Characteristics of de novo structural changes in the human genome

Genome of the Netherlands Consortium

Research output: Contribution to journalArticle

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)792-801
Number of pages10
JournalGenome Research
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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