Patterns of meiotic recombination in human fetal oocytes

Am J Hum Genet. 2002 Jun;70(6):1469-79. doi: 10.1086/340734. Epub 2002 May 1.


Abnormal patterns of meiotic recombination (i.e., crossing-over) are believed to increase the risk of chromosome nondisjunction in human oocytes. To date, information on recombination has been obtained using indirect, genetic methods. Here we use an immunocytological approach, based on detection of foci of a DNA mismatch-repair protein, MLH1, on synaptonemal complexes at prophase I of meiosis, to provide the first direct estimate of the frequency of meiotic recombination in human oocytes. At pachytene, the stage of maximum homologous chromosome pairing, we found a mean of 70.3 foci (i.e., crossovers) per oocyte, with considerable intercell variability (range 48-102 foci). This mean equates to a genetic-map length of 3,515 cM. The numbers and positions of foci were determined for chromosomes 21, 18, 13, and X. These chromosomes yielded means of 1.23 foci (61.5 cM), 2.36 foci (118 cM), 2.5 foci (125 cM), and 3.22 foci (161 cM), respectively. The foci were almost invariably located interstitially and were only occasionally located close to chromosome ends. These data confirm the large difference, in recombination frequency, between human oocytes and spermatocytes and demonstrate a clear intersex variation in distribution of crossovers. In a few cells, chromosomes 21 and 18 did not have any foci (i.e., were presumptively noncrossover); however, configurations that lacked foci were not observed for chromosomes 13 and X. For the latter two chromosome pairs, the only instances of absence of foci were observed in abnormal cells that showed chromosome-pairing errors affecting these chromosomes. We speculate that these abnormal fetal oocytes may be the source of the nonrecombinant chromosomes 13 and X suggested, by genetic studies, to be associated with maternally derived chromosome nondisjunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Chromosome Pairing / genetics
  • Chromosome Segregation / genetics
  • Chromosomes, Human / genetics*
  • Chromosomes, Human / metabolism
  • Crossing Over, Genetic / genetics
  • Female
  • Fetus / cytology*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Meiosis / genetics*
  • MutL Protein Homolog 1
  • Neoplasm Proteins / metabolism
  • Nondisjunction, Genetic
  • Nuclear Proteins
  • Oocytes / cytology*
  • Oocytes / metabolism*
  • Recombination, Genetic / genetics*
  • Spermatocytes / cytology
  • Spermatocytes / metabolism
  • Synaptonemal Complex / metabolism


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • MutL Protein Homolog 1