Characterization and Evolution of Copy Number Variation Among Primates

描述（由申请人提供）：本研究的目的是了解人类和其他灵长类动物的基因组拷贝数变异。拷贝数变异是在正常人的基因组中重复不同次数的DNA序列的大片段，其可以影响转录和翻译水平（为特定基因产生的mRNA和蛋白质的量），从而影响对诸如HIV感染等疾病的易感性。我们将描述人类和其他灵长类动物内部和之间的拷贝数变异和基因表达变异之间的关系，这将使我们能够识别可能具有相当大的功能和生物医学意义的拷贝数变异。 叙述：本研究的目的是了解灵长类动物基因组拷贝数变异的结构和进化及其对基因表达的影响。具体而言，我们将（i）评估非人灵长类动物中拷贝数变异的水平和模式是否与人类相似，并测试拷贝数增加和减少的种间固定率的异质性，以及（ii）表征灵长类进化不同时间尺度上拷贝数变异（CNV）与基因表达变异之间的关系。我们的工作将提供最全面的理解，迄今为止的灵长类动物的拷贝数和基因表达变异之间的关系，使我们能够确定特定的CNV，可能是相当大的进化和生物医学意义。我们的研究团队包括灵长类动物拷贝数变异和基因表达领域的领导者，能够很好地合作解决这些重要问题。

DESCRIPTION (provided by applicant): The goal of this study is to gain an understanding of genomic copy number variants in humans and other primates. Copy number variants are large stretches of DNA sequence repeated a different number of times among the genomes of normal humans, which can influence transcriptional and translational levels (the amount of mRNA and protein created for a particular gene) and therefore susceptibility to diseases such as HIV infection. We will characterize the relationship between copy number variants and gene expression variation within and between humans and other primates, which will allow us to identify copy number variants that may be of considerable functional and biomedical significance. Narrative: The goal of this study is to gain an understanding of the structure and evolution of genomic copy number variation in primates and its impact on gene expression. Specifically, we will (i) assess whether levels and patterns of copy number variation in non-human primates are similar to those for humans and test for heterogeneity in the inter-specific fixation rate for copy number gains and losses, and (ii) characterize the relationship between copy number variants (CNVs) and gene expression variation across different timescales of primate evolution. Our work will provide the most comprehensive understanding to date of the relationship between copy number and gene expression variation in primates, allowing us to identify specific CNVs that may be of considerable evolutionary and biomedical significance. Our research team, which includes leaders in both the primate copy number variation and gene expression fields, is well positioned to collaboratively address these important issues.