Errors during meiotic cell division are a leading cause of mental retardation and pregnancy failure in our species. Research over the past decade has demonstrated that the vast majority of meiotic errors are maternal in origin and that the incidence of these errors is strongly correlated with maternal age. The mechanism(s) of error, however, and the manner in which age influences the process of meiotic chromosome segregation remain unknown. The proposed research approaches this problem by focusing on an essential feature of meiotic chromosomes that mediates chromosome segregation at the first meiotic division; reciprocal exchange (recombination) events between homologous chromosomes. Our understanding of the high meiotic error rate in our species has been hampered by the lack of a suitable animal model. The advent of gene targeting technology, however, has provided a means of creating mutations in specific gene. Targeted disruption of genes involved in DNA mismatch repair has resulted in the first mammalian mutants that show a reduction in recombination levels. We will utilize these mutants as well as naturally occurring murine variants to understand the role of recombination in meiotic chromosome segregation. These studies will provide valuable insight to the control of the normal female meiotic process and will allow us to test hypotheses about the mechanism of meiotic errors in the human female.
| Melin, Vanessa E; Potineni, Haritha; Hunt, Patricia et al. (2014) Exposure to common quaternary ammonium disinfectants decreases fertility in mice. Reprod Toxicol 50:163-70 |
| Murdoch, Brenda; Owen, Nichole; Stevense, Michelle et al. (2013) Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior. PLoS Genet 9:e1003241 |
| Nagaoka, So Iha; Hodges, Craig A; Albertini, David F et al. (2011) Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr Biol 21:651-7 |
| Hassold, T; Hansen, T; Hunt, P et al. (2009) Cytological studies of recombination in rhesus males. Cytogenet Genome Res 124:132-8 |
| Hassold, Terry; Hunt, Patricia (2009) Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew. Curr Opin Pediatr 21:703-8 |
| Hunt, Patricia A; Hassold, Terry J (2008) Human female meiosis: what makes a good egg go bad? Trends Genet 24:86-93 |
| Hunt, Patricia A; Jackson, Jodi M; Horan, Sonia et al. (2008) The mouse A/HeJ Y chromosome: another good Y gone bad. Chromosome Res 16:623-36 |
| Hassold, Terry; Hall, Heather; Hunt, Patricia (2007) The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 16 Spec No. 2:R203-8 |
| Johnson, Mark T; Freeman, Edward A; Gardner, David K et al. (2007) Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo. Biol Reprod 77:2-8 |
| Cherry, Sheila M; Adelman, Carrie A; Theunissen, Jan W et al. (2007) The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr Biol 17:373-8 |
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