Human Molecular Genetics, 2015, Vol. 24, No. 9
2673–2680
doi: 10.1093/hmg/ddv014 Advance Access Publication Date: 22 January 2015 Original Article
ORIGINAL ARTICLE
Common polymorphisms in WNT10A affect tooth Ryosuke Kimura1, *, Chiaki Watanabe1, Akira Kawaguchi1, Yong-Il Kim2, Soo-Byung Park2, Koutaro Maki3, Hajime Ishida1 and Tetsutaro Yamaguchi3, * 1
Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan, 2Department of Orthodontics, Pusan National University Dental Hospital, Beomeori, Mulgeumeup, Yangsan, Kyeongsangnamdo 626-787, Korea and 3 Department of Orthodontics, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ota-ku, Tokyo 145-8515, Japan *To whom correspondence should be addressed. Tel: +81 988951211; Fax: +81 988951400; Email: [email protected] (R.K.); Tel: +81 337871151; Fax: +81 337846641; Email: [email protected] (T.Y.)
Abstract Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated nonmetric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared from the subjects and genotyped for the hair morphology-associated SNPs. We observed a significant association of crown size with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans. Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages.
Introduction Teeth are vertebrate-specific organs that are used for catching and masticating food, for defense and for other purposes. In humans, teeth also play an important role in speech and in making tools. Depending on dietary specialization and other factors, dentition patterns vary between species. Therefore, dental characteristics have been the object of study in a wide range of fields, including ecology, comparative morphology and paleontology. In particular, dental characteristics have greatly contributed to the phylogenetic reconstructions in studies of primates including ancient hominids. Moreover, variations in detailed dental traits
have been used for comparisons of human populations in anthropology. Technological advances in the past two decades have rapidly elucidated the mechanisms of tooth morphogenesis. Skin appendages including teeth, hair and exocrine glands such as sweat, mammary and salivary glands are of ectodermal origin. Although these ectodermal organs diverge greatly in shape and form, the early stages in their development are highly similar depending on inductive epithelial–mesenchymal interactions (1–3). Our knowledge on the molecular basis of the development of ectodermal derivatives is based on studies of gene expression
Received: September 2, 2014. Revised: January 4, 2015. Accepted: January 16, 2015 © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
2673
Downloaded from http://hmg.oxfordjournals.org/ at Nanyang Technological University on November 13, 2015
morphology as well as hair shape
0.018 −0.149 0.087 −0.005 −0.005 3.3E−01 2.9E−03 9.3E−01 8.7E−01 3.2E−01 6.7E−01 8.1E−02 1.6E−02 9.8E−01 3.0E−01 Allele reportedly associated with thin (rs4752566) or curly (others) hair.
Bold, P < 0.05.
a
C Ta G G T 2 2 4 4 10 rs6732426 rs7349332 rs1268789 rs6840361 rs4752566
43322995 211610963 75027015 15159491921 116898581
THADA WNT10A FRAS1 (NAF1) FGFR2
Intron Intron Intron Intergenic Intron
Ta C Aa Ca Ga
0.959 0.208 0.287 0.048 0.892
−0.026 −0.107 0.146 0.001 −0.063
0.946 0.304 0.266 0.072 0.899
0.066 −0.199 0.006 −0.011 0.067
Combined β P P β Korean Freq. D P β Japanese Freq. D Derived allele (D) Ancestral allele (A) Location Gene Position Chr
Of the five examined SNPs that are reportedly associated with hair morphology, two SNPs, rs6732426 and rs6840361, had a relatively low minor allele frequency (
2673–2680
doi: 10.1093/hmg/ddv014 Advance Access Publication Date: 22 January 2015 Original Article
ORIGINAL ARTICLE
Common polymorphisms in WNT10A affect tooth Ryosuke Kimura1, *, Chiaki Watanabe1, Akira Kawaguchi1, Yong-Il Kim2, Soo-Byung Park2, Koutaro Maki3, Hajime Ishida1 and Tetsutaro Yamaguchi3, * 1
Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan, 2Department of Orthodontics, Pusan National University Dental Hospital, Beomeori, Mulgeumeup, Yangsan, Kyeongsangnamdo 626-787, Korea and 3 Department of Orthodontics, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ota-ku, Tokyo 145-8515, Japan *To whom correspondence should be addressed. Tel: +81 988951211; Fax: +81 988951400; Email: [email protected] (R.K.); Tel: +81 337871151; Fax: +81 337846641; Email: [email protected] (T.Y.)
Abstract Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated nonmetric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared from the subjects and genotyped for the hair morphology-associated SNPs. We observed a significant association of crown size with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans. Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages.
Introduction Teeth are vertebrate-specific organs that are used for catching and masticating food, for defense and for other purposes. In humans, teeth also play an important role in speech and in making tools. Depending on dietary specialization and other factors, dentition patterns vary between species. Therefore, dental characteristics have been the object of study in a wide range of fields, including ecology, comparative morphology and paleontology. In particular, dental characteristics have greatly contributed to the phylogenetic reconstructions in studies of primates including ancient hominids. Moreover, variations in detailed dental traits
have been used for comparisons of human populations in anthropology. Technological advances in the past two decades have rapidly elucidated the mechanisms of tooth morphogenesis. Skin appendages including teeth, hair and exocrine glands such as sweat, mammary and salivary glands are of ectodermal origin. Although these ectodermal organs diverge greatly in shape and form, the early stages in their development are highly similar depending on inductive epithelial–mesenchymal interactions (1–3). Our knowledge on the molecular basis of the development of ectodermal derivatives is based on studies of gene expression
Received: September 2, 2014. Revised: January 4, 2015. Accepted: January 16, 2015 © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
2673
Downloaded from http://hmg.oxfordjournals.org/ at Nanyang Technological University on November 13, 2015
morphology as well as hair shape
0.018 −0.149 0.087 −0.005 −0.005 3.3E−01 2.9E−03 9.3E−01 8.7E−01 3.2E−01 6.7E−01 8.1E−02 1.6E−02 9.8E−01 3.0E−01 Allele reportedly associated with thin (rs4752566) or curly (others) hair.
Bold, P < 0.05.
a
C Ta G G T 2 2 4 4 10 rs6732426 rs7349332 rs1268789 rs6840361 rs4752566
43322995 211610963 75027015 15159491921 116898581
THADA WNT10A FRAS1 (NAF1) FGFR2
Intron Intron Intron Intergenic Intron
Ta C Aa Ca Ga
0.959 0.208 0.287 0.048 0.892
−0.026 −0.107 0.146 0.001 −0.063
0.946 0.304 0.266 0.072 0.899
0.066 −0.199 0.006 −0.011 0.067
Combined β P P β Korean Freq. D P β Japanese Freq. D Derived allele (D) Ancestral allele (A) Location Gene Position Chr
Of the five examined SNPs that are reportedly associated with hair morphology, two SNPs, rs6732426 and rs6840361, had a relatively low minor allele frequency (
