2012 Fiscal Year Final Research Report
Genome analysis for elucidation of genetic factors in orofacial traits and diseases
| Project/Area Number |
22390393
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthodontic/Pediatric dentistry
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Ituro 国立遺伝学研究所, 人類遺伝学, 教授 (00192500)
KIMURA Ryosuke 琉球大学, 医学部, 准教授 (00453712)
MAKI Koutaro 昭和大学, 歯学部, 教授 (80219295)
WATANABE Miyuki 昭和大学, 歯学部, 普通研究生 (30407572)
TOMOYASU Yoko 昭和大学, 歯学部, 助教 (50551206)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ゲノム / 遺伝(子) / 歯 / 顎 / 原発性萌出不全 |
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| Research Abstract |
Massively parallel sequencing of target regions, exomes, and complete genomes has begun to dramatically increase the opportunities for identifying genetic variants underlying rare and common diseases. Here we applied exome resequencing to primary failure of tooth eruption (PFE) to identify the genetic causality of the disease. Two Japanese families having PFE were recruited and examined by genome-wide linkage study and subsequently exome analyses. Linkage analyses of these two families comprising eight affected individuals and two unaffected individuals revealed linkage signals at ten loci with a maximum LOD score of 1.5. Four affected individuals in one family were pooled and further processed for exome analysis followed by massive parallel sequencing. After three-step filtering including annotation and functional expectation, three variants were found to be candidates for PFE. Among the three variants, only a novel variant of parathyroid hormone 1 receptor gene (PTH1R), R383Q, was co-segregated in the first PFE family. Accordingly, we screened the gene for variants at all coding exons and the respective intron-exon boundaries in the second family and two sporadic individuals with PFE. We also identified a novel missense variant, P119L, co-segregating in the second family, and missense variants, P132L and R147C, in the sporadic cases. These variants were all in the highly-conserved region across zebrafish to chimpanzee and not observed in 192 unrelated controls, supporting the pathogenicity of the variants. The combination of linkage and exome analyses employed in this study provides a powerful strategy for identifying genes responsible for Mendelian disorders.
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Research Products
(70 results)
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[Journal Article] Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits2012
Author(s)
Park JH, Yamaguchi T, Watanabe C, Kawaguchi A, Haneji K, Takeda M, Kim YI, Tomoyasu Y, Watanabe M, Oota H, Hanihara T, Ishida H, Maki K, Park SB, Kimura R
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Journal Title
J Hum Genet
Volume: 57
Pages: 508-514
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[Journal Article] Association of common PAX9 variants with permanent tooth size variation in non-syndromic East Asian populations2012
Author(s)
Lee WC, Yamaguchi T, Watanabe C, Kawaguchi A, Takeda M, Kim YI, Haga S, Tomoyasu Y, Ishida H, Maki K, Park SB, Kimura R
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Journal Title
J Hum Genet
Volume: 57
Pages: 654-659
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