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An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction

Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increas...

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Autores principales: Oliver, Tiffany Renee, Middlebrooks, Candace D., Tinker, Stuart W., Allen, Emily Graves, Bean, Lora J. H., Begum, Ferdouse, Feingold, Eleanor, Chowdhury, Reshmi, Cheung, Vivian, Sherman, Stephanie L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057233/
https://www.ncbi.nlm.nih.gov/pubmed/24926858
http://dx.doi.org/10.1371/journal.pone.0099560
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author Oliver, Tiffany Renee
Middlebrooks, Candace D.
Tinker, Stuart W.
Allen, Emily Graves
Bean, Lora J. H.
Begum, Ferdouse
Feingold, Eleanor
Chowdhury, Reshmi
Cheung, Vivian
Sherman, Stephanie L.
author_facet Oliver, Tiffany Renee
Middlebrooks, Candace D.
Tinker, Stuart W.
Allen, Emily Graves
Bean, Lora J. H.
Begum, Ferdouse
Feingold, Eleanor
Chowdhury, Reshmi
Cheung, Vivian
Sherman, Stephanie L.
author_sort Oliver, Tiffany Renee
collection PubMed
description Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A)/Poly(T) fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. These observations led us to ask whether the altered patterns of recombination associated with maternal nondisjunction of chromosome 21 could be explained by differences in the relationship between recombination placement and recombination-related genomic features (i.e., GC content, CpG fraction, Poly(A)/Poly(T) fraction or gene density) on 21q or differential hot-spot usage along the nondisjoined chromosome 21. We found several significant associations between our genomic features of interest and recombination, interestingly, these results were not consistent among recombination types (single and double proximal or distal events). We also found statistically significant relationships between the frequency of hotspots and the distribution of recombination along nondisjoined chromosomes. Collectively, these findings suggest that factors that affect the accessibility of a specific chromosome region to recombination may be altered in at least a proportion of oocytes with MI and MII errors.
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spelling pubmed-40572332014-06-18 An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction Oliver, Tiffany Renee Middlebrooks, Candace D. Tinker, Stuart W. Allen, Emily Graves Bean, Lora J. H. Begum, Ferdouse Feingold, Eleanor Chowdhury, Reshmi Cheung, Vivian Sherman, Stephanie L. PLoS One Research Article Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A)/Poly(T) fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. These observations led us to ask whether the altered patterns of recombination associated with maternal nondisjunction of chromosome 21 could be explained by differences in the relationship between recombination placement and recombination-related genomic features (i.e., GC content, CpG fraction, Poly(A)/Poly(T) fraction or gene density) on 21q or differential hot-spot usage along the nondisjoined chromosome 21. We found several significant associations between our genomic features of interest and recombination, interestingly, these results were not consistent among recombination types (single and double proximal or distal events). We also found statistically significant relationships between the frequency of hotspots and the distribution of recombination along nondisjoined chromosomes. Collectively, these findings suggest that factors that affect the accessibility of a specific chromosome region to recombination may be altered in at least a proportion of oocytes with MI and MII errors. Public Library of Science 2014-06-13 /pmc/articles/PMC4057233/ /pubmed/24926858 http://dx.doi.org/10.1371/journal.pone.0099560 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Oliver, Tiffany Renee
Middlebrooks, Candace D.
Tinker, Stuart W.
Allen, Emily Graves
Bean, Lora J. H.
Begum, Ferdouse
Feingold, Eleanor
Chowdhury, Reshmi
Cheung, Vivian
Sherman, Stephanie L.
An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title_full An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title_fullStr An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title_full_unstemmed An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title_short An Examination of the Relationship between Hotspots and Recombination Associated with Chromosome 21 Nondisjunction
title_sort examination of the relationship between hotspots and recombination associated with chromosome 21 nondisjunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057233/
https://www.ncbi.nlm.nih.gov/pubmed/24926858
http://dx.doi.org/10.1371/journal.pone.0099560
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