PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans
- Autores
- Liu, Qing; Faux, Pierre; Wentworth Winchester, Emma; Yang, Guangrui; Chen, Yingjie; Ramírez, Luis Miguel; Fuentes Guajardo, Macarena; Poloni, Lauriane; Steimetz, Emilie; Gonzalez José, Rolando; Acuña, Victor; Bortolini, Maria Catira; Poletti, Giovanni; Gallo, Carla; Rothhammer, Francisco; Rojas, Winston; Zheng, Youyi; Cox, James C.; Patel, Vaishali; Hoffman, Matthew P.; Ding, Li; Peng, Chenchen; Cotney, Justin; Navarro, Nicolas; Cox, Timothy C.; Delgado Burbano, Miguel Eduardo; Adhikari, Kaustubh; Ruiz Linares, Andrés
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution.
Fil: Liu, Qing. School Of Life Sciences Fudan University; China
Fil: Faux, Pierre. Centre National de la Recherche Scientifique; Francia
Fil: Wentworth Winchester, Emma. Centre National de la Recherche Scientifique; Francia
Fil: Yang, Guangrui. Fudan University; China
Fil: Chen, Yingjie. Fudan University; China
Fil: Ramírez, Luis Miguel. Universidad de Antioquia; Colombia
Fil: Fuentes Guajardo, Macarena. Universidad de Chile; Chile
Fil: Poloni, Lauriane. Centre National de la Recherche Scientifique; Francia
Fil: Steimetz, Emilie. Centre National de la Recherche Scientifique; Francia
Fil: Gonzalez José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina
Fil: Acuña, Victor. Centre National de la Recherche Scientifique; Francia
Fil: Bortolini, Maria Catira. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú
Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú
Fil: Rothhammer, Francisco. Universidad de Chile; Chile
Fil: Rojas, Winston. Universidad de Antioquia; Colombia
Fil: Zheng, Youyi. Fudan University; China
Fil: Cox, James C.. Centre National de la Recherche Scientifique; Francia
Fil: Patel, Vaishali. Centre National de la Recherche Scientifique; Francia
Fil: Hoffman, Matthew P.. Centre National de la Recherche Scientifique; Francia
Fil: Ding, Li. Fudan University; China
Fil: Peng, Chenchen. Fudan University; China
Fil: Cotney, Justin. Centre National de la Recherche Scientifique; Francia
Fil: Navarro, Nicolas. Centre National de la Recherche Scientifique; Francia
Fil: Cox, Timothy C.. Centre National de la Recherche Scientifique; Francia
Fil: Delgado Burbano, Miguel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Antropológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Adhikari, Kaustubh. The Open University; Reino Unido
Fil: Ruiz Linares, Andrés. Centre National de la Recherche Scientifique; Francia - Materia
-
NEANDERTHALS
MODERN HUMANS
GWAS
TEETH - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/255593
Ver los metadatos del registro completo
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PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humansLiu, QingFaux, PierreWentworth Winchester, EmmaYang, GuangruiChen, YingjieRamírez, Luis MiguelFuentes Guajardo, MacarenaPoloni, LaurianeSteimetz, EmilieGonzalez José, RolandoAcuña, VictorBortolini, Maria CatiraPoletti, GiovanniGallo, CarlaRothhammer, FranciscoRojas, WinstonZheng, YouyiCox, James C.Patel, VaishaliHoffman, Matthew P.Ding, LiPeng, ChenchenCotney, JustinNavarro, NicolasCox, Timothy C.Delgado Burbano, Miguel EduardoAdhikari, KaustubhRuiz Linares, AndrésNEANDERTHALSMODERN HUMANSGWASTEETHhttps://purl.org/becyt/ford/6.1https://purl.org/becyt/ford/6Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution.Fil: Liu, Qing. School Of Life Sciences Fudan University; ChinaFil: Faux, Pierre. Centre National de la Recherche Scientifique; FranciaFil: Wentworth Winchester, Emma. Centre National de la Recherche Scientifique; FranciaFil: Yang, Guangrui. Fudan University; ChinaFil: Chen, Yingjie. Fudan University; ChinaFil: Ramírez, Luis Miguel. Universidad de Antioquia; ColombiaFil: Fuentes Guajardo, Macarena. Universidad de Chile; ChileFil: Poloni, Lauriane. Centre National de la Recherche Scientifique; FranciaFil: Steimetz, Emilie. Centre National de la Recherche Scientifique; FranciaFil: Gonzalez José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Acuña, Victor. Centre National de la Recherche Scientifique; FranciaFil: Bortolini, Maria Catira. Universidade Federal do Rio Grande do Sul; BrasilFil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; PerúFil: Gallo, Carla. Universidad Peruana Cayetano Heredia; PerúFil: Rothhammer, Francisco. Universidad de Chile; ChileFil: Rojas, Winston. Universidad de Antioquia; ColombiaFil: Zheng, Youyi. Fudan University; ChinaFil: Cox, James C.. Centre National de la Recherche Scientifique; FranciaFil: Patel, Vaishali. Centre National de la Recherche Scientifique; FranciaFil: Hoffman, Matthew P.. Centre National de la Recherche Scientifique; FranciaFil: Ding, Li. Fudan University; ChinaFil: Peng, Chenchen. Fudan University; ChinaFil: Cotney, Justin. Centre National de la Recherche Scientifique; FranciaFil: Navarro, Nicolas. Centre National de la Recherche Scientifique; FranciaFil: Cox, Timothy C.. Centre National de la Recherche Scientifique; FranciaFil: Delgado Burbano, Miguel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Antropológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Adhikari, Kaustubh. The Open University; Reino UnidoFil: Ruiz Linares, Andrés. Centre National de la Recherche Scientifique; FranciaCell Press2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/255593Liu, Qing; Faux, Pierre; Wentworth Winchester, Emma; Yang, Guangrui; Chen, Yingjie; et al.; PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans; Cell Press; Current Biology; 35; 1; 12-2024; 131-144.e60960-9822CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0960982224015689info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cub.2024.11.027info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:15:08Zoai:ri.conicet.gov.ar:11336/255593instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:15:08.85CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| title |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| spellingShingle |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans Liu, Qing NEANDERTHALS MODERN HUMANS GWAS TEETH |
