TY - JOUR
T1 - Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21
AU - Middlebrooks, Candace D.
AU - Mukhopadhyay, Nandita
AU - Tinker, Stuart W.
AU - Allen, Emily Graves
AU - Bean, Lora J.H.
AU - Begum, Ferdouse
AU - Chowdhury, Reshmi
AU - Cheung, Vivian
AU - Doheny, Kimberly
AU - Adams, Marcia
AU - Feingold, Eleanor
AU - Sherman, Stephanie L.
N1 - Funding Information:
This work was supported by the National Institutes of Health [1T32MH087977 (T.O.), R01 HD057029 and R01 HD38979 (S.S., E.F.), R01 HL083300, R01-DE 014899 and U01-DE018903 (M.M.)] and the Center for Inherited Disease Research [HHSN268200782096C (M.M.)] and the Children’s Healthcare of Atlanta Cardiac Research Committee.
PY - 2014/1
Y1 - 2014/1
N2 - In oocytes with nondisjoined chromosomes 21 due to a meiosis I (MI) error, recombination is significantly reduced along chromosome 21; several lines of evidence indicate that this contributes to the nondisjunction event. A pilot study found evidence that these oocytes also have reduced recombination genome-wide when compared with controls. This suggests that factors that act globally may be contributing to the reduced recombination on chromosome 21, and hence, the nondisjunction event. To identify the source of these factors, we examined two levels of recombination count regulation in oocytes: (i) regulation at the maternal level that leads to correlation in genome-wide recombination across her oocytes and (ii) regulation at the oocyte level that leads to correlation in recombination count among the chromosomes of an oocyte. We sought to determine whether either of these properties was altered in oocytes with an MI error. As it relates to maternal regulation, we found that both oocytes with an MI error (N=94) and their siblings (N=64) had reduced recombination when compared with controls (N=2723) At the oocyte level, we found that the correlation in recombination count among the chromosomes of an oocyte is reduced in oocytes with MI errors compared with that of their siblings or controls. These results suggest that regulation at the maternal level predisposes MI error oocytes to reduced levels of recombination, but additional oocyte-specific dysregulation contributes to the nondisjunction event.
AB - In oocytes with nondisjoined chromosomes 21 due to a meiosis I (MI) error, recombination is significantly reduced along chromosome 21; several lines of evidence indicate that this contributes to the nondisjunction event. A pilot study found evidence that these oocytes also have reduced recombination genome-wide when compared with controls. This suggests that factors that act globally may be contributing to the reduced recombination on chromosome 21, and hence, the nondisjunction event. To identify the source of these factors, we examined two levels of recombination count regulation in oocytes: (i) regulation at the maternal level that leads to correlation in genome-wide recombination across her oocytes and (ii) regulation at the oocyte level that leads to correlation in recombination count among the chromosomes of an oocyte. We sought to determine whether either of these properties was altered in oocytes with an MI error. As it relates to maternal regulation, we found that both oocytes with an MI error (N=94) and their siblings (N=64) had reduced recombination when compared with controls (N=2723) At the oocyte level, we found that the correlation in recombination count among the chromosomes of an oocyte is reduced in oocytes with MI errors compared with that of their siblings or controls. These results suggest that regulation at the maternal level predisposes MI error oocytes to reduced levels of recombination, but additional oocyte-specific dysregulation contributes to the nondisjunction event.
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U2 - 10.1093/hmg/ddt433
DO - 10.1093/hmg/ddt433
M3 - Article
C2 - 24014426
AN - SCOPUS:84903824967
SN - 0964-6906
VL - 23
SP - 408
EP - 417
JO - Human molecular genetics
JF - Human molecular genetics
IS - 2
ER -