Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene
Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palat...
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| Published in | PLoS genetics Vol. 12; no. 3; p. e1005914 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
11.03.2016
Public Library of Science (PLoS) |
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| Abstract | Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. |
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| AbstractList |
Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10-14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13x10.sup.-14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, P.sub.diff <0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10-14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP ( P = 8.13×10 −14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO ( P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 ( GREM1 ), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, P diff <0.05). While we did not find lip or palate defects in Grem1 -deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein ( P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary management. Their etiology involves genetic factors and environmental influences and/or a combination of both, however, these interactions are poorly defined. Moreover, although clefts of the lip may or may not involve the palate, the determinants predisposing to specific subphenotypes are largely unknown. Here we demonstrate that variations in the non-coding region near the GREM1 gene show a highly significant association with a particular phenotype in which cleft lip and cleft palate co-occur (nsCLP; P = 8.13×10 −14 ). Our data suggest that the risk is even higher for patients who have a cleft lip and a cleft of the soft palate, but not of the hard palate. Interestingly, this subphenotype corresponds to the expression of the mouse Grem1 gene, which is found in the developing lip and soft palate but not in the hard palate. While Grem1 -deficient mice display no lip or palate defects, we demonstrate that ectopic Grem1 protein alters palatal shelve morphogenesis. Together, our results identify a region near GREM1 as the second, genome-wide significant risk locus for nsCLP, and suggest that deregulated GREM1 expression during craniofacial development may contribute to this common birth defect. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.1310-14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. |
| Audience | Academic |
| Author | Graf, Daniel Rojas-Martinez, Augusto Borck, Guntram Gültepe, Pinar Rubini, Michele Peters, Heiko Schuenke, Hannah Hofmann, Andrea Aldhorae, Khalid Ahmed Knapp, Michael Nakatomi, Mitsushiro Varghese, Sheryil Ludwig, Kerstin U Reiter, Rudolf Ahmed, Syeda Tasnim Klamt, Johanna Sangani, Nasim Bahram Böhmer, Anne C Steegers-Theunissen, Regine P Mangold, Elisabeth |
| AuthorAffiliation | 3 Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom 1 Institute of Human Genetics, University of Bonn, Bonn, Germany 7 Department of Epidemiology, Radboud University Medical Center, Nijmegen, Netherlands 12 Division of Anatomy, Kyushu Dental University, Kitakyushu, Japan 2 Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany 13 Orofacial Development and Regeneration, Institute of Oral Biology, Center for Dental Medicine, University of Zurich, Zurich, Switzerland 5 Orthodontic Department, College of Dentistry, Thamar University, Thamar, Yemen 10 Institute of Human Genetics, University of Ulm, Ulm, Germany University of Oxford, UNITED KINGDOM 6 Department of Obstetrics and Gynaecology, ErasmusMC, Rotterdam, Netherlands 9 Department of Otolaryngology—Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany 11 Institute of Medical Biometry, Informatics and Epidemiology, |
