Effect of meiotic recombination on the production of aneuploid gametes in humans.
Within the last decade, aberrant meiotic recombination has been confirmed as a molecular risk factor for chromosome nondisjunction in humans. Recombination tethers homologous chromosomes, linking and guiding them through proper segregation at meiosis I. In model organisms, mutations that disturb the recombination pathway increase the frequency of chromosome malsegregation and alterations in both the amount and placement of meiotic recombination are associated with nondisjunction. This association has been established for humans as well. Significant alterations in recombination have been found for all meiosis I-derived trisomies studied to date and a subset of so called "meiosis II" trisomy. Often exchange levels are reduced in a subset of cases where the nondisjoining chromosome fails to undergo recombination. For other trisomies, the placement of meiotic recombination has been altered. It appears that recombination too near the centromere or too far from the centromere imparts an increased risk for nondisjunction. Recent evidence from trisomy 21 also suggests an association may exist between recombination and maternal age, the most widely identified risk factor for aneuploidy. Among cases of maternal meiosis I-derived trisomy 21, increasing maternal age is associated with a decreasing frequency of recombination in the susceptible pericentromeric and telomeric regions. It is likely that multiple risk factors lead to nondisjunction, some age dependent and others age independent, some that act globally and others that are chromosome specific. Future studies are expected to shed new light on the timing and placement of recombination, providing additional clues to the link between altered recombination and chromosome nondisjunction.
Lamb
N E
NE
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. nlamb@genetics.emory.edu
Sherman
S L
SL
Hassold
T J
TJ
D000782:Aneuploidy; D005260:Female; D006801:Humans; D008297:Male; D008540:Meiosis; D009630:Nondisjunction, Genetic; D010063:Ovum / Q000502:physiology; D011995:Recombination, Genetic; D013094:Spermatozoa / Q000502:physiology