TY - JOUR
T1 - Characteristics of de novo structural changes in the human genome
AU - Genome of the Netherlands Consortium
AU - Kloosterman, Wigard P.
AU - Francioli, Laurent C.
AU - Hormozdiari, Fereydoun
AU - Marschall, Tobias
AU - Hehir-Kwa, Jayne Y.
AU - Abdellaoui, Abdel
AU - Lameijer, Eric Wubbo
AU - Moed, Matthijs H.
AU - Koval, Vyacheslav
AU - Renkens, Ivo
AU - Van Roosmalen, Markus J.
AU - Arp, Pascal
AU - Karssen, Lennart C.
AU - Coe, Bradley P.
AU - Handsaker, Robert E.
AU - Suchiman, Eka D.
AU - Cuppen, Edwin
AU - Thung, Djie Tjwan
AU - McVey, Mitch
AU - Wendl, Michael C.
AU - Uitterlinden, André
AU - Van Duijn, Cornelia M.
AU - Swertz, Morris A.
AU - Wijmenga, Cisca
AU - Van Ommen, Gert Jan B.
AU - Slagboom, P. Eline
AU - Boomsma, Dorret I.
AU - Schönhuth, Alexander
AU - Eichler, Evan E.
AU - De Bakker, Paul I.W.
AU - Ye, Kai
AU - Guryev, Victor
AU - Van Ommen, Gert Jan B.
AU - Bovenberg, Jasper A.
AU - De Craen, Anton J.M.
AU - Beekman, Marian
AU - Hofman, Albert
AU - Willemsen, Gonneke
AU - Wolffenbuttel, Bruce
AU - Platteel, Mathieu
AU - Du, Yuanping
AU - Chen, Ruoyan
AU - Cao, Hongzhi
AU - Cao, Rui
AU - Sun, Yushen
AU - Cao, Jeremy Sujie
AU - Van Dijk, Freerk
AU - Neerincx, Pieter B.T.
AU - Deelen, Patrick
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2015 Kloosterman et al.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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 (120 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.
AB - 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 (120 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.
UR - https://www.scopus.com/pages/publications/84931833875
U2 - 10.1101/gr.185041.114
DO - 10.1101/gr.185041.114
M3 - Article
C2 - 25883321
AN - SCOPUS:84931833875
SN - 1088-9051
VL - 25
SP - 792
EP - 801
JO - Genome Research
JF - Genome Research
IS - 6
ER -