The Sequence of the Human Genome
Authors: Venter J. Craig , Adams Mark D. , Myers Eugene W. , Li Peter W. , Mural Richard J. , Sutton Granger G. , Smith Hamilton O. , Yandell Mark , Evans Cheryl A. , Holt Robert A. , Gocayne Jeannine D. , Amanatides Peter , Ballew Richard M. , Huson Daniel H. , Wortman Jennifer Russo , Zhang Qing , Kodira Chinnappa D. , Zheng Xiangqun H. , Chen Lin , Skupski Marian , Subramanian Gangadharan , Thomas Paul D. , Zhang Jinghui , Gabor Miklos George L. , Nelson Catherine , Broder Samuel , Clark Andrew G. , Nadeau Joe , McKusick Victor A. , Zinder Norton , Levine Arnold J. , Roberts Richard J. , Simon Mel , Slayman Carolyn , Hunkapiller Michael , Bolanos Randall , Delcher Arthur , Dew Ian , Fasulo Daniel , Flanigan Michael , Florea Liliana , Halpern Aaron , Hannenhalli Sridhar , Kravitz Saul , Levy Samuel , Mobarry Clark , Reinert Knut , Remington Karin , Abu-Threideh Jane , Beasley Ellen , Biddick Kendra , Bonazzi Vivien , Brandon Rhonda , Cargill Michele , Chandramouliswaran Ishwar , Charlab Rosane , Chaturvedi Kabir , Deng Zuoming , Francesco Valentina Di , Dunn Patrick , Eilbeck Karen , Evangelista Carlos , Gabrielian Andrei E. , Gan Weiniu , Ge Wangmao , Gong Fangcheng , Gu Zhiping , Guan Ping , Heiman Thomas J. , Higgins Maureen E. , Ji Rui-Ru , Ke Zhaoxi , Ketchum Karen A. , Lai Zhongwu , Lei Yiding , Li Zhenya , Li Jiayin , Liang Yong , Lin Xiaoying , Lu Fu , Merkulov Gennady V. , Milshina Natalia , Moore Helen M. , Naik Ashwinikumar K , Narayan Vaibhav A. , Neelam Beena , Nusskern Deborah , Rusch Douglas B. , Salzberg Steven , Shao Wei , Shue Bixiong , Sun Jingtao , Wang Zhen Yuan , Wang Aihui , Wang Xin , Wang Jian , Wei Ming-Hui , Wides Ron , Xiao Chunlin , Yan Chunhua , Yao Alison , Ye Jane , Zhan Ming , Zhang Weiqing , Zhang Hongyu , Zhao Qi , Zheng Liansheng , Zhong Fei , Zhong Wenyan , Zhu Shiaoping C. , Zhao Shaying , Gilbert Dennis , Baumhueter Suzanna , Spier Gene , Carter Christine , Cravchik Anibal , Woodage Trevor , Ali Feroze , An Huijin , Awe Aderonke , Baldwin Danita , Baden Holly , Barnstead Mary , Barrow Ian , Beeson Karen , Busam Dana , Carver Amy , Center Angela , Cheng Ming Lai , Curry Liz , Danaher Steve , Davenport Lionel , Desilets Raymond , Dietz Susanne , Dodson Kristina , Doup Lisa , Ferriera Steven , Garg Neha , Gluecksmann Andres , Hart Brit , Haynes Jason , Haynes Charles , Heiner Cheryl , Hladun Suzanne , Hostin Damon , Houck Jarrett , Howland Timothy , Ibegwam Chinyere , Johnson Jeffery , Kalush Francis , Kline Lesley , Koduru Shashi , Love Amy , Mann Felecia , May David , McCawley Steven , McIntosh Tina , McMullen Ivy , Moy Mee , Moy Linda , Murphy Brian , Nelson Keith , Pfannkoch Cynthia , Pratts Eric , Puri Vinita , Qureshi Hina , Reardon Matthew , Rodriguez Robert , Rogers Yu-Hui , Romblad Deanna , Ruhfel Bob , Scott Richard , Sitter Cynthia , Smallwood Michelle , Stewart Erin , Strong Renee , Suh Ellen , Thomas Reginald , Tint Ni Ni , Tse Sukyee , Vech Claire , Wang Gary , Wetter Jeremy , Williams Sherita , Williams Monica , Windsor Sandra , Winn-Deen Emily , Wolfe Keriellen , Zaveri Jayshree , Zaveri Karena , Abril Josep F. , Guigó Roderic , Campbell Michael J. , Sjolander Kimmen V. , Karlak Brian , Kejariwal Anish , Mi Huaiyu , Lazareva Betty , Hatton Thomas , Narechania Apurva , Diemer Karen , Muruganujan Anushya , Guo Nan , Sato Shinji , Bafna Vineet , Istrail Sorin , Lippert Ross , Schwartz Russell , Walenz Brian , Yooseph Shibu , Allen David , Basu Anand , Baxendale James , Blick Louis , Caminha Marcelo , Carnes-Stine John , Caulk Parris , Chiang Yen-Hui , Coyne My , Dahlke Carl , Mays Anne Deslattes , Dombroski Maria , Donnelly Michael , Ely Dale , Esparham Shiva , Fosler Carl , Gire Harold , Glanowski Stephen , Glasser Kenneth , Glodek Anna , Gorokhov Mark , Graham Ken , Gropman Barry , Harris Michael , Heil Jeremy , Henderson Scott , Hoover Jeffrey , Jennings Donald , Jordan Catherine , Jordan James , Kasha John , Kagan Leonid , Kraft Cheryl , Levitsky Alexander , Lewis Mark , Liu Xiangjun , Lopez John , Ma Daniel , Majoros William , McDaniel Joe , Murphy Sean , Newman Matthew , Nguyen Trung , Nguyen Ngoc , Nodell Marc , Pan Sue , Peck Jim , Peterson Marshall , Rowe William , Sanders Robert , Scott John , Simpson Michael , Smith Thomas , Sprague Arlan , Stockwell Timothy , Turner Russell , Venter Eli , Wang Mei , Wen Meiyuan , Wu David , Wu Mitchell , Xia Ashley , Zandieh Ali , Zhu Xiaohong 
Published: July 2002

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.