Large-Scale Discovery of Functional Genetic Variation in Rhesus Macaques

描述（由申请人提供）：恒河猴（Macaca mulatta）是生物医学研究中使用最广泛的非人灵长类动物。恒河猴在理解艾滋病毒/艾滋病的发病机制，开发新的治疗方法和新的艾滋病毒感染疫苗方面至关重要。此外，恒河猴通常用于基础神经生物学、代谢疾病（如糖尿病和骨质疏松症）以及生殖生物学的研究。恒河猴在干细胞生物学分析中非常重要。该物种也经常被用作酒精中毒、药物成瘾、焦虑症和抑郁症相关研究的动物模型。该项目将通过产生大量关于恒河猴功能遗传变异的新信息，大大增加这种灵长类动物物种对所有类型生物医学研究的价值和意义。现在已经确定，人与人之间的遗传差异会影响他们患上上述常见疾病，包括传染病的风险。遗传变异也可以影响疾病的进展和不同人对特定治疗的反应。我们将通过鉴定恒河猴基因组中功能基因的大量新DNA序列变异，促进疾病易感性和治疗反应的遗传基础研究。为了实现这一点，我们将测序外显子组（所有功能基因外显子）从96个无关的恒河猴，印度和中国起源的动物。我们还将为这96只动物中的8只制作全基因组序列。外显子组和全基因组数据将用于鉴定该物种中存在的新DNA序列变异。我们还将对所有96只动物的淋巴细胞的RNA进行测序，以开始评估该组织内基因表达的个体差异，并将差异RNA表达与相关基因中的DNA序列变异相关联。所有产生的数据将通过适当的NCB 1数据库（例如Short Read Archive，dbVAR和dbSNP）以及通过创建我们自己的恒河猴遗传变异的公共可搜索在线数据库来提供。

DESCRIPTION (provided by applicant): Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research. Rhesus are critically important in efforts to understand the pathogenesis of HIV-AIDS, to develop novel treatments and new vaccines against HIV infection. In addition, rhesus macaques are commonly used in studies of basic neurobiology, metabolic diseases such as diabetes and osteoporosis, and reproductive biology. Rhesus monkeys are important in analyses of stem cell biology. This species is also frequently used as an animal model in studies related to alcoholism, drug addiction, anxiety disorders and depression. This proposed project will dramatically increase the value and significance of this primate species for all types of biomedical research by generating a substantial amount of new information about functional genetic variation among rhesus macaques. It is now well established that genetic differences among people influence their risk of developing common diseases such as those listed above, including infectious diseases. Genetic variation can also influence the progression of disease and the responses of different people to a specific treatment. We will facilitate research on the genetic basis of disease susceptibility and response to treatment by identifying large numbers of new DNA sequence variants in functional genes within the rhesus genome. To accomplish this, we will sequence the exome (all functional gene exons) from 96 unrelated rhesus macaques, both Indian-origin and Chinese-origin animals. We will also produce whole genome sequences for 8 of those 96 animals. The exome and whole genome data will be used to identify new DNA sequence variation present in this species. We will also sequence RNA from the lymphocytes of all 96 animals to begin assessment of individual variation in gene expression within that tissue, and to correlate differential RNA expression with DNA sequence variation in the relevant genes. All the data generated will be made publically available through appropriate NCBl databases (e.g. Short Read Archive, dbVAR and dbSNP) and by creating our own public searchable on-line database of rhesus genetic variation.