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Meiotic recombination in human oocytes.

Cheng EY, Hunt PA, Naluai-Cecchini TA, Fligner CL, Fujimoto VY, Pasternack TL, Schwartz JM, Steinauer JE, Woodruff TJ, Cherry SM, Hansen TA, Vallente RU, Broman KW, Hassold TJ - PLoS Genet. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America.

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.

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Related in: MedlinePlus

Chromosomal locations of MLH1 foci on chromosome 13 (Figure 2), considered by the number of MLH1 foci per SC.
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pgen-1000661-g002: Chromosomal locations of MLH1 foci on chromosome 13 (Figure 2), considered by the number of MLH1 foci per SC.

Mentions: Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, and Figure 7 show the approximate location of MLH1 foci, ordered by the number of MLH1 foci per SC, for chromosomes 13, 16, 17, 18, 21 and 22 (Figure S2, S3, S4, S5, S6, S7 show the same information, but with the data pooled by the number of MLH1 foci per SC). For this analysis, we simply divided the chromosome arms into five equal segments, and specified the segmental location for each MLH1 focus. Clearly, this only provides a general assessment of MLH1 localization, since it does not take into account the variation in arm-arm physical lengths for individual chromosomes. Nevertheless, it provides a mechanism for generating initial cytological maps and for examining spatial relationships between foci that are located on the same chromosomes.


Meiotic recombination in human oocytes.

Cheng EY, Hunt PA, Naluai-Cecchini TA, Fligner CL, Fujimoto VY, Pasternack TL, Schwartz JM, Steinauer JE, Woodruff TJ, Cherry SM, Hansen TA, Vallente RU, Broman KW, Hassold TJ - PLoS Genet. (2009)

Chromosomal locations of MLH1 foci on chromosome 13 (Figure 2), considered by the number of MLH1 foci per SC.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2735652&req=5

pgen-1000661-g002: Chromosomal locations of MLH1 foci on chromosome 13 (Figure 2), considered by the number of MLH1 foci per SC.
Mentions: Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, and Figure 7 show the approximate location of MLH1 foci, ordered by the number of MLH1 foci per SC, for chromosomes 13, 16, 17, 18, 21 and 22 (Figure S2, S3, S4, S5, S6, S7 show the same information, but with the data pooled by the number of MLH1 foci per SC). For this analysis, we simply divided the chromosome arms into five equal segments, and specified the segmental location for each MLH1 focus. Clearly, this only provides a general assessment of MLH1 localization, since it does not take into account the variation in arm-arm physical lengths for individual chromosomes. Nevertheless, it provides a mechanism for generating initial cytological maps and for examining spatial relationships between foci that are located on the same chromosomes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America.

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.

Show MeSH
Related in: MedlinePlus