Genetics of ALS

这种多中心ROT的目标是确定易患肌萎缩侧索硬化症(ALS)的遗传风险因素。这一RO1是自1993年以来一直在进行的合作努力的延续，当时该小组发现了第一个ALS基因(SOF1基因)。我们的肌萎缩侧索硬化症遗传学协作组(ALSGCG)通过使用常染色体显性大家系识别2、9、15、16、18、20和X染色体上的基因座，极大地扩展了ALS的遗传学知识；我们已经生成了较小多重家系中1、2、7、8、17、18和19号染色体上其他基因座的初步数据。ALSGCG代表西北大学范伯格医学院(NUFSM)、马萨诸塞州综合医院(MGH)、杜克大学医学中心(DUMC)、 范德比尔特大学医学院(VUMS)。我们已经收集了世界上最大的一组多重和单一基因资源，现在有足够的家族材料开始在这些区域内发现基因，并在候选基因可用时测试它们。 这项RO1在四个地点进行。站点1(NUFSM)将使用位置候选方法来识别在较小的多基因家族中出现的基因。这将包括使用连锁分析来提炼连锁峰，以及使用等位基因关联研究来测试候选基因。站点2(MGH)将使用与站点1类似的方法，使用定位候选方法来确定在常染色体显性遗传的大型家系中出现的基因。它还将使用等位基因关联方法来测试其他运动神经元疾病基因在ALS中的潜在作用。这些网站由西北大学的一名行政助理以及DUMC和VUMS的遗传流行病学和生物信息学支持的项目提供支持。分析项目的所有数据，包括临床、风险因素、系谱和NUFSM(站点1)和MGH的基因数据 (站点2)在DUMSC和VUMS分析站点进行。这些也提供了对站点1和2的所有连锁和等位基因关联分析。

The goal of this Multicenter ROt is to identify genetic risk factors that predispose individuals to amyotrophic lateral sclerosis (ALS). This RO1 is a continuation of collaborative efforts that have been ongoing since 1993, when this group identified the first ALS gene (the SOD 1 gene). Our Amyotrophic Lateral Sclerosis Genetics Collaborative Group (ALSGCG) has greatly extended the genetic knowledge of ALS by identifying loci on chromosomes 2, 9, 15, 16, 18, 20 and X using large autosomal dominant families; we have generated preliminary data for additional loci on chromosomes 1, 2, 7, 8, 17, 18, and 19 in smaller multiplex families. The ALSGCG represents the collaborative efforts of groups at Northwestern University Feinberg School of Medicine (NUFSM), Massachusetts General Hospital (MGH), Duke University Medical Center (DUMC), and Vanderbilt University Medical School (VUMS). We have collected the largest set of multiplex and singleton resources in the world and now have sufficient family material to begin gene discovery within these regions and test candidate genes as they become available. This RO1 is carried out at four sites. Site 1 (NUFSM) will use the locational candidate approach to identify the genes arising in the smaller multiplex families. This will include refining the linkage peaks using linkage analysis and testing candidate genes using allelic association studies. Site 2 (MGH) will use the locational candidate approach to identify the genes arising in the large autosomal dominant families using approaches similar to Site 1. It will also test the potential role of other motor neuron disease genes in ALS using an allelic association approach. The sites are supported by an Administrative Assistant from Northwestern, and a Genetic Epidemiology and Bioinformatics supported programs at DUMC and VUMS. Analysis of all data from the projects, including clinical, risk factor, pedigree, and genotypic data for NUFSM (Site 1) and MGH (Site 2) is carried out at DUMSC and VUMS analyses sites. Those also provide all linkage and allelic association analyses for Sites 1 and 2.