Rosen D R, Sapp P, O'Regan J, McKenna-Yasek D, Schlumpf K S, Haines J L, Gusella J F, Horvitz H R, Brown R H
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown 02129-2060.
Am J Med Genet. 1994 May 15;51(1):61-9. doi: 10.1002/ajmg.1320510114.
Amyotrophic lateral sclerosis (ALS: Lou Gehrig's Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers [Siddique et al.: N Engl J Med 324:1381-1384, 1991] and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families [Rosen et al.: Nature 362:59-62, 1993]. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517 [VanKeuren et al.: Am J Hum Genet 38:793-804, 1986]. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS families for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers revealed recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219.(ABSTRACT TRUNCATED AT 250 WORDS)
肌萎缩侧索硬化症（ALS：卢伽雷氏病）是一种累及大脑和脊髓上下运动神经元的致命性神经退行性疾病。我们之前使用4个限制性片段长度多态性DNA标记报道了家族性ALS（FALS）基因与人类21号染色体的连锁关系[Siddique等人：《新英格兰医学杂志》324：1381 - 1384，1991]，并在一些ALS家族中鉴定出超氧化物歧化酶（SOD）-1基因中的疾病相关突变[Rosen等人：《自然》362：59 - 62，1993]。我们在此报告引导我们检测SOD -1基因是否存在突变的遗传连锁数据。我们还报告了一个源自黏粒PW517的D21S63新微卫星DNA标记[VanKeuren等人：《美国人类遗传学杂志》38：793 - 804，1986]。包括新标记D21S63在内的10个微卫星DNA标记被用于重新研究FALS与21号染色体的连锁关系。对这10个DNA标记与13个ALS家族进行的遗传连锁分析证实了21号染色体上存在FALS基因。所有家族的最高两点LOD总分是4.33，在距标记D21S223 10厘摩的距离处获得。对于与21号染色体连锁的5个ALS家族，在DNA标记D21S223处获得了峰值两点LOD分数5.94。对于5个与21号染色体连锁的ALS家族，标记D21S213、D21S223、D21S167和FALS的多点分数为6.50。这些家族针对这一10个DNA标记的单倍型揭示了重组事件，进一步将FALS基因的位置精确到D21S213和D21S219之间大约5兆碱基（Mb）的区段。（摘要截短于250字）
