MOLECULAR GENETICS OF HYPODONTIA

缺牙是指遗传性缺失一个 四颗恒牙 牙齿形态发生依赖于 上皮细胞和间充质细胞之间的相互作用。 调节黑腹果蝇的同源异型基因 最近的研究表明， 与牙齿和肢体相关的上皮-间质相互作用 形态发生 同源异型RNA的突变或转基因敲除 基因、转录因子或它们的下游靶点导致了 阻碍牙齿发育。 我们的假设是缺牙是一种 不同基因突变导致的共同表型 控制牙齿的发育。 我们发现了一种新的 和不寻常的双侧上颌尖牙缺牙谱系， study. 具体目标是：（一）召集合理的候选人 基因标记并使用适当的标记进行连锁分析 微卫星标记，导致包含一个位点或排除 与这种缺牙表型无关的基因 如果成功， 我们打算对受影响的候选基因进行测序， 突变的本质 ii）候选基因方法是 我们将开始一个全基因组的随机映射 寻找缺牙基因 我们预测，类似的研究 一些不同形式的缺牙将导致识别 控制牙齿和四肢的早期步骤 发展

Hypodontia is defined as the hereditary absence of between one and four permanent teeth. Tooth morphogenesis relies upon reciprocal interactions between epithelial and mesenchymal cells. Homeotic genes that regulate Drosophila melangaster development were recently shown to be expressed during inductive epithelial-mesenchymal interactions associated with tooth and limb morphogenesis. Mutations or transgenic knockouts of homeotic genes, transcription factors or their downstream targets have led to blocked tooth development. Our hypothesis is that hypodontia is a common phenotype resulting from mutations in different genes controlling the development of teeth. We have identified a new and unusual bilateral maxillary cuspid hypodontia pedigree for study. Specific Aims are: I) to assemble reasonable candidate gene markers and carry out linkage analyses using appropriate microsatellite markers, leading to inclusion of a locus or exclusion of a locus not linked to this hypodontia phenotype. If successful, we intend to sequence the affected candidate gene to determine the nature of the mutation. ii) the candidate gene approach is uninformative, we will begin a genome-wide random mapping search for the hypodontia gene. We predict that similar studies on a number of distinct forms of hypodontia will lead to identification of the early steps in pathways controlling tooth and limb development.