?一種數(shù)學(xué)進(jìn)展提高了人類基因組測(cè)序的能力，這為腫瘤生物學(xué)提供了一種比傳統(tǒng)DNA測(cè)序法快速和高性價(jià)比的新工具。
??USC的分子和計(jì)算生物學(xué)教授Michael Waterman小組的學(xué)生最近發(fā)展了一種數(shù)學(xué)運(yùn)算來(lái)處理限制性內(nèi)切酶圖譜技術(shù)得到的大量數(shù)據(jù),。這種方法又被叫做“可見(jiàn)圖譜”。
??可見(jiàn)圖譜技術(shù)在染色體上得到坐標(biāo),，這就像高速公路上的公里牌一樣,。Standford大學(xué)博士后，文章第一作者Anton Valouev表示,，這種算法使得可見(jiàn)圖譜技術(shù)可被用于人類基因組,。他說(shuō)：“這為醫(yī)學(xué)應(yīng)用提供了極大的便利，特別是尋找基因組異常方面,。”
??這一結(jié)果發(fā)表在上周的《Proceeding of the National Academy of Science》上,。
??可見(jiàn)圖譜技術(shù)是上世紀(jì)90年代末由Wisconsin-Madison大學(xué)化學(xué)和基因?qū)W教授David Schwartz發(fā)明的，這種技術(shù)能檢測(cè)基因組的大小和大尺度的結(jié)構(gòu),。它利用熒光顯微鏡對(duì)用酶分離的單個(gè)DNA分子成像,。對(duì)大量DNA成像后，就可以得到基因組圖譜了,。
??可見(jiàn)圖譜技術(shù)缺少基因組序列的微小細(xì)節(jié),，但是這可以用其它手段補(bǔ)償?；?qū)W家常說(shuō)99.9%的人類DNA是一致的,，但有時(shí)我們會(huì)發(fā)現(xiàn)一些區(qū)域有很大的改變。這些改變包括大片基因結(jié)構(gòu)的缺失或多余,。癌癥基因就具有這樣的特征,。
??作者之一的Philip Green說(shuō)：“這很難被傳統(tǒng)方法檢測(cè)到。”而可見(jiàn)圖譜技術(shù)可以得到基因組的長(zhǎng)度,，以及快速檢測(cè)結(jié)構(gòu)和長(zhǎng)度上的差別,。將以上結(jié)果和正常基因組比較就能知道變異是否發(fā)生,。
英文原文：
Genome ID Method Extended to Humans
A mathematical discovery has extended the reach of a novel genome mapping method to humans, potentially giving cancer biology a faster and more cost-effective tool than traditional DNA sequencing.
student-led group from the laboratory of Michael Waterman, University Professor in molecular and computational biology in USC College, has developed an algorithm to handle the massive amounts of data created by a restriction mapping technology known as “optical mapping.”
Restriction maps provide coordinates on chromosomes analogous to mile markers on freeways.
Lead author Anton Valouev, a recent graduate of Waterman’s lab and now a postdoctoral fellow at Stanford University, said the algorithm makes it possible to optically map the human genome.
“It carries tremendous benefits for medical applications, specifically for finding genomic abnormalities,” he said.
The algorithm appears in this week’s PNAS Early Edition.
Optical mapping was developed at New York University in the late 1990s by David Schwartz, now a professor of chemistry and genetics at the University of Wisconsin-Madison. Schwartz and a collaborator at Wisconsin, Shiguo Zhou, co-authored the PNAS paper.
The power of optical mapping lies in its ability to reveal the size and large-scale structure of a genome. The method uses fluorescence microscopy to image individual DNA molecules that have been divided into orderly fragments by so-called restriction enzymes.
By imaging large numbers of an organism’s DNA molecules, optical mapping can produce a map of its genome at a relatively low cost.
An optical map lacks the minute detail of a genetic sequence, but it makes up for that shortcoming in other ways, said Philip Green, a professor of genome sciences at the University of Washington who edited the PNAS paper.
Geneticists often say that humans have 99.9 percent of their DNA in common. But, Green said, “individuals occasionally have big differences in their chromosome structure. You sometimes find regions where there are larger changes.”
Such changes could include wholesale deletions of chunks of the genome or additions of extra copies. Cancer genomes, in particular, mutate rapidly and contain frequent abnormalities.
“That’s something that’s very hard to detect” by conventional sequencing, Green said, adding that sequencing can simply miss part of a genome.
Optical mapping, by contrast, can estimate the absolute length of a genome and quickly detect differences in length and structure between two genomes. Comparing optical maps of healthy and diseased genomes can guide researchers to crucial mutations.
Though he called optical mapping “potentially very powerful,” Green added that it requires such a high level of expertise that only a couple of laboratories in the world use the method.
