I have a long-standing interest in recombination and meiotic nondisjunction. Chromosome nondisjunction (NDJ) is defined as the failure of chromosomes to separate during anaphase resulting in the production of aneuploid gametes. Aneuploidy, either too many or too few chromosomes, is estimated to occur in 10-25% of all human conceptions, the majority of which do not survive to term. Thus, NDJ is the leading cause of pregnancy loss, intellectual disabilities and birth defects.
Trisomy 21 is the most common autosomal aneuploidy observed among live-born individuals thus it is often used as a model to understand the genetics and molecular biology underlying NDJ. Studies have long identified altered recombination as a risk factor for chromosome 21 nondisjunction. However, it is unclear what may be causing these exchanges to occur in sub-optimal locations on 21q.
Along normally segregating chromosomes, recombination does not occur along chromosome arms in a random way, rather, it typically clusters in narrow regions known as “hotspots”. My past work was successful in identifying patterns of recombination and other risk factors that predispose to chromosome 21 nondisjunction. My most recent findings suggest that recombinant events along nondisjoined chromosomes 21 display differential hot spot usage (Oliver et al. 2013 in prep).
