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Rapid molecular assays to study human centromere genomics

The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for s...

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Autores principales: Contreras-Galindo, Rafael, Fischer, Sabrina, Saha, Anjan K., Lundy, John D., Cervantes, Patrick W., Mourad, Mohamad, Wang, Claire, Qian, Brian, Dai, Manhong, Meng, Fan, Chinnaiyan, Arul, Omenn, Gilbert S., Kaplan, Mark H., Markovitz, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741061/
https://www.ncbi.nlm.nih.gov/pubmed/29141960
http://dx.doi.org/10.1101/gr.219709.116
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author Contreras-Galindo, Rafael
Fischer, Sabrina
Saha, Anjan K.
Lundy, John D.
Cervantes, Patrick W.
Mourad, Mohamad
Wang, Claire
Qian, Brian
Dai, Manhong
Meng, Fan
Chinnaiyan, Arul
Omenn, Gilbert S.
Kaplan, Mark H.
Markovitz, David M.
author_facet Contreras-Galindo, Rafael
Fischer, Sabrina
Saha, Anjan K.
Lundy, John D.
Cervantes, Patrick W.
Mourad, Mohamad
Wang, Claire
Qian, Brian
Dai, Manhong
Meng, Fan
Chinnaiyan, Arul
Omenn, Gilbert S.
Kaplan, Mark H.
Markovitz, David M.
author_sort Contreras-Galindo, Rafael
collection PubMed
description The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings.
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spelling pubmed-57410612018-06-01 Rapid molecular assays to study human centromere genomics Contreras-Galindo, Rafael Fischer, Sabrina Saha, Anjan K. Lundy, John D. Cervantes, Patrick W. Mourad, Mohamad Wang, Claire Qian, Brian Dai, Manhong Meng, Fan Chinnaiyan, Arul Omenn, Gilbert S. Kaplan, Mark H. Markovitz, David M. Genome Res Method The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings. Cold Spring Harbor Laboratory Press 2017-12 /pmc/articles/PMC5741061/ /pubmed/29141960 http://dx.doi.org/10.1101/gr.219709.116 Text en © 2017 Contreras-Galindo et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Contreras-Galindo, Rafael
Fischer, Sabrina
Saha, Anjan K.
Lundy, John D.
Cervantes, Patrick W.
Mourad, Mohamad
Wang, Claire
Qian, Brian
Dai, Manhong
Meng, Fan
Chinnaiyan, Arul
Omenn, Gilbert S.
Kaplan, Mark H.
Markovitz, David M.
Rapid molecular assays to study human centromere genomics
title Rapid molecular assays to study human centromere genomics
title_full Rapid molecular assays to study human centromere genomics
title_fullStr Rapid molecular assays to study human centromere genomics
title_full_unstemmed Rapid molecular assays to study human centromere genomics
title_short Rapid molecular assays to study human centromere genomics
title_sort rapid molecular assays to study human centromere genomics
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741061/
https://www.ncbi.nlm.nih.gov/pubmed/29141960
http://dx.doi.org/10.1101/gr.219709.116
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