生物谷报道：备受争议的基因组研究先锋Craig Venter又有新动作！他的研究小组详细地测定了他自己的基因组序列，使得人们能够观测单个基因组中基因的变化。初步分析报告发表在最新一期的《PLoS生物学》上。
此次研究的领导者、美国J. Craig Venter研究所的Samuel Levy表示，此次的测序与之前的有所不同。之前的测序没有在每个染色体的两个副本之间、甚至是不同捐赠者的DNA之间作出区分，从而混淆了等位基因（alleles）。
在此次研究中，Levy和研究小组利用从Venter DNA中提取的1900万条基因序列和另外的1300万条序列，使用最新的方法详细检测了不同版本的相同染色体的基因序列。最终他们发现了400万种变异，包括单个核苷差异、序列插入和删除以及单个基因副本数的不同。大约有44％的Venter基因在来自每个染色体的副本之间存在遗传差异。Levy 说，Venter的两组染色体存在0.5％的差异，这表明DNA变异可能比之前认为的要多出7倍多。
在发表的论文中，研究人员重点突出了Venter基因组的一些特点。比如他的ABCC11基因序列表明，Venter耳朵可能产生潮湿的耳垢；在紧靠他的MAOA基因之前，有四条重复序列，而只具有三个重复序列被认为会增加反社会行为的倾向；另外，他的APOE序列和SORL1 gene基因均表明可能会增加患早老性痴呆病（Alzheimer）和心血管病的风险。
美国加州联合基因组研究所（Joint Genome Institute）的主任Edward Rubin表示，此次研究描绘了更加清晰的人类基因组图谱，它表明基因组并不是统计学意义上的，而应该是一种线性的排列。
为了更好地阐述基因组怎样影响他的生活，Venter即将推出一本新书——《解码生命》（A Life Decoded）。美国冷泉港实验室Banbury中心的执行理事Jan Witkowski将在10月4号的《自然》杂志上为这本书撰写书评。
Venter表示，单个基因的改变并不能控制他的命运，大多数疾病都归因于人性因素和环境因素。Witkowski对此表示赞同，他同时认为阅读别人的基因组会给别人带来不自在的感觉，就像看别人的病历一样。（科学网 梅进/编译）
原始出处:
PLoS Biology
Received: May 9, 2007; Accepted: July 30, 2007; Published: September 4, 2007
The Diploid Genome Sequence of an Individual Human
Samuel Levy1*, Granger Sutton1, Pauline C. Ng1, Lars Feuk2, Aaron L. Halpern1, Brian P. Walenz1, Nelson Axelrod1, Jiaqi Huang1, Ewen F. Kirkness1, Gennady Denisov1, Yuan Lin1, Jeffrey R. MacDonald2, Andy Wing Chun Pang2, Mary Shago2, Timothy B. Stockwell1, Alexia Tsiamouri1, Vineet Bafna3, Vikas Bansal3, Saul A. Kravitz1, Dana A. Busam1, Karen Y. Beeson1, Tina C. McIntosh1, Karin A. Remington1, Josep F. Abril4, John Gill1, Jon Borman1, Yu-Hui Rogers1, Marvin E. Frazier1, Stephen W. Scherer2, Robert L. Strausberg1, J. Craig Venter1
1 J. Craig Venter Institute, Rockville, Maryland, United States of America, 2 Program in Genetics and Genomic Biology, The Hospital for Sick Children, and Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada, 3 Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, United States of America, 4 Genetics Department, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain
Presented here is a genome sequence of an individual human. It was produced from 32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.
全文链接：
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050254
