Quantitative genomics of sexual dimorphism

描述(申请人提供)：性二型和维系 遗传变异是动物生物学中普遍存在的两个特征。尽管 传统的定量遗传分析在我们的 对这些过程的理解，一种新的方法将注入对这些过程的研究 新的活力和新的视角带来的问题。在这项提案中，我们将 利用一种新技术--使用cDNA的全基因组表达谱 微阵列，以识别导致种内变异的基因 果蝇的性别分化和二形性 黑猩猩。我们将汇集六家公司的资源和多样化的人才 发展、生理、进化、数量和统计 遗传学家提供对变异来源的全面分析 影响整个基因组的转录。在第一个实验中，一个完整的 用10个随机选择的近等基因系进行双等位基因杂交，我们将 描述1)基因组的哪一部分在不同的基因之间有差异表达 雄性和雌性成虫果蝇；2)差异表达的比例是多少 跨基因类型，包括性别偏见和跨性别；以及3)计算 这些效应的方差分量和可加性程度 每个基因的转录。此数据集将代表第一个全面的 任何物种中基因表达的遗传结构的观点。在相同的 在一组150个重组自交系中，我们将测量 果蝇具有代表性的一组性别二态特征的表型 包括男性梳齿数、腹部色素沉着、发育时间、 死亡率、卵巢数和对多种药物的敏感性。QTL 将进行作图实验，候选基因(有性基因 位于QTL中的差异表达)将被测试 候选基因的表达与相关表型的协变。这个 结合高分辨率QTL定位、定量表达谱分析、 而功能标注将为身份识别提供有力的工具 每种性别二态特征的候选基因。跟进 对这些基因中的一小部分进行验证和基因表征将 将在资助期结束时启动。在整个提案过程中，我们 将开发新的统计程序，这些程序将有助于 试图将表达数据与定量数据联系起来的研究人员 人类和脊椎动物模型对疾病的易感性，特别是那些 具有特定性别的易感性、病因或治疗的疾病。这个 我们开发的遗传资源将用于果蝇的研究 群落，并将构成数量遗传的重要资源 对广泛的特征进行分析。我们希望我们的结果将产生深远的影响 对我们理解性别二态进化的影响，以及它的作用 性别分化在表型多样性的产生中起到了作用。

DESCRIPTION (provided by applicant): Sexual dimorphism and the maintenance of genetic variation are two of the ubiquitous features of animal biology. Though traditional quantitative genetic analysis has provided useful insights in our understanding of these processes, a novel approach will infuse studies of these problems with renewed vigor and a fresh perspective. In this proposal, we will take advantage of a new technology, genome-wide expression profiling using cDNA microarrays, to identify genes that are responsible for intraspecific variation for sexual differentiation and dimorphism, in the fruit fly Drosophila melanogaster. We will pool the resources and diverse talents of six developmental, physiological, evolutionary, quantitative, and statistical geneticists to provide a comprehensive analysis of the sources of variance affecting transcription throughout the genome. ln the first experiment, a full diallele cross involving 10 randomly chosen, near isogenic lines, we will characterize 1) what fraction of the genome is differentially expressed between male and female adult flies; 2) what fraction is differentially expressed across genotypes, both in a sex-biased manner and across sexes; and 3) compute the variance components of these effects and the degree of additivity for the transcription of each gene. This dataset will represent the first comprehensive view of the genetic architecture of gene expression in any species. In the same lines, as well as in a set of 150 recombinant inbred lines, we will measure the phenotypes of the flies for a representative set of sexually dimorphic traits including male sex comb tooth number, abdominal pigmentation, development time, mortality, ovariole number, and susceptibility to a variety of drugs. QTL mapping experiments will be performed, and candidate genes (genes with sexually differentiated expression, which are located in the QTL) will be tested for covariation of expression of candidate genes with the relevant phenotypes. The combination of high resolution QTL mapping, quantitative expression profiling, and functional annotation will establish a powerful tool for the identification of candidate genes for each of the sexually dimorphic traits. Follow-up validation and genetic characterization of a small number of these genes will be initiated toward the end of the funding period. Throughout the proposal, we will develop novel statistical procedures that will be of utility to investigators who are trying to link expression data with quantitative susceptibility to disease in humans and vertebrate models, particularly those diseases with gender-specific susceptibility, etiology, or treatment. The genetic resources we develop will be made available to the Drosophila research community and will constitute an important resource for quantitative genetic analysis of a wide range of traits. We expect our results to have a profound impact on our understanding of the evolution of sexual dimorphism, and the role that sexual differentiation plays in the generation of phenotypic diversity.