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: 6681681
• 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/6681681
• 关键词: Mennonite; congenital disorders; congenital oral /facial /cranial defect; family genetics; genetic disorder; genetic mapping; glycogen storage disease type VI; human genetic material tag; human population genetics; human subject; hypotonia; information systems; mental retardation; micrencephaly; molecular biology information system; molecular pathology; muscle disorders; patient oriented research

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 are currently working on an animal model for this disorder where we can test hypotheses of pathogenesis and possible treatments.

本研究的目的有两个方面。首先是开发家谱资源，以便对旧秩序阿米什人和相关的再洗礼派教派的疾病遗传性进行深入研究。这些群体对于研究很重要，因为它们是小的、明确定义的群体分离株。此外，他们是热情的历史学家，并有出色的印刷家谱记录。我们已经完成了大部分的第一个目标，通过建立阿米什家谱数据库（AGDB）和几个计算工具来分析该数据库，包括PedHunter。这些工具使我们能够以准确和快速的方式为遗传研究生成准确的谱系。第二个目标是研究这些群体中遗传性疾病的遗传学。为此，我们已经克隆了6型糖原累积病、McKusick-Kaufman综合征、Amish Nemaline肌病中改变的基因，目前正在研究Amish小头畸形。我们已经确定了阿米什人小头畸形的基因改变，这是一种编码将脱氧核苷酸转运到线粒体中的蛋白质的基因。我们目前正在研究这种疾病的动物模型，我们可以在其中测试发病机制和可能的治疗方法的假设。