| AuthorAffiliation_xml | – name: 5 Orthodontic Department, College of Dentistry, Thamar University, Thamar, Yemen – name: 8 Department of Biochemistry and Molecular Medicine, School of Medicine, and Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico – name: 1 Institute of Human Genetics, University of Bonn, Bonn, Germany – name: 12 Division of Anatomy, Kyushu Dental University, Kitakyushu, Japan – name: 11 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany – name: 7 Department of Epidemiology, Radboud University Medical Center, Nijmegen, Netherlands – name: 2 Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – name: 10 Institute of Human Genetics, University of Ulm, Ulm, Germany – name: University of Oxford, UNITED KINGDOM – name: 9 Department of Otolaryngology—Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany – name: 3 Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom – name: 6 Department of Obstetrics and Gynaecology, ErasmusMC, Rotterdam, Netherlands – name: 14 Departments of Dentistry and Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada – name: 13 Orofacial Development and Regeneration, Institute of Oral Biology, Center for Dental Medicine, University of Zurich, Zurich, Switzerland – name: 4 Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy |
| Author_xml | – sequence: 1 givenname: Kerstin U surname: Ludwig fullname: Ludwig, Kerstin U organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 2 givenname: Syeda Tasnim surname: Ahmed fullname: Ahmed, Syeda Tasnim organization: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom – sequence: 3 givenname: Anne C surname: Böhmer fullname: Böhmer, Anne C organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 4 givenname: Nasim Bahram surname: Sangani fullname: Sangani, Nasim Bahram organization: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom – sequence: 5 givenname: Sheryil surname: Varghese fullname: Varghese, Sheryil organization: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom – sequence: 6 givenname: Johanna surname: Klamt fullname: Klamt, Johanna organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 7 givenname: Hannah surname: Schuenke fullname: Schuenke, Hannah organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 8 givenname: Pinar surname: Gültepe fullname: Gültepe, Pinar organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 9 givenname: Andrea surname: Hofmann fullname: Hofmann, Andrea organization: Department of Genomics, Life&Brain Center, University of Bonn, Bonn, Germany – sequence: 10 givenname: Michele surname: Rubini fullname: Rubini, Michele organization: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy – sequence: 11 givenname: Khalid Ahmed surname: Aldhorae fullname: Aldhorae, Khalid Ahmed organization: Orthodontic Department, College of Dentistry, Thamar University, Thamar, Yemen – sequence: 12 givenname: Regine P surname: Steegers-Theunissen fullname: Steegers-Theunissen, Regine P organization: Department of Epidemiology, Radboud University Medical Center, Nijmegen, Netherlands – sequence: 13 givenname: Augusto surname: Rojas-Martinez fullname: Rojas-Martinez, Augusto organization: Department of Biochemistry and Molecular Medicine, School of Medicine, and Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico – sequence: 14 givenname: Rudolf surname: Reiter fullname: Reiter, Rudolf organization: Department of Otolaryngology-Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Ulm, Germany – sequence: 15 givenname: Guntram surname: Borck fullname: Borck, Guntram organization: Institute of Human Genetics, University of Ulm, Ulm, Germany – sequence: 16 givenname: Michael surname: Knapp fullname: Knapp, Michael organization: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany – sequence: 17 givenname: Mitsushiro surname: Nakatomi fullname: Nakatomi, Mitsushiro organization: Division of Anatomy, Kyushu Dental University, Kitakyushu, Japan – sequence: 18 givenname: Daniel surname: Graf fullname: Graf, Daniel organization: Departments of Dentistry and Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada – sequence: 19 givenname: Elisabeth surname: Mangold fullname: Mangold, Elisabeth organization: Institute of Human Genetics, University of Bonn, Bonn, Germany – sequence: 20 givenname: Heiko surname: Peters fullname: Peters, Heiko organization: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26968009$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1016/S0092-8674(03)00310-6 