Common Complex Trait Genetics of Reproductive Phenotypes

生殖表型的常见复杂性状遗传学

• 批准号: 9180127
• 负责人: Benjamin Michael Neale
• 金额: $ 25.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9180127
• 关键词: Age; Amenorrhea; Bioinformatics; Biological; Biological Assay; Biological Process; Clinical; Complex; Complex Genetic Trait; Data; Disease; Endocrine; Ensure; Etiology; Evaluation; Female infertility; Fertility; Functional disorder; Genes; Genetic; Genetic Risk; Genetic Variation; Genotype; Goals; Hypothalamic structure; Individual; Infertility; International; Investigation; Maps; Menarche; Meta-Analysis; Methods; Modeling; Neurons; Neurosecretory Systems; Output; Ovarian; Overlapping Genes; Patients; Phenotype; Play; Population; Regulation; Reproductive Health; Resources; Risk Factors; Role; Science; Series; Services; Syndrome; TACR3 gene; Validation; Variant; Zebrafish; abstracting; base; biobank; cohort; cost; follow-up; genetic analysis; genetic association; genetic risk factor; genetic variant; genome wide association study; hypothalamic pituitary axis; insight; novel; primary ovarian insufficiency; reproductive; trait

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.

项目摘要/摘要：项目 2 对罕见、严重的孟德尔生殖状况的遗传分析凸显了其至关重要性 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过程，我们将扩展 遗传研究以分析以下常见生殖临床的常见变异 疾病：多囊卵巢综合征 (PCOS)、原发性卵巢功能不全 (POI) 和 下丘脑闭经（HA）。具体来说，我们将1）加速新基因的发现 通过大型国际联盟对生殖表型的影响； 2）整合这些新的 通过 P1 的孟德尔分析进行遗传发现，以指定 P3 的基因和变体；和 3) 综合复杂生殖特征的遗传结果，以了解它们之间的关系以及 表征斑马鱼经过验证的基因和变异的表型和生物学后果 P3 通过深度表型分析。如果成功，我们将发现新的生殖基因和变异 临床终点，提供这些用于功能验证，然后解释全部表型 这些遗传影响的后果。