Chromosome-specific meiotic biology

About This Grant

Project Summary (30 lines) Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (e.g. eggs or sperm). Inheritance of the incorrect number of chromosomes is a leading cause of fertility and birth defects. However, the reasons for chromosome missegregation are not always the same for all chromosomes. Why inter-chromosomal differences exist is still unclear. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome-specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a set of mutants in a partial loss-of-function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over. The long-term goal of this project is to understand the chromosome-specific mechanisms that lead to error-free meiotic outcomes. This work will investigate 1) how chromosomes are identified as unique by the meiotic machinery and 2) how positioning of DSBs and crossovers is regulated on specific chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.