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1. Targeted next generation sequencing for newborn screening of Menkes disease

Author

Richard B. Parad, Stephen G. Kaler, Evan Mauceli, Tanya Sokolsky, Ling Yi, and Arindam Bhattacharjee

Subjects
Menkes disease, ATP7A, Molecular genetics, Targeted next generation sequencing, Dried blood spots, Newborn screening, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Purpose: Population-based newborn screening (NBS) allows early detection and treatment of inherited disorders. For certain medically-actionable conditions, however, NBS is limited by the absence of reliable biochemical signatures amenable to detection by current platforms. We sought to assess the analytic validity of an ATP7A targeted next generation DNA sequencing assay as a potential newborn screen for one such disorder, Menkes disease. Methods: Dried blood spots from control or Menkes disease subjects (n = 22) were blindly analyzed for pathogenic variants in the copper transport gene, ATP7A. The analytical method was optimized to minimize cost and provide rapid turnaround time. Results: The algorithm correctly identified pathogenic ATP7A variants, including missense, nonsense, small insertions/deletions, and large copy number variants, in 21/22 (95.5%) of subjects, one of whom had inconclusive diagnostic sequencing previously. For one false negative that also had not been detected by commercial molecular laboratories, we identified a deep intronic variant that impaired ATP7A mRNA splicing. Conclusions: Our results support proof-of-concept that primary DNA-based NBS would accurately detect Menkes disease, a disorder that fulfills Wilson and Jungner screening criteria and for which biochemical NBS is unavailable. Targeted next generation sequencing for NBS would enable improved Menkes disease clinical outcomes, establish a platform for early identification of other unscreened disorders, and complement current NBS by providing immediate data for molecular confirmation of numerous biochemically screened conditions.

Published
2020
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2. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

Author

Noriko Tonomura, Ingegerd Elvers, Rachael Thomas, Kate Megquier, Jason Turner-Maier, Cedric Howald, Aaron L Sarver, Ross Swofford, Aric M Frantz, Daisuke Ito, Evan Mauceli, Maja Arendt, Hyun Ji Noh, Michele Koltookian, Tara Biagi, Sarah Fryc, Christina Williams, Anne C Avery, Jong-Hyuk Kim, Lisa Barber, Kristine Burgess, Eric S Lander, Elinor K Karlsson, Chieko Azuma, Jaime F Modiano, Matthew Breen, and Kerstin Lindblad-Toh

Subjects
Genetics, QH426-470
Abstract

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

Published
2015
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3. An improved canine genome and a comprehensive catalogue of coding genes and non-coding transcripts.

Author

Marc P Hoeppner, Andrew Lundquist, Mono Pirun, Jennifer R S Meadows, Neda Zamani, Jeremy Johnson, Görel Sundström, April Cook, Michael G FitzGerald, Ross Swofford, Evan Mauceli, Behrooz Torabi Moghadam, Anna Greka, Jessica Alföldi, Amr Abouelleil, Lynne Aftuck, Daniel Bessette, Aaron Berlin, Adam Brown, Gary Gearin, Annie Lui, J Pendexter Macdonald, Margaret Priest, Terrance Shea, Jason Turner-Maier, Andrew Zimmer, Eric S Lander, Federica di Palma, Kerstin Lindblad-Toh, and Manfred G Grabherr

Subjects
Medicine, Science
Abstract

The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.

Published
2014
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4. Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea.

Author

Joelle Amselem, Christina A Cuomo, Jan A L van Kan, Muriel Viaud, Ernesto P Benito, Arnaud Couloux, Pedro M Coutinho, Ronald P de Vries, Paul S Dyer, Sabine Fillinger, Elisabeth Fournier, Lilian Gout, Matthias Hahn, Linda Kohn, Nicolas Lapalu, Kim M Plummer, Jean-Marc Pradier, Emmanuel Quévillon, Amir Sharon, Adeline Simon, Arjen ten Have, Bettina Tudzynski, Paul Tudzynski, Patrick Wincker, Marion Andrew, Véronique Anthouard, Ross E Beever, Rolland Beffa, Isabelle Benoit, Ourdia Bouzid, Baptiste Brault, Zehua Chen, Mathias Choquer, Jérome Collémare, Pascale Cotton, Etienne G Danchin, Corinne Da Silva, Angélique Gautier, Corinne Giraud, Tatiana Giraud, Celedonio Gonzalez, Sandrine Grossetete, Ulrich Güldener, Bernard Henrissat, Barbara J Howlett, Chinnappa Kodira, Matthias Kretschmer, Anne Lappartient, Michaela Leroch, Caroline Levis, Evan Mauceli, Cécile Neuvéglise, Birgitt Oeser, Matthew Pearson, Julie Poulain, Nathalie Poussereau, Hadi Quesneville, Christine Rascle, Julia Schumacher, Béatrice Ségurens, Adrienne Sexton, Evelyn Silva, Catherine Sirven, Darren M Soanes, Nicholas J Talbot, Matt Templeton, Chandri Yandava, Oded Yarden, Qiandong Zeng, Jeffrey A Rollins, Marc-Henri Lebrun, and Marty Dickman

Subjects
Genetics, QH426-470
Abstract

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to

Published
2011
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5. A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs.

Author

Mia Olsson, Jennifer R S Meadows, Katarina Truvé, Gerli Rosengren Pielberg, Francesca Puppo, Evan Mauceli, Javier Quilez, Noriko Tonomura, Giordana Zanna, Maria José Docampo, Anna Bassols, Anne C Avery, Elinor K Karlsson, Anne Thomas, Daniel L Kastner, Erik Bongcam-Rudloff, Matthew T Webster, Armand Sanchez, Ake Hedhammar, Elaine F Remmers, Leif Andersson, Lluis Ferrer, Linda Tintle, and Kerstin Lindblad-Toh

Subjects
Genetics, QH426-470
Abstract

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 × 10⁻⁶, p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.

Published
2011
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6. Exploiting nucleotide composition to engineer promoters.

Author

Manfred G Grabherr, Jens Pontiller, Evan Mauceli, Wolfgang Ernst, Martina Baumann, Tara Biagi, Ross Swofford, Pamela Russell, Michael C Zody, Federica Di Palma, Kerstin Lindblad-Toh, and Reingard M Grabherr

Subjects
Medicine, Science
Abstract

The choice of promoter is a critical step in optimizing the efficiency and stability of recombinant protein production in mammalian cell lines. Artificial promoters that provide stable expression across cell lines and can be designed to the desired strength constitute an alternative to the use of viral promoters. Here, we show how the nucleotide characteristics of highly active human promoters can be modelled via the genome-wide frequency distribution of short motifs: by overlapping motifs that occur infrequently in the genome, we constructed contiguous sequence that is rich in GC and CpGs, both features of known promoters, but lacking homology to real promoters. We show that snippets from this sequence, at 100 base pairs or longer, drive gene expression in vitro in a number of mammalian cells, and are thus candidates for use in protein production. We further show that expression is driven by the general transcription factors TFIIB and TFIID, both being ubiquitously present across cell types, which results in less tissue- and species-specific regulation compared to the viral promoter SV40. We lastly found that the strength of a promoter can be tuned up and down by modulating the counts of GC and CpGs in localized regions. These results constitute a "proof-of-concept" for custom-designing promoters that are suitable for biotechnological and medical applications.

Published
2011
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10. Targeted next generation sequencing for newborn screening of Menkes disease

Author

Stephen G. Kaler, Evan Mauceli, Ling Yi, Arindam Bhattacharjee, Richard B. Parad, and Tanya D. Sokolsky

Subjects
Newborn screening, medicine.medical_specialty, ATP7A, Population, Computational biology, DNA sequencing, Endocrinology, Dried blood spots, Molecular genetics, Genetics, Medicine, Missense mutation, Copy-number variation, education, Molecular Biology, lcsh:QH301-705.5, education.field_of_study, lcsh:R5-920, business.industry, food and beverages, Menkes disease, medicine.disease, lcsh:Biology (General), business, lcsh:Medicine (General), Targeted next generation sequencing, Research Paper
Abstract

Purpose Population-based newborn screening (NBS) allows early detection and treatment of inherited disorders. For certain medically-actionable conditions, however, NBS is limited by the absence of reliable biochemical signatures amenable to detection by current platforms. We sought to assess the analytic validity of an ATP7A targeted next generation DNA sequencing assay as a potential newborn screen for one such disorder, Menkes disease. Methods Dried blood spots from control or Menkes disease subjects (n = 22) were blindly analyzed for pathogenic variants in the copper transport gene, ATP7A. The analytical method was optimized to minimize cost and provide rapid turnaround time. Results The algorithm correctly identified pathogenic ATP7A variants, including missense, nonsense, small insertions/deletions, and large copy number variants, in 21/22 (95.5%) of subjects, one of whom had inconclusive diagnostic sequencing previously. For one false negative that also had not been detected by commercial molecular laboratories, we identified a deep intronic variant that impaired ATP7A mRNA splicing. Conclusions Our results support proof-of-concept that primary DNA-based NBS would accurately detect Menkes disease, a disorder that fulfills Wilson and Jungner screening criteria and for which biochemical NBS is unavailable. Targeted next generation sequencing for NBS would enable improved Menkes disease clinical outcomes, establish a platform for early identification of other unscreened disorders, and complement current NBS by providing immediate data for molecular confirmation of numerous biochemically screened conditions.

Published
2020

11. The African coelacanth genome provides insights into tetrapod evolution

Author

Mariko Forconi, Tereza Manousaki, Peter F. Stadler, Anna Maria Fausto, Simon D. M. White, Shigehiro Kuraku, Sumir Panji, Marcia Lara, Andreas Gnirke, Hervé Philippe, Shaohua Fan, Axel Meyer, Jean Nicolas Volff, Tsutomu Miyake, Sante Gnerre, Thorsten Burmester, Anne Nitsche, Igor Schneider, John J. Stegeman, Alison P. Lee, Kerstin Lindblad-Toh, Peter van Heusden, Chris T. Amemiya, Michael S. Campbell, Ettore Olmo, Vydianathan Ravi, Jason Turner-Maier, Denis Baurain, Gary W. Litman, Federica Di Palma, Nicolas Rohner, Manfred Schartl, Giuseppe Scapigliati, Oleg Simakov, Aaron M. Berlin, Barbara Picone, Ingo Braasch, Byrappa Venkatesh, David R. Nelson, Wilfried Haerty, Diana Tabbaa, M. Gail Mueller, Francesco Buonocore, Eric S. Lander, Gianluca De Moro, Uljana Hesse, Chris P. Ponting, Nathalie Feiner, Junaid Gamieldien, Clifford J. Tabin, Gregory L. Blatch, Tatsuya Ota, Steve Hoffmann, Maria Assunta Biscotti, John H. Postlethwait, Chris L. Organ, Jessica Alföldi, Lin Fan, Mark Robinson, Stephen M. J. Searle, Louise Williams, Mark E. Hahn, Sonja J. Prohaska, Jared V. Goldstone, Dariusz Przybylski, Iain MacCallum, Rosemary A. Dorrington, Joshua Z. Levin, Tatjana Sauka-Spengler, Kenta Sumiyama, Nil Ratan Saha, Henner Brinkmann, Jeremy Johnson, John P. Cannon, Filipe J. Ribeiro, Marco Gerdol, David B. Jaffe, Adriana Canapa, Hakim Tafer, Marco Barucca, Mark Yandell, Evan Mauceli, Alan Christoffels, Sibel I. Karchner, Adrienne L. Edkins, J. Joshua Smith, Bronwen Aken, Neil H. Shubin, Ted Sharpe, Domitille Chalopin, Alberto Pallavicini, Molecular Genetics Program, Benaroya Research Institute, Department of Biology, Northern Arizona University [Flagstaff], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Partenaires INRAE, Université de Montréal (UdeM), Institute of Neuroscience, University of Oregon [Eugene], University of Konstanz, Instituto de Ciências Biológicas, Federal University of Para - Universidade Federal do Para [Belem - Brésil], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Utah State University (USU), Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Rhodes University, Grahamstown, Department of Life Sciences, Università degli studi di Trieste, Wellcome Trust Sanger Institute, Università Politecnica delle Marche [Ancona] (UNIVPM), Université de Liège, Victoria University [Melbourne], Department for Innovation in Biological, Agro-Food and Forest Systems, Tuscia University, University of Hamburg, Eccles Institute of Human Genetics, University of Utah, University of South Florida [Tampa] (USF), South African National Bioinformatics Institute (SANBI), University of the Western Cape, International Max Planck Research School for Organismal Biology (IMPRS), Max Planck Institute for Ornithology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft-University of Konstanz, Biology Department (WHOI), Woods Hole Oceanographic Institution (WHOI), University of Oxford [Oxford], Leipzig University, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA, Keio University, All Children’s Hospital, University of Tennessee, Bioinformatics Group, Department of Computer Science, Universität Leipzig [Leipzig], Graduate University for Advanced Studies, Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673, Singapore, European Molecular Biology Laboratory (EMBL), National Institute of Genetics (NIG), University of Chicago, Department Physiological Chemistry, Biocenter, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), South African National Department of Science and Technology, National Human Genome Research Institute (NHGRI), European Science Foundation, Amemiya, Chris T., Alföldi, Jessica, Meyer, Axel, Lindblad-Toh, Kerstin, Federal University of Para - Universidade Federal do Pará - UFPA [Belém, Brazil] (UFPA), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Trieste = University of Trieste, Università degli studi della Tuscia [Viterbo], University of the Western Cape (UWC), University of Oxford, Universität Leipzig, Julius-Maximilians-Universität Würzburg (JMU), Chris T., Amemiya, Jessica, Alföldi, Alison P., Lee, Shaohua, Fan, Hervé, Philippe, Iain, Maccallum, Ingo, Braasch, Tereza, Manousaki, Igor, Schneider, Nicolas, Rohner, Chris, Organ, Domitille, Chalopin, Jeramiah J., Smith, Mark, Robinson, Rosemary A., Dorrington, Gerdol, Marco, Bronwen, Aken, Maria Assunta, Biscotti, Marco, Barucca, Denis, Baurain, Aaron M., Berlin, Gregory L., Blatch, Francesco, Buonocore, Thorsten, Burmester, Michael S., Campbell, Adriana, Canapa, John P., Cannon, Alan, Christoffel, DE MORO, Gianluca, Adrienne L., Edkin, Lin, Fan, Anna Maria, Fausto, Nathalie, Feiner, Mariko, Forconi, Junaid, Gamieldien, Sante, Gnerre, Andreas, Gnirke, Jared V., Goldstone, Wilfried, Haerty, Mark E., Hahn, Uljana, Hesse, Steve, Hoffmann, Jeremy, Johnson, Sibel I., Karchner, Shigehiro, Kuraku, Marcia, Lara, Joshua Z., Levin, Gary W., Litman, Evan, Mauceli, Tsutomu, Miyake, M., Gail Mueller, David R., Nelson, Anne, Nitsche, Ettore, Olmo, Tatsuya, Ota, Pallavicini, Alberto, Sumir, Panji, Barbara, Picone, Chris P., Ponting, Sonja J., Prohaska, Dariusz, Przybylski, Nil Ratan, Saha, Vydianathan, Ravi, Filipe J., Ribeiro, Tatjana Sauka, Spengler, Giuseppe, Scapigliati, Stephen M. J., Searle, Ted, Sharpe, Oleg, Simakov, Peter F., Stadler, John J., Stegeman, Kenta, Sumiyama, Diana, Tabbaa, Hakim, Tafer, Jason Turner, Maier, Peter van, Heusden, Simon, White, Louise, William, Mark, Yandell, Henner, Brinkmann, Jean Nicolas, Volff, Clifford J., Tabin, Neil, Shubin, Manfred, Schartl, David B., Jaffe, John H., Postlethwait, Byrappa, Venkatesh, Federica Di, Palma, Eric S., Lander, Axel, Meyer, and Kerstin Lindblad, Toh

Subjects
0106 biological sciences, terrestrial environment, adaptation, ancestry, brain, excretion, finfish, gene expression, genome, immunity, olfaction, phylogenetics, protein, terrestrial environment, tetrapod, [SDV]Life Sciences [q-bio], LATIMERIA-MENADOENSIS, adaptation, Chick Embryo, MITOCHONDRIAL GENOME, LIVING FOSSIL, SEQUENCE, GENES, MODEL, TRANSCRIPTION, CHROMOSOMES, RETENTION, CHALUMNAE, 01 natural sciences, Genome, Animals, Genetically Modified, Mice, poisson, Coelacanth, Conserved Sequence, Phylogeny, Lungfish, 0303 health sciences, Multidisciplinary, biology, Latimeria, Fishes, Genes, Homeobox, Vertebrate, Genomics, Biological Evolution, phylogenetics, Enhancer Elements, Genetic, évolution du génome, Vertebrates, excretion, Comperative genomics, Living fossil, olfaction, Genome evolution, finfish, brain, Molecular Sequence Data, tetrapod, 010603 evolutionary biology, Article, Evolution, Molecular, 03 medical and health sciences, ddc:570, biology.animal, Animals, [INFO]Computer Science [cs], 14. Life underwater, 030304 developmental biology, Comparative genomics, ancestry, génome, Extremities, Molecular Sequence Annotation, Sequence Analysis, DNA, biology.organism_classification, immunity, body regions, Immunoglobulin M, Evolutionary biology, gene expression, protein, Sequence Alignment
Abstract

Acquisition and storage of Latimeria chalumnae samples was supported by grants from the African Coelacanth Ecosystem Programme of the South African National Department of Science and Technology. Generation of the Latimeria chalumnae and Protopterus annectens sequences by the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University was supported by grants from the National Human Genome Research Institute (NHGRI). K.L.T. is the recipient of a EURYI award from the European Science Foundation. We would also like to thank the Genomics Sequencing Platform of the Broad Institute for sequencing the L. chalumnae genome and L. chalumnae and P. annectens transcriptomes, S. Ahamada, R. Stobbs and the Association pour le Protection de Gombesa (APG) for their help in obtaining coelacanth samples, Y. Zhao for the use of data from Rana chensinensis, and L. Gaffney, C. Hamilton and J. Westlund for assistance with figure preparation. 10; International audience; The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.

Published
2013
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12. Genome sequence of Aedes aegypti, a major arbovirus vector

Author

Sergio Verjovski-Almeida, James E. Galagan, Ryan C. Kennedy, Zhiyong Xi, Jason R. Miller, Eric Eisenstadt, Kyanne R. Reidenbach, Robert V. Bruggner, Yu-Hui Rogers, Hadi Quesneville, Doreen Werner, Owen White, Alexander S. Raikhel, Mario Stanke, J. Spencer Johnston, Diane D. Lovin, Evgenia V. Kriventseva, Ian T. Paulsen, Kathryn S. Campbell, Norman H. Lee, Ewan Birney, Karyn Megy, Hean Koo, David Kulp, Shelby L. Bidwell, Jingsong Zhu, Philip Montgomery, Paolo Amedeo, Yongmei Zhao, Chinnappa D. Kodira, Javier Costas, Michael C. Schatz, Steven P. Sinkins, Claire M. Fraser-Liggett, Martin Shumway, Kurt LaButti, Akio Mori, Brendan J. Loftus, Manfred Grabherr, Eric O. Stinson, Frank H. Collins, Zhijian Jake Tu, Monique R. Coy, Matt Crawford, Janice P. Vanzee, William M. Gelbart, Joshua Orvis, Peter Arensburger, Chunhong Mao, Evgeny M. Zdobnov, Saul A. Kravitz, Suely Lopes Gomes, David DeCaprio, David G. Hogenkamp, Daniel Lawson, Dennis L. Knudson, David W. Severson, George Dimopoulos, Marcelo B. Soares, Sinéad B. O'Leary, Peter W. Atkinson, David M. Jaffe, Becky deBruyn, Martin Hammond, Ana L. T. O. Nascimento, Jim Biedler, Stefan Wyder, Jose M. C. Tubio, Bruce W. Birren, Catherine A. Hill, Chad Nusbaum, Eduardo Lee, Song Li, Susan E. Brown, Jennifer R. Wortman, James R. Hogan, Hamza El-Dorry, Qi Zhao, Linda Hannick, Carlos Frederico Martins Menck, Vishvanath Nene, Jonathan Crabtree, Steven L. Salzberg, Michael H. Holmes, Maria de Fatima Bonaldo, Quinghu Ren, Mihaela Pertea, Charles Roth, Evan Mauceli, Karin Eiglmeier, Horacio Naveira, Brian J. Haas, Qiandong Zeng, Neil F. Lobo, Jennifer R. Schneider, The Institute for Genomic Research, The Institute for Genomic Research, Rockville, European Bioinformatics Institute [Hinxton] ( EMBL-EBI ), European Molecular Biology Laboratory [Hinxton], Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Broad Institute of MIT and Harvard, Virginia Polytechnic Institute and State University [Blacksburg], University College Dublin [Dublin] ( UCD ), Bloomberg School of Public Health, Johns Hopkins University ( JHU ) -Bloomberg School of Public Health, University of Geneva Medical School, Swiss Institute of Bioinformatics-University of Geneva Medical School, University of Notre Dame ( UND ), Harvard University [Cambridge], College of Agricultural Sciences Colorado State University, Colorado State University [Fort Collins] ( CSU ) -College of Agricultural Sciences, Northwestern University [Evanston], University of California [Riverside] ( UCR ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), University of Oxford [Oxford], Purdue University [West Lafayette], Centro Nacional de Genotipado Fundación Pública Galega de Medicina Xenómica Hospital Clínico Universitario de Santiago, Centro Nacional de Genotipado-Fundación Pública Galega de Medicina Xenómica-Hospital Clínico Universitario de Santiago, Institut Pasteur [Paris], Universidade de Sao Paulo Instituto de Quimica, Universidade de São Paulo ( USP ) -Instituto de Quimica, Texas A&M University [College Station], Joint Technology Center, University of Massachusetts [Amherst] ( UMass Amherst ), Universidade de Sao Paulo, Institute of Biomedical Sciences, Universidade de São Paulo ( USP ) -Institute of Biomedical Sciences, Instituto Butantan [São Paulo], Universidade da Coruña, University of Maryland [College Park], Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University of California [Santa Cruz] ( UCSC ), Complexo Hospitalario Universitario de Santiago, Universität Göttingen, Georg-August-Universität Göttingen, George Washington University Medical Center, George Washington University ( GW ), The Institute for Genomic Research (TIGR), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University College Dublin [Dublin] (UCD), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL)-University of Geneva Medical School, University of Notre Dame [Indiana] (UND), Colorado State University [Fort Collins] (CSU)-College of Agricultural Sciences, University of California [Riverside] (UCR), University of California, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), Universidade de São Paulo (USP)-Instituto de Quimica, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Universidade de São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP), University of Maryland System, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of California [Santa Cruz] (UCSC), Georg-August-University [Göttingen], The George Washington University (GW), George Washington University (GW), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL)-University of Geneva Medical School, Harvard University, University of California [Riverside] (UC Riverside), University of California (UC), University of Oxford, Institut Pasteur [Paris] (IP), Universidade de São Paulo = University of São Paulo (USP)-Instituto de Quimica, Universidade de São Paulo = University of São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo = University of São Paulo (USP), University of California [Santa Cruz] (UC Santa Cruz), Georg-August-University = Georg-August-Universität Göttingen, Zdobnov, Evgeny, and Wyder, Stefan