| title_short |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| title_full |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| title_fullStr |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| title_full_unstemmed |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| title_sort |
PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans |
| dc.creator.none.fl_str_mv |
Liu, Qing Faux, Pierre Wentworth Winchester, Emma Yang, Guangrui Chen, Yingjie Ramírez, Luis Miguel Fuentes Guajardo, Macarena Poloni, Lauriane Steimetz, Emilie Gonzalez José, Rolando Acuña, Victor Bortolini, Maria Catira Poletti, Giovanni Gallo, Carla Rothhammer, Francisco Rojas, Winston Zheng, Youyi Cox, James C. Patel, Vaishali Hoffman, Matthew P. Ding, Li Peng, Chenchen Cotney, Justin Navarro, Nicolas Cox, Timothy C. Delgado Burbano, Miguel Eduardo Adhikari, Kaustubh Ruiz Linares, Andrés |
| author |
Liu, Qing |
| author_facet |
Liu, Qing Faux, Pierre Wentworth Winchester, Emma Yang, Guangrui Chen, Yingjie Ramírez, Luis Miguel Fuentes Guajardo, Macarena Poloni, Lauriane Steimetz, Emilie Gonzalez José, Rolando Acuña, Victor Bortolini, Maria Catira Poletti, Giovanni Gallo, Carla Rothhammer, Francisco Rojas, Winston Zheng, Youyi Cox, James C. Patel, Vaishali Hoffman, Matthew P. Ding, Li Peng, Chenchen Cotney, Justin Navarro, Nicolas Cox, Timothy C. Delgado Burbano, Miguel Eduardo Adhikari, Kaustubh Ruiz Linares, Andrés |
| author_role |
author |
| author2 |
Faux, Pierre Wentworth Winchester, Emma Yang, Guangrui Chen, Yingjie Ramírez, Luis Miguel Fuentes Guajardo, Macarena Poloni, Lauriane Steimetz, Emilie Gonzalez José, Rolando Acuña, Victor Bortolini, Maria Catira Poletti, Giovanni Gallo, Carla Rothhammer, Francisco Rojas, Winston Zheng, Youyi Cox, James C. Patel, Vaishali Hoffman, Matthew P. Ding, Li Peng, Chenchen Cotney, Justin Navarro, Nicolas Cox, Timothy C. Delgado Burbano, Miguel Eduardo Adhikari, Kaustubh Ruiz Linares, Andrés |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
NEANDERTHALS MODERN HUMANS GWAS TEETH |
| topic |
NEANDERTHALS MODERN HUMANS GWAS TEETH |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/6.1 https://purl.org/becyt/ford/6 |
| dc.description.none.fl_txt_mv |
Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution. Fil: Liu, Qing. School Of Life Sciences Fudan University; China Fil: Faux, Pierre. Centre National de la Recherche Scientifique; Francia Fil: Wentworth Winchester, Emma. Centre National de la Recherche Scientifique; Francia Fil: Yang, Guangrui. Fudan University; China Fil: Chen, Yingjie. Fudan University; China Fil: Ramírez, Luis Miguel. Universidad de Antioquia; Colombia Fil: Fuentes Guajardo, Macarena. Universidad de Chile; Chile Fil: Poloni, Lauriane. Centre National de la Recherche Scientifique; Francia Fil: Steimetz, Emilie. Centre National de la Recherche Scientifique; Francia Fil: Gonzalez José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Acuña, Victor. Centre National de la Recherche Scientifique; Francia Fil: Bortolini, Maria Catira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Rothhammer, Francisco. Universidad de Chile; Chile Fil: Rojas, Winston. Universidad de Antioquia; Colombia Fil: Zheng, Youyi. Fudan University; China Fil: Cox, James C.. Centre National de la Recherche Scientifique; Francia Fil: Patel, Vaishali. Centre National de la Recherche Scientifique; Francia Fil: Hoffman, Matthew P.. Centre National de la Recherche Scientifique; Francia Fil: Ding, Li. Fudan University; China Fil: Peng, Chenchen. Fudan University; China Fil: Cotney, Justin. Centre National de la Recherche Scientifique; Francia Fil: Navarro, Nicolas. Centre National de la Recherche Scientifique; Francia Fil: Cox, Timothy C.. Centre National de la Recherche Scientifique; Francia Fil: Delgado Burbano, Miguel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Antropológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Adhikari, Kaustubh. The Open University; Reino Unido Fil: Ruiz Linares, Andrés. Centre National de la Recherche Scientifique; Francia |
| description |
Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-12 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/255593 Liu, Qing; Faux, Pierre; Wentworth Winchester, Emma; Yang, Guangrui; Chen, Yingjie; et al.; PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans; Cell Press; Current Biology; 35; 1; 12-2024; 131-144.e6 0960-9822 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/255593 |
| identifier_str_mv |
Liu, Qing; Faux, Pierre; Wentworth Winchester, Emma; Yang, Guangrui; Chen, Yingjie; et al.; PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans; Cell Press; Current Biology; 35; 1; 12-2024; 131-144.e6 0960-9822 CONICET Digital CONICET |
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eng |
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eng |
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openAccess |
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Cell Press |
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Cell Press |
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