Failure to recombine is a common feature of human oogenesis

Am J Hum Genet. 2021 Jan 7;108(1):16-24. doi: 10.1016/j.ajhg.2020.11.010. Epub 2020 Dec 10.


Failure of homologous chromosomes to recombine is arguably the most important cause of human meiotic nondisjunction, having been linked to numerous autosomal and sex chromosome trisomies of maternal origin. However, almost all information on these "exchangeless" homologs has come from genetic mapping studies of trisomic conceptuses, so the incidence of this defect and its impact on gametogenesis are not clear. If oocytes containing exchangeless homologs are selected against during meiosis, the incidence may be much higher in developing germ cells than in zygotes. To address this, we initiated studies of exchangeless chromosomes in fetal ovarian samples from elective terminations of pregnancy. In total, we examined more than 7,000 oocytes from 160 tissue samples, scoring for the number of foci per cell of the crossover-associated protein MLH1. We identified a surprisingly high level of recombination failure, with more than 7% of oocytes containing at least one chromosome pair that lacked an MLH1 focus. Detailed analyses indicate striking chromosome-specific differences, with a preponderance of MLH1-less homologs involving chromosomes 21 or 22. Further, the effect was linked to the overall level of recombination in the cell, with the presence of one or two exchangeless chromosomes in a cell associated with a 10%-20% reduction in the total number of crossovers. This suggests individuals with lower rates of meiotic recombination are at an increased risk of producing aneuploid offspring.

Keywords: aneuploidy; exchangeless homologs; meiosis; oogenesis; recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aneuploidy
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Female
  • Humans
  • Meiosis / genetics
  • MutL Protein Homolog 1 / genetics
  • Nondisjunction, Genetic / genetics
  • Oocytes / physiology
  • Oogenesis / genetics*
  • Pregnancy
  • Recombination, Genetic / genetics*
  • Young Adult


  • MutL Protein Homolog 1