System Genetics of Male Infertility in the Collaborative Cross

描述（由申请人提供）：不育症背后的遗传学悖论是不育个体必须是生育父母的后代。尽管如此，以前的研究将不孕症部分归因于遗传基因因素。与许多普遍的人类健康状况一样，这是多个基因、环境因素及其相互作用的组合效应的结果。这种小的影响和相互作用通常难以在人类群体和小鼠模型中检测到。这项拟议中的研究将使用一种名为协作杂交（CC）的新小鼠种群来确定男性不育症的遗传变异。CC的设计是为了便于绘制与复杂性状相关的基因。在繁殖过程中，多达50%的早期品系停止生产后代并被宣布灭绝，雄性不育是这种灭绝的主要机制。这个庞大而多样的不育雄性小鼠群体可用于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，如精子计数和睾丸结构。该项目对于开发适用于CC人群的新方法也很有价值。

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.