Properties and rates of germline mutations in humans

Trends Genet. 2013 Oct;29(10):575-84. doi: 10.1016/j.tig.2013.04.005. Epub 2013 May 16.


All genetic variation arises via new mutations; therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. However, advances in sequencing technology have allowed for empirical assessments of genome-wide rates of mutation. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age. Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). Here, we review the genome-wide analyses for the mutation rate of several types of variants and suggest areas for future research.

Keywords: de novo mutation; genome wide; germline mutation rate; paternal age; paternal bias.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Evolution
  • DNA Copy Number Variations / genetics
  • Disease / genetics
  • Germ-Line Mutation / genetics*
  • Humans
  • Mutation Rate*
  • Polymorphism, Single Nucleotide / genetics