Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22
Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22
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DOI：
10.1001/jama.284.13.1664
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发表时间：
2000-10-04
影响因子：
120.7
通讯作者：
Brown, RH
中科院分区：
文献类型：
--
作者：
Hosler, BA;Siddique, T;Brown, RH
背景 有时，两种或多种主要的神经退行性疾病会同时出现，了解联合疾病的遗传基础，例如肌萎缩侧索硬化症 (ALS) 伴额颞叶痴呆 (FTD)，可能会深入了解这些疾病及相关神经退行性疾病的机制，目的是识别包含缺陷导致 ALS 的基因的基因座。设计全基因组 对 2 个数据集进行连锁分析，该研究来自 2 个数据集，该研究始于 20 世纪 80 年代中期，在 4 个大学研究中心开始进行研究，受试者最初的 16 个家庭（549 人）子集可能为遗传分析提供信息，其中 2 个或更多个体被诊断为患有 ALS，从 400 个家庭的波士顿数据集中识别出，随后从 300 多个家庭的芝加哥数据集中识别出 4 个可能提供信息的家庭（244 人），以检验基于 波士顿家庭的发现，主要结果测量连锁计算假设具有年龄依赖性外显率的常染色体显性遗传（进一步研究潜在位点所需的参数对数对数 [lod] 得分为 1.0 或更高）；涉及 ALS-FTD 基因座的交叉分析，结果在一组同时患有 ALS 和 FTD 或单独患有 ALS 或 FTD 的家庭中，在人类染色体 9q21-q22 上鉴定出一个与 ALS 连锁且 FTD 位于标记 D9S301 和 D9S167 之间的遗传基因座，单独患有 ALS 的家庭并未显示出与该基因座的连锁。交叉分析表明该区域覆盖约 77 cM。结论这些数据表明位于染色体 9q21-q22 区域的缺陷基因可能与伴有 FTD 的 ALS 相关。
Context Occasionally, 2 or more major neurodegenerative diseases arise simultaneously, An understanding of the genetic bases of combined disorders, such as amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), will likely provide insight into mechanisms of these and related neurodegenerative diseases,Objective To identify loci that contain genes whose defects cause ALS.Design A genome-wide linkage analysis of 2 data sets from an ongoing study begun in the mid-1980s at 4 university research centers,Subjects An initial subset of 16 families (549 people) potentially informative for genetic analysis, in which 2 or more individuals were diagnosed as having ALS, identified from a Boston data set of 400 families and 4 families potentially informative (244 people) subsequently identified from a Chicago data set of more than 300 families to test a hypothesis based on findings from the Boston families,Main Outcome Measures Linkage calculations assuming autosomal dominant inheritance with age-dependent penetrance (a parametric logarithm-of-odds [lod] score of 1.0 or greater required for further study of a potential locus); crossover analysis involving the ALS-FTD locus,Results In a set of families in which persons develop both ALS and FTD or either ALS or FTD alone, a genetic locus that is linked to ALS with FTD located between markers D9S301 and D9S167 was identified on human chromosome 9q21-q22, Families with ALS alone did not show linkage to this locus. Crossover analysis indicates this region covers approximately 77 cM,Conclusion These data suggest that a defective gene located in the chromosome 9q21-q22 region may be linked to ALS with FTD.