Genetics and evolution of gene copy number polymorphism

描述(由申请人提供)：拟议研究的目标是解决我们对物种内基因拷贝数多态的起源和进化的理解中的一个关键差距。初步的工作表明，果蝇体内存在拷贝数变异，因此，我的训练目标是研究两种果蝇拷贝数变异的遗传和进化。这项研究的长期目标是：(I)使用微阵列比较基因组杂交(ACGH)、聚合酶链式反应和实时定量聚合酶链式反应来表征和量化基因拷贝得失的变异；(Ii)利用多线染色体的原位杂交来广泛地确定拷贝得失的基因组分布；(Iii)利用与转座相关的序列标志来表征新的倒退基因；(Iv)通过实时RT-qPCR来量化与重复拷贝相关的基因表达调控的变化；以及(V)使用qPCR、RT-qPCR和测序来表征基因拷贝数和表达的自然变异。这些长期目标的制定是为了测试对具有可变拷贝的基因的特定预测。

DESCRIPTION (provided by applicant): The goal of the proposed research is to address a critical gap in our understanding of the origin and evolution of gene copy number polymorphism within species. Preliminary work suggests copy number variation exists in Drosophila melanogaster; therefore, my training goals are to study the genetics and evolution of copy number variation in two species of Drosophila. The broad, long term objectives of the proposed research are (i) to characterize and quantify variation in gene copy gains and losses using microarray comparative genomic hybridization (aCGH), PCR, and real-time qPCR; (ii) to broadly define the genomic distribution for copy gains and losses using in situ hybridization of polytene chromosomes; (iii) to characterize new retroposed genes by taking advantages of sequence hallmarks associated with transposition; (iv) to quantify changes in the regulation of gene expression associated with duplicate copies by using real- time RT-qPCR; and (v) to characterize natural variation in gene copy number and expression using qPCR, RT-qPCR, and sequencing. These long-term objectives have been formulated to test specific predictions for genes with variable copies.