System Genetics of Male Infertility in the Collaborative Cross

合作杂交中男性不育的系统遗传学

• 批准号: 8003213
• 负责人: David Lawrence Aylor
• 金额: $ 5.05万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003213
• 关键词: Affect; Biology; Breeding; Chromosome Mapping; Complex; Couples; Environmental Risk Factor; Extinction (Psychology); Fertility; Genes; Genetic; Genetic Variation; Health; Human; Individual; Infertility; Inherited; Male Infertility; Methods; Mus; Parents; Population; Population Heterogeneity; Process; Reporting; Research; Sperm Count Procedure; Structure; System; Testis; combinatorial; design; fitness; male; mouse model; offspring; public health relevance; reproductive; trait

DESCRIPTION (provided by applicant): The paradox of the genetics underlying infertility is that infertile individuals must have descended from fertile parents. Nonetheless, previous studies have attributed infertility in part to inherited genetic factors. As is the case with many pervasive human health conditions, this results from combinatorial effects of multiple genes, environmental factors and their interactions. Such small effects and interactions are often difficult to detect in both human populations and mouse models. The proposed research will identify genetic variation underlying male infertility using a new mouse population called the Collaborative Cross (CC). The CC is designed to facilitate mapping genes associated with complex traits. During the breeding process, up to 50% of incipient lines stop producing offspring and are declared extinct, and male infertility is a major mechanism of this extinction. This large and diverse population of infertile male mice can be used to better understand the biology and genetics of male infertility and its associated reproductive parameters such as sperm count and testis structure. This project is also valuable to develop new methods that apply to the CC population.

描述（由申请人提供）：不育背后的遗传学悖论是，不育个体必须是有生育能力的父母的后代。尽管如此，之前的研究将不孕部分归因于遗传因素。与许多普遍存在的人类健康状况一样，这是多种基因、环境因素及其相互作用的综合影响的结果。这种微小的影响和相互作用通常很难在人类种群和小鼠模型中检测到。这项拟议中的研究将利用一种名为协作杂交（CC）的新小鼠种群来确定男性不育的遗传变异。CC的设计是为了方便定位与复杂性状相关的基因。在繁殖过程中，多达50%的早期系停止生产后代并被宣布灭绝，而雄性不育是这种灭绝的主要机制。这一庞大而多样的不育雄性小鼠种群可以用来更好地了解雄性不育的生物学和遗传学及其相关的生殖参数，如精子数量和睾丸结构。该项目对于开发适用于CC人群的新方法也很有价值。