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Characteristics of de novo structural changes in the human genome
Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de no...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448676/ https://www.ncbi.nlm.nih.gov/pubmed/25883321 http://dx.doi.org/10.1101/gr.185041.114 |
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author | Kloosterman, Wigard P. Francioli, Laurent C. Hormozdiari, Fereydoun Marschall, Tobias Hehir-Kwa, Jayne Y. Abdellaoui, Abdel Lameijer, Eric-Wubbo Moed, Matthijs H. Koval, Vyacheslav Renkens, Ivo van Roosmalen, Markus J. Arp, Pascal Karssen, Lennart C. Coe, Bradley P. Handsaker, Robert E. Suchiman, Eka D. Cuppen, Edwin Thung, Djie Tjwan McVey, Mitch Wendl, Michael C. Uitterlinden, André van Duijn, Cornelia M. Swertz, Morris A. Wijmenga, Cisca van Ommen, GertJan B. Slagboom, P. Eline Boomsma, Dorret I. Schönhuth, Alexander Eichler, Evan E. de Bakker, Paul I.W. Ye, Kai Guryev, Victor |
author_facet | Kloosterman, Wigard P. Francioli, Laurent C. Hormozdiari, Fereydoun Marschall, Tobias Hehir-Kwa, Jayne Y. Abdellaoui, Abdel Lameijer, Eric-Wubbo Moed, Matthijs H. Koval, Vyacheslav Renkens, Ivo van Roosmalen, Markus J. Arp, Pascal Karssen, Lennart C. Coe, Bradley P. Handsaker, Robert E. Suchiman, Eka D. Cuppen, Edwin Thung, Djie Tjwan McVey, Mitch Wendl, Michael C. Uitterlinden, André van Duijn, Cornelia M. Swertz, Morris A. Wijmenga, Cisca van Ommen, GertJan B. Slagboom, P. Eline Boomsma, Dorret I. Schönhuth, Alexander Eichler, Evan E. de Bakker, Paul I.W. Ye, Kai Guryev, Victor |
author_sort | Kloosterman, Wigard P. |
collection | PubMed |
description | Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1–20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations. |
format | Online Article Text |
id | pubmed-4448676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44486762015-12-01 Characteristics of de novo structural changes in the human genome Kloosterman, Wigard P. Francioli, Laurent C. Hormozdiari, Fereydoun Marschall, Tobias Hehir-Kwa, Jayne Y. Abdellaoui, Abdel Lameijer, Eric-Wubbo Moed, Matthijs H. Koval, Vyacheslav Renkens, Ivo van Roosmalen, Markus J. Arp, Pascal Karssen, Lennart C. Coe, Bradley P. Handsaker, Robert E. Suchiman, Eka D. Cuppen, Edwin Thung, Djie Tjwan McVey, Mitch Wendl, Michael C. Uitterlinden, André van Duijn, Cornelia M. Swertz, Morris A. Wijmenga, Cisca van Ommen, GertJan B. Slagboom, P. Eline Boomsma, Dorret I. Schönhuth, Alexander Eichler, Evan E. de Bakker, Paul I.W. Ye, Kai Guryev, Victor Genome Res Research Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1–20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations. Cold Spring Harbor Laboratory Press 2015-06 /pmc/articles/PMC4448676/ /pubmed/25883321 http://dx.doi.org/10.1101/gr.185041.114 Text en © 2015 Kloosterman 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 | Research Kloosterman, Wigard P. Francioli, Laurent C. Hormozdiari, Fereydoun Marschall, Tobias Hehir-Kwa, Jayne Y. Abdellaoui, Abdel Lameijer, Eric-Wubbo Moed, Matthijs H. Koval, Vyacheslav Renkens, Ivo van Roosmalen, Markus J. Arp, Pascal Karssen, Lennart C. Coe, Bradley P. Handsaker, Robert E. Suchiman, Eka D. Cuppen, Edwin Thung, Djie Tjwan McVey, Mitch Wendl, Michael C. Uitterlinden, André van Duijn, Cornelia M. Swertz, Morris A. Wijmenga, Cisca van Ommen, GertJan B. Slagboom, P. Eline Boomsma, Dorret I. Schönhuth, Alexander Eichler, Evan E. de Bakker, Paul I.W. Ye, Kai Guryev, Victor Characteristics of de novo structural changes in the human genome |
title | Characteristics of de novo structural changes in the human genome |
title_full | Characteristics of de novo structural changes in the human genome |
title_fullStr | Characteristics of de novo structural changes in the human genome |
title_full_unstemmed | Characteristics of de novo structural changes in the human genome |
title_short | Characteristics of de novo structural changes in the human genome |
title_sort | characteristics of de novo structural changes in the human genome |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448676/ https://www.ncbi.nlm.nih.gov/pubmed/25883321 http://dx.doi.org/10.1101/gr.185041.114 |
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