Missegregation of Chromosome 21 In Oocyte: What Genetic Causes Imperil a Healthy Egg to Have Bad Fate?

Down syndrome represents the most frequent live born aneuploidy and genetic form of intellectual disability. The overwhelming majority of live born Down syndrome is caused by trisomy 21 condition, although a small fraction is due to the inheritance of de novo translocated chromosome 21. The extra copy of chromosome 21 originates owing to non-separation or nondisjunction of chromosome at anaphase in meiotic cell division of gametogenesis. Sincere research attempt have recognized that the higher incidence of Down syndrome birth is associated with maternal advanced age of conception and reduced recombination on chromosome 21. Using panel of short tandem repeat (STR) markers scientists have proved for overwhelming majority of cases, the error originates in maternal first meiotic division when the oocyte grows in fetal ovary and the maternal age effect is restricted only to these maternally originated cases. Several hypotheses have been proposed to explain this maternal age associated increase in the incidence of Down syndrome birth. With large population sample and refined analytical approaches scientists have determined that the effect of recombination error on the nondisjunction is bimodal. On one hand, overall reduction in recombination frequency imparts a risk of nondisjunction irrespective of maternal age. On other hand, some susceptible chiasma configurations increase the chance of chromosome malsegregation with advancing maternal age. Thus the risk factors for the chromosome 21 nondisjunction are of two categories namely, maternal age independent and maternal age dependent. Beside these, some genetic polymorphisms show high degree of susceptibility for Down syndrome conception among women. The gene MTHFR is such candidate which is actually involved in folic acid metabolism pathway and its specific polymorphisms exhibits predisposition to missegregation of Ch21 irrespective of ethnicity of population across the globe. The present review is focused to address the latest development in understanding the role of genetic and molecular risk factors for Down syndrome birth.