Back to Search Start Over

An evolutionary genomic approach to identify genes involved in human birth timing.

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
Vineta Fellman
Emily A DeFranco
Bimal P Chaudhari
Tracy L McGregor
Jude J McElroy
Matthew T Oetjens
Kari Teramo
Ingrid Borecki
Justin Fay
Louis Muglia
Source :
PLoS Genetics, Vol 7, Iss 4, p e1001365 (2011)
Publication Year :
2011
Publisher :
Public Library of Science (PLoS), 2011.

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.

Subjects

Subjects :
Genetics
QH426-470

Details

Language :
English
ISSN :
15537390, 15537404, and 34471596
Volume :
7
Issue :
4
Database :
Directory of Open Access Journals
Journal :
PLoS Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.2c6d010dbe34471596d2b451f42ee54d
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pgen.1001365