Subjects
0106 biological sciences, Male, Transcription, Genetic, Genome, Insect, transposons, receptors, Genes, Insect, Aedes/ genetics/metabolism, MESH: Genes, Insect, Yellow Fever/prevention & control/transmission, MESH: Base Sequence, 01 natural sciences, Dengue/prevention & control/transmission, MESH: Protein Structure, Tertiary, MESH: Arboviruses, MESH : Insect Vectors, MESH: Insect Proteins, MESH : Anopheles gambiae, MESH: Animals, MESH : Arboviruses, insects, MESH: Yellow Fever, superfamily, ddc:616, 0303 health sciences, Anopheles, MESH : Genes, Insect, 3. Good health, yellow-fever mosquito, anopheles-gambiae, drosophila-melanogaster, expression, evolution, organization, Drosophila melanogaster, MESH: DNA Transposable Elements, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Multigene Family, Public Health, MESH : Protein Structure, Tertiary, MESH: Sex Characteristics, Molecular Sequence Data, MESH : Multigene Family, MESH: Sex Determination (Genetics), MESH : Sex Determination (Genetics), Arbovirus, Article, 03 medical and health sciences, Species Specificity, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Anopheles gambiae, Yellow Fever, MESH: Species Specificity, Humans, MESH: Humans, MESH: Molecular Sequence Data, fungi, MESH : Humans, MESH : Sex Characteristics, Membrane Transport Proteins, Sex Determination Processes, medicine.disease, Insect Vectors, Protein Structure, Tertiary, Sex Determination (Genetics), MESH: Multigene Family, MESH: Female, MESH : Sequence Analysis, DNA, MESH: Sequence Analysis, DNA, Drosophila melanogaster/genetics, MESH : Molecular Sequence Data, Odorant binding, Insect Proteins/genetics, Anopheles gambiae, MESH: Dengue, Genome, MESH: Membrane Transport Proteins, Dengue, MESH : Membrane Transport Proteins, Aedes, Insect Vectors/ genetics/metabolism, MESH : Drosophila melanogaster, MESH : Female, Membrane Transport Proteins/genetics, Genetics, MESH : Insect Proteins, Sex Characteristics, Multidisciplinary, MESH: Synteny, MESH: Aedes, MESH : Genome, Insect, MESH : DNA Transposable Elements, Insect Proteins, Female, Orthologous Gene, MESH : Male, MESH : Dengue, Aedes aegypti, MESH: Insect Vectors, Biology, 010603 evolutionary biology, Synteny, MESH: Drosophila melanogaster, Protein Structure, Tertiary/genetics, MESH : Yellow Fever, parasitic diseases, medicine, MESH : Species Specificity, Animals, 030304 developmental biology, MESH : Aedes, Base Sequence, MESH: Genome, Insect, MESH: Transcription, Genetic, MESH : Synteny, MESH : Transcription, Genetic, Sequence Analysis, DNA, biology.organism_classification, MESH: Male, DNA Transposable Elements, MESH : Base Sequence, MESH : Animals, Arboviruses, Anopheles gambiae/genetics/metabolism
Abstract

