The Sequence of the Human Genome
Author:
Venter J. Craig1, Adams Mark D.1, Myers Eugene W.1, Li Peter W.1, Mural Richard J.1, Sutton Granger G.1, Smith Hamilton O.1, Yandell Mark1, Evans Cheryl A.1, Holt Robert A.1, Gocayne Jeannine D.1, Amanatides Peter1, Ballew Richard M.1, Huson Daniel H.1, Wortman Jennifer Russo1, Zhang Qing1, Kodira Chinnappa D.1, Zheng Xiangqun H.1, Chen Lin1, Skupski Marian1, Subramanian Gangadharan1, Thomas Paul D.1, Zhang Jinghui1, Gabor Miklos George L.2, Nelson Catherine3, Broder Samuel1, Clark Andrew G.4, Nadeau Joe5, McKusick Victor A.6, Zinder Norton7, Levine Arnold J.7, Roberts Richard J.8, Simon Mel9, Slayman Carolyn10, Hunkapiller Michael11, Bolanos Randall1, Delcher Arthur1, Dew Ian1, Fasulo Daniel1, Flanigan Michael1, Florea Liliana1, Halpern Aaron1, Hannenhalli Sridhar1, Kravitz Saul1, Levy Samuel1, Mobarry Clark1, Reinert Knut1, Remington Karin1, Abu-Threideh Jane1, Beasley Ellen1, Biddick Kendra1, Bonazzi Vivien1, Brandon Rhonda1, Cargill Michele1, Chandramouliswaran Ishwar1, Charlab Rosane1, Chaturvedi Kabir1, Deng Zuoming1, Francesco Valentina Di1, Dunn Patrick1, Eilbeck Karen1, Evangelista Carlos1, Gabrielian Andrei E.1, Gan Weiniu1, Ge Wangmao1, Gong Fangcheng1, Gu Zhiping1, Guan Ping1, Heiman Thomas J.1, Higgins Maureen E.1, Ji Rui-Ru1, Ke Zhaoxi1, Ketchum Karen A.1, Lai Zhongwu1, Lei Yiding1, Li Zhenya1, Li Jiayin1, Liang Yong1, Lin Xiaoying1, Lu Fu1, Merkulov Gennady V.1, Milshina Natalia1, Moore Helen M.1, Naik Ashwinikumar K1, Narayan Vaibhav A.1, Neelam Beena1, Nusskern Deborah1, Rusch Douglas B.1, Salzberg Steven12, Shao Wei1, Shue Bixiong1, Sun Jingtao1, Wang Zhen Yuan1, Wang Aihui1, Wang Xin1, Wang Jian1, Wei Ming-Hui1, Wides Ron13, Xiao Chunlin1, Yan Chunhua1, Yao Alison1, Ye Jane1, Zhan Ming1, Zhang Weiqing1, Zhang Hongyu1, Zhao Qi1, Zheng Liansheng1, Zhong Fei1, Zhong Wenyan1, Zhu Shiaoping C.1, Zhao Shaying12, Gilbert Dennis1, Baumhueter Suzanna1, Spier Gene1, Carter Christine1, Cravchik Anibal1, Woodage Trevor1, Ali Feroze1, An Huijin1, Awe Aderonke1, Baldwin Danita1, Baden Holly1, Barnstead Mary1, Barrow Ian1, Beeson Karen1, Busam Dana1, Carver Amy1, Center Angela1, Cheng Ming Lai1, Curry Liz1, Danaher Steve1, Davenport Lionel1, Desilets Raymond1, Dietz Susanne1, Dodson Kristina1, Doup Lisa1, Ferriera Steven1, Garg Neha1, Gluecksmann Andres1, Hart Brit1, Haynes Jason1, Haynes Charles1, Heiner Cheryl1, Hladun Suzanne1, Hostin Damon1, Houck Jarrett1, Howland Timothy1, Ibegwam Chinyere1, Johnson Jeffery1, Kalush Francis1, Kline Lesley1, Koduru Shashi1, Love Amy1, Mann Felecia1, May David1, McCawley Steven1, McIntosh Tina1, McMullen Ivy1, Moy Mee1, Moy Linda1, Murphy Brian1, Nelson Keith1, Pfannkoch Cynthia1, Pratts Eric1, Puri Vinita1, Qureshi Hina1, Reardon Matthew1, Rodriguez Robert1, Rogers Yu-Hui1, Romblad Deanna1, Ruhfel Bob1, Scott Richard1, Sitter Cynthia1, Smallwood Michelle1, Stewart