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美國Helicos BioSciences  
螺旋生物科學（Helicos BioSciences）公司公司研究人員近日稱，他們開發(fā)出了一種新型的測序設備——單分子DNA測序儀（single-molecule DNA sequencers）。該儀器能夠“閱讀”單分子DNA的單個堿基。相關研究文章發(fā)表在4月4日的《科學》（Science）上。

傳統(tǒng)上，在測序之前，要先對DNA鏈進行擴增。這一過程往往會引入錯誤，并且對某些DNA片斷來說無法很好地實現(xiàn)，從而使得對整個基因組進行測序變得尤為困難。

Helicos BioSciences公司以病毒M13為實驗對象，首先將它的基因組截成小的片斷，用一種酶將短小DNA標簽附于每個片斷的末端，在適當?shù)奈恢缅^定DNA片斷。之后加入DNA復制酶和帶有熒光標簽的堿基或堿基對。當熒光DNA形成鏈時，就用相機拍下每個新加上的堿基對。

這一新方法稱為“合成測序”，原則上與其它一些方法相同。不同之處在于，其它一些方法需要同時測序數(shù)千個相同的基因組片斷以使信號足夠“明亮”，新方法能夠偵測到單個堿基的熒光。

新方法避開了繁瑣的擴增過程，將能大大降低測序的時間和成本。Helicos BioSciences公司估計，新儀器能夠用8周的時間測序一個人的基因組，代價是7萬2000美元，而儀器本身則價值135萬美元。

美國能源部聯(lián)合基因組研究所主任Edward Rubin說：“這太酷了！最終，單分子測序?qū)⒊蔀橥ㄐ械姆椒ā！?/p>

新的發(fā)現(xiàn)無疑又朝著1000美元/人的宏偉基因組測序計劃邁近了堅實的一步。論文第一作者Timothy Harris認為，這一目標將會在5年以內(nèi)實現(xiàn)。

  Helicos BioSciences Corporation is a life sciences company focused on innovative genetic analysis technologies for the research, drug discovery and clinical diagnostics markets. Our products are based on our proprietary True Single Molecule Sequencing (tSMS)? technology which enables rapid analysis of large quantities of genetic material by directly sequencing single molecules of DNA or single DNA copies of RNA. This approach differs from current methods of sequencing DNA because it analyzes individual molecules of DNA directly instead of analyzing a large number of copies of the molecule produced through complex sample preparation techniques. Our tSMS technology eliminates the need for costly, labor-intensive and time-consuming sample preparation techniques, such as amplification or cloning, which are required by other methods to produce a sufficient quantity of genetic material for analysis. By enabling direct sequencing of single DNA molecules, we believe that our tSMS technology represents a fundamental breakthrough in genetic analysis.

Most of the common diseases that account for significant morbidity and mortality, such as cancer, heart disease and diabetes, have complex genetic components, which researchers are seeking to understand fully through genetic analysis. In the last 20 to 30 years, scientists have developed a variety of genetic analysis methods, including DNA sequencing, gene expression analysis and genotyping. In 2006, sales of systems, supplies and reagents for performing these genetic analysis methods represented an approximately $5 billion market worldwide according to Strategic Directions International. Despite their broad use, most existing technologies have significant cost, accuracy and throughput limitations and lack the capacity for cost-effective and comprehensive genome-wide analysis on large numbers of samples. Knowledge of the human genome has grown dramatically since the first genome sequence was determined earlier this decade. Recent research suggests that a significant portion of what was once thought to be non-functional "junk DNA" is functionally active. To fully understand the biology of gene and genome regulation, we believe that researchers are contemplating experiments on an exponentially larger scale involving thousands of patients or thousands of compounds. Many scientists believe that these experiments would be enabled by a 10,000-fold decrease in the cost per base of reagents and supplies for DNA sequencing.

The 2007 calendar year represented an inflection point in both our knowledge of genome structure and function, and in the application of this knowledge to understanding the genetics of disease and of health. We have seen remarkable progress in the elucidation of the genetic factors of common disease. The international ENCODE research program revealed new insight into the complexity of the human genome through a detailed examination of approximately 1% of the human genome. In confirming the hypothesis that the genome is composed of many more functional units than thought plausible six years previously when the human genome was first sequenced, the scientific community also recognized that new analytical tools which allow unbiased views of the entire genome are required. Whole genome association studies which assess some one million common human genetic differences called single nucleotide polymorphisms, or SNPs, have shone light on regions of the genome associated with disease and health. These variations, valuable in their own right, do not begin to tell the whole story of human genetics. The sequencing of two human genomes, including both copies of their 26 chromosomes completed in 2007 revealed a much greater level of human genome variation (some 10 fold more) than expected. Lastly, consumer genetics companies were formed in 2007, offering people around the world access to portions of their common genome variation for the first time. This momentum continues with the announcement of the 1,000 Genomes Project in January 2008, an international consortium was formed to sequence 1,000 human genomes to create a database of human variation unprecedented in the history of science.