Linkage analysis of skeletal mandibular prognathism in Japanese

下颌前突是一种表现为颌骨畸形的畸形。这种疾病不接受出生时的下颌畸形，但在青春期被归类为发育异常，因为畸形变得明显。下颌前突的原因尚不清楚。但有许多是在家族中看到的，很明显，从它持续几代人的事实来看，遗传因素对家庭系统有很大的贡献，而且这种疾病被认为是欧洲皇室哈布斯堡家族的人。然而，从遗传性角度对该疾病进行综述的报道不多，从基因水平对下颌前突进行的分析研究在国际上也未见报道。本研究的目的是对一个符合常染色体显性遗传的家系进行全基因组连锁搜索，以阐明下颌前突畸形的致病基因座。研究对象是在东京牙科大学医院收集的两个日本人下颌前突畸形家系的19名成员。该研究方案得到了东京牙科学院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。经知情同意后，用标准方法从两个下颌前突家系的19名成员的外周静脉血中提取基因组DNA。利用微卫星标记(ABI PRISM Linkage Set V2.5)进行连锁分析，结果在两个下颌前突家系的19个成员中识别到连锁，因为在10、13、16条常染色体上接受LOD评分1.75。今后我们将增加家系样本的数量，并在10.13.16常染色体上进行补充测试和突变分析。

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.