We present a draft sequence of the genome of Aedes aegypti , the primary vector for yellow fever and dengue fever, which at ∼1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae . Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of ∼4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster . Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of ∼2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.

Published
2016
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13. The genome of the green anole lizard and a comparative analysis with birds and mammals

Author

Andreas Heger, John K. Colbourne, Daniel E. Janes, Federica Di Palma, Todd A. Castoe, Chris P. Ponting, Stéphane Boissinot, Maxim Koriabine, Craig B. Lowe, Kevin de Queiroz, Jeremy A. Johnson, Kerstin Lindblad-Toh, Marcia Lara, Jason Turner-Maier, Jonathan B. Losos, Richard E. Glor, Thomas J. Sanger, Evan Mauceli, David I. Heiman, Juli Wade, Christina L. Williams, Pieter J. de Jong, Boudewijn F.H. Ten Hallers, David D. Pollock, Steven Poe, Zachary Smith, Sarah Young, Christopher J. Schneider, Amonida Zadissa, Manfred Grabherr, Jessica Alföldi, Jeremy Smith, Christopher W. Botka, David Haussler, Matthew K. Fujita, Ross Swofford, Peter A. Novick, Andrew M. Shedlock, Jacob D. Jaffe, Chris L. Organ, Scott V. Edwards, Eric S. Lander, Sally E. Peach, Matthew Breen, Travis C. Glenn, David A. Ray, Steve Searle, Pamela Russell, Lesheng Kong, Ricardo Moreno, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.

Subjects
0106 biological sciences, X Chromosome, Molecular Sequence Data, Zoology, Genomics, 010603 evolutionary biology, 01 natural sciences, Genome, Synteny, Article, Birds, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, biology.animal, Animals, Humans, Herpetology, Phylogeny, 030304 developmental biology, Comparative genomics, Mammals, 0303 health sciences, Multidisciplinary, biology, Lizard, Dactyloidae, Lizards, biology.organism_classification, GC Rich Sequence, Evolutionary biology, Chickens
Abstract

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse—more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations., National Science Foundation (U.S.) (NSF grant DEB-0920892), National Science Foundation (U.S.) (NSF grant DEB-0844624), National Human Genome Research Institute (U.S.)

Published
2016
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14. Orthogonal NGS for High Throughput Clinical Diagnostics

Author

Tristen Ross, Anastasia Nikiforov, Rebecca Batorsky, Evan Mauceli, Marcia M. Nizzari, Niru Chennagiri, Alexander Frieden, Patrice M. Milos, Timothy W. Yu, Eric J. White, Daniel S. Lieber, Lovelace J. Luquette, Nichole Napolitano, Va Lip, John F. Thompson, Sherry Hansen, David H. Margulies, and Edgardo Lopez

Subjects
0301 basic medicine, computer.software_genre, Polymerase Chain Reaction, Sensitivity and Specificity, DNA sequencing, Article, law.invention, 03 medical and health sciences, Target capture, law, Medicine, Molecular diagnostic techniques, Humans, Exome, Polymerase chain reaction, Multidisciplinary, business.industry, High-Throughput Nucleotide Sequencing, Ion semiconductor sequencing, Sequence Analysis, DNA, 030104 developmental biology, Molecular Diagnostic Techniques, Data mining, business, computer
Abstract

