title: DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia.
abstract: Hypodontia is caused by interactions among genetic, epigenetic, and environmental factors during tooth development, but the actual mechanism is unknown. DNA methylation now appears to play a significant role in abnormal developments, flawed phenotypes, and acquired diseases. Methylated DNA immunoprecipitation (MeDIP) has been developed as a new method of scanning large-scale DNA-methylation profiles within particular regions or in the entire genome. Here, we performed a genome-wide scan of paired DNA samples obtained from 4 patients lacking two mandibular incisors and 4 healthy controls with normal dentition. We scanned another female with non-syndromic anodontia and her younger brother with the same gene mutations of the PAX9,MSX1,AXIN2 and EDA, but without developmental abnormalities in the dentition. Results showed significant differences in the methylation level of the whole genome between the hypodontia and the normal groups. Nine genes were spotted, some of which have not been associated with dental development; these genes were related mainly to the development of cartilage, bone, teeth, and neural transduction, which implied a potential gene cascade network in hypodontia at the methylation level. This pilot study reveals the critical role of DNA methylation in hypodontia and might provide insights into developmental biology and the pathobiology of acquired diseases.
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14., 3rd Sec, Ren Min Nan Road, Chengdu 610041, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14., 3rd Sec, Ren Min Nan Road, Chengdu 610041, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14., 3rd Sec, Ren Min Nan Road, Chengdu 610041, P.R. China.
authors.forename: Renhuan
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Middle Yanchang Road, Shanghai 200072, P.R. China.
authors.forename: Raorao
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14., 3rd Sec, Ren Min Nan Road, Chengdu 610041, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000848:Anodontia / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D019295:Computational Biology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D009805:Odontogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic