Patterns of meiotic recombination in human fetal oocytes - PubMed (original) (raw)

. 2002 Jun;70(6):1469-79.

doi: 10.1086/340734. Epub 2002 May 1.

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Patterns of meiotic recombination in human fetal oocytes

Charles Tease et al. Am J Hum Genet. 2002 Jun.

Abstract

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.

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Figures

Figure 1

Figure 1

Paired images of two pachytene oocytes. SCs are shown in red, and MLH1 foci are shown in yellow. a and b, Oocyte with normal chromosome synapsis. The cell is shown after detection of MLH1 (a) and after FISH to identify selected chromosome pairs (b). Chromosome 21 has 1 focus, chromosome 18 has 3 foci, chromosome 13 is obscured by overlaps, and chromosome X has 5 foci. c and d, Abnormal oocyte showing synaptic errors. The cell is shown after MLH1 detection (c) and subsequent FISH (d). Chromosome X displays synaptic failure and, as a result, is present as two separate AEs (leftward-pointing arrowheads); chromosome 18 shows partial synapsis (downward-pointing arrow). MLH1 foci are present along fully synapsed bivalents and on the synapsed segment of chromosome 18 (c); there are no foci on the asynapsed axes of chromosomes X.

Figure 2

Figure 2

Histograms showing the distributions of foci. Each chromosome is divided into 5% intervals (see “Material and Methods”), and the position of the centromere is indicated by a blackened oval on the _X-_axis. The positions of foci are shown separately (for bivalents with 1, 2, 3, etc., foci). For ease of presentation, the chromosome pairs are not shown to scale.

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