An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

Research output: Contribution to journalArticle

Abstract

Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened.8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.

Details

Authors
  • Jevon Plunkett
  • Scott Doniger
  • Guilherme Orabona
  • Thomas Morgan
  • Ritva Haataja
  • Mikko Hallman
  • Hilkka Puttonen
  • Ramkumar Menon
  • Edward Kuczynski
  • Errol Norwitz
  • Victoria Snegovskikh
  • Aarno Palotie
  • Leena Peltonen
  • Emily A. DeFranco
  • Bimal P. Chaudhari
  • Tracy L. McGregor
  • Jude J. McElroy
  • Matthew T. Oetjens
  • Kari Teramo
  • Ingrid Borecki
  • Justin Fay
  • Louis Muglia
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics
Original languageEnglish
JournalPLoS Genetics
Volume7
Issue number4
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes