%0 Journal Article %J Nature %D 2011 %T A high-resolution map of human evolutionary constraint using 29 mammals. %A Lindblad-Toh, Kerstin %A Garber, Manuel %A Zuk, Or %A Lin, Michael F %A Parker, Brian J %A Washietl, Stefan %A Kheradpour, Pouya %A Ernst, Jason %A Jordan, Gregory %A Mauceli, Evan %A Ward, Lucas D %A Lowe, Craig B %A Holloway, Alisha K %A Clamp, Michele %A Gnerre, Sante %A Alföldi, Jessica %A Beal, Kathryn %A Chang, Jean %A Clawson, Hiram %A Cuff, James %A Di Palma, Federica %A Fitzgerald, Stephen %A Flicek, Paul %A Guttman, Mitchell %A Hubisz, Melissa J %A Jaffe, David B %A Jungreis, Irwin %A Kent, W James %A Kostka, Dennis %A Lara, Marcia %A Martins, André L %A Massingham, Tim %A Moltke, Ida %A Raney, Brian J %A Rasmussen, Matthew D %A Robinson, Jim %A Stark, Alexander %A Vilella, Albert J %A Wen, Jiayu %A Xie, Xiaohui %A Zody, Michael C %A Baldwin, Jen %A Bloom, Toby %A Chin, Chee Whye %A Heiman, Dave %A Nicol, Robert %A Nusbaum, Chad %A Young, Sarah %A Wilkinson, Jane %A Worley, Kim C %A Kovar, Christie L %A Muzny, Donna M %A Gibbs, Richard A %A Cree, Andrew %A Dihn, Huyen H %A Fowler, Gerald %A Jhangiani, Shalili %A Joshi, Vandita %A Lee, Sandra %A Lewis, Lora R %A Nazareth, Lynne V %A Okwuonu, Geoffrey %A Santibanez, Jireh %A Warren, Wesley C %A Mardis, Elaine R %A Weinstock, George M %A Wilson, Richard K %A Delehaunty, Kim %A Dooling, David %A Fronik, Catrina %A Fulton, Lucinda %A Fulton, Bob %A Graves, Tina %A Minx, Patrick %A Sodergren, Erica %A Birney, Ewan %A Margulies, Elliott H %A Herrero, Javier %A Green, Eric D %A Haussler, David %A Siepel, Adam %A Goldman, Nick %A Pollard, Katherine S %A Pedersen, Jakob S %A Lander, Eric S %A Kellis, Manolis %K Animals %K Disease %K Evolution, Molecular %K Exons %K Genome %K Genome, Human %K Genomics %K Health %K Humans %K Mammals %K Molecular Sequence Annotation %K Phylogeny %K RNA %K Selection, Genetic %K Sequence Alignment %K Sequence Analysis, DNA %X

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

%B Nature %V 478 %P 476-82 %8 2011 Oct 12 %G eng %N 7370 %1 https://www.ncbi.nlm.nih.gov/pubmed/21993624?dopt=Abstract %R 10.1038/nature10530 %0 Journal Article %J Genome Res %D 2007 %T 28-way vertebrate alignment and conservation track in the UCSC Genome Browser. %A Miller, Webb %A Rosenbloom, Kate %A Hardison, Ross C %A Hou, Minmei %A Taylor, James %A Raney, Brian %A Burhans, Richard %A King, David C %A Baertsch, Robert %A Blankenberg, Daniel %A Kosakovsky Pond, Sergei L %A Nekrutenko, Anton %A Giardine, Belinda %A Harris, Robert S %A Tyekucheva, Svitlana %A Diekhans, Mark %A Pringle, Thomas H %A Murphy, William J %A Lesk, Arthur %A Weinstock, George M %A Lindblad-Toh, Kerstin %A Gibbs, Richard A %A Lander, Eric S %A Siepel, Adam %A Haussler, David %A Kent, W James %K Animals %K Base Sequence %K Cats %K Cattle %K Codon, Initiator %K Codon, Terminator %K Conserved Sequence %K Databases, Genetic %K Dogs %K Genome, Human %K Guinea Pigs %K Humans %K Mice %K Molecular Sequence Data %K Mutagenesis, Insertional %K Rabbits %K Rats %K Sequence Alignment %K Sequence Deletion %X

This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006 assembly) at http://genome.ucsc.edu, downloaded in bulk by anonymous FTP from http://hgdownload.cse.ucsc.edu/goldenPath/hg18/multiz28way, or analyzed with the Galaxy server at http://g2.bx.psu.edu. This article illustrates the power of this resource for exploring vertebrate and mammalian evolution, using three examples. First, we present several vignettes involving insertions and deletions within protein-coding regions, including a look at some human-specific indels. Then we study the extent to which start codons and stop codons in the human sequence are conserved in other species, showing that start codons are in general more poorly conserved than stop codons. Finally, an investigation of the phylogenetic depth of conservation for several classes of functional elements in the human genome reveals striking differences in the rates and modes of decay in alignability. Each functional class has a distinctive period of stringent constraint, followed by decays that allow (for the case of regulatory regions) or reject (for coding regions and ultraconserved elements) insertions and deletions.

%B Genome Res %V 17 %P 1797-808 %8 2007 Dec %G eng %N 12 %1 https://www.ncbi.nlm.nih.gov/pubmed/17984227?dopt=Abstract %R 10.1101/gr.6761107 %0 Journal Article %J Genome Res %D 2007 %T Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome. %A Margulies, Elliott H %A Cooper, Gregory M %A Asimenos, George %A Thomas, Daryl J %A Dewey, Colin N %A Siepel, Adam %A Birney, Ewan %A Keefe, Damian %A Schwartz, Ariel S %A Hou, Minmei %A Taylor, James %A Nikolaev, Sergey %A Montoya-Burgos, Juan I %A Löytynoja, Ari %A Whelan, Simon %A Pardi, Fabio %A Massingham, Tim %A Brown, James B %A Bickel, Peter %A Holmes, Ian %A Mullikin, James C %A Ureta-Vidal, Abel %A Paten, Benedict %A Stone, Eric A %A Rosenbloom, Kate R %A Kent, W James %A Bouffard, Gerard G %A Guan, Xiaobin %A Hansen, Nancy F %A Idol, Jacquelyn R %A Maduro, Valerie V B %A Maskeri, Baishali %A McDowell, Jennifer C %A Park, Morgan %A Thomas, Pamela J %A Young, Alice C %A Blakesley, Robert W %A Muzny, Donna M %A Sodergren, Erica %A Wheeler, David A %A Worley, Kim C %A Jiang, Huaiyang %A Weinstock, George M %A Gibbs, Richard A %A Graves, Tina %A Fulton, Robert %A Mardis, Elaine R %A Wilson, Richard K %A Clamp, Michele %A Cuff, James %A Gnerre, Sante %A Jaffe, David B %A Chang, Jean L %A Lindblad-Toh, Kerstin %A Lander, Eric S %A Hinrichs, Angie %A Trumbower, Heather %A Clawson, Hiram %A Zweig, Ann %A Kuhn, Robert M %A Barber, Galt %A Harte, Rachel %A Karolchik, Donna %A Field, Matthew A %A Moore, Richard A %A Matthewson, Carrie A %A Schein, Jacqueline E %A Marra, Marco A %A Antonarakis, Stylianos E %A Batzoglou, Serafim %A Goldman, Nick %A Hardison, Ross %A Haussler, David %A Miller, Webb %A Pachter, Lior %A Green, Eric D %A Sidow, Arend %K Animals %K Evolution, Molecular %K Genome, Human %K Human Genome Project %K Humans %K Mammals %K Open Reading Frames %K Phylogeny %K Sequence Alignment %X

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.

%B Genome Res %V 17 %P 760-74 %8 2007 Jun %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/17567995?dopt=Abstract %R 10.1101/gr.6034307 %0 Journal Article %J Science %D 2007 %T Evolutionary and biomedical insights from the rhesus macaque genome. %A Richard A Gibbs %A Jeffrey Rogers %A Katze, Michael G %A Bumgarner, Roger %A Weinstock, George M %A Mardis, Elaine R %A Remington, Karin A %A Strausberg, Robert L %A Venter, J Craig %A Wilson, Richard K %A Batzer, Mark A %A Bustamante, Carlos D %A Eichler, Evan E %A Hahn, Matthew W %A Hardison, Ross C %A Makova, Kateryna D %A Miller, Webb %A Milosavljevic, Aleksandar %A Palermo, Robert E %A Siepel, Adam %A Sikela, James M %A Attaway, Tony %A Bell, Stephanie %A Bernard, Kelly E %A Buhay, Christian J %A Chandrabose, Mimi N %A Dao, Marvin %A Davis, Clay %A Delehaunty, Kimberly D %A Ding, Yan %A Dinh, Huyen H %A Dugan-Rocha, Shannon %A Fulton, Lucinda A %A Gabisi, Ramatu Ayiesha %A Garner, Toni T %A Godfrey, Jennifer %A Hawes, Alicia C %A Hernandez, Judith %A Hines, Sandra %A Holder, Michael %A Hume, Jennifer %A Jhangiani, Shalini N %A Joshi, Vandita %A Ziad Khan %A Kirkness, Ewen F %A Cree, Andrew %A Fowler, R Gerald %A Lee, Sandra %A Lewis, Lora R %A Li, Zhangwan %A Liu, Yih-Shin %A Moore, Stephanie M %A Donna M Muzny %A Nazareth, Lynne V %A Ngo, Dinh Ngoc %A Okwuonu, Geoffrey O %A Pai, Grace %A Parker, David %A Paul, Heidie A %A Pfannkoch, Cynthia %A Pohl, Craig S %A Rogers, Yu-Hui %A Ruiz, San Juana %A Aniko Sabo %A Santibanez, Jireh %A Schneider, Brian W %A Smith, Scott M %A Sodergren, Erica %A Svatek, Amanda F %A Utterback, Teresa R %A Vattathil, Selina %A Warren, Wesley %A White, Courtney Sherell %A Chinwalla, Asif T %A Feng, Yucheng %A Halpern, Aaron L %A Hillier, LaDeana W %A Huang, Xiaoqiu %A Minx, Pat %A Nelson, Joanne O %A Pepin, Kymberlie H %A Xiang Qin %A Sutton, Granger G %A Venter, Eli %A Walenz, Brian P %A Wallis, John W %A Kim C Worley %A Yang, Shiaw-Pyng %A Jones, Steven M %A Marra, Marco A %A Rocchi, Mariano %A Schein, Jacqueline E %A Baertsch, Robert %A Clarke, Laura %A Csuros, Miklos %A Glasscock, Jarret %A R. Alan Harris %A Havlak, Paul %A Jackson, Andrew R %A Jiang, Huaiyang %A Liu, Yue %A Messina, David N %A Shen, Yufeng %A Song, Henry Xing-Zhi %A Wylie, Todd %A Zhang, Lan %A Birney, Ewan %A Han, Kyudong %A Konkel, Miriam K %A Lee, Jungnam %A Smit, Arian F A %A Ullmer, Brygg %A Wang, Hui %A Xing, Jinchuan %A Burhans, Richard %A Cheng, Ze %A Karro, John E %A Ma, Jian %A Raney, Brian %A She, Xinwei %A Cox, Michael J %A Demuth, Jeffery P %A Dumas, Laura J %A Han, Sang-Gook %A Hopkins, Janet %A Karimpour-Fard, Anis %A Kim, Young H %A Pollack, Jonathan R %A Vinar, Tomas %A Addo-Quaye, Charles %A Degenhardt, Jeremiah %A Denby, Alexandra %A Hubisz, Melissa J %A Indap, Amit %A Kosiol, Carolin %A Lahn, Bruce T %A Lawson, Heather A %A Marklein, Alison %A Nielsen, Rasmus %A Vallender, Eric J %A Clark, Andrew G %A Ferguson, Betsy %A Hernandez, Ryan D %A Hirani, Kashif %A Kehrer-Sawatzki, Hildegard %A Kolb, Jessica %A Patil, Shobha %A Pu, Ling-Ling %A Ren, Yanru %A Smith, David Glenn %A David A Wheeler %A Schenck, Ian %A Ball, Edward V %A Rui Chen %A Cooper, David N %A Giardine, Belinda %A Hsu, Fan %A Kent, W James %A Lesk, Arthur %A Nelson, David L %A O'brien, William E %A Prüfer, Kay %A Stenson, Peter D %A Wallace, James C %A Ke, Hui %A Liu, Xiao-Ming %A Wang, Peng %A Xiang, Andy Peng %A Yang, Fan %A Barber, Galt P %A Haussler, David %A Karolchik, Donna %A Kern, Andy D %A Kuhn, Robert M %A Smith, Kayla E %A Zwieg, Ann S %K Animals %K Biomedical Research %K Evolution, Molecular %K Female %K Gene Duplication %K Gene Rearrangement %K Genetic Diseases, Inborn %K Genetic Variation %K Genome %K Humans %K Macaca mulatta %K Male %K Multigene Family %K Mutation %K Pan troglodytes %K Sequence Analysis, DNA %K Species Specificity %X

