Nanoscale DNA Sequencing: Health Revolution?
納米尺度DNA測(cè)序引爆醫(yī)學(xué)革 命？
Nanoscale DNA Sequencing Could Spur Revolution in Personal Health Care
納米尺度的DNA測(cè)序可能加速個(gè)體化醫(yī)療革 命
譯者：Docofsoul
ScienceDaily (Aug. 21, 2010) — In experiments with potentially broad health care implications, a research team led by a University of Washington physicist has devised a method that works at a very small scale to sequence DNA quickly and relatively inexpensively.
《每日科學(xué)》2010年8月21日?qǐng)?bào)道 —— 由華盛頓大學(xué)的一名物理學(xué)家所率領(lǐng)的一個(gè)研究小組設(shè)計(jì)了一種方法，可在極小尺度上對(duì)DNA進(jìn)行測(cè)序，并且測(cè)序速度更快、相對(duì)更加便宜。他們的實(shí)驗(yàn)表明，這一方法具有對(duì)衛(wèi)生保健產(chǎn)生廣泛影響的潛力。
This illustration depicts a single strand of DNA moving through a nanopore that is being used to sequence the DNA. (Credit: Image courtesy of University of Washington)
本示意圖描述了單鏈DNA穿越用以測(cè)序的納米孔（圖片來源：華盛頓大學(xué)）
That could open the door for more effective individualized medicine, for example providing blueprints of genetic predispositions for specific conditions and diseases such as cancer, diabetes or addiction.
這一成果將為更有效的個(gè)體化醫(yī)學(xué)，比如說為特定癥狀與疾?。ㄈ缒[瘤、糖尿病或毒癮）提供遺傳傾向藍(lán)圖。
"The hope is that in 10 years people will have all their DNA sequenced, and this will lead to personalized, predictive medicine," said Jens Gundlach, a UW physics professor and lead author of a paper describing the new technique published the week of Aug. 16 in the Proceedings of the National Academy of Sciences.
華盛頓大學(xué)物理學(xué)教授Jens Gundlach以第一作者身份在8月16號(hào)的《美國(guó)國(guó)家科學(xué)院院刊》上發(fā)表了一篇論文來描述這項(xiàng)新的技術(shù)，他說： “希望在于：10年內(nèi)大家可讓自己的全部DNA都得到測(cè)序，并且個(gè)體化、預(yù)防性藥品也將由此誕生。”
The technique creates a DNA reader that combines biology and nanotechnology using a nanopore taken from Mycobacterium smegmatis porin A. The nanopore has an opening 1 billionth of a meter in size, just large enough to measure a single strand of DNA as it passes through.
通過結(jié)合生物學(xué)與納米技術(shù)并利用取之于恥垢分枝桿菌porin A（Mycobacterium smegmatis porin A.）的納米孔，研究者以該論文所介紹的技術(shù)創(chuàng)建一個(gè)DNA電子閱讀器。該閱讀器上納米孔有個(gè)十億分之一米尺度的開口，剛好能讓單鏈DNA通過以便測(cè)量。
The scientists placed the pore in a membrane surrounded by potassium-chloride solution. A small voltage was applied to create an ion current flowing through the nanopore, and the current's electrical signature changed depending on the nucleotides traveling through the nanopore. Each of the nucleotides that are the essence of DNA -- cytosine, guanine, adenine and thymine -- produced a distinctive signature.
研究小組的科學(xué)們將該小孔放置于浸潤(rùn)于氯化鉀溶液的一塊膜上，然后加上小電壓以產(chǎn)生流過該納米孔的離子流。該離子流的電簽名（electrical signature）會(huì)根據(jù)穿越該納米孔的核苷酸發(fā)生變化。 核苷酸是DNA的基本組成部分（DNA含四種脫氧核苷酸：胞核嘧啶、鳥嘌呤、腺嘌呤與胸腺嘧啶），每種核苷酸產(chǎn)生一個(gè)與眾不同的簽名。
The team had to solve two major problems. One was to create a short and narrow opening just large enough to allow a single strand of DNA to pass through the nanopore and for only a single DNA molecule to be in the opening at any time. Michael Niederweis at the University of Alabama at Birmingham modified the M. smegmatis bacterium to produce a suitable pore.
