Common Complex Trait Genetics of Reproductive Phenotypes

项目概要/摘要：项目2 对罕见的严重孟德尔生殖疾病的遗传分析强调了 GnRH神经元在病理生理学中的作用。为了进一步阐明这些生物学过程，我们将扩展 遗传学调查，以分析以下常见生殖临床 疾病：多囊卵巢综合征（PCOS），原发性卵巢功能不全（POI），和 下丘脑性闭经（HA）。具体来说，我们将1）加速发现新的遗传基因 通过大型国际财团对生殖表型的影响; 2）整合这些新的 P1的孟德尔分析的遗传发现，以提名P3的基因和变体;以及3） 综合复杂生殖性状的遗传结果，以了解它们之间的关系， 表征来自斑马鱼的经验证的基因和变体的表型和生物学后果 P3通过深度表型分析。如果成功，我们将发现新的基因和变异， 临床终点，提供这些功能验证，然后解释全范围的表型 这些基因影响的后果。

Project Summary/Abstract: Project 2 Genetic analysis of rare, severe Mendelian reproductive conditions has highlighted the critical importance of GnRH neurons in pathophysiology. To further elucidate these biological processes, we will extend the genetic investigations to analyses of common variation on the following common reproductive clinical disorders: polycystic ovarian syndrome (PCOS), primary ovarian insufficiency (POI), and hypothalamic amenorrhea (HA). Specifically, we will 1) accelerate the discovery of novel genetic influences on reproductive phenotypes through large-scale international consortia; 2) integrate these new genetic discoveries with the Mendelian analyses of P1 to nominate genes and variants for P3; and 3) synthesize the genetic results across complex reproductive traits to understand how they relate as well as characterizing the phenotypic and biological consequences of validated genes and variants from zebrafish P3 through deep phenotyping. If successful, we will uncover new genes and variants for reproductive clinical endpoints, provide these for functional validation and then interpret the full range of phenotypic consequences of these genetic influences.