The impact of recombination on human mutation load and disease

Philos Trans R Soc Lond B Biol Sci. 2017 Dec 19;372(1736):20160465. doi: 10.1098/rstb.2016.0465.

Abstract

Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict regulation of the molecular mechanisms associated with proper chromosomal disjunction. In humans, congenital defects and recurrent structural abnormalities can be attributed to aberrant meiotic recombination. Moreover, mutations affecting genes involved in recombination pathways are directly linked to pathologies including infertility and cancer. Recombination is among the most prominent mechanism shaping genome variation, and is associated with not only the structuring of genomic variability, but is also tightly linked with the purging of deleterious mutations from populations. Together, these observations highlight the multiple roles of recombination in human genetics: its ability to act as a major force of evolution, its molecular potential to maintain genome repair and integrity in cell division and its mutagenic cost impacting disease evolution.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.

Keywords: PRDM9; cancer; disease; gene conversion; mutation load; recombination.

Publication types

  • Review

MeSH terms

  • Communicable Diseases / genetics*
  • Evolution, Molecular*
  • Genetic Linkage
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Mutation*
  • Recombination, Genetic*

Substances

  • Histone-Lysine N-Methyltransferase
  • PRDM9 protein, human