該研究小組必須解決兩個(gè)主要難題：其一是建立短而狹窄的開口，剛好讓DNA單鏈通過納米孔，并且任何時(shí)間都只讓單個(gè)DNA分子容身于該開口。阿拉巴馬大學(xué)伯明翰分校的Michael Niederweis負(fù)責(zé)改造恥垢分枝桿菌以產(chǎn)生合適的小孔。
The second problem, Gundlach said, was that the nucleotides flowed through the nanopore at a rate of one every millionth of a second, far too fast to sort out the signal from each DNA molecule. To compensate, the researchers attached a section of double-stranded DNA between each nucleotide they wanted to measure. The second strand would briefly catch on the edge of the nanopore, halting the flow of DNA long enough for the single nucleotide to be held within the nanopore DNA reader. After a few milliseconds, the double-stranded section would separate and the DNA flow continued until another double strand was encountered, allowing the next nucleotide to be read.
Gundlach指出，第二個(gè)難題則是流過該納米孔的核苷酸的速度必須是百萬分之一秒內(nèi)通過一個(gè)核苷酸，這樣就太快了，無法檢測(cè)來自每個(gè)DNA分子的信號(hào)。為了彌補(bǔ)這一點(diǎn)，研究者將位于想測(cè)量的每個(gè)核苷酸之間的雙鏈DNA的一部分固定，第二條鏈會(huì)在短暫的時(shí)間內(nèi)抓住納米孔的邊緣，使DNA流停留時(shí)間足夠長(zhǎng)，讓單個(gè)核苷酸停在納米孔DNA閱讀器上。在幾個(gè)毫秒后，雙鏈部分會(huì)分開，于是DNA流繼續(xù)流動(dòng)直到下一個(gè)雙鏈來到，這樣下一個(gè)核苷酸的測(cè)量又開始了。
The delay, though measured in thousandths of a second, is long enough to read the electrical signals from the target nucleotides, Gundlach said.
Gundlach說該延遲雖然在測(cè)量時(shí)間上只有一秒的千分之幾，卻足夠讓閱讀器讀出來自目標(biāo)核苷酸上的電信號(hào)。
"We can practically read the DNA sequence from an oscilloscope trace," he said.
他說：“我們實(shí)際上能夠從示波器描跡上直接讀出DNA序列。”
Besides Gundlach and Niederweiss, other authors are Ian Derrington, Tom Butler, Elizabeth Manrao and Marcus Collins of the UW; and Mikhail Pavlenok at Alabama-Birmingham.
除了Gundlach 與 Niederweiss，其他作者是華盛頓大學(xué)的Ian Derrington、Tom Butler、Elizabeth Manrao 、Marcus Collins 與阿拉巴馬大學(xué)伯明翰分校的Mikhail Pavlenok。
The work was funded by the National Institutes of Health and its National Human Genome Research Institute as part of a program to create technology to sequence a human genome for $1,000 or less. That program began in 2004, when it cost on the order of $10 million to sequence a human-sized genome.
作為一項(xiàng)建立相關(guān)技術(shù)以求在1000美元之內(nèi)的成本對(duì)人類基因組進(jìn)行測(cè)序的計(jì)劃的一倍分，本研究工作得到國(guó)立衛(wèi)生研究院及其附屬單位國(guó)立人類基因組研究研究院的資金支持。該計(jì)劃始于2004年，當(dāng)時(shí)耗資一千萬美元對(duì)人類全基因組進(jìn)行了測(cè)序。
The new research is a major step toward achieving DNA sequencing at a cost of $1,000 or less.
本項(xiàng)新的研究是向1000美元之內(nèi)成本對(duì)DNA進(jìn)行測(cè)序的目標(biāo)邁出的重大一步。
"Our experiments outline a novel and fundamentally very simple sequencing technology that we hope can now be expanded into a mechanized process," Gundlach said.
Gundlach說：“我們的實(shí)驗(yàn)顯示了一種新的、從根本上說非常簡(jiǎn)單的測(cè)序技術(shù)。我們希望，該技術(shù)現(xiàn)在能夠拓展為一個(gè)機(jī)械化過程。”
（Docofsoul 譯于2010-8-22）
