據(jù)sciencedaily網(wǎng)站2006年11月29日?qǐng)?bào)道,，美國(guó)科學(xué)家將基因篩查作為研究肌萎縮性脊髓側(cè)索硬化癥(amyotrophic lateral sclerosis ,，簡(jiǎn)稱ALS)最普通形式——偶發(fā)性ALS的基礎(chǔ)。通過(guò)對(duì)1,000多名病人和對(duì)照健康人（controls）身上的基因信息成功編譯,，科學(xué)家對(duì)基因最大范圍的搜索已跨過(guò)了第一道障礙,。
從事此項(xiàng)研究的研究人員主要來(lái)自約翰•霍普金斯醫(yī)院負(fù)責(zé)ALS研究的Packard中心、美國(guó)國(guó)家神經(jīng)疾病與中風(fēng)協(xié)會(huì)(NINDS)以及ALS協(xié)會(huì),。他們于本周在日本橫濱召開(kāi)的第17屆肌萎縮側(cè)索硬化癥國(guó)際學(xué)術(shù)會(huì)議上介紹他們的最初發(fā)現(xiàn)。此次學(xué)術(shù)會(huì)議為全世界科學(xué)家報(bào)導(dǎo)這種疾病的研究提供了一個(gè)主要場(chǎng)所,。
首次大范圍地對(duì)“自發(fā)性”疾病如所有的ALS的基因進(jìn)行甄別,，這是一個(gè)良好的開(kāi)端。此類(lèi)“自發(fā)性”疾病會(huì)破壞運(yùn)作,，以及包括呼吸在內(nèi)各種活動(dòng)的運(yùn)動(dòng)神經(jīng)神經(jīng)元,。
布賴恩•特雷洛和約翰•哈代作為Packard中心的負(fù)責(zé)人，同時(shí)也是美國(guó)國(guó)立衛(wèi)生研究院(NIH)的成員,。他們正帶領(lǐng)一個(gè)美國(guó)－意大利聯(lián)合研究小組從事這項(xiàng)百萬(wàn)美元項(xiàng)目,。特雷洛稱，“如果一切進(jìn)展順利,，這項(xiàng)工作將闡明基因或它的缺少在偶發(fā)性ALS中所擔(dān)當(dāng)?shù)慕巧?rdquo;他解釋稱,，“例如，我們不知道ALS是不是由大量相互作用的基因,、基因加上環(huán)境或者只是環(huán)境所引起的,。我們工作的目標(biāo)就是對(duì)此進(jìn)行解釋。”
在此項(xiàng)研究當(dāng)中,，科學(xué)家從病人和健康的對(duì)照人身上搜集脫氧核糖核酸（DNA）并成功進(jìn)行篩查,，以選出特定的樣本。與沒(méi)有感染此疾病的人相比,，這些特定的樣本在ALS患者身上出現(xiàn)的頻率更高,。
這項(xiàng)工作的關(guān)鍵在于科學(xué)家們采用高分析率和全基因組相關(guān)性研究的技術(shù)，這是一種具有高通量的方法（也就是說(shuō),，它可以同時(shí)處理許多樣本）,，該方法使用自動(dòng)化和最新的基因探測(cè)芯片技術(shù)，以一種6個(gè)月前不可能達(dá)到的速度和精確度來(lái)挖掘每一個(gè)病人的DNA信息,。
該研究項(xiàng)目開(kāi)始于2005年春天,，并已完成預(yù)期進(jìn)展,，這反映出各國(guó)科學(xué)家和臨床醫(yī)生間具有高度的協(xié)作精神。例如,，美國(guó)國(guó)家神經(jīng)疾病與中風(fēng)協(xié)會(huì)將在全美范圍內(nèi)多個(gè)醫(yī)學(xué)中心的ALS臨床醫(yī)生為此項(xiàng)研究收集的樣本捐獻(xiàn)出來(lái),。
研究人員期望在接下來(lái)的幾個(gè)月內(nèi)開(kāi)始進(jìn)行重要的分析并得出結(jié)論。發(fā)現(xiàn)直接導(dǎo)致ALS的基因,，或者使人們?nèi)菀赘腥敬祟?lèi)疾病的基因?qū)橹委熖峁┬碌哪繕?biāo),。自發(fā)現(xiàn)過(guò)氧化物歧化酶（SOD1）突變形式導(dǎo)致ALS發(fā)病以來(lái)的10年里，科學(xué)家還發(fā)現(xiàn)了大量的其他ALS相關(guān)基因突變,。
然而,，偶發(fā)性ALS的基因基礎(chǔ)仍然遠(yuǎn)遠(yuǎn)不能確定。90%的ALS患者屬于偶發(fā)性ALS,，它似乎可以無(wú)需家族性病史自然發(fā)生,。即使此類(lèi)疾病與家族性ALS在臨床上無(wú)法進(jìn)行辨別，但不同的基因可能是其發(fā)病的原因,。無(wú)論如何,，它們?cè)谄茐倪\(yùn)動(dòng)神經(jīng)神經(jīng)元的方式上有著共同之處。那就是為什么在一種類(lèi)型里被證實(shí)的一個(gè)基因突變可以幫助理解其他的基因突變,。
通過(guò)這項(xiàng)研究工作在一個(gè)基因或多個(gè)基因與ALS之間找到一種科學(xué)的重要的聯(lián)系將為更為廣泛的國(guó)際研究創(chuàng)造條件,。特雷洛稱，“但即使我們沒(méi)有找到這種聯(lián)系,，那就間接地表明偶發(fā)性ALS并不是基于基因,。那時(shí)，我們應(yīng)將研究集中于環(huán)境,。”
注：這篇報(bào)告是由在約翰斯•霍普金斯醫(yī)院從事ALS研究的Packard中心發(fā)表的,，這是一個(gè)得到約翰斯•霍普金斯大學(xué)醫(yī)學(xué)院部分支持的組織。研究小組成員包括：Packard中心和約翰斯•霍普金斯醫(yī)院醫(yī)學(xué)和哲學(xué)博士杰弗里•羅斯坦,，國(guó)家防老研究所神經(jīng)遺傳學(xué)實(shí)驗(yàn)室詹尼弗•斯凱米克,、索尼阿•斯庫(kù)爾茲、安吉拉•布利頓,、薩姆帕斯•阿勒帕里,、方洪春（音）和J拉斐爾•吉布斯，意大利都靈大學(xué)艾德里安•奇奧,。
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.
