Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth
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Peltonen-2010-Primate-specific evolution of noncoding element.pdf
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Author(s)
Plunkett, Jevon
Doniger, Scott
Morgan, Thomas
Haataja, Ritva
Hallman, Mikko
Puttonen, Hilkka
Menon, Ramkumar
Kuczynski, Edward
Norwitz, Errol
Snegovskikh, Victoria
Date Issued
December 2010
Journal
BMC Medical Genomics
Publisher
Springer (Biomed Central Ltd.)
Citation
Plunkett, Jevon et al. “Primate-specific Evolution of Noncoding Element Insertion into PLA2G4C and Human Preterm Birth.” BMC Medical Genomics 3.1 (2010): 62. Web. 1 Mar. 2012.
Version
Final published version
Abstract
Background
The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance.
Methods
We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers.
Results
Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity.
Conclusions
Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
MIT Department
Broad Institute of MIT and Harvard
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DOI of Published Version
https://doi.org/10.1186/1755-8794-3-62
