Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Sep;5(9):e1000661.
doi: 10.1371/journal.pgen.1000661. Epub 2009 Sep 18.

Meiotic Recombination in Human Oocytes

Affiliations
Free PMC article

Meiotic Recombination in Human Oocytes

Edith Y Cheng et al. PLoS Genet. .
Free PMC article

Abstract

Studies of human trisomies indicate a remarkable relationship between abnormal meiotic recombination and subsequent nondisjunction at maternal meiosis I or II. Specifically, failure to recombine or recombination events located either too near to or too far from the centromere have been linked to the origin of human trisomies. It should be possible to identify these abnormal crossover configurations by using immunofluorescence methodology to directly examine the meiotic recombination process in the human female. Accordingly, we initiated studies of crossover-associated proteins (e.g., MLH1) in human fetal oocytes to analyze their number and distribution on nondisjunction-prone human chromosomes and, more generally, to characterize genome-wide levels of recombination in the human female. Our analyses indicate that the number of MLH1 foci is lower than predicted from genetic linkage analysis, but its localization pattern conforms to that expected for a crossover-associated protein. In studies of individual chromosomes, our observations provide evidence for the presence of "vulnerable" crossover configurations in the fetal oocyte, consistent with the idea that these are subsequently translated into nondisjunctional events in the adult oocyte.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Representative images from (A) leptotene, (B) zygotene, and (C) pachytene stage human fetal oocytes.
Antibodies against SYCP3 (representing the axial elements of the synaptonemal complex) are visualized in red and against the DNA mismatch repair protein MLH1 in green, and CREST antiserum-positive signals (recognizing centromeric regions) are visualized in blue.
Figure 2
Figure 2. Chromosomal locations of MLH1 foci on chromosome 13 (Figure 2), considered by the number of MLH1 foci per SC.
Figure 3
Figure 3. Chromosomal locations of MLH1 foci on chromosome 16, considered by the number of MLH1 foci per SC.
Figure 4
Figure 4. Chromosomal locations of MLH1 foci on chromosome 17, considered by the number of MLH1 foci per SC.
Figure 5
Figure 5. Chromosomal locations of MLH1 foci on chromosome 18, considered by the number of MLH1 foci per SC.
Figure 6
Figure 6. Chromosomal locations of MLH1 foci on chromosome 21, considered by the number of MLH1 foci per SC.
Figure 7
Figure 7. Chromosomal locations of MLH1 foci on chromosome 22, considered by the number of MLH1 foci per SC.
Figure 8
Figure 8. Estimates of coincidence (and 95% confidence intervals) for intervals of different lengths on chromosomes 13, 16, 17, 18, 21, and 22.
For this analysis, coincidence was defined as: Pr (MLH1 foci in both intervals)/Pr (MLH1 focus in interval 1)×Pr (MLH1 focus in interval 2). Evidence for positive interference is denoted by coincidence values<1.0. For example, for chromosome 13, coincidence values were significantly under 1.0 over one, two, and three intervals, indicating that the presence of an MLH1 focus inhibited the presence of a second focus over as many as three intervals (e.g., from the p arm telomeric interval to the p arm proximal interval). Similarly, for chromosome 18 the effect extended over two intervals (e.g., from the p arm telomeric interval to the p arm medial interval).
Figure 9
Figure 9. Analysis of the location of adjacent short (p) arm and long (q) arm exchanges on chromosomes 16, 17, and 18.
For bivalents involving chromosomes 16, 17, and 18 in which we observed a single MLH1 focus on the p arm and a single MLH1 focus on the q arm, we examined the location of the p arm focus (centomeric/proximal, medial or distal/telomeric), ordered by the location of the q arm focus.

Similar articles

See all similar articles

Cited by 40 articles

See all "Cited by" articles

References

    1. Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007;16 Spec No. 2:R203–208. - PubMed
    1. Hall HE, Chan ER, Collins A, Judis L, Shirley S, et al. The origin of trisomy 13. Am J Med Genet A. 2007;143:2242–2248. - PubMed
    1. Bugge M, Collins A, Hertz JM, Eiberg H, Lundsteen C, et al. Non-disjunction of chromosome 13. Hum Mol Genet. 2007;16:2004–2010. - PubMed
    1. Robinson WP, Kuchinka BD, Bernasconi F, Petersen MB, Schulze A, et al. Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Hum Mol Genet. 1998;7:1011–1019. - PubMed
    1. Hassold TJ, Pettay D, Freeman SB, Grantham M, Takaesu N. Molecular studies of non-disjunction in trisomy 16. J Med Genet. 1991;28:159–162. - PMC - PubMed

Publication types

MeSH terms

Feedback