| Project/Area Number |
22390393
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthodontic/Pediatric dentistry
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
|
|---|
| Keywords | ゲノム / 遺伝(子) / 歯 / 顎 / 原発性萌出不全 / 遺伝（子） / 顎変形症 / 咬合異常 / 不正咬合 / 歯の形態 / 顎顔面形態 / 歯の萌出 / 歯科矯正 / 下顎前突症 / 遺伝統計学 / 下顎頭軟骨 / 遺伝子 |
|---|
| 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.
|
