A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3
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Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.
KeywordsDental Tissue Hypothetical Gene Enamel Matrix Amelogenesis Imperfecta Dentinogenesis Imperfecta
This research was supported by grants DE14102 (P.I.P.) and DE06988 (M.L.S.) from the National Institute of Dental and Craniofacial Research. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number N01-HG-65403. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 (RR10600-01, CA62528-01, RR14514-01) from the National Center for Research Resources, National Institutes of Health.
- Aubin I, Adams CP, Opsahl S, Septier D, Bishop CE, Auge N, Salvayre R, Negre-Salvayre A, Goldberg M, Guenet J-L, Poirier C (2005) A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 37:803–805PubMedCrossRefGoogle Scholar
- Espiritu-Santo AR, Line SRP (2005) The enamel organic matrix: structure and function. Braz. J Oral Sci 4:716–724Google Scholar
- Fujiwara S, Takeo N, Otani Y, Parry DAD, Kunimatsu M, Lu R, Sasaki M, Matsuo N, Khaleduzzaman M, Yoshioka H (2001) Epiplakin, a novel member of the Plakin family originally identified as a 450-kDa human epidermal autoantigen. Structure and tissue localization. J Biol Chem 276:13340–13347PubMedCrossRefGoogle Scholar
- Gentleman R, Carey V, Bates D, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini A, Sawitzki G, Smith C, Smyth G, Tierney L, Yang J, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80PubMedCrossRefGoogle Scholar
- Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:Article 3Google Scholar
- Solban N, Jia H-P, Richard S, Tremblay S, Devlin AM, Peng J, Gossard F, Guo D-F, Morel G, Hamet P, Lewanczuk R, Tremblay J (2000) HCaRG, a novel calcium-regulated gene coding for a nuclear protein, is potentially involved in the regulation of cell proliferation. J Biol Chem 275:32234–32243PubMedCrossRefGoogle Scholar