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1. Using shared genomic synteny and shared protein functions to enhance the identification of orthologous gene pairs

Author

Jeffrey Hoover, Fei Zhong, Fu Lu, Xiangqun H. Zheng, Richard J. Mural, and Zhen-Yuan Wang

Subjects
Statistics and Probability, Genetic Linkage, Genomics, Computational biology, Biology, Biochemistry, Genome, Pattern Recognition, Automated, Conserved sequence, Evolution, Molecular, Mice, Sequence Homology, Nucleic Acid, Animals, Humans, Gene family, Molecular Biology, Conserved Sequence, Synteny, Genetics, Chromosome Mapping, Proteins, Sequence Analysis, DNA, Gene Annotation, Chromosomes, Mammalian, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, Human genome, Sequence Alignment, Algorithms, Orthologous Gene
Abstract

Motivation: The identification of orthologous gene pairs is generally based on sequence similarity. Gene pairs that are mutually ‘best hits’ between the genomes being compared are asserted to be orthologs. Although this method identifies most orthologous gene pairs with high confidence, it will miss a fraction of them, especially genes in duplicated gene families. In addition, the approach depends heavily on the completeness and quality of gene annotation. When the gene sequences are not correctly represented the approach is unlikely to find the correct ortholog. To overcome these limitations, we have developed an approach to identify orthologous gene pairs using shared chromosomal synteny and the annotation of protein function. Results: Assembled mouse and human genomes were used to identify the regions of conserved synteny between these genomes. ‘Syntenic anchors’ are conserved non-repetitive locations between mouse and human genomes. Using these anchors, we identified blocks of sequences that contain consistently ordered anchors between the two genomes (syntenic blocks). The synteny information has been used to help us identify orthologous gene pairs between mouse and human genomes. The approach combines the mutual selection of the best tBlastX hits between human and mouse transcripts, and inferring gene orthologous relationships based on sharing syntenic anchors, collocating in the same syntenic blocks and sharing the same annotated protein function. Using this approach, we were able to find 19 357 orthologous gene pairs between human and mouse genomes, a 20% increase in the number of orthologs identified by conventional approaches. Contact: richard.mural@celera.com

Published
2004
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2. An Avian Sarcoma/Leukosis Virus-Based Gene Trap Vector for Mammalian Cells

Author

Xiangqun H. Zheng and Stephen H. Hughes

Subjects
Genetic Vectors, Green Fluorescent Proteins, Immunology, Mutagenesis (molecular biology technique), Gene delivery, Microbiology, Avian sarcoma virus, Green fluorescent protein, Viral vector, Mice, Genes, Reporter, Virology, Murine leukemia virus, Animals, Mammals, Reporter gene, Avian Leukosis Virus, biology, 3T3 Cells, Gene Therapy, biology.organism_classification, Molecular biology, Luminescent Proteins, Avian sarcoma leukosis virus, Avian Sarcoma Viruses, Insect Science
Abstract

RCASBP-M2C is a retroviral vector derived from an avian sarcoma/leukosis virus which has been modified so that it uses the envelope gene from an amphotropic murine leukemia virus (E. V. Barsov and S. H. Hughes, J. Virol. 70:3922–3929, 1996). The vector replicates efficiently in avian cells and infects, but does not replicate in, mammalian cells. This makes the vector useful for gene delivery, mutagenesis, and other applications in mammalian systems. Here we describe the development of a derivative of RCASBP-M2C, pGT-GFP, that can be used in gene trap experiments in mammalian cells. The gene trap vector pGT-GFP contains a green fluorescent protein (GFP) reporter gene. Appropriate insertion of the vector into genes causes GFP expression; this facilitates the rapid enrichment and cloning of the trapped cells and provides an opportunity to select subpopulations of trapped cells based on the subcellular localization of GFP. With this vector, we have generated about 90 gene-trapped lines using D17 and NIH 3T3 cells. Five trapped NIH 3T3 lines were selected based on the distribution of GFP in cells. The cellular genes disrupted by viral integration have been identified in four of these lines by using a 5′ rapid amplification of cDNA ends protocol.

Published
1999
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3. More on the sequencing of the human genome

Author

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

Subjects
Male, Cancer genome sequencing, Chromosomes, Artificial, Bacterial, Databases, Factual, Clinical Biochemistry, Genome, Gene Duplication, Databases, Genetic, Human Genome Project, Genetics, Multidisciplinary, Chromosome Mapping, Exons, Genomics, Genome project, Physical Chromosome Mapping, Phenotype, Genetic Techniques, Perspective, DNA, Intergenic, Female, Algorithms, Pseudogenes, Personal genomics, Genome evolution, Retroelements, Hybrid genome assembly, Biology, ENCODE, Polymorphism, Single Nucleotide, Evolution, Molecular, Sequence-tagged site, Species Specificity, Gene density, Consensus Sequence, Animals, Humans, Genome size, Repetitive Sequences, Nucleic Acid, Whole genome sequencing, Comparative genomics, Genome, Human, Biochemistry (medical), Computational Biology, Genetic Variation, Proteins, Sequence Analysis, DNA, Introns, Chromosome Banding, Genes, CpG Islands, Reference genome
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.

Published
2003
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4. Human chromosome 7: DNA sequence and biology

Author

Jennifer Skaug, Karen W. Gripp, Luis Armengol, Sanaa Choufani, Lisa G. Shaffer, Ikuko Teshima, Dorota Kwasnicka, Elena Belloni, Peter M. Kroisel, Qing Zhang, Miguel Angel Pujana, David Chitayat, Hartmut Döhner, Sarah J. Mould, David G. Oscier, Andrew P. Boright, Steven R. Herrick, Peter Szatmari, Simone Gentles, May Haddad, Lucy R. Osborne, Azra H. Ligon, J. Craig Venter, Karl Heinz Grzeschik, James F. Gusella, Emiko Kanematsu, Junjun Zhang, Jeffrey R. MacDonald, Eitan Zlotorynski, Zhongwu Lai, Anne W. Higgins, Zhiping Gu, Theresa A. Grebe, Johanna M. Rommens, Barbara R. Pober, Stephen W. Scherer, Constantine C. Christopoulos, Pier Giuseppe Pelicci, Cynthia C. Morton, Anne M. Summers, Razi Khaja, Michael D. Wilson, Berge A. Minassian, Chantal Farra, Hyung Goo Kim, Ahmed Teebi, Elizabeth J.T. Winsor, Gudrun E. Moore, Nazneen Rahman, Heather L. Ferguson, John B. Vincent, Kazuhiko Nakabayashi, Henry H.Q. Heng, Batsheva Kerem, Wendy Roberts, Xiangqun H. Zheng, Jan M. Friedman, Martin Li, Francesco Lo-Coco, Susan Zeesman, Juha Kere, Richard J. Mural, Małgorzata J.M. Nowaczyk, Ben F. Koop, Jo Anne Herbrick, Bradley J. Quade, Alexander K. Hudek, Bridget A. Fernandez, Lap-Chee Tsui, Fu Lu, Peter W. Li, Gavin E. Duggan, Joseph Y. Cheung, Gail A. P. Bruns, Susan J. Kirkpatrick, Konstanze Döhner, Bruce R. Korf, Elaine H. Zackai, Xavier Estivill, Silvano Tosi, Rosanna Weksberg, Erwin Petek, Natalia T. Leach, Deborah R. Nusskern, Sarah R. Cox, Emmanuelle Lemyre, Andrew R. Carson, Cheryl Shuman, Mark Raymond Adams, and Layla Parker-Katiraee

Subjects
Williams Syndrome, Euchromatin, Congenital, Mice, Complementary, Gene Duplication, Neoplasms, Databases, Genetic, Genes, Overlapping, In Situ Hybridization, Fluorescence, In Situ Hybridization, Segmental duplication, Overlapping, Genetics, Chromosome 7 (human), Expressed Sequence Tags, Multidisciplinary, Chromosome Fragile Sites, Chromosome Mapping, Limb Deformities, Genetic Diseases, Animals, Autistic Disorder, Chromosome Aberrations, Chromosome Fragility, Chromosomes, Human, Pair 7, Computational Biology, Congenital Abnormalities, CpG Islands, DNA, Complementary, Genetic Diseases, Inborn, Genomic Imprinting, Humans, Limb Deformities, Congenital, Molecular Sequence Data, Mutation, Pseudogenes, RNA, Retroelements, Sequence Analysis, DNA, Pair 7, Sequence Analysis, Human, Sequence analysis, Genetic diseases, inborn - genetics, Chromosomal rearrangement, Biology, Article, Chromosomes, Fluorescence, Databases, Genetic, Chromosome 19, DNA, Inborn, Genes, Human genome, Chromosome 21, Chromosomes, human, pair 7 - genetics, Chromosome 22, Settore MED/15 - Malattie del Sangue
Abstract

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism., link_to_OA_fulltext

Published
2003

5. A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome

Author

Richard J, Mural, Mark D, Adams, Eugene W, Myers, Hamilton O, Smith, George L Gabor, Miklos, Ron, Wides, Aaron, Halpern, Peter W, Li, Granger G, Sutton, Joe, Nadeau, Steven L, Salzberg, Robert A, Holt, Chinnappa D, Kodira, Fu, Lu, Lin, Chen, Zuoming, Deng, Carlos C, Evangelista, Weiniu, Gan, Thomas J, Heiman, Jiayin, Li, Zhenya, Li, Gennady V, Merkulov, Natalia V, Milshina, Ashwinikumar K, Naik, Rong, Qi, Bixiong Chris, Shue, Aihui, Wang, Jian, Wang, Xin, Wang, Xianghe, Yan, Jane, Ye, Shibu, Yooseph, Qi, Zhao, Liansheng, Zheng, Shiaoping C, Zhu, Kendra, Biddick, Randall, Bolanos, Arthur L, Delcher, Ian M, Dew, Daniel, Fasulo, Michael J, Flanigan, Daniel H, Huson, Saul A, Kravitz, Jason R, Miller, Clark M, Mobarry, Knut, Reinert, Karin A, Remington, Qing, Zhang, Xiangqun H, Zheng, Deborah R, Nusskern, Zhongwu, Lai, Yiding, Lei, Wenyan, Zhong, Alison, Yao, Ping, Guan, Rui-Ru, Ji, Zhiping, Gu, Zhen-Yuan, Wang, Fei, Zhong, Chunlin, Xiao, Chia-Chien, Chiang, Mark, Yandell, Jennifer R, Wortman, Peter G, Amanatides, Suzanne L, Hladun, Eric C, Pratts, Jeffery E, Johnson, Kristina L, Dodson, Kerry J, Woodford, Cheryl A, Evans, Barry, Gropman, Douglas B, Rusch, Eli, Venter, Mei, Wang, Thomas J, Smith, Jarrett T, Houck, Donald E, Tompkins, Charles, Haynes, Debbie, Jacob, Soo H, Chin, David R, Allen, Carl E, Dahlke, Robert, Sanders, Kelvin, Li, Xiangjun, Liu, Alexander A, Levitsky, William H, Majoros, Quan, Chen, Ashley C, Xia, John R, Lopez, Michael T, Donnelly, Matthew H, Newman, Anna, Glodek, Cheryl L, Kraft, Marc, Nodell, Feroze, Ali, Hui-Jin, An, Danita, Baldwin-Pitts, Karen Y, Beeson, Shuang, Cai, Mark, Carnes, Amy, Carver, Parris M, Caulk, Angela, Center, Yen-Hui, Chen, Ming-Lai, Cheng, My D, Coyne, Michelle, Crowder, Steven, Danaher, Lionel B, Davenport, Raymond, Desilets, Susanne M, Dietz, Lisa, Doup, Patrick, Dullaghan, Steven, Ferriera, Carl R, Fosler, Harold C, Gire, Andres, Gluecksmann, Jeannine D, Gocayne, Jonathan, Gray, Brit, Hart, Jason, Haynes, Jeffery, Hoover, Tim, Howland, Chinyere, Ibegwam, Mena, Jalali, David, Johns, Leslie, Kline, Daniel S, Ma, Steven, MacCawley, Anand, Magoon, Felecia, Mann, David, May, Tina C, McIntosh, Somil, Mehta, Linda, Moy, Mee C, Moy, Brian J, Murphy, Sean D, Murphy, Keith A, Nelson, Zubeda, Nuri, Kimberly A, Parker, Alexandre C, Prudhomme, Vinita N, Puri, Hina, Qureshi, John C, Raley, Matthew S, Reardon, Megan A, Regier, Yu-Hui C, Rogers, Deanna L, Romblad, Jakob, Schutz, John L, Scott, Richard, Scott, Cynthia D, Sitter, Michella, Smallwood, Arlan C, Sprague, Erin, Stewart, Renee V, Strong, Ellen, Suh, Karena, Sylvester, Reginald, Thomas, Ni Ni, Tint, Christopher, Tsonis, Gary, Wang, George, Wang, Monica S, Williams, Sherita M, Williams, Sandra M, Windsor, Keriellen, Wolfe, Mitchell M, Wu, Jayshree, Zaveri, Kabir, Chaturvedi, Andrei E, Gabrielian, Zhaoxi, Ke, Jingtao, Sun, Gangadharan, Subramanian, J Craig, Venter, Cynthia M, Pfannkoch, Mary, Barnstead, and Lisa D, Stephenson

Subjects
Genetic Markers, Genome evolution, Mice, Inbred A, Molecular Sequence Data, Genomics, Mice, Inbred Strains, Biology, Genome, Synteny, Chromosomes, Evolution, Molecular, Mice, Species Specificity, Gene density, Animals, Chromosomes, Human, Humans, Conserved Sequence, Genetics, Base Composition, Multidisciplinary, Shotgun sequencing, Genome, Human, Computational Biology, Proteins, Genome project, Sequence Analysis, DNA, Physical Chromosome Mapping, Genes, Mice, Inbred DBA, Human genome, Databases, Nucleic Acid, Sequence Alignment, Reference genome
Abstract

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.

Published
2002

6. The genome sequence of Drosophila melanogaster

Author

Mark D. Adams, Susan E. Celniker, Robert A. Holt, Cheryl A. Evans, Jeannine D. Gocayne, Peter G. Amanatides, Steven E. Scherer, Peter W. Li, Roger A. Hoskins, Richard F. Galle, Reed A. George, Suzanna E. Lewis, Stephen Richards, Michael Ashburner, Scott N. Henderson, Granger G. Sutton, Jennifer R. Wortman, Mark D. Yandell, Qing Zhang, Lin X. Chen, Rhonda C. Brandon, Yu-Hui C. Rogers, Robert G. Blazej, Mark Champe, Barret D. Pfeiffer, Kenneth H. Wan, Clare Doyle, Evan G. Baxter, Gregg Helt, Catherine R. Nelson, George L. Gabor, null Miklos, Josep F. Abril, Anna Agbayani, Hui-Jin An, Cynthia Andrews-Pfannkoch, Danita Baldwin, Richard M. Ballew, Anand Basu, James Baxendale, Leyla Bayraktaroglu, Ellen M. Beasley, Karen Y. Beeson, P. V. Benos, Benjamin P. Berman, Deepali Bhandari, Slava Bolshakov, Dana Borkova, Michael R. Botchan, John Bouck, Peter Brokstein, Phillipe Brottier, Kenneth C. Burtis, Dana A. Busam, Heather Butler, Edouard Cadieu, Angela Center, Ishwar Chandra, J. Michael Cherry, Simon Cawley, Carl Dahlke, Lionel B. Davenport, Peter Davies, Beatriz de Pablos, Arthur Delcher, Zuoming Deng, Anne Deslattes Mays, Ian Dew, Suzanne M. Dietz, Kristina Dodson, Lisa E. Doup, Michael Downes, Shannon Dugan-Rocha, Boris C. Dunkov, Patrick Dunn, Kenneth J. Durbin, Carlos C. Evangelista, Concepcion Ferraz, Steven Ferriera, Wolfgang Fleischmann, Carl Fosler, Andrei E. Gabrielian, Neha S. Garg, William M. Gelbart, Ken Glasser, Anna Glodek, Fangcheng Gong, J. Harley Gorrell, Zhiping Gu, Ping Guan, Michael Harris, Nomi L. Harris, Damon Harvey, Thomas J. Heiman, Judith R. Hernandez, Jarrett Houck, Damon Hostin, Kathryn A. Houston, Timothy J. Howland, Ming-Hui Wei, Chinyere Ibegwam, Mena Jalali, Francis Kalush, Gary H. Karpen, Zhaoxi Ke, James A. Kennison, Karen A. Ketchum, Bruce E. Kimmel, Chinnappa D. Kodira, Cheryl Kraft, Saul Kravitz, David Kulp, Zhongwu Lai, Paul Lasko, Yiding Lei, Alexander A. Levitsky, Jiayin Li, Zhenya Li, Yong Liang, Xiaoying Lin, Xiangjun Liu, Bettina Mattei, Tina C. McIntosh, Michael P. McLeod, Duncan McPherson, Gennady Merkulov, Natalia V. Milshina, Clark Mobarry, Joe Morris, Ali Moshrefi, Stephen M. Mount, Mee Moy, Brian Murphy, Lee Murphy, Donna M. Muzny, David L. Nelson, David R. Nelson, Keith A. Nelson, Katherine Nixon, Deborah R. Nusskern, Joanne M. Pacleb, Michael Palazzolo, Gjange S. Pittman, Sue Pan, John Pollard, Vinita Puri, Martin G. Reese, Knut Reinert, Karin Remington, Robert D. C. Saunders, Frederick Scheeler, Hua Shen, Bixiang Christopher Shue, Inga Sidén-Kiamos, Michael Simpson, Marian P. Skupski, Tom Smith, Eugene Spier, Allan C. Spradling, Mark Stapleton, Renee Strong, Eric Sun, Robert Svirskas, Cyndee Tector, Russell Turner, Eli Venter, Aihui H. Wang, Xin Wang, Zhen-Yuan Wang, David A. Wassarman, George M. Weinstock, Jean Weissenbach, Sherita M. Williams, Trevor Woodage, Kim C. Worley, David Wu, Song Yang, Q. Alison Yao, Jane Ye, Ru-Fang Yeh, Jayshree S. Zaveri, Ming Zhan, Guangren Zhang, Qi Zhao, Liansheng Zheng, Xiangqun H. Zheng, Fei N. Zhong, Wenyan Zhong, Xiaojun Zhou, Shiaoping Zhu, Xiaohong Zhu, Hamilton O. Smith, Richard A. Gibbs, Eugene W. Myers, Gerald M. Rubin, and J. Craig Venter

Subjects
DNA Replication, Genome evolution, DNA Repair, Transcription, Genetic, Genes, Insect, Computational biology, Biology, Genome, Euchromatin, Contig Mapping, Cytochrome P-450 Enzyme System, Gene density, Heterochromatin, Animals, Cloning, Molecular, Genome size, Gene Library, Whole genome sequencing, Genetics, Bacterial artificial chromosome, Multidisciplinary, Shotgun sequencing, Computational Biology, Nuclear Proteins, Biological Transport, Genome project, Sequence Analysis, DNA, Chromatin, Drosophila melanogaster, Protein Biosynthesis, Insect Proteins
Abstract

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the ∼120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes ∼13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Published
2000

7. Comparative genomics of the eukaryotes

Author

Mark E. Fortini, Gerald M. Rubin, Qi Zhao, Thomas Brody, Fangcheng Gong, Oxana K. Pickeral, Stephen A. Chervitz, Anibal Cravchik, Suzanna E. Lewis, Sima Misra, Roger A. Hoskins, Nomi L. Harris, Wolfgang Fleischmann, Susan E. Celniker, Ping Guan, Mark S. Boguski, Zhenya Li, Jiong Zhang, Reed A. George, Bruce A. Hay, David Coates, Lawrence S.B. Goldstein, J. Michael Cherry, Richard A. Gibbs, Peter W. Li, Peter M. Kuehl, Mark Raymond Adams, Richard F. Galle, William M. Gelbart, Fei Zhong, Bruno Lemaitre, Steven Henikoff, Mark Yandell, Catherine R. Nelson, Rolf Apweiler, Peter Brokstein, Michael Ashburner, J. Troy Littleton, Patrick H. O'Farrell, Christopher J. Mungall, Jennifer R. Wortman, Andrei Gabrielian, Marian P. Skupski, Iswar K. Hariharan, Xiangqun H. Zheng, Miklos, J. Craig Venter, Chris Shue, Leslie B. Vosshall, Ewan Birney, Deborah K. Morrison, George L. Gabor, Jiayin Li, Richard O. Hynes, Steven J.M. Jones, and Wenyan Zhong

Subjects
Proteome, Genetics, Medical, Apoptosis, Saccharomyces cerevisiae, Genome, Article, Fungal Proteins, Genes, Duplicate, Drosophilidae, Neoplasms, Cell Adhesion, Gene family, Animals, Humans, Caenorhabditis elegans, Gene, Genetics, Comparative genomics, Multidisciplinary, biology, fungi, Cell Cycle, Genetic Diseases, Inborn, Immunity, Helminth Proteins, biology.organism_classification, Biological Evolution, Protein Structure, Tertiary, Drosophila melanogaster, Multigene Family, Insect Proteins, Signal Transduction
Abstract

A comparative analysis of the genomes of Drosophila melanogaster , Caenorhabditis elegans , and Saccharomyces cerevisiae —and the proteins they are predicted to encode—was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Published
2000

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