The sequence of the human genome

Authors
Venter, JC Adams, MD Myers, EW Li, PW Mural, RJ Sutton, GG Smith, HO Yandell, M Evans, CA Holt, RA Gocayne, JD Amanatides, P Ballew, RM Huson, DH Wortman, JR Zhang, Q Kodira, CD Zheng, XQH Chen, L Skupski, M Subramanian, G Thomas, PD Zhang, JH Miklos, GLG Nelson, C Broder, S Clark, AG Nadeau, C McKusick, VA Zinder, N Levine, AJ Roberts, RJ Simon, M Slayman, C Hunkapiller, M Bolanos, R Delcher, A Dew, I Fasulo, D Flanigan, M Florea, L Halpern, A Hannenhalli, S Kravitz, S Levy, S Mobarry, C Reinert, K Remington, K Abu-Threideh, J Beasley, E Biddick, K Bonazzi, V Brandon, R Cargill, M Chandramouliswaran, I Charlab, R Chaturvedi, K Deng, ZM Di Francesco, V Dunn, P Eilbeck, K Evangelista, C Gabrielian, AE Gan, W Ge, WM Gong, FC Gu, ZP Guan, P Heiman, TJ Higgins, ME Ji, RR Ke, ZX Ketchum, KA Lai, ZW Lei, YD Li, ZY Li, JY Liang, Y Lin, XY Lu, F Merkulov, GV Milshina, N Moore, HM Naik, AK Narayan, VA Neelam, B Nusskern, D Rusch, DB Salzberg, S Shao, W Shue, BX Sun, JT Wang, ZY Wang, AH Wang, X Wang, J Wei, MH Wides, R Xiao, CL Yan, CH Yao, A Ye, J Zhan, M Zhang, WQ Zhang, HY Zhao, Q Zheng, LS Zhong, F Zhong, WY Zhu, SPC Zhao, SY Gilbert, D Baumhueter, S Spier, G Carter, C Cravchik, A Woodage, T Ali, F An, HJ Awe, A Baldwin, D Baden, H Barnstead, M Barrow, I Beeson, K Busam, D Carver, A Center, A Cheng, ML Curry, L Danaher, S Davenport, L Desilets, R Dietz, S Dodson, K Doup, L Ferriera, S Garg, N Gluecksmann, A Hart, B Haynes, J Haynes, C Heiner, C Hladun, S Hostin, D Houck, J Howland, T Ibegwam, C Johnson, J Kalush, F Kline, L Koduru, S Love, A Mann, F May, D McCawley, S McIntosh, T McMullen, I Moy, M Moy, L Murphy, B Nelson, K Pfannkoch, C Pratts, E Puri, V Qureshi, H Reardon, M Rodriguez, R Rogers, YH Romblad, D Ruhfel, B Scott, R Sitter, C Smallwood, M Stewart, E Strong, R Suh, E Thomas, R Tint, NN Tse, S Vech, C Wang, G Wetter, J Williams, S Williams, M Windsor, S Winn-Deen, E Wolfe, K Zaveri, J Zaveri, K Abril, JF Guigo, R Campbell, MJ Sjolander, KV Karlak, B Kejariwal, A Mi, HY Lazareva, B Hatton, T Narechania, A Diemer, K Muruganujan, A Guo, N Sato, S Bafna, V Istrail, S Lippert, R Schwartz, R Walenz, B Yooseph, S Allen, D Basu, A Baxendale, J Blick, L Caminha, M Carnes-Stine, J Caulk, P Chiang, YH Coyne, M Dahlke, C Mays, AD Dombroski, M Donnelly, M Ely, D Esparham, S Fosler, C Gire, H Glanowski, S Glasser, K Glodek, A Gorokhov, M Graham, K Gropman, B Harris, M Heil, J Henderson, S Hoover, J Jennings, D Jordan, C Jordan, J Kasha, J Kagan, L Kraft, C Levitsky, A Lewis, M Liu, XJ Lopez, J Ma, D Majoros, W McDaniel, J Murphy, S Newman, M Nguyen, T Nguyen, N Nodell, M Pan, S Peck, J Peterson, M Rowe, W Sanders, R Scott, J Simpson, M Smith, T Sprague, A Stockwell, T Turner, R Venter, E Wang, M Wen, MY Wu, D Wu, M Xia, A Zandieh, A Zhu, XH
Citation
Jc. Venter et al., The sequence of the human genome, SCIENCE, 291(5507), 2001, pp. 1304
Citations number
192
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
SCIENCE
ISSN journal
0036-8075 → ACNP
Volume
291
Issue
5507
Year of publication
2001
Database
ISI
SICI code
0036-8075(20010216)291:5507<1304:TSOTHG>2.0.ZU;2-2
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 m ethod. 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) fro m both ends of plasmid clones made from the DNA of five individuals. Two as sembly strategies-a whole-genome assembly and a regional chromosome assembl y-were used, each combining sequence data from Celera and the publicly fund ed genome effort. The public data were shredded into 550-bp segments to cre ate a 2.9-fold coverage of those genome regions that had been sequenced, wi thout including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the as semblies to eightfold, reducing the number and size of gaps in the final as sembly over what would be obtained with 5.11-fold coverage. The two assembl y strategies yielded very similar results that Largely agree with independe nt mapping data. The assemblies effectively cover the euchromatic regions o f the human chromosomes. More than 90% of the genome is in scaffold assembl ies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 mill ion bp or larger. Analysis of the genome sequence revealed 26,588 protein-e ncoding transcripts for which there was strong corroborating evidence and a n additional similar to 12,000 computationally derived genes with mouse mat ches or other weak supporting evidence. Although gene-dense clusters are ob vious, 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 i ntergenic DNA. Duplications of segmental blocks, ranging in size up to chro mosomal Lengths, are abundant throughout the genome and reveal a complex ev olutionary history. Comparative genomic analysis indicates vertebrate expan sions of genes associated with neuronal function, with tissue-specific deve lopmental regulation, and with the hemostasis and immune systems. DNA seque nce comparisons between the consensus sequence and publicly funded genome d ata 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 12 50 on average, but there was marked heterogeneity in the Level of polymorph ism across the genome. Less than 1% of all SNPs resulted in variation in pr oteins, but the task of determining which SNPs have functional consequences remains an open challenge.