Genetic studies of Amish and Anabaptist sects

阿米什教派和再洗礼教派的遗传学研究

• 批准号: 6830477
• 负责人: LESLIE G BIESECKER
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6830477
• 关键词: Mennonite; computer data analysis; congenital brain disorder; congenital oral /facial /cranial defect; developmental disease /disorder; disease /disorder model; family genetics; gene mutation; genetic disorder; glycogen storage disease type VI; human subject; micrencephaly; mitochondria; model design /development; molecular biology information system; molecular cloning; nucleotides; pathologic process; religious group; transport proteins

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 an animal model for this disorder and we are now testing hypotheses of pathogenesis and possible treatments.

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动物模型，我们现在正在测试发病机制和可能的治疗方法的假说。