Quantitative genomics of sexual dimorphism

描述（由申请人提供）：性二态性和维持 遗传变异是动物生物学的两个普遍存在的特征。虽然 传统的定量遗传分析为我们提供了有用的见解， 了解这些过程，一种新的方法将注入这些研究 以新的活力和新的视角解决问题。在本提案中，我们将 利用一种新技术，使用cDNA进行全基因组表达谱分析， 微阵列，以确定基因是负责种内变异 果蝇的性别分化和二型性 黑腹菌我们将汇集六个不同的资源和人才， 发育、生理、进化、定量和统计 遗传学家提供了一个全面的分析来源的差异 影响整个基因组的转录。在第一个实验中， 涉及10个随机选择的近等基因系的双等位基因杂交，我们将 表征1）基因组的哪一部分在以下之间差异表达： 雄性和雌性成年果蝇; 2）差异表达的部分是什么 跨基因型，无论是在性别偏见的方式和跨性别;和3）计算 这些效应的方差分量和 每个基因的转录。该数据集将代表第一个全面的 任何物种基因表达的遗传结构的观点。在同一 线，以及在一组150重组自交系，我们将测量 果蝇的一组代表性的性二态性状的表型 包括雄性梳齿数、腹部色素沉着、发育时间、 死亡率、卵巢管数量和对多种药物的敏感性。QTL 将进行作图实验，并将候选基因（具有性功能的基因） 差异表达，其位于QTL中）将被测试用于 候选基因表达与相关表型的共变。的 高分辨率QTL作图，定量表达谱分析， 和功能注释将建立一个强有力的工具， 每种性二态性状的候选基因。后续行动 对少数这些基因的验证和遗传表征将 在融资期结束时启动。在整个提案中，我们 将开发新的统计程序， 研究人员试图将表达数据与定量数据联系起来， 在人类和脊椎动物模型中对疾病的易感性，特别是那些 具有性别特异性易感性、病因学或治疗的疾病。的 我们开发的遗传资源将用于果蝇研究， 社区，并将构成数量遗传学的重要资源 分析各种各样的特征。我们希望我们的研究结果能对 对我们理解两性异形进化的影响， 性别分化在表型多样性的产生中起着重要作用。

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.