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Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Plunkett, Jevon; Doniger, Scott; Morgan, Thomas; Haataja, Ritva; Hallman, Mikko; Puttonen, Hilkka; Menon, Ramkumar; Kuczynski, Edward; Norwitz, Errol and Snegovskikh, Victoria, et al. (2010) In BMC Medical Genomics 3.
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 =... (More)
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. (Less)
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BMC Medical Genomics
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3
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BioMed Central
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  • wos:000285966400001
  • scopus:78650506843
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1755-8794
DOI
10.1186/1755-8794-3-62
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English
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41f57f9b-9f5f-4f1f-8ebb-b7786cf58d9f (old id 1815062)
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@article{41f57f9b-9f5f-4f1f-8ebb-b7786cf58d9f,
  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 &lt; 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.},
  author       = {Plunkett, Jevon and Doniger, Scott and Morgan, Thomas and Haataja, Ritva and Hallman, Mikko and Puttonen, Hilkka and Menon, Ramkumar and Kuczynski, Edward and Norwitz, Errol and Snegovskikh, Victoria and Palotie, Aarno and Peltonen, Leena and Fellman, Vineta and DeFranco, Emily A. and Chaudhari, Bimal P. and Oates, John and Boutaud, Olivier and McGregor, Tracy L. and McElroy, Jude J. and Teramo, Kari and Borecki, Ingrid and Fay, Justin C. and Muglia, Louis J.},
  issn         = {1755-8794},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Medical Genomics},
  title        = {Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth},
  url          = {http://dx.doi.org/10.1186/1755-8794-3-62},
  volume       = {3},
  year         = {2010},
}