Relationship of recombination patterns and maternal age among non-disjoined chromosomes 21

Abstract

Advancing maternal age has long been identified as the primary risk factor for human chromosome trisomy. More recently, altered patterns of meiotic recombination have been found to be associated with non-disjunction. We have used trisomy 21 as a model for human non-disjunction that occurs during the formation of oocytes to understand the role of maternal age and recombination. Patterns of recombination that increase the risk for non-disjunction of chromosome 21 include absence of any exchange, an exchange near the centromere or a single, telomeric exchange. Our recent work has shown that different susceptibility patterns are associated with the origin of the meiotic error and maternal age. For MI (meiosis I) errors, the proportion of oocytes with susceptible recombination patterns is highest among young mothers and decreases significantly in the oldest age group. In fact, the pattern of exchanges among the oldest age group mimics the pattern observed among normally disjoining chromosomes 21. These results suggest that oocytes of younger women, with functional meiotic apparatus and/or robust ovarian environment, are able to properly resolve all but the most susceptible exchange patterns. As women age, however, meiotic mechanisms erode, making it difficult to resolve even stable exchange events. Interestingly, our preliminary recombination results on MII errors reveal the opposite relationship with maternal age: susceptible pericentromeric exchanges occur most often in the older age group compared with the younger age group. If confirmed, we will have further evidence for multiple risk factors for non-disjunction that act at different times in the meiotic process.