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

%B Science %V 316 %P 222-34 %8 2007 Apr 13 %G eng %N 5822 %1 https://www.ncbi.nlm.nih.gov/pubmed/17431167?dopt=Abstract %R 10.1126/science.1139247 %0 Journal Article %J Genome Res %D 2005 %T Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. %A Siepel, Adam %A Bejerano, Gill %A Pedersen, Jakob S %A Hinrichs, Angie S %A Hou, Minmei %A Rosenbloom, Kate %A Clawson, Hiram %A Spieth, John %A Hillier, LaDeana W %A Richards, Stephen %A Weinstock, George M %A Wilson, Richard K %A Gibbs, Richard A %A Kent, W James %A Miller, Webb %A Haussler, David %K 3' Untranslated Regions %K Animals %K Base Pairing %K Base Sequence %K Caenorhabditis elegans %K Conserved Sequence %K DNA, Intergenic %K Evolution, Molecular %K Genome %K Humans %K Insecta %K Molecular Sequence Data %K Saccharomyces %K Vertebrates %K Yeasts %X

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo-HMM to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37%-53%), Caenorhabditis elegans (18%-37%), and Saccharaomyces cerevisiae (47%-68%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements (HCEs), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, HCEs are associated with the 3' UTRs of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding HCEs also show strong statistical evidence of an enrichment for RNA secondary structure.

%B Genome Res %V 15 %P 1034-50 %8 2005 Aug %G eng %N 8 %1 https://www.ncbi.nlm.nih.gov/pubmed/16024819?dopt=Abstract %R 10.1101/gr.3715005 %0 Journal Article %J Nature %D 2003 %T The DNA sequence of human chromosome 7. %A Hillier, LaDeana W %A Fulton, Robert S %A Fulton, Lucinda A %A Graves, Tina A %A Pepin, Kymberlie H %A Wagner-McPherson, Caryn %A Layman, Dan %A Maas, Jason %A Jaeger, Sara %A Walker, Rebecca %A Wylie, Kristine %A Sekhon, Mandeep %A Becker, Michael C %A O'Laughlin, Michelle D %A Schaller, Mark E %A Fewell, Ginger A %A Delehaunty, Kimberly D %A Miner, Tracie L %A Nash, William E %A Cordes, Matt %A Du, Hui %A Sun, Hui %A Edwards, Jennifer %A Bradshaw-Cordum, Holland %A Ali, Johar %A Andrews, Stephanie %A Isak, Amber %A Vanbrunt, Andrew %A Nguyen, Christine %A Du, Feiyu %A Lamar, Betty %A Courtney, Laura %A Kalicki, Joelle %A Ozersky, Philip %A Bielicki, Lauren %A Scott, Kelsi %A Holmes, Andrea %A Harkins, Richard %A Harris, Anthony %A Strong, Cynthia Madsen %A Hou, Shunfang %A Tomlinson, Chad %A Dauphin-Kohlberg, Sara %A Kozlowicz-Reilly, Amy %A Leonard, Shawn %A Rohlfing, Theresa %A Rock, Susan M %A Tin-Wollam, Aye-Mon %A Abbott, Amanda %A Minx, Patrick %A Maupin, Rachel %A Strowmatt, Catrina %A Latreille, Phil %A Miller, Nancy %A Johnson, Doug %A Murray, Jennifer %A Woessner, Jeffrey P %A Wendl, Michael C %A Yang, Shiaw-Pyng %A Schultz, Brian R %A Wallis, John W %A Spieth, John %A Bieri, Tamberlyn A %A Nelson, Joanne O %A Berkowicz, Nicolas %A Wohldmann, Patricia E %A Cook, Lisa L %A Hickenbotham, Matthew T %A Eldred, James %A Williams, Donald %A Bedell, Joseph A %A Mardis, Elaine R %A Clifton, Sandra W %A Chissoe, Stephanie L %A Marra, Marco A %A Raymond, Christopher %A Haugen, Eric %A Gillett, Will %A Zhou, Yang %A James, Rose %A Phelps, Karen %A Iadanoto, Shawn %A Bubb, Kerry %A Simms, Elizabeth %A Levy, Ruth %A Clendenning, James %A Kaul, Rajinder %A Kent, W James %A Furey, Terrence S %A Baertsch, Robert A %A Brent, Michael R %A Keibler, Evan %A Flicek, Paul %A Bork, Peer %A Suyama, Mikita %A Bailey, Jeffrey A %A Portnoy, Matthew E %A Torrents, David %A Chinwalla, Asif T %A Gish, Warren R %A Eddy, Sean R %A McPherson, John D %A Olson, Maynard V %A Eichler, Evan E %A Green, Eric D %A Waterston, Robert H %A Wilson, Richard K %K Animals %K Base Sequence %K Chromosomes, Human, Pair 7 %K Gene Duplication %K Humans %K Mice %K Molecular Sequence Data %K Physical Chromosome Mapping %K Proteins %K Pseudogenes %K RNA, Untranslated %K Sequence Analysis, DNA %K Species Specificity %K Williams Syndrome %X

Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame.

%B Nature %V 424 %P 157-64 %8 2003 Jul 10 %G eng %N 6945 %1 https://www.ncbi.nlm.nih.gov/pubmed/12853948?dopt=Abstract %R 10.1038/nature01782 %0 Journal Article %J Nature %D 2002 %T Initial sequencing and comparative analysis of the mouse genome. %A Waterston, Robert H %A Lindblad-Toh, Kerstin %A Birney, Ewan %A Rogers, Jane %A Abril, Josep F %A Agarwal, Pankaj %A Agarwala, Richa %A Ainscough, Rachel %A Alexandersson, Marina %A An, Peter %A Antonarakis, Stylianos E %A Attwood, John %A Baertsch, Robert %A Bailey, Jonathon %A Barlow, Karen %A Beck, Stephan %A Berry, Eric %A Birren, Bruce %A Bloom, Toby %A Bork, Peer %A Botcherby, Marc %A Bray, Nicolas %A Brent, Michael R %A Brown, Daniel G %A Brown, Stephen D %A Bult, Carol %A Burton, John %A Butler, Jonathan %A Campbell, Robert D %A Carninci, Piero %A Cawley, Simon %A Chiaromonte, Francesca %A Chinwalla, Asif T %A Church, Deanna M %A Clamp, Michele %A Clee, Christopher %A Collins, Francis S %A Cook, Lisa L %A Copley, Richard R %A Coulson, Alan %A Couronne, Olivier %A Cuff, James %A Curwen, Val %A Cutts, Tim %A Daly, Mark %A David, Robert %A Davies, Joy %A Delehaunty, Kimberly D %A Deri, Justin %A Dermitzakis, Emmanouil T %A Dewey, Colin %A Dickens, Nicholas J %A Diekhans, Mark %A Dodge, Sheila %A Dubchak, Inna %A Dunn, Diane M %A Eddy, Sean R %A Elnitski, Laura %A Emes, Richard D %A Eswara, Pallavi %A Eyras, Eduardo %A Felsenfeld, Adam %A Fewell, Ginger A %A Flicek, Paul %A Foley, Karen %A Frankel, Wayne N %A Fulton, Lucinda A %A Fulton, Robert S %A Furey, Terrence S %A Gage, Diane %A Gibbs, Richard A %A Glusman, Gustavo %A Gnerre, Sante %A Goldman, Nick %A Goodstadt, Leo %A Grafham, Darren %A Graves, Tina A %A Green, Eric D %A Gregory, Simon %A Guigó, Roderic %A Guyer, Mark %A Hardison, Ross C %A Haussler, David %A Hayashizaki, Yoshihide %A Hillier, LaDeana W %A Hinrichs, Angela %A Hlavina, Wratko %A Holzer, Timothy %A Hsu, Fan %A Hua, Axin %A Hubbard, Tim %A Hunt, Adrienne %A Jackson, Ian %A Jaffe, David B %A Johnson, L Steven %A Jones, Matthew %A Jones, Thomas A %A Joy, Ann %A Kamal, Michael %A Karlsson, Elinor K %A Karolchik, Donna %A Kasprzyk, Arkadiusz %A Kawai, Jun %A Keibler, Evan %A Kells, Cristyn %A Kent, W James %A Kirby, Andrew %A Kolbe, Diana L %A Korf, Ian %A Kucherlapati, Raju S %A Kulbokas, Edward J %A Kulp, David %A Landers, Tom %A Leger, J P %A Leonard, Steven %A Letunic, Ivica %A Levine, Rosie %A Li, Jia %A Li, Ming %A Lloyd, Christine %A Lucas, Susan %A Ma, Bin %A Maglott, Donna R %A Mardis, Elaine R %A Matthews, Lucy %A Mauceli, Evan %A Mayer, John H %A McCarthy, Megan %A McCombie, W Richard %A McLaren, Stuart %A McLay, Kirsten %A McPherson, John D %A Meldrim, Jim %A Meredith, Beverley %A Mesirov, Jill P %A Miller, Webb %A Miner, Tracie L %A Mongin, Emmanuel %A Montgomery, Kate T %A Morgan, Michael %A Mott, Richard %A Mullikin, James C %A Muzny, Donna M %A Nash, William E %A Nelson, Joanne O %A Nhan, Michael N %A Nicol, Robert %A Ning, Zemin %A Nusbaum, Chad %A O'Connor, Michael J %A Okazaki, Yasushi %A Oliver, Karen %A Overton-Larty, Emma %A Pachter, Lior %A Parra, Genís %A Pepin, Kymberlie H %A Peterson, Jane %A Pevzner, Pavel %A Plumb, Robert %A Pohl, Craig S %A Poliakov, Alex %A Ponce, Tracy C %A Ponting, Chris P %A Potter, Simon %A Quail, Michael %A Reymond, Alexandre %A Roe, Bruce A %A Roskin, Krishna M %A Rubin, Edward M %A Rust, Alistair G %A Santos, Ralph %A Sapojnikov, Victor %A Schultz, Brian %A Schultz, Jörg %A Schwartz, Matthias S %A Schwartz, Scott %A Scott, Carol %A Seaman, Steven %A Searle, Steve %A Sharpe, Ted %A Sheridan, Andrew %A Shownkeen, Ratna %A Sims, Sarah %A Singer, Jonathan B %A Slater, Guy %A Smit, Arian %A Smith, Douglas R %A Spencer, Brian %A Stabenau, Arne %A Stange-Thomann, Nicole %A Sugnet, Charles %A Suyama, Mikita %A Tesler, Glenn %A Thompson, Johanna %A Torrents, David %A Trevaskis, Evanne %A Tromp, John %A Ucla, Catherine %A Ureta-Vidal, Abel %A Vinson, Jade P %A Von Niederhausern, Andrew C %A Wade, Claire M %A Wall, Melanie %A Weber, Ryan J %A Weiss, Robert B %A Wendl, Michael C %A West, Anthony P %A Wetterstrand, Kris %A Wheeler, Raymond %A Whelan, Simon %A Wierzbowski, Jamey %A Willey, David %A Williams, Sophie %A Wilson, Richard K %A Winter, Eitan %A Worley, Kim C %A Wyman, Dudley %A Yang, Shan %A Yang, Shiaw-Pyng %A Zdobnov, Evgeny M %A Zody, Michael C %A Lander, Eric S %K Animals %K Base Composition %K Chromosomes, Mammalian %K Conserved Sequence %K CpG Islands %K Evolution, Molecular %K Gene Expression Regulation %K Genes %K Genetic Variation %K Genome %K Genome, Human %K Genomics %K Humans %K Mice %K Mice, Knockout %K Mice, Transgenic %K Models, Animal %K Multigene Family %K Mutagenesis %K Neoplasms %K Physical Chromosome Mapping %K Proteome %K Pseudogenes %K Quantitative Trait Loci %K Repetitive Sequences, Nucleic Acid %K RNA, Untranslated %K Selection, Genetic %K Sequence Analysis, DNA %K Sex Chromosomes %K Species Specificity %K Synteny %X

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

%B Nature %V 420 %P 520-62 %8 2002 Dec 05 %G eng %N 6915 %1 https://www.ncbi.nlm.nih.gov/pubmed/12466850?dopt=Abstract %R 10.1038/nature01262