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Copy Number Variation Is a Fundamental Aspect of the Placental Genome
Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000N polyploid trophoblast giant cells (TGCs) of the mouse pl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006706/ https://www.ncbi.nlm.nih.gov/pubmed/24785991 http://dx.doi.org/10.1371/journal.pgen.1004290 |
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author | Hannibal, Roberta L. Chuong, Edward B. Rivera-Mulia, Juan Carlos Gilbert, David M. Valouev, Anton Baker, Julie C. |
author_facet | Hannibal, Roberta L. Chuong, Edward B. Rivera-Mulia, Juan Carlos Gilbert, David M. Valouev, Anton Baker, Julie C. |
author_sort | Hannibal, Roberta L. |
collection | PubMed |
description | Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication. |
format | Online Article Text |
id | pubmed-4006706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40067062014-05-09 Copy Number Variation Is a Fundamental Aspect of the Placental Genome Hannibal, Roberta L. Chuong, Edward B. Rivera-Mulia, Juan Carlos Gilbert, David M. Valouev, Anton Baker, Julie C. PLoS Genet Research Article Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication. Public Library of Science 2014-05-01 /pmc/articles/PMC4006706/ /pubmed/24785991 http://dx.doi.org/10.1371/journal.pgen.1004290 Text en © 2014 Hannibal et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hannibal, Roberta L. Chuong, Edward B. Rivera-Mulia, Juan Carlos Gilbert, David M. Valouev, Anton Baker, Julie C. Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title | Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title_full | Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title_fullStr | Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title_full_unstemmed | Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title_short | Copy Number Variation Is a Fundamental Aspect of the Placental Genome |
title_sort | copy number variation is a fundamental aspect of the placental genome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006706/ https://www.ncbi.nlm.nih.gov/pubmed/24785991 http://dx.doi.org/10.1371/journal.pgen.1004290 |
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