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

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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.