Erin1, Strong Renee1, Suh Ellen1, Thomas Reginald1, Tint Ni Ni1, Tse Sukyee1, Vech Claire1, Wang Gary1, Wetter Jeremy1, Williams Sherita1, Williams Monica1, Windsor Sandra1, Winn-Deen Emily1, Wolfe Keriellen1, Zaveri Jayshree1, Zaveri Karena1, Abril Josep F.14, Guigó Roderic14, Campbell Michael J.1, Sjolander Kimmen V.1, Karlak Brian1, Kejariwal Anish1, Mi Huaiyu1, Lazareva Betty1, Hatton Thomas1, Narechania Apurva1, Diemer Karen1, Muruganujan Anushya1, Guo Nan1, Sato Shinji1, Bafna Vineet1, Istrail Sorin1, Lippert Ross1, Schwartz Russell1, Walenz Brian1, Yooseph Shibu1, Allen David1, Basu Anand1, Baxendale James1, Blick Louis1, Caminha Marcelo1, Carnes-Stine John1, Caulk Parris1, Chiang Yen-Hui1, Coyne My1, Dahlke Carl1, Mays Anne Deslattes1, Dombroski Maria1, Donnelly Michael1, Ely Dale1, Esparham Shiva1, Fosler Carl1, Gire Harold1, Glanowski Stephen1, Glasser Kenneth1, Glodek Anna1, Gorokhov Mark1, Graham Ken1, Gropman Barry1, Harris Michael1, Heil Jeremy1, Henderson Scott1, Hoover Jeffrey1, Jennings Donald1, Jordan Catherine1, Jordan James1, Kasha John1, Kagan Leonid1, Kraft Cheryl1, Levitsky Alexander1, Lewis Mark1, Liu Xiangjun1, Lopez John1, Ma Daniel1, Majoros William1, McDaniel Joe1, Murphy Sean1, Newman Matthew1, Nguyen Trung1, Nguyen Ngoc1, Nodell Marc1, Pan Sue1, Peck Jim1, Peterson Marshall1, Rowe William1, Sanders Robert1, Scott John1, Simpson Michael1, Smith Thomas1, Sprague Arlan1, Stockwell Timothy1, Turner Russell1, Venter Eli1, Wang Mei1, Wen Meiyuan1, Wu David1, Wu Mitchell1, Xia Ashley1, Zandieh Ali1, Zhu Xiaohong1
Affiliation:
1. Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. 2. GenetixXpress, 78 Pacific Road, Palm Beach, Sydney 2108, Australia. 3. Berkeley Drosophila Genome Project, University of California, Berkeley, CA 94720, USA. 4. Department of Biology, Penn State University, 208 Mueller Lab, University Park, PA 16802, USA. 5. Department of Genetics, Case Western Reserve University School of Medicine, BRB-630, 10900 Euclid Avenue, Cleveland, OH 44106, USA. 6. Johns Hopkins University School of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 1007, Baltimore, MD 21287–4922, USA. 7. Rockefeller University, 1230 York Avenue, New York, NY 10021–6399, USA. 8. New England BioLabs, 32 Tozer Road, Beverly, MA 01915, USA. 9. Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. 10. Yale University School of Medicine, 333 Cedar Street, P.O. Box 208000, New Haven, CT 06520–8000, USA. 11. Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404, USA. 12. The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA. 13. Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900 Israel. 14. Grup de Recerca en Informàtica Mèdica, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003-Barcelona, Catalonia, Spain.
Abstract
A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
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