10.1002/bdra.20689 10.1371/journal.pgen.1002932 10.1093/nar/gkr917 10.1016/j.cell.2014.11.021 10.1038/44157 10.1002/ajmg.a.33136 10.1242/dev.02861 10.1042/BJ20140771 10.1371/journal.pgen.1000529 10.1242/dev.129.17.4135 10.1002/bdra.23244 10.1086/422475 10.1242/dev.121.10.3151 10.1038/ng.2756 10.1038/nrg2933 10.1038/ng.580 10.1002/bdra.23221 10.1177/0022034514523987 10.1371/journal.pone.0059463 10.1093/hmg/ddp185 10.1038/ng.506 10.1016/j.ajhg.2015.01.004 10.1016/j.stem.2012.07.006 10.1038/nrm2346 10.1038/ng.2360 10.1002/bdra.23076 10.1111/j.1529-8817.2005.00175.x 10.1159/000337617 10.1093/bioinformatics/btq419 10.1002/ajmg.a.36891 10.1073/pnas.1424958112 10.1007/s00439-013-1283-6 10.1016/j.tcb.2014.12.004 10.1093/nar/gkt1155 10.1038/nature11247 10.1016/j.ajhg.2009.02.002 10.1038/ncomms7414 10.1093/aje/kwg005 10.1242/dev.01251 10.1016/j.ydbio.2011.02.033 10.1016/j.ydbio.2008.06.030 10.1016/j.jpeds.2009.06.020 10.1038/ng1178 10.1038/ejhg.2011.110 10.1016/j.molmed.2011.07.007 10.1126/science.1241006 10.1038/ng.242 10.1016/j.ydbio.2010.08.014 10.1242/dev.129.19.4647 10.1111/j.1601-6343.2006.00339.x 10.1136/jmg.2009.069385 10.1093/bioinformatics/btn564 10.1093/hmg/ddp444 10.1038/ng.333 10.1093/hmg/ddr329 10.1101/gad.299904 10.1038/nature11232 10.1016/j.mod.2005.10.007 10.1086/519795 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2016 Public Library of Science 2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: As a Plausible Causative Gene. PLoS Genet 12(3): e1005914. doi:10.1371/journal.pgen.1005914 2016 Ludwig et al 2016 Ludwig et al 2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: As a Plausible Causative Gene. PLoS Genet 12(3): e1005914. doi:10.1371/journal.pgen.1005914 |
| Copyright_xml | – notice: COPYRIGHT 2016 Public Library of Science – notice: 2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: As a Plausible Causative Gene. PLoS Genet 12(3): e1005914. doi:10.1371/journal.pgen.1005914 – notice: 2016 Ludwig et al 2016 Ludwig et al – notice: 2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: As a Plausible Causative Gene. PLoS Genet 12(3): e1005914. doi:10.1371/journal.pgen.1005914 |
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| DocumentTitleAlternate | GREM1 in Palate and Lip Formation |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 The authors have declared that no competing interests exist. Conceived and designed the experiments: KUL DG EM HP. Performed the experiments: KUL STA ACB NBS SV JK HS PG MN DG HP. Analyzed the data: KUL AH MK DG EM HP. Contributed reagents/materials/analysis tools: MR KAA RPST ARM RR GB EM. Wrote the paper: KUL HP. |
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| References | DP Brazil (ref19) 2015; 25 A Zuniga (ref48) 1999; 401 L Richardson (ref41) 2014; 42 A Rojas-Martinez (ref30) 2010; 88 G Levi (ref49) 2006; 123 O Michos (ref18) 2004; 131 A Rada-Iglesias (ref35) 2012; 11 KU Ludwig (ref12) 2012; 44 E Mangold (ref10) 2010; 42 C Parada (ref20) 2012; 16 A Mostowska (ref15) 2015 XJ Yang (ref40) 2008; 9 IA van Rooij (ref57) 2003; 157 C Attanasio (ref34) 2013; 342 E Mangold (ref2) 2011; 17 D Grosen (ref13) 2010; 47 DC Chan (ref53) 1995; 121 RJ Pruim (ref28) 2010; 26 AM Ashique (ref25) 2002; 129 F Rahimov (ref5) 2008; 40 S Purcell (ref60) 2007; 81 S Birnbaum (ref8) 2009; 41 SR Cuddapah (ref46) 2015 ML Marazita (ref3) 2004; 75 KU Ludwig (ref56) 2014; 93 T Kouskoura (ref61) 2013; 8 MK Khokha (ref17) 2003; 34 RE Thurman (ref33) 2012; 489 TH Beaty (ref7) 2013; 132 SM Weinberg (ref52) 2006; 9 E Lana-Elola (ref27) 2011; 20 TH Beaty (ref6) 2010; 42 A Zuniga (ref44) 2004; 18 F Zhou (ref54) 2009; 18 AD Johnson (ref63) 2008; 24 LM Moreno (ref4) 2009; 18 HA Thomason (ref21) 2008; 321 E Mangold (ref29) 2009; 149A O Michos (ref62) 2007; 134 Z Zhang (ref22) 2002; 129 HJ Westra (ref37) 2013; 45 T Al Chawa (ref16) 2014; 100 V Moskvina (ref55) 2005; 69 SA Ament (ref47) 2015; 112 ZL Jia (ref14) 2015; 167A I Dunham (ref32) 2012; 489 S Suzuki (ref23) 2009; 84 S Boehringer (ref50) 2011; 19 LD Ward (ref36) 2012; 40 SS Rao (ref38) 2014; 159 H Hochheiser (ref42) 2011; 355 SF Grant (ref9) 2009; 155 F He (ref26) 2010; 347 BN Howie (ref59) 2009; 5 KA Aldhorae (ref31) 2014; 100 F Spitz (ref45) 2003; 113 EJ Leslie (ref39) 2015; 96 R Reiter (ref58) 2015; 167A MJ Dixon (ref1) 2011; 12 EJ Leslie (ref43) 2012; 94 F Liu (ref51) 2012; 8 Y Sun (ref11) 2015; 6 RH Church (ref24) 2015; 466 |
