Identification of genes important for accurate segregation of non-exchange homologs during meiosis I

染色体数目异常是人类不育的常见原因。晚育的趋势对年龄相关性不孕的妇女有重要影响，这通常是由染色体数目异常引起的。的？两个打？假设提出，第一次打击是缺乏？交叉？两个人的相似之处是什么？同源的？）染色体在一起。第二个命中与染色体在细胞分裂之前保持在一起的程度有关（纺锤体检查点）。我们建议使用芽殖酵母作为模式生物，以找到高度进化保守的基因，影响配子染色体数目异常。我们的初步数据表明，包括温度在内的几个因素会影响没有交叉的染色体彼此分离的程度。有趣的是，这些基因也在交叉形成中起作用。在我们尝试产生小鼠模型之前，我们将在分子和细胞水平上分析我们在芽殖酵母中鉴定的基因。我们希望确定与年龄相关的女性不孕症的基因，以了解这种现象，并开发诊断测试来预防这种情况。

Chromosome number abnormalities are a common cause of infertility in humans. The trend to have children at a later age has important implications for women due to age-related infertility, often caused by chromosome number abnormalities. The ?two hit? hypothesis proposes that the first hit is the lack of a ?crossover? which holds the two similar (?homologous?) chromosomes together. The second hit is related to the how well chromosomes are kept together until the cell divides ( spindle checkpoint ). We propose to use budding yeast as a model organism to find highly evolutionarily conserved genes that affect chromosome number abnormalities in gametes. Our preliminary data suggest that several factors, including temperature, affects how well chromosomes that have not received a crossover disjoin from each other. Interestingly, these genes also function in crossover formation. The genes that we identify in budding yeast will be analysed at the molecular and cellular level before we attempt to generate mouse models. We hope to identify genes that underlie age-related infertility in women in order to understand this phenomenon and to develop diagnostic test to prevent the condition.