Lill Christina M, Abel Olubunmi, Bertram Lars, Al-Chalabi Ammar
Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Amyotroph Lateral Scler. 2011 Jul;12(4):238-49. doi: 10.3109/17482968.2011.584629.
Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous disorder that shows a characteristic dichotomy of familial forms typically displaying Mendelian inheritance patterns, and sporadic ALS showing no or less obvious familial aggregation. While the former is caused by rare, highly penetrant, and pathogenic mutations, risk for sporadic ALS is probably the result of the combined effects of common polymorphisms with minor to moderate effect sizes. Owing to recent advances in high-throughput genotyping and sequencing technologies, genetic research in both fields is evolving at a rapidly increasing pace making it more and more difficult to follow and evaluate the most significant progress in the field. To alleviate this problem, our groups have created dedicated and freely available online databases, ALSoD ( http://alsod.iop.kcl.ac.uk/ ) and ALSGene ( http://www.alsgene.org ), which provide systematic and in-depth qualitative and quantitative overviews of genetic research in both familial and sporadic ALS. This review briefly introduces the background and main features of both databases and provides an overview of the currently most compelling genetic findings in ALS derived from analyses using these resources.
肌萎缩侧索硬化症（ALS）是一种基因异质性疾病，其特征表现为家族性形式呈现典型的孟德尔遗传模式，而散发性ALS则无家族聚集或家族聚集不明显。前者由罕见、高外显率的致病突变引起，散发性ALS的发病风险可能是常见多态性综合作用的结果，这些多态性的效应大小为轻度至中度。由于高通量基因分型和测序技术的最新进展，这两个领域的遗传学研究正以越来越快的速度发展，使得跟踪和评估该领域最重要的进展变得越来越困难。为缓解这一问题，我们团队创建了专门的、免费在线数据库ALSoD（http://alsod.iop.kcl.ac.uk/）和ALSGene（http://www.alsgene.org），它们对家族性和散发性ALS的遗传学研究提供了系统、深入的定性和定量概述。本综述简要介绍了这两个数据库的背景和主要特征，并概述了目前使用这些资源进行分析得出的ALS中最有说服力的遗传学发现。