| References_xml | – volume: 113 start-page: 405 issue: 3 year: 2003 ident: ref45 article-title: A global control region defines a chromosomal regulatory landscape containing the HoxD cluster publication-title: Cell doi: 10.1016/S0092-8674(03)00310-6 contributor: fullname: F Spitz – volume: 88 start-page: 535 issue: 7 year: 2010 ident: ref30 article-title: Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25 publication-title: Birth Defects Res A Clin Mol Teratol doi: 10.1002/bdra.20689 contributor: fullname: A Rojas-Martinez – volume: 8 start-page: e1002932 issue: 9 year: 2012 ident: ref51 article-title: A genome-wide association study identifies five loci influencing facial morphology in Europeans publication-title: PLoS Genet doi: 10.1371/journal.pgen.1002932 contributor: fullname: F Liu – volume: 40 start-page: D930 year: 2012 ident: ref36 article-title: HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants publication-title: Nucleic Acids Res doi: 10.1093/nar/gkr917 contributor: fullname: LD Ward – volume: 159 start-page: 1665 issue: 7 year: 2014 ident: ref38 article-title: A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping publication-title: Cell doi: 10.1016/j.cell.2014.11.021 contributor: fullname: SS Rao – volume: 401 start-page: 598 issue: 6753 year: 1999 ident: ref48 article-title: Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds publication-title: Nature doi: 10.1038/44157 contributor: fullname: A Zuniga – volume: 149A start-page: 2680 issue: 12 year: 2009 ident: ref29 article-title: Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin publication-title: Am J Med Genet A doi: 10.1002/ajmg.a.33136 contributor: fullname: E Mangold – volume: 134 start-page: 2397 issue: 13 year: 2007 ident: ref62 article-title: Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis publication-title: Development doi: 10.1242/dev.02861 contributor: fullname: O Michos – volume: 466 start-page: 55 year: 2015 ident: ref24 article-title: Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4 over BMP-7 publication-title: Biochem J doi: 10.1042/BJ20140771 contributor: fullname: RH Church – volume: 5 start-page: e1000529 issue: 6 year: 2009 ident: ref59 article-title: A flexible and accurate genotype imputation method for the next generation of genome-wide association studies publication-title: PLoS Genet doi: 10.1371/journal.pgen.1000529 contributor: fullname: BN Howie – volume: 129 start-page: 4135 issue: 17 year: 2002 ident: ref22 article-title: Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis publication-title: Development doi: 10.1242/dev.129.17.4135 contributor: fullname: Z Zhang – volume: 100 start-page: 493 issue: 6 year: 2014 ident: ref16 article-title: Nonsyndromic cleft lip with or without cleft palate: Increased burden of rare variants within Gremlin-1, a component of the bone morphogenetic protein 4 pathway publication-title: Birth Defects Res A Clin Mol Teratol doi: 10.1002/bdra.23244 contributor: fullname: T Al Chawa – volume: 75 start-page: 161 issue: 2 year: 2004 ident: ref3 article-title: Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35 publication-title: Am J Hum Genet doi: 10.1086/422475 contributor: fullname: ML Marazita – volume: 121 start-page: 3151 issue: 10 year: 1995 ident: ref53 article-title: Formin isoforms are differentially expressed in the mouse embryo and are required for normal expression of fgf-4 and shh in the limb bud publication-title: Development doi: 10.1242/dev.121.10.3151 contributor: fullname: DC Chan – volume: 45 start-page: 1238 issue: 10 year: 2013 ident: ref37 article-title: Systematic identification of trans eQTLs as putative drivers of known disease associations publication-title: Nat Genet doi: 10.1038/ng.2756 contributor: fullname: HJ Westra – volume: 12 start-page: 167 issue: 3 year: 2011 ident: ref1 article-title: