RT Journal
A1 Kloosterman, Wigard P
A1 Francioli, Laurent C
A1 Hormozdiari, Fereydoun
A1 Marschall, Tobias
A1 Hehir-Kwa, Jayne Y
A1 Abdellaoui, Abdel
A1 Lameijer, Eric-Wubbo
A1 Moed, Matthijs H
A1 Koval, Vyacheslav
A1 Renkens, Ivo
A1 van Roosmalen, Markus J
A1 Arp, Pascal
A1 Karssen, Lennart C
A1 Coe, Bradley P
A1 Handsaker, Robert E
A1 Suchiman, Eka D
A1 Cuppen, Edwin
A1 Thung, Djie T
A1 McVey, Mitch
A1 Wendl, Michael C
A1 Uitterlinden, Andre
A1 van Duijn, Cornelia M
A1 Swertz, Morris
A1 Wijmenga, Cisca
A1 van Ommen, Gertjan
A1 Slagboom, P. Eline
A1 Boomsma, Dorret I
A1 Schönhuth, Alexander
A1 Eichler, Evan E
A1 de Bakker, Paul I.W
A1 Ye, Kai
A1 Guryev, Victor
T1 Characteristics of de novo structural changes in the human genome
JF Genome Research 
JO Genome Research 
YR 2015 
FD April 16 
DO 10.1101/gr.185041.114 
SP gr.185041.114 
UL http://genome.cshlp.org/content/early/2015/04/14/gr.185041.114.abstract 
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 (1-20bp) and 0.16 SVs (>20bp) per generation. De novo structural changes affect on average 4.1kbp 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 non-uniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations.