Genome-wide variation in recombination in female meiosis: a risk factor for non-disjunction of chromosome 21

Altered recombination patterns along non-disjoined chromosomes is the first molecular correlate identified for non-disjunction in humans. To understan d better the factors related to this correlate, we have asked to what exten t is recombination altered in an egg with a disomic chromosome: are pattern s limited to the non-disjoined chromosome or do they extend to the entire c ell? More specifically, we asked whether there is reduced recombination in the total genome of an egg with a non-disjoined chromosome 21 and no detect able recombination. We chose this subclass of non-disjoined chromosomes to enrich potentially for extremes in recombination. We found a statistically significant cell-wide reduction in the mean recombination rate in these egg s with non-disjoined chromosomes 21; no specific chromosomes were driving t his effect. Most importantly, we found that this reduction was consistent w ith normal variation in recombination observed among eggs. Thus, given that recombination is a multifactorial trait, these data suggest that when the number of genome-wide recombination events is less than some threshold, spe cific chromosomes may be at an increased risk for non-disjunction. Further studies are required to confirm these results, to determine the importance of genetic and environmental factors that regulate recombination and to det ermine their impact on non-disjunction.