Cleft lip and palate: understanding genetic and environmental influences publication-title: Nat Rev Genet doi: 10.1038/nrg2933 contributor: fullname: MJ Dixon – volume: 42 start-page: 525 issue: 6 year: 2010 ident: ref6 article-title: A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4 publication-title: Nat Genet doi: 10.1038/ng.580 contributor: fullname: TH Beaty – volume: 100 start-page: 307 issue: 4 year: 2014 ident: ref31 article-title: Nonsyndromic cleft lip with or without cleft palate in arab populations: genetic analysis of 15 risk loci in a novel case-control sample recruited in Yemen publication-title: Birth Defects Res A Clin Mol Teratol doi: 10.1002/bdra.23221 contributor: fullname: KA Aldhorae – volume: 93 start-page: 376 issue: 4 year: 2014 ident: ref56 article-title: Strong association of variants around FOXE1 and orofacial clefting publication-title: J Dent Res doi: 10.1177/0022034514523987 contributor: fullname: KU Ludwig – volume: 8 start-page: e59463 issue: 3 year: 2013 ident: ref61 article-title: The etiology of cleft palate formation in BMP7-deficient mice publication-title: PLoS One doi: 10.1371/journal.pone.0059463 contributor: fullname: T Kouskoura – volume: 18 start-page: 2472 issue: 13 year: 2009 ident: ref54 article-title: Formin1 disruption confers oligodactylism and alters Bmp signaling publication-title: Hum Mol Genet doi: 10.1093/hmg/ddp185 contributor: fullname: F Zhou – volume: 42 start-page: 24 issue: 1 year: 2010 ident: ref10 article-title: Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate publication-title: Nat Genet doi: 10.1038/ng.506 contributor: fullname: E Mangold – volume: 96 start-page: 397 issue: 3 year: 2015 ident: ref39 article-title: Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci publication-title: Am J Hum Genet doi: 10.1016/j.ajhg.2015.01.004 contributor: fullname: EJ Leslie – volume: 11 start-page: 633 issue: 5 year: 2012 ident: ref35 article-title: Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest publication-title: Cell Stem Cell doi: 10.1016/j.stem.2012.07.006 contributor: fullname: A Rada-Iglesias – volume: 9 start-page: 206 issue: 3 year: 2008 ident: ref40 article-title: The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men publication-title: Nat Rev Mol Cell Biol doi: 10.1038/nrm2346 contributor: fullname: XJ Yang – volume: 44 start-page: 968 issue: 9 year: 2012 ident: ref12 article-title: Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci publication-title: Nat Genet doi: 10.1038/ng.2360 contributor: fullname: KU Ludwig – volume: 94 start-page: 934 issue: 11 year: 2012 ident: ref43 article-title: Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22 publication-title: Birth Defects Res A Clin Mol Teratol doi: 10.1002/bdra.23076 contributor: fullname: EJ Leslie – volume: 69 start-page: 566 issue: Pt 5 year: 2005 ident: ref55 article-title: Design of case-controls studies with unscreened controls publication-title: Ann Hum Genet doi: 10.1111/j.1529-8817.2005.00175.x contributor: fullname: V Moskvina – volume: 16 start-page: 60 year: 2012 ident: ref20 article-title: Roles of BMP signaling pathway in lip and palate development publication-title: Front Oral Biol doi: 10.1159/000337617 contributor: fullname: C Parada – volume: 26 start-page: 2336 issue: 18 year: 2010 ident: ref28 article-title: LocusZoom: regional visualization of genome-wide association scan results publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq419 contributor: fullname: RJ Pruim – volume: 167A start-page: 670 issue: 3 year: 2015 ident: ref58 article-title: A post GWAS association study of SNPs associated with cleft lip with or without cleft palate in submucous cleft palate publication-title: Am J Med Genet A doi: 10.1002/ajmg.a.36891 contributor: fullname: R Reiter – volume: 112 start-page: 3576 issue: 11 year: 2015 ident: ref47 article-title: Rare variants in neuronal excitability genes influence risk for bipolar disorder publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1424958112 contributor: fullname: SA Ament – volume: 132 start-page: 771 issue: 7 year: 2013 ident: ref7 