Linkage analysis of skeletal mandibular prognathism in Japanese

下颌无颌症是一种表现颌骨畸形的疾病。该病不接受出生时的颌骨畸形，但由于畸形在青春期变得显著而被归类为发育异常。下颌骨肥大的原因尚不清楚。但也有很多，它是在家庭中看到的，很明显，遗传因素强烈有助于家庭系统的事实，它持续了几代人，这种疾病被认为是像一个人的欧洲皇家家庭哈布斯堡。然而，目前国内外对该疾病的遗传性研究报道较少，对下颌前突的基因水平分析研究也未见报道。本研究的目的是尽可能多地与遵循常染色体显性遗传的家族进行全基因组连锁搜索，并阐明成为下颌骨无颌症病因的基因位点。研究方案得到了东京牙科大学机构审查委员会的批准，并获得了所有家庭成员的知情同意。在知情同意后，通过标准技术从外周静脉血样品中分离出两个下颌骨多颌畸形家族的19名成员的基因组DNA。利用微卫星标记进行连锁分析（ABI PRISM Linkage Mapping Set v2.5），结果在两个下颌骨无颌症家系的19名成员中均发现了连锁，LOD值为1.75的常染色体上有10、13、16条常染色体，今后将进一步增加家系样本的数量，并在10.13.16常染色体上进行补充试验和突变分析。

Mandibular prognathism is a disorder to show jaw malformation. The disease does not accept jaw malformation at birth, but be categorized as abnormality of development in puberty because malformation becomes remarkable. A cause of mandibular prognathism is not clear. But there is many that it is seen in familial, and it is clear that a genetic factor strongly contributes to family system from the fact that it lasts for several generations, and the disease is recognized like a person of European royal families Hapsburg. However, there are a few reports that reviewed the disease hereditarily, and analysis study with a gene level of mandibular prognathism is not elucidated in the world at all either. An aim of this study does genome-wide linkage search with a family obeying autosomal-dominant inheritance as much as possible, and it is to elucidate gene loci becoming causal of mandibular prognathism.Subject of study were nineteen members of two mandibular prognathism families in Japanese who had collected at the Tokyo Dental College Hospital. The study protocol was approved by the Tokyo Dental College Institutional Review Board, and informed consent was obtained from all family members. After informed consent, Genomic DNA of nineteen members of two mandibular prognathism families were isolated from peripheral venous blood samples by standard techniques. Linkage analysis was performed by using microsatellite markers (ABI PRISM Linkage mapping set v2.5).In result, linkage was recognized in nineteen members of two mandibular prognathism families because LOD score 1.75 was accepted into 10,13,16 autosomal chromosomes.In future, we will increase the number of the family samples, and perform supplementary tests and mutation analysis at 10.13.16 autosomal chromosomes.