Crossover Interference, Crossover Maturation, and Human Aneuploidy

A striking feature of human female sexual reproduction is the high level of gametes that exhibit an aberrant number of chromosomes (aneuploidy). A high baseline observed in women of prime reproductive age is followed by a dramatic increase in older women. Proper chromosome segregation requires one or more DNA crossovers (COs) between homologous maternal and paternal chromosomes, in combination with cohesion between sister chromatid arms. In human females, CO designations occur normally, according to the dictates of CO interference, giving early CO-fated intermediates. However, ≈25% of these intermediates fail to mature to final CO products. This effect explains the high baseline of aneuploidy and is predicted to synergize with age-dependent cohesion loss to explain the maternal age effect. Here, modern advances in the understanding of crossing over and CO interference are reviewed, the implications of human female CO maturation inefficiency are further discussed, and areas of interest for future studies are suggested.