article-title: Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study publication-title: Hum Genet doi: 10.1007/s00439-013-1283-6 contributor: fullname: TH Beaty – volume: 25 start-page: 249 issue: 5 year: 2015 ident: ref19 article-title: BMP signalling: agony and antagony in the family publication-title: Trends Cell Biol doi: 10.1016/j.tcb.2014.12.004 contributor: fullname: DP Brazil – volume: 42 start-page: D835 year: 2014 ident: ref41 article-title: EMAGE mouse embryo spatial gene expression database: 2014 update publication-title: Nucleic Acids Res doi: 10.1093/nar/gkt1155 contributor: fullname: L Richardson – volume: 489 start-page: 57 issue: 7414 year: 2012 ident: ref32 article-title: An integrated encyclopedia of DNA elements in the human genome publication-title: Nature doi: 10.1038/nature11247 contributor: fullname: I Dunham – volume: 84 start-page: 406 issue: 3 year: 2009 ident: ref23 article-title: Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip publication-title: Am J Hum Genet doi: 10.1016/j.ajhg.2009.02.002 contributor: fullname: S Suzuki – volume: 6 start-page: 6414 year: 2015 ident: ref11 article-title: Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate publication-title: Nat Commun doi: 10.1038/ncomms7414 contributor: fullname: Y Sun – volume: 157 start-page: 583 issue: 7 year: 2003 ident: ref57 article-title: Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate? publication-title: Am J Epidemiol doi: 10.1093/aje/kwg005 contributor: fullname: IA van Rooij – volume: 167A start-page: 1054 issue: 5 year: 2015 ident: ref14 article-title: Replication of 13q31.1 Association in Nonsyndromic Cleft Lip with Cleft Palate in Europeans publication-title: Am J Med Genet A contributor: fullname: ZL Jia – volume: 131 start-page: 3401 issue: 14 year: 2004 ident: ref18 article-title: Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis publication-title: Development doi: 10.1242/dev.01251 contributor: fullname: O Michos – volume: 355 start-page: 175 issue: 2 year: 2011 ident: ref42 article-title: The FaceBase Consortium: a comprehensive program to facilitate craniofacial research publication-title: Dev Biol doi: 10.1016/j.ydbio.2011.02.033 contributor: fullname: H Hochheiser – volume: 321 start-page: 273 issue: 1 year: 2008 ident: ref21 article-title: Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh signaling publication-title: Dev Biol doi: 10.1016/j.ydbio.2008.06.030 contributor: fullname: HA Thomason – volume: 155 start-page: 909 issue: 6 year: 2009 ident: ref9 article-title: A genome-wide association study identifies a locus for nonsyndromic cleft lip with or without cleft palate on 8q24 publication-title: J Pediatr doi: 10.1016/j.jpeds.2009.06.020 contributor: fullname: SF Grant – volume: 34 start-page: 303 issue: 3 year: 2003 ident: ref17 article-title: Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning publication-title: Nat Genet doi: 10.1038/ng1178 contributor: fullname: MK Khokha – volume: 19 start-page: 1192 issue: 11 year: 2011 ident: ref50 article-title: Genetic determination of human facial morphology: links between cleft-lips and normal variation publication-title: Eur J Hum Genet doi: 10.1038/ejhg.2011.110 contributor: fullname: S Boehringer – volume: 17 start-page: 725 issue: 12 year: 2011 ident: ref2 article-title: Breakthroughs in the genetics of orofacial clefting publication-title: Trends Mol Med doi: 10.1016/j.molmed.2011.07.007 contributor: fullname: E Mangold – year: 2015 ident: ref15 article-title: Association between polymorphisms at the GREM1 locus and the risk of nonsyndromic cleft lip with or without cleft palate in the Polish population publication-title: Birth Defects Res A Clin Mol Teratol contributor: fullname: A Mostowska – volume: 342 start-page: 1241006 issue: 6157 year: 2013 ident: ref34 article-title: Fine tuning of craniofacial morphology by distant-acting enhancers publication-title: Science doi: 10.1126/science.1241006 contributor: fullname: C Attanasio – volume: 40 start-page: 1341 issue: 11 year: 2008 ident: ref5 article-title: Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip publication-title: Nat Genet doi: 10.1038/ng.242 