据sciencedaily网站2006年11月29日报道，美国科学家将基因筛查作为研究肌萎缩性脊髓侧索硬化症(amyotrophic lateral sclerosis ，简称ALS)最普通形式——偶发性ALS的基础。通过对1,000多名病人和对照健康人（controls）身上的基因信息成功编译，科学家对基因最大范围的搜索已跨过了第一道障碍。
从事此项研究的研究人员主要来自约翰•霍普金斯医院负责ALS研究的Packard中心、美国国家神经疾病与中风协会(NINDS)以及ALS协会。他们于本周在日本横滨召开的第17届肌萎缩侧索硬化症国际学术会议上介绍他们的最初发现。此次学术会议为全世界科学家报导这种疾病的研究提供了一个主要场所。
首次大范围地对“自发性”疾病如所有的ALS的基因进行甄别，这是一个良好的开端。此类“自发性”疾病会破坏运作，以及包括呼吸在内各种活动的运动神经神经元。
布赖恩•特雷洛和约翰•哈代作为Packard中心的负责人，同时也是美国国立卫生研究院(NIH)的成员。他们正带领一个美国－意大利联合研究小组从事这项百万美元项目。特雷洛称，“如果一切进展顺利，这项工作将阐明基因或它的缺少在偶发性ALS中所担当的角色。”他解释称，“例如，我们不知道ALS是不是由大量相互作用的基因、基因加上环境或者只是环境所引起的。我们工作的目标就是对此进行解释。”
在此项研究当中，科学家从病人和健康的对照人身上搜集脱氧核糖核酸（DNA）并成功进行筛查，以选出特定的样本。与没有感染此疾病的人相比，这些特定的样本在ALS患者身上出现的频率更高。
这项工作的关键在于科学家们采用高分析率和全基因组相关性研究的技术，这是一种具有高通量的方法（也就是说，它可以同时处理许多样本），该方法使用自动化和最新的基因探测芯片技术，以一种6个月前不可能达到的速度和精确度来挖掘每一个病人的DNA信息。
该研究项目开始于2005年春天，并已完成预期进展，这反映出各国科学家和临床医生间具有高度的协作精神。例如，美国国家神经疾病与中风协会将在全美范围内多个医学中心的ALS临床医生为此项研究收集的样本捐献出来。
研究人员期望在接下来的几个月内开始进行重要的分析并得出结论。发现直接导致ALS的基因，或者使人们容易感染此类疾病的基因将为治疗提供新的目标。自发现过氧化物歧化酶（SOD1）突变形式导致ALS发病以来的10年里，科学家还发现了大量的其他ALS相关基因突变。
然而，偶发性ALS的基因基础仍然远远不能确定。90%的ALS患者属于偶发性ALS，它似乎可以无需家族性病史自然发生。即使此类疾病与家族性ALS在临床上无法进行辨别，但不同的基因可能是其发病的原因。无论如何，它们在破坏运动神经神经元的方式上有着共同之处。那就是为什么在一种类型里被证实的一个基因突变可以帮助理解其他的基因突变。
通过这项研究工作在一个基因或多个基因与ALS之间找到一种科学的重要的联系将为更为广泛的国际研究创造条件。特雷洛称，“但即使我们没有找到这种联系，那就间接地表明偶发性ALS并不是基于基因。那时，我们应将研究集中于环境。”
注：这篇报告是由在约翰斯•霍普金斯医院从事ALS研究的Packard中心发表的，这是一个得到约翰斯•霍普金斯大学医学院部分支持的组织。研究小组成员包括：Packard中心和约翰斯•霍普金斯医院医学和哲学博士杰弗里•罗斯坦，国家防老研究所神经遗传学实验室詹尼弗•斯凯米克、索尼阿•斯库尔兹、安吉拉•布利顿、萨姆帕斯•阿勒帕里、方洪春（音）和J拉斐尔•吉布斯，意大利都灵大学艾德里安•奇奥。
英文原文：
First International Gene Screen For Typical ALS Is On Track
The largest-scale search for genes that underlie sporadic amyotrophic lateral sclerosis (ALS), the most common form of the disease, has crossed its first hurdle with the successful compiling of genetic information on more than 1,000 patients and controls.
Researchers in the study, supported by The Packard Center for ALS Research at Johns Hopkins, the National Institute of Neurological Disorders and Stroke (NINDS) and the ALS Association, present their initial findings this week at the 17th International Symposium on ALS/MDA at Yokohama, Japan. The symposium is the major venue, worldwide, for reporting studies on the disease.
It's a good beginning to the first broad screening for genes for the "spontaneous" illness which, like all ALS, destroys the motor neurons that enable movement, including breathing.
Packard Center grantee Bryan Traynor and John Hardy, both with the NIH, are leading an American and Italian team of researchers in the million-dollar project. "If all goes well," Traynor says, "the work will clarify the role of genes-or lack of it-in sporadic ALS. That role has long been uncertain," he explains. "We don't know, for example, if sALS is triggered by a handful of interacting genes or genes plus environment or environment alone. Our work aims to clarify that."
In the study, DNA was collected from patients and healthy controls and successfully scanned for specific patterns that appear more frequently in those with the disease than those without it.
Critical to the work-known to scientists as a high resolution, genome-wide association study-is its technology. It's a high-throughput approach (that is, it treats many samples simultaneously) that uses robotics and just-available gene finder chips to mine each patient's DNA for information with a speed and accuracy not possible six months ago.
The project, which began last spring, was completed in record time, reflecting the highly collaborative nature of the involved scientists and clinicians. The NINDS, for example, contributed the American samples in the study from among those that ALS clinicians at multiple medical centers nationwide sent to its new national repository.
The researchers anticipate important analysis and conclusion-drawing will occur in the next few months.
Finding genes that lead directly to ALS or that predispose people to the disease should provide new targets for therapies. In the decade since discovering the cause of some inherited forms of ALS-namely, a mutation producing a flawed version of the enzyme superoxide dismutase (SOD1)-a handful of other ALS-related mutations have been brought to light.
The genetic underpinnings of sporadic ALS, however, are far less certain. Sporadic ALS, affecting 90 percent of ALS patients, apparently arises spontaneously without family history. Even though the disease is clinically indistinguishable from the ALS that runs in families, different genes may be responsible for each. Something is held in common, however, in the way that they both kill motor neurons. That's why a gene change identified in one type can help understand the other.
Finding a scientifically significant tie between a gene or genes and ALS in this work will set the stage for even larger international investigations. "But even if we get no associations," says Traynor, "that would suggest that sALS isn't gene-based, that we should focus instead on the environment."
This release was generated by The Packard Center for ALS Research at Johns Hopkins, an organization supported, in part, by the Johns Hopkins University School of Medicine.
