Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21

Candace D. Middlebrooks, Nandita Mukhopadhyay, Stuart W. Tinker, Emily Graves Allen, Lora J.H. Bean, Ferdouse Begum, Reshmi Chowdhury, Vivian Cheung, Kimberly Doheny, Marcia Adams, Eleanor Feingold, Stephanie L. Sherman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalHuman molecular genetics
Volume23
Issue number2
DOIs
StatePublished - Jan 1 2014

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Chromosomes, Human, Pair 21
Genetic Recombination
Oocytes
Genome
Meiosis
Mothers
Chromosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Middlebrooks, C. D., Mukhopadhyay, N., Tinker, S. W., Allen, E. G., Bean, L. J. H., Begum, F., ... Sherman, S. L. (2014). Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21. Human molecular genetics, 23(2), 408-417. https://doi.org/10.1093/hmg/ddt433

Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21. / Middlebrooks, Candace D.; Mukhopadhyay, Nandita; Tinker, Stuart W.; Allen, Emily Graves; Bean, Lora J.H.; Begum, Ferdouse; Chowdhury, Reshmi; Cheung, Vivian; Doheny, Kimberly; Adams, Marcia; Feingold, Eleanor; Sherman, Stephanie L.

In: Human molecular genetics, Vol. 23, No. 2, 01.01.2014, p. 408-417.

Research output: Contribution to journalArticle

Middlebrooks, CD, Mukhopadhyay, N, Tinker, SW, Allen, EG, Bean, LJH, Begum, F, Chowdhury, R, Cheung, V, Doheny, K, Adams, M, Feingold, E & Sherman, SL 2014, 'Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21', Human molecular genetics, vol. 23, no. 2, pp. 408-417. https://doi.org/10.1093/hmg/ddt433
Middlebrooks CD, Mukhopadhyay N, Tinker SW, Allen EG, Bean LJH, Begum F et al. Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21. Human molecular genetics. 2014 Jan 1;23(2):408-417. https://doi.org/10.1093/hmg/ddt433
Middlebrooks, Candace D. ; Mukhopadhyay, Nandita ; Tinker, Stuart W. ; Allen, Emily Graves ; Bean, Lora J.H. ; Begum, Ferdouse ; Chowdhury, Reshmi ; Cheung, Vivian ; Doheny, Kimberly ; Adams, Marcia ; Feingold, Eleanor ; Sherman, Stephanie L. / Evidence for dysregulation of genome-wide recombination in oocytes with nondisjoined chromosomes 21. In: Human molecular genetics. 2014 ; Vol. 23, No. 2. pp. 408-417.
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