Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth
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....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
Springer (Biomed Central Ltd.)
2012
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| Online Access: | http://hdl.handle.net/1721.1/69548 |
| _version_ | 1826192235944738816 |
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| author | Plunkett, Jevon Doniger, Scott Morgan, Thomas Haataja, Ritva Hallman, Mikko Puttonen, Hilkka Menon, Ramkumar Kuczynski, Edward Norwitz, Errol Snegovskikh, Victoria 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. Palotie, Aarno Peltonen, Leena |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Plunkett, Jevon Doniger, Scott Morgan, Thomas Haataja, Ritva Hallman, Mikko Puttonen, Hilkka Menon, Ramkumar Kuczynski, Edward Norwitz, Errol Snegovskikh, Victoria 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. Palotie, Aarno Peltonen, Leena |
| author_sort | Plunkett, Jevon |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:08:25Z |
| format | Article |
| id | mit-1721.1/69548 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:08:25Z |
| publishDate | 2012 |
| publisher | Springer (Biomed Central Ltd.) |
| record_format | dspace |
| spelling | mit-1721.1/695482022-09-26T10:42:52Z 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 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. Palotie, Aarno Peltonen, Leena Broad Institute of MIT and Harvard Peltonen, Leena Palotie, Aarno Peltonen, Leena 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. Children’s Discovery Institute March of Dimes Birth Defects Foundation National Institute of General Medical Sciences (U.S.) (grant T32 GM081739) Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study) Sigrid Jusélius Foundation Signe and Anne Gyllenberg Foundation Academy of Finland Vanderbilt University (Turner-Hazinski grant award) 2012-03-01T18:59:11Z 2012-03-01T18:59:11Z 2010-12 2010-07 Article http://purl.org/eprint/type/JournalArticle 1755-8794 http://hdl.handle.net/1721.1/69548 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. en_US http://dx.doi.org/10.1186/1755-8794-3-62 BMC Medical Genomics Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 application/pdf Springer (Biomed Central Ltd.) BioMed Central |
| spellingShingle | Plunkett, Jevon Doniger, Scott Morgan, Thomas Haataja, Ritva Hallman, Mikko Puttonen, Hilkka Menon, Ramkumar Kuczynski, Edward Norwitz, Errol Snegovskikh, Victoria 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. Palotie, Aarno Peltonen, Leena Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title | Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title_full | Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title_fullStr | Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title_full_unstemmed | Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title_short | Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth |
| title_sort | primate specific evolution of noncoding element insertion into pla2g4c and human preterm birth |
| url | http://hdl.handle.net/1721.1/69548 |
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