Initial sequencing and analysis of the human genome.

Lander, E. S.; Linton, L M; Birren, B; Nusbaum, C; Zody, M C; Baldwin, J.; Devon, K; Dewar, K; Doyle, M.; FitzHugh, W; Funke, R; GAGE, D.; Harris, K.; Heaford, A; Howland, J; Kann, L; Lehoczky, J; Levine, R.; McEwan, P; McKernan, K; Meldrim, J; Mesirov, J. P.; Miranda, C.; Morris, W.; Naylor, J.; Raymond, C.; Rosetti, M.; Santos, R.; Sheridan, A.; Sougnez, C.; Stange-Thomann, Y; Stojanovic, N.; Subramanian, A.; Wyman, D; Rogers, J.; Sulston, J.; Ainscough, R; Beck, S.; Bentley, D.; Burton, J.; Clee, C; Carter, N.; Coulson, A; Deadman, R; Deloukas, P.; DUNHAM, A.; Dunham, I; Durbin, R.; French, L.; Grafham, D.; Gregory, S.; Hubbard, T; Humphray, S.; Hunt, A.; Jones, M.; Lloyd, C.; McMurray, A.; Matthews, L.; Mercer, S.; Milne, S.; Mullikin, J C; Mungall, A.; Plumb, R.; Ross, M.; Shownkeen, R; Sims, S; Waterston, R. H.; Wilson, R K; Hillier, L. W.; McPherson, J D; Marra, M. A.; Mardis, E. R.; Fulton, L A; Chinwalla, A T; Pepin, K H; Gish, W. R.; Chissoe, S L; Wendl, M. C.; Delehaunty, K D; Miner, T L; Delehaunty, A; Kramer, J. B.; Cook, L L; Fulton, R. S.; Johnson, D L; Minx, P J; Clifton, S. W.; Hawkins, T.; Branscomb, E; Prędki, P.; Richardson, P.; Wenning, S; Slezak, T.; Doggett, N; Cheng, J F; Olsen, A.; Lucas, S.; Elkin, C; Uberbacher, E; Frazier, M.; Gibbs, R A; Muzny, D M; Scherer, S E; Bouck, J B; Sodergren, E. J.; Worley, K. C.; Rives, C M; Gorrell, J H; Metzker, M L; Naylor, S L; Kucherlapati, R S; Nelson, D. L.; Weinstock, G M; Sakaki, Y; Fujiyama, A; Hattori, M; Yada, T; Toyoda, A; Itoh, T.; Kawagoe, C; Watanabe, H.; Totoki, Y; Taylor, T.; Weissenbach, J; Heilig, R; Saurin, W; Artiguenave, F; Brottier, P; Brüls, T; Pelletier, E; Robert, C.; Wincker, P; Smith, D R; Doucette-Stamm, L; Rubenfield, M; Weinstock, K; Lee, H. M.; Dubois, J.; Rosenthal, A.; Platzer, M; Nyakatura, G; Taudien, S; Rump, A.; Yang, H.; Yu, J.; Wang, J.; Huang, G.; Gu, J; Hood, L.; Rowen, L; Madan, A.; Qin, S; Davis, R W; Federspiel, N A; Abola, A P; Proctor, M J; Myers, R M; Schmutz, J.; Dickson, M.; Grimwood, J.; Cox, D R; Olson, M V; Kaul, R.; Shimizu, N; Kawasaki, K; Minoshima, S; Evans, G A; Athanasiou, M.; Schultz, R.; Roe, B A; Chen, F.; Pan, H.; Ramser, J; Lehrach, H; Reinhardt, R.; McCombie, W R; de la Bastide, M; Dedhia, N M; Blöcker, H; Hornischer, K.; Nordsiek, G; Agarwala, R.; Aravind, L; Bailey, J. A.; Bateman, A.; Batzoglou, S; Birney, E.; Bork, P.; Brown, D G; Burge, C. B.; Cerutti, L; Chen, H C; Church, D.; Clamp, M; Copley, R. R.; Doerks, T.; Eddy, S. R.; Eichler, E E; Furey, T. S.; Galagan, James; Gilbert, J. G.; Harmon, C.; Hayashizaki, Y; Haussler, D.; Hermjakob, H; Hokamp, K.; Jang, W.; Johnson, L S; Jones, T. A.; Kasif, S; Kaspryzk, A; Kennedy, S; Kent, W. J.; Kitts, P; Koonin, E. V.; Korf, I; Kulp, D; Lancet, D.; Lowe, T. M.; McLysaght, A; Mikkelsen, T.; Morán, J.; Mulder, N.; Pollara, V. J.; Ponting, C P; Schuler, G.; Schultz, J.; Slater, G.; Smit, A. F.; Stupka, E; Szustakowki, J; Thierry-Mieg, D.; Thierry-Mieg, J; Wagner, L.; WALLIS, J.; Wheeler, R.; Williams, A.; Wolf, Y I; Wolfe, K. H.; Yang, S P; Yeh, R F; Collins, F.; Guyer, M. S.; Peterson, J.; Felsenfeld, A; Wetterstrand, K A; Patrinos, A; Morgan, M. J.; de Jong, P.; Catanese, J. J.; Osoegawa, K; Shizuya, H; Choi, S.; Chen, Y. -J.

doi:10.1038/35057062

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Initial sequencing and analysis of the human genome.