contributor: fullname: F Rahimov – volume: 347 start-page: 109 issue: 1 year: 2010 ident: ref26 article-title: Modulation of BMP signaling by Noggin is required for the maintenance of palatal epithelial integrity during palatogenesis publication-title: Dev Biol doi: 10.1016/j.ydbio.2010.08.014 contributor: fullname: F He – volume: 129 start-page: 4647 issue: 19 year: 2002 ident: ref25 article-title: Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion publication-title: Development doi: 10.1242/dev.129.19.4647 contributor: fullname: AM Ashique – volume: 9 start-page: 18 issue: 1 year: 2006 ident: ref52 article-title: Parental craniofacial morphology in cleft lip with or without cleft palate as determined by cephalometry: a meta-analysis publication-title: Orthod Craniofac Res doi: 10.1111/j.1601-6343.2006.00339.x contributor: fullname: SM Weinberg – volume: 47 start-page: 162 issue: 3 year: 2010 ident: ref13 article-title: A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance publication-title: J Med Genet doi: 10.1136/jmg.2009.069385 contributor: fullname: D Grosen – volume: 24 start-page: 2938 issue: 24 year: 2008 ident: ref63 article-title: SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap publication-title: Bioinformatics doi: 10.1093/bioinformatics/btn564 contributor: fullname: AD Johnson – volume: 18 start-page: 4879 issue: 24 year: 2009 ident: ref4 article-title: FOXE1 association with both isolated cleft lip with or without cleft palate, and isolated cleft palate publication-title: Hum Mol Genet doi: 10.1093/hmg/ddp444 contributor: fullname: LM Moreno – volume: 41 start-page: 473 issue: 4 year: 2009 ident: ref8 article-title: Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24 publication-title: Nat Genet doi: 10.1038/ng.333 contributor: fullname: S Birnbaum – volume: 20 start-page: 4005 issue: 20 year: 2011 ident: ref27 article-title: Noggin null allele mice exhibit a microform of holoprosencephaly publication-title: Hum Mol Genet doi: 10.1093/hmg/ddr329 contributor: fullname: E Lana-Elola – year: 2015 ident: ref46 article-title: 3rd, Robin NH. IRF6 Sequencing in Interrupted Clefting publication-title: Cleft Palate Craniofac J contributor: fullname: SR Cuddapah – volume: 18 start-page: 1553 issue: 13 year: 2004 ident: ref44 article-title: Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression publication-title: Genes Dev doi: 10.1101/gad.299904 contributor: fullname: A Zuniga – volume: 489 start-page: 75 issue: 7414 year: 2012 ident: ref33 article-title: The accessible chromatin landscape of the human genome publication-title: Nature doi: 10.1038/nature11232 contributor: fullname: RE Thurman – volume: 123 start-page: 3 issue: 1 year: 2006 ident: ref49 article-title: Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation publication-title: Mech Dev doi: 10.1016/j.mod.2005.10.007 contributor: fullname: G Levi – volume: 81 start-page: 559 issue: 3 year: 2007 ident: ref60 article-title: PLINK: a tool set for whole-genome association and population-based linkage analyses publication-title: Am J Hum Genet doi: 10.1086/519795 contributor: fullname: S Purcell |
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| Snippet | Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft... Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft... |
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| SubjectTerms | Alleles Animals Biology and Life Sciences Birth defects Brain - abnormalities Brain - pathology Chromosomes, Human, Pair 15 Cleft lip Cleft Lip - genetics Cleft Lip - pathology Cleft palate Cleft Palate - genetics Cleft Palate - pathology Confidence intervals Datasets European Continental Ancestry Group Genes Genetic aspects Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genotype Humans Intercellular Signaling Peptides and Proteins - genetics Medicine and Health Sciences Meta-analysis Mice Morphogenesis Mutation Physical Sciences Proteins Research and Analysis Methods Studies |
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| Title | Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene |
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