Genetic studies of Amish and Anabaptist sects

这项研究的目的有两个方面。首先是开发家谱资源，以便对旧秩序亚米什教派和相关的再洗礼教派的疾病遗传性进行高级研究。研究这些种群很重要，因为它们是小的、定义明确的种群隔离。此外，他们都是热心的历史学家，有很好的印刷家谱记录。我们通过建立阿米什族谱数据库(AGDB)和几个用于分析该数据库的计算工具，包括PedHunter，已经实现了第一个目标的大部分。这些工具使我们能够以准确和快速的方式为遗传学研究生成准确的家系。第二个目标是研究这些群体中可遗传疾病的遗传学。为此，我们已经克隆了糖原储存疾病6型、McKusick-Kaufman综合征、Amish线虫肌病等改变的基因，目前正在研究Amish小头畸形。我们已经确定了阿米什小头症的基因变化，这是一种编码一种将脱氧核苷酸运输到线粒体的蛋白质的基因。我们目前已经为这种疾病开发了一个小鼠和斑马鱼动物模型，现在我们正在对表型进行特征描述。

The aim of this study is two fold. First is to develop genealogical resources to allow advanced studies of the heritability of disorders in the Old Order Amish and related Anabaptist sects. These groups are important to study because they are small, well defined population isolates. In addition, they are enthusiastic historians and have excellent printed genealogical records. We have accomplished much of the first goal by building the Amish Genealogy Database (AGDB) and several computational tools to analyze that database including PedHunter. These tools allow us to generate accurate pedigrees for genetic study in a accurate and rapid fashion. The second goal is to study the genetics of heritable disorders in these groups. To that end we have already cloned the genes that are altered in Glycogen storage disease type 6, McKusick-Kaufman syndrome, Amish Nemaline Myopathy, and are currently working on Amish Microcephaly. We have identified the gene alteration in Amish microcephaly, which is a gene that codes for a protein that transports deoxynucleotides into the mitochondria. We have currently developed both a mouse and zebrafish animal model for this disorder and we are now chararcterizing the phenotypes.