生物谷報(bào)道：備受爭議的基因組研究先鋒Craig Venter又有新動作！他的研究小組詳細(xì)地測定了他自己的基因組序列，使得人們能夠觀測單個(gè)基因組中基因的變化。初步分析報(bào)告發(fā)表在最新一期的《PLoS生物學(xué)》上,。
此次研究的領(lǐng)導(dǎo)者、美國J. Craig Venter研究所的Samuel Levy表示，此次的測序與之前的有所不同,。之前的測序沒有在每個(gè)染色體的兩個(gè)副本之間、甚至是不同捐贈者的DNA之間作出區(qū)分，從而混淆了等位基因（alleles）,。
在此次研究中,，Levy和研究小組利用從Venter DNA中提取的1900萬條基因序列和另外的1300萬條序列，使用最新的方法詳細(xì)檢測了不同版本的相同染色體的基因序列,。最終他們發(fā)現(xiàn)了400萬種變異,，包括單個(gè)核苷差異、序列插入和刪除以及單個(gè)基因副本數(shù)的不同,。大約有44％的Venter基因在來自每個(gè)染色體的副本之間存在遺傳差異,。Levy 說，Venter的兩組染色體存在0.5％的差異,，這表明DNA變異可能比之前認(rèn)為的要多出7倍多,。
在發(fā)表的論文中，研究人員重點(diǎn)突出了Venter基因組的一些特點(diǎn),。比如他的ABCC11基因序列表明,，Venter耳朵可能產(chǎn)生潮濕的耳垢；在緊靠他的MAOA基因之前,，有四條重復(fù)序列,，而只具有三個(gè)重復(fù)序列被認(rèn)為會增加反社會行為的傾向；另外,，他的APOE序列和SORL1 gene基因均表明可能會增加患早老性癡呆?。ˋlzheimer）和心血管病的風(fēng)險(xiǎn)。
美國加州聯(lián)合基因組研究所（Joint Genome Institute）的主任Edward Rubin表示,，此次研究描繪了更加清晰的人類基因組圖譜,，它表明基因組并不是統(tǒng)計(jì)學(xué)意義上的，而應(yīng)該是一種線性的排列,。
為了更好地闡述基因組怎樣影響他的生活,，Venter即將推出一本新書——《解碼生命》（A Life Decoded）。美國冷泉港實(shí)驗(yàn)室Banbury中心的執(zhí)行理事Jan Witkowski將在10月4號的《自然》雜志上為這本書撰寫書評,。
Venter表示,，單個(gè)基因的改變并不能控制他的命運(yùn)，大多數(shù)疾病都?xì)w因于人性因素和環(huán)境因素,。Witkowski對此表示贊同,，他同時(shí)認(rèn)為閱讀別人的基因組會給別人帶來不自在的感覺，就像看別人的病歷一樣,。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
原始出處:
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.
全文鏈接：
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050254
