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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
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.
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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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