花鸵 - 2008-2-20 10:23:00
International genome project launched
国际基因组工程启动
Three-year study will capture variation in 1,000 people.
A much-anticipated international project to sequence the entire genomes of 1,000 people was launched on Tuesday, but some question whether the three-year project is ambitious enough in its scope.
星期二，期望很高的一个国际项目－千人基因组测序启动了, 但在预计的时间内能否完成这个项目仍有疑问。
The '1,000 Genomes Project' will create a highly detailed reference map of human genetic variation and is the largest such project announced to date. "This is a historic turning point in genomics," says Yang Huanming, director of the Beijing Genomics Institute, whose Shenzen branch is one of the three institutes launching the project. The other two are the Wellcome Trust Sanger Institute in Cambridge, UK; and the National Human Genome Research Institute in Bethesda, Maryland.
' 千人基因组计划' 将绘制一张关于人类基因变异高度详细的参考地图并且是现今最大的项目。"这是基因组学的一个历史转折点,"北京基因组学院的杨焕明主任说, 其下属的深圳华大基因研究院是参与项目的三所研究所当中一个。其它两个是英国剑桥韦尔科姆基金会桑格学院和国立卫生研究院下属的美国人类基因组研究所。
The project is expected to cost just US$30 million to $50 million — a fraction of what it would cost if they used the 'older' technologies used in the Human Genome Project. Instead, the initiative will use 'next-generation' sequencing technologies, although these are still being tested. "Projects such as this drive technology development," says David Altshuler, a geneticist at Massachusetts General Hospital in Boston. The project leaders have not yet decided what the depth of coverage of the genome will be — that is, how many repeats they will carry out for each chromosome.
项目被预计花费大概三千万到五千万美元－一部分取决于采用什么样的技术。如果他们使用' 更旧的' 技术用于人类基因组计划，那么成本要高一些；反之, 如果积极使用仍然在测试中的' 下一代' 测序技术，成本就会降低。波士顿麻省总医院的一位遗传学家David Altshuler说，"像这样的项目将驱动新技术的开发。"项目负责人还未决定覆盖基因组的深度－每个染色体上重复多少次。
All the participants in the first phase of the project will be drawn from the International HapMap Project, a large study on genetic diversity, although more people may be recruited later. HapMap has guided scientists to hundreds of 'single nucleotide polymorphisms', or SNPs — places where people's genetic codes differ by a single DNA base — in genetic regions associated with disease. But these associations explain only a small part of an individual's risk for any particular disease. And scientists must undertake large, expensive follow-up studies to hunt down the specific causes of disease risk lurking in these genetic regions.
所有参加者在项目的第一阶段将被绘制关于基因多样性的一项大研究－国际人类基因组单体型图, 以后可能更多人将参加这个项目。人类基因组单体型图引导科学家对上百个'单核苷酸多态性'即不同于单一DNA碱基的人类遗传密码子－与疾病相关的基因区域进行研究。但这些相关性只能解释一小部份个体患有任何一种特殊疾病风险的原因。并且科学家为此必须承担巨大的,昂贵的跟踪研究以搜寻潜伏在这些基因区域中导致疾病风险的具体基因。
The new project aims both to guide scientists towards more disease-associated regions, and to hasten much of the costly follow-up research. Sequencing 1,000 individuals will allow scientists to look at more types of variation — most notably, structural variation, in which large stretches of DNA are duplicated, deleted or rearranged in different individuals. And it will capture more rare variants than the HapMap, which aimed to catalogue SNPs present in 10% of the human population.
新项目打算旨在引导科学家向更多与疾病相关的基因区域研究和加速许多昂贵的跟踪研究的进展。测序1000 名个体将使科学家发现更多类型的变异－最明显的结构变异（不同的个体中大片段DNA区段重复,缺失或重排），旨在当前10% 人口中对单核苷酸多态性编目的千人基因组计划将获得比人类基因组单体型图更加罕见的变异。
"This will give us a much more complete catalogue of genetic variation, and that is going to have a profound impact on our ability to understand the risk factors underlying disease," says Francis Collins, director of the National Human Genome Research Institute.
"这将给我们带来关于基因变异更加完全的编目, 并且将对我们理解基础疾病的风险因素的能力产生深远影响。" 美国国立人类基因组研究所（NHGRI）所长Francis Collins博士说
Yet some scientists question how accurate the finished genomes will be, given the project's short timeline and low budget. Others say that the project should have included some phenotypic information about the participants — such as medical records or basic data such as height and weight. "It's curious that the disease-association studies don't exploit much sequencing — and the sequencing studies don't use the disease data. It would be helpful to hear a clear explanation of why, after 17 years and billions of dollars, these studies still aren't coordinated," says George Church, who is leading a venture called the Personal Genome Project out of his lab at Harvard University in Cambridge, Massachusetts. Church's project is collecting and releasing genetic and phenotypic data on ten individuals, including himself.
然而，一些科学家质疑在如此之短的时间内和如此之低的预算下完成的基因组准确性。其他人认为, 项目应该包括关于参加者的一些表形信息－病历或身高和体重之类的基本数据。"疾病相关性的基因研究不利用测序技术，测序研究不使用疾病数据是奇怪的；这就是为什么在17 年和花费了亿万美元以后, 这些研究结果仍然不协调的合理解释。 " George Church说, George Church在马萨诸塞镇剑桥城的哈佛大学实验室外领导个人基因组计划。他的项目是收集和发布包括他自己在内的十个人的基因和表形数据。
But leaders of the 1,000 Genomes Project say that their venture isn't large enough to give definitive answers about the genetic roots of traits. They also say that collecting phenotypic information might bias their study and raise difficult issues, such as how to protect participants' identities while still releasing all the relevant data. The project will not collect or release any information about its participants, beyond their ethnicity and genome sequence.
"No single study with 1,000 people is going to contain enough individuals with any condition to give you any power at all to say whether genotypes or phenotypes are correlated," Collins says. Such work is best left to follow-up studies, he says.
但千人基因组计划的负责人说, 他们的计划无法提供关于基因谱特征足够的信息量。他们并且说收集表型的信息也许会使他们的研究偏差和对研究提出难题, 例如在发表所有相关的数据的同时如何保护参加者的身分。除了参加者的种族和基因组序列，项目不会收集或不会发表关于它的参加者的任何信息。" 千人基因组计划没有包含任何一种情况下的个体给你足够的证据断言基因型或表现型是否被关联。" Collins 说，这样的工作最好给跟踪研究留下。