Characteristics of de novo structural changes in the human genome.

نویسندگان

  • Wigard P Kloosterman
  • Laurent C Francioli
  • Fereydoun Hormozdiari
  • Tobias Marschall
  • Jayne Y Hehir-Kwa
  • Abdel Abdellaoui
  • Eric-Wubbo Lameijer
  • Matthijs H Moed
  • Vyacheslav Koval
  • Ivo Renkens
  • Markus J van Roosmalen
  • Pascal Arp
  • Lennart C Karssen
  • Bradley P Coe
  • Robert E Handsaker
  • Eka D Suchiman
  • Edwin Cuppen
  • Djie Tjwan Thung
  • Mitch McVey
  • Michael C Wendl
  • André Uitterlinden
  • Cornelia M van Duijn
  • Morris A Swertz
  • Cisca Wijmenga
  • GertJan B van Ommen
  • P Eline Slagboom
  • Dorret I Boomsma
  • Alexander Schönhuth
  • Evan E Eichler
  • Paul I W de Bakker
  • Kai Ye
  • Victor Guryev
چکیده

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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عنوان ژورنال:
  • Genome research

دوره 25 6  شماره 

صفحات  -

تاریخ انتشار 2015