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

Jevon Plunkett, Scott Doniger, 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, John Oates, Olivier Boutaud, Tracy L. McGregor, Jude J. McElroy, Kari TeramoIngrid Borecki, Justin C. Fay, Louis J. Muglia

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article number62
JournalBMC Medical Genomics
Volume3
DOIs
StatePublished - 2010
Externally publishedYes

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Premature Birth
Primates
Prostaglandins
Hispanic Americans
Genes
Single Nucleotide Polymorphism
Parturition
Phospholipases A
Chromosomes, Human, Pair 1
Thromboxanes
Hominidae
Genomics
Mammals
Protein Isoforms
Mothers

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Plunkett, J., Doniger, S., Morgan, T., Haataja, R., Hallman, M., Puttonen, H., ... Muglia, L. J. (2010). Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth. BMC Medical Genomics, 3, [62]. https://doi.org/10.1186/1755-8794-3-62

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; Snegovskikh, Victoria; Palotie, Aarno; Peltonen, Leena; Fellman, Vineta; Defranco, Emily A.; Chaudhari, Bimal P.; Oates, John; Boutaud, Olivier; McGregor, Tracy L.; McElroy, Jude J.; Teramo, Kari; Borecki, Ingrid; Fay, Justin C.; Muglia, Louis J.

In: BMC Medical Genomics, Vol. 3, 62, 2010.

Research output: Contribution to journalArticle

Plunkett, J, Doniger, S, Morgan, T, Haataja, R, Hallman, M, Puttonen, H, Menon, R, Kuczynski, E, Norwitz, E, Snegovskikh, V, Palotie, A, Peltonen, L, Fellman, V, Defranco, EA, Chaudhari, BP, Oates, J, Boutaud, O, McGregor, TL, McElroy, JJ, Teramo, K, Borecki, I, Fay, JC & Muglia, LJ 2010, 'Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth', BMC Medical Genomics, vol. 3, 62. https://doi.org/10.1186/1755-8794-3-62
Plunkett, Jevon ; Doniger, Scott ; Morgan, Thomas ; Haataja, Ritva ; Hallman, Mikko ; Puttonen, Hilkka ; Menon, Ramkumar ; Kuczynski, Edward ; Norwitz, Errol ; Snegovskikh, Victoria ; Palotie, Aarno ; Peltonen, Leena ; Fellman, Vineta ; Defranco, Emily A. ; Chaudhari, Bimal P. ; Oates, John ; Boutaud, Olivier ; McGregor, Tracy L. ; McElroy, Jude J. ; Teramo, Kari ; Borecki, Ingrid ; Fay, Justin C. ; Muglia, Louis J. / Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth. In: BMC Medical Genomics. 2010 ; Vol. 3.
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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.",
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AU - Plunkett, Jevon

AU - Doniger, Scott

AU - Morgan, Thomas

AU - Haataja, Ritva

AU - Hallman, Mikko

AU - Puttonen, Hilkka

AU - Menon, Ramkumar

AU - Kuczynski, Edward

AU - Norwitz, Errol

AU - Snegovskikh, Victoria

AU - Palotie, Aarno

AU - Peltonen, Leena

AU - Fellman, Vineta

AU - Defranco, Emily A.

AU - Chaudhari, Bimal P.

AU - Oates, John

AU - Boutaud, Olivier

AU - McGregor, Tracy L.

AU - McElroy, Jude J.

AU - Teramo, Kari

AU - Borecki, Ingrid

AU - Fay, Justin C.

AU - Muglia, Louis J.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

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