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Helicos

Helicos BioSciences

美国Helicos BioSciences   www.helicosbio.com
螺旋生物科学(Helicos BioSciences)公司公司研究人员近日称,他们开发出了一种新型的测序设备——单分子DNA测序仪(single-molecule DNA sequencers)。该仪器能够“阅读”单分子DNA的单个碱基。相关研究文章发表在4月4日的《科学》(Science)上。
传统上,在测序之前,要先对DNA链进行扩增。这一过程往往会引入错误,并且对某些DNA片断来说无法很好地实现,从而使得对整个基因组进行测序变得尤为困难。
Helicos BioSciences公司以病毒M13为实验对象,首先将它的基因组截成小的片断,用一种酶将短小DNA标签附于每个片断的末端,在适当的位置锚定DNA片断。之后加入DNA复制酶和带有荧光标签的碱基或碱基对。当荧光DNA形成链时,就用相机拍下每个新加上的碱基对。
这一新方法称为“合成测序”,原则上与其它一些方法相同。不同之处在于,其它一些方法需要同时测序数千个相同的基因组片断以使信号足够“明亮”,新方法能够侦测到单个碱基的荧光。
新方法避开了繁琐的扩增过程,将能大大降低测序的时间和成本。Helicos BioSciences公司估计,新仪器能够用8周的时间测序一个人的基因组,代价是7万2000美元,而仪器本身则价值135万美元。
美国能源部联合基因组研究所主任Edward Rubin说:“这太酷了!最终,单分子测序将成为通行的方法。”
新的发现无疑又朝着1000美元/人的宏伟基因组测序计划迈近了坚实的一步。论文第一作者Timothy Harris认为,这一目标将会在5年以内实现。

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.