法影响了罕见的感染。基因组连锁扫描 将被执行以识别狒狒基因组中影响 通过血清转换证明对克氏毛滴虫感染的易感性。 最后，提出了一种新的连杆和连杆机构设计方法 不平衡分析以精细定位连锁区域并识别特定的 影响克氏毛滴虫感染的候选基因。

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.