An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2011
|
| Online Access: | http://hdl.handle.net/1721.1/65895 |
| _version_ | 1826196988383723520 |
|---|---|
| author | Plunkett, Jevon Doniger, Scott Orabona, Guilherme 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. McGregor, Tracy L. McElroy, Jude J. Oetjens, Matthew T. Teramo, Kari Borecki, Ingrid Fay, Justin C. Muglia, Louis J. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Plunkett, Jevon Doniger, Scott Orabona, Guilherme 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. McGregor, Tracy L. McElroy, Jude J. Oetjens, Matthew T. Teramo, Kari Borecki, Ingrid Fay, Justin C. Muglia, Louis J. |
| author_sort | Plunkett, Jevon |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:40:59Z |
| format | Article |
| id | mit-1721.1/65895 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:40:59Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/658952022-09-30T22:13:17Z An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing Plunkett, Jevon Doniger, Scott Orabona, Guilherme 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. McGregor, Tracy L. McElroy, Jude J. Oetjens, Matthew T. Teramo, Kari Borecki, Ingrid Fay, Justin C. Muglia, Louis J. Broad Institute of MIT and Harvard Peltonen, Leena Peltonen, Leena Palotie, Aarno 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. Children's Discovery Institute March of Dimes Birth Defects Foundation National Institute of General Medical Sciences (U.S.) (T32 GM081739) Washington University (Saint Louis, Mo.) Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study) Sigrid Jusélius stiftelse Signe and Anne Gyllenberg Foundation Academy of Finland 2011-09-21T14:43:50Z 2011-09-21T14:43:50Z 2011-04 2010-07 Article http://purl.org/eprint/type/JournalArticle 1553-7358 1553-734X http://hdl.handle.net/1721.1/65895 Plunkett, Jevon et al. “An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing.” Ed. Gregory S. Barsh. PLoS Genetics 7 (2011): e1001365. en_US http://dx.doi.org/10.1371/journal.pgen.1001365 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Plunkett, Jevon Doniger, Scott Orabona, Guilherme 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. McGregor, Tracy L. McElroy, Jude J. Oetjens, Matthew T. Teramo, Kari Borecki, Ingrid Fay, Justin C. Muglia, Louis J. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title | An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title_full | An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title_fullStr | An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title_full_unstemmed | An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title_short | An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing |
| title_sort | evolutionary genomic approach to identify genes involved in human birth timing |
| url | http://hdl.handle.net/1721.1/65895 |
| work_keys_str_mv | AT plunkettjevon anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT donigerscott anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT orabonaguilherme anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT morganthomas anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT haatajaritva anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT hallmanmikko anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT puttonenhilkka anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT menonramkumar anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT kuczynskiedward anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT norwitzerrol anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT snegovskikhvictoria anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT palotieaarno anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT peltonenleena anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT fellmanvineta anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT defrancoemilya anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT chaudharibimalp anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT mcgregortracyl anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT mcelroyjudej anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT oetjensmatthewt anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT teramokari anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT boreckiingrid anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT fayjustinc anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT muglialouisj anevolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT plunkettjevon evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT donigerscott evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT orabonaguilherme evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT morganthomas evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT haatajaritva evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT hallmanmikko evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT puttonenhilkka evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT menonramkumar evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT kuczynskiedward evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT norwitzerrol evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT snegovskikhvictoria evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT palotieaarno evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT peltonenleena evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT fellmanvineta evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT defrancoemilya evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT chaudharibimalp evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT mcgregortracyl evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT mcelroyjudej evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT oetjensmatthewt evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT teramokari evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT boreckiingrid evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT fayjustinc evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming AT muglialouisj evolutionarygenomicapproachtoidentifygenesinvolvedinhumanbirthtiming |