Author(s): E. S. Lander, L M Linton, B Birren, C Nusbaum, M C Zody, J. Baldwin, K Devon, K Dewar, M. Doyle, W FitzHugh, R Funke, D. GAGE, K. Harris, A Heaford, J Howland, L Kann, J Lehoczky, R. Levine, P McEwan, K McKernan, J Meldrim, J. P. Mesirov, C. Miranda, W. Morris, J. Naylor, C. Raymond, M. Rosetti, R. Santos, A. Sheridan, C. Sougnez, Y Stange-Thomann, N. Stojanovic, A. Subramanian, D Wyman, J. Rogers, J. Sulston, R Ainscough, S. Beck, D. Bentley, J. Burton, C Clee, N. Carter, A Coulson, R Deadman, P. Deloukas, A. DUNHAM, I Dunham, R. Durbin, L. French, D. Grafham, S. Gregory, T Hubbard, S. Humphray, A. Hunt, M. Jones, C. Lloyd, A. McMurray, L. Matthews, S. Mercer, S. Milne, J C Mullikin, A. Mungall, R. Plumb, M. Ross, R Shownkeen, S Sims, R. H. Waterston, R K Wilson, L. W. Hillier, J D McPherson, M. A. Marra, E. R. Mardis, L A Fulton, A T Chinwalla, K H Pepin, W. R. Gish, S L Chissoe, M. C. Wendl, K D Delehaunty, T L Miner, A Delehaunty, J. B. Kramer, L L Cook, R. S. Fulton, D L Johnson, P J Minx, S. W. Clifton, T. Hawkins, E Branscomb, P. Prędki, P. Richardson, S Wenning, T. Slezak, N Doggett, J F Cheng, A. Olsen, S. Lucas, C Elkin, E Uberbacher, M. Frazier, R A Gibbs, D M Muzny, S E Scherer, J B Bouck, E. J. Sodergren, K. C. Worley, C M Rives, J H Gorrell, M L Metzker, S L Naylor, R S Kucherlapati, D. L. Nelson, G M Weinstock, Y Sakaki, A Fujiyama, M Hattori, T Yada, A Toyoda, T. Itoh, C Kawagoe, H. Watanabe, Y Totoki, T. Taylor, J Weissenbach, R Heilig, W Saurin, F Artiguenave, P Brottier, T Brüls, E Pelletier, C. Robert, P Wincker, D R Smith, L Doucette-Stamm, M Rubenfield, K Weinstock, H. M. Lee, J. Dubois, A. Rosenthal, M Platzer, G Nyakatura, S Taudien, A. Rump, H. Yang, J. Yu, J. Wang, G. Huang, J Gu, L. Hood, L Rowen, A. Madan, S Qin, R W Davis, N A Federspiel, A P Abola, M J Proctor, R M Myers, J. Schmutz, M. Dickson, J. Grimwood, D R Cox, M V Olson, R. Kaul, N Shimizu, K Kawasaki, S Minoshima, G A Evans, M. Athanasiou, R. Schultz, B A Roe, F. Chen, H. Pan, J Ramser, H Lehrach, R. Reinhardt, W R McCombie, M de la Bastide, N Dedhia, H Blöcker, K. Hornischer, G Nordsiek, R. Agarwala, L Aravind, J. A. Bailey, A. Bateman, S Batzoglou, E. Birney, P. Bork, D G Brown, C. B. Burge, L Cerutti, H C Chen, D. Church, M Clamp, R. R. Copley, T. Doerks, S. R. Eddy, E E Eichler, T. S. Furey, James Galagan, J. G. Gilbert, C. Harmon, Y Hayashizaki, D. Haussler, H Hermjakob, K. Hokamp, W. Jang, L S Johnson, T. A. Jones, S Kasif, A Kaspryzk, S Kennedy, W. J. Kent, P Kitts, E. V. Koonin, I Korf, D Kulp, D. Lancet, T. M. Lowe, A McLysaght, T. Mikkelsen, J. Morán, N. Mulder, V. J. Pollara, C P Ponting, G. Schuler, J. Schultz, G. Slater, A. F. Smit, E Stupka, J Szustakowki, D. Thierry-Mieg, J Thierry-Mieg, L. Wagner, J. WALLIS, R. Wheeler, A. Williams, Y I Wolf, K. H. Wolfe, S P Yang, R F Yeh, F. Collins, M. S. Guyer, J. Peterson, A Felsenfeld, K A Wetterstrand, A Patrinos, M. J. Morgan, P. de Jong, J. J. Catanese, K Osoegawa, H Shizuya, S. Choi, Y. -J. Chen

Publication date: 2001-02-15

Journal: Nature

Publisher: Springer Science and Business Media LLC

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Abstract

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

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Identification of common molecular subsequences.

T.F. Smith, M.S. Waterman (1981)

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Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.

A. Fraser, R. S. Kamath, P Zipperlen … (2000)

Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We have assigned function to 13.9% of the genes analysed, increasing the number of sequenced genes with known phenotypes on chromosome I from 70 to 378. Although most genes with sterile or embryonic lethal RNAi phenotypes are involved in basal cell metabolism, many genes giving post-embryonic phenotypes have conserved sequences but unknown function. In addition, conserved genes are significantly more likely to have an RNAi phenotype than are genes with no conservation. We have constructed a reusable library of bacterial clones that will permit unlimited RNAi screens in the future; this should help develop a more complete view of the relationships between the genome, gene function and the environment.

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The structural basis of ribosome activity in peptide bond synthesis.

P Nissen, J Hansen, N Ban … (2000)

Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.

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PubMed ID:: 11237011

DOI:: 10.1038/35057062

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Initial sequencing and analysis of the human genome.

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Most cited references 350

Identification of common molecular subsequences.

Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.

The structural basis of ribosome activity in peptide bond synthesis.

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