Characteristics of de novo structural changes in the human genome
Publication date
2015-01-01
Authors
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, I.J.
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Article
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Abstract
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.
Keywords
Genetics, Genetics(clinical)
Citation
Kloosterman, W P, Francioli, L C, Hormozdiari, F, Marschall, T, Hehir-Kwa, J Y, Abdellaoui, A, Lameijer, E W, Moed, M H, Koval, V, Renkens, I, Van Roosmalen, M J, Arp, P, Karssen, L C, Coe, B P, Handsaker, R E, Suchiman, E D, Cuppen, E, Thung, D T, McVey, M, Wendl, M C, Uitterlinden, A, Van Duijn, C M, Swertz, M A, Wijmenga, C, Van Ommen, G J B, Slagboom, P E, Boomsma, D I, Schönhuth, A, Eichler, E E, De Bakker, P I W, Ye, K, Guryev, V, Van Ommen, G J B, Bovenberg, J A, De Craen, A J M, Beekman, M, Hofman, A, Willemsen, G, Wolffenbuttel, B, Platteel, M, Du, Y, Chen, R, Cao, H, Cao, R, Sun, Y, Cao, J S, Van Dijk, F, Neerincx, P B T, Deelen, P, Dijkstra, M, Byelas, G, Kanterakis, A, Bot, J, Vermaat, M, Laros, J F J, Den Dunnen, J T, De Knijff, P, Van Leeuwen, E M, Amin, N, Rivadeneira, F, Estrada, K, De Ligt, J, Hottenga, J J, Kattenberg, V M, Van Enckevort, D, Mei, H, Santcroos, M, Van Schaik, B D C, McCarroll, S A, Ko, A, Sudmant, P & Nijman, I J 2015, 'Characteristics of de novo structural changes in the human genome', Genome Research, vol. 25, no. 6, pp. 792-801. https://doi.org/10.1101/gr.185041.114