Next generation sequencing is a transformative technology for discovering and diagnosing genetic disorders. However, high-throughput sequencing remains error-prone, necessitating variant confirmation in order to meet the exacting demands of clinical diagnostic sequencing. To address this, we devised an orthogonal, dual platform approach employing complementary target capture and sequencing chemistries to improve speed and accuracy of variant calls at a genomic scale. We combined DNA selection by bait-based hybridization followed by Illumina NextSeq reversible terminator sequencing with DNA selection by amplification followed by Ion Proton semiconductor sequencing. This approach yields genomic scale orthogonal confirmation of ~95% of exome variants. Overall variant sensitivity improves as each method covers thousands of coding exons missed by the other. We conclude that orthogonal NGS offers improvements in variant calling sensitivity when two platforms are used, better specificity for variants identified on both platforms, and greatly reduces the time and expense of Sanger follow-up, thus enabling physicians to act on genomic results more quickly.

Published
2016

15. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher

Author

Kerstin Lindblad-Toh, Sunshine Lahmers, Stephen N. White, Kathryn M. Meurs, Mark A. Oyama, Evan Mauceli, and Bruce W. Keene

Subjects
Cardiomyopathy, Dilated, medicine.medical_specialty, RNA Splicing, Blotting, Western, PDK4, Genome-wide association study, Biology, Real-Time Polymerase Chain Reaction, Lipofuscin, Dogs, Internal medicine, Genetics, medicine, Animals, Dog Diseases, Genetics (clinical), Splice site mutation, Myocardium, Megamitochondria, Chromosome Mapping, Dilated cardiomyopathy, medicine.disease, Doberman Pinscher, Microscopy, Electron, Endocrinology, Heart failure, Mutation, Protein Kinases, Genome-Wide Association Study
Abstract

Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p < 0.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.

Published
2012
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16. A high-resolution map of human evolutionary constraint using 29 mammals

Author

Kerstin, Lindblad-Toh, Manuel, Garber, Or, Zuk, Michael F, Lin, Brian J, Parker, Stefan, Washietl, Pouya, Kheradpour, Jason, Ernst, Gregory, Jordan, Evan, Mauceli, Lucas D, Ward, Craig B, Lowe, Alisha K, Holloway, Michele, Clamp, Sante, Gnerre, Jessica, Alföldi, Kathryn, Beal, Jean, Chang, Hiram, Clawson, James, Cuff, Federica, Di Palma, Stephen, Fitzgerald, Paul, Flicek, Mitchell, Guttman, Melissa J, Hubisz, David B, Jaffe, Irwin, Jungreis, W James, Kent, Dennis, Kostka, Marcia, Lara, Andre L, Martins, Tim, Massingham, Ida, Moltke, Brian J, Raney, Matthew D, Rasmussen, Jim, Robinson, Alexander, Stark, Albert J, Vilella, Jiayu, Wen, Xiaohui, Xie, Michael C, Zody, Jen, Baldwin, Toby, Bloom, Chee Whye, Chin, Dave, Heiman, Robert, Nicol, Chad, Nusbaum, Sarah, Young, Jane, Wilkinson, Kim C, Worley, Christie L, Kovar, Donna M, Muzny, Richard A, Gibbs, Andrew, Cree, Huyen H, Dihn, Gerald, Fowler, Shalili, Jhangiani, Vandita, Joshi, Sandra, Lee, Lora R, Lewis, Lynne V, Nazareth, Geoffrey, Okwuonu, Jireh, Santibanez, Wesley C, Warren, Elaine R, Mardis, George M, Weinstock, Richard K, Wilson, Kim, Delehaunty, David, Dooling, Catrina, Fronik, Lucinda, Fulton, Bob, Fulton, Tina, Graves, Patrick, Minx, Erica, Sodergren, Ewan, Birney, Elliott H, Margulies, Javier, Herrero, Eric D, Green, David, Haussler, Adam, Siepel, Nick, Goldman, Katherine S, Pollard, Jakob S, Pedersen, Eric S, Lander, Manolis, Kellis, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Mag Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Ward, Lucas D., Jungreis, Irwin, and Rasmussen, Matthew D.

Subjects
Genome evolution, Genomics, Computational biology, Biology, Human accelerated regions, Genome, Article, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Coding region, Disease, Selection, Genetic, Gene, Phylogeny, 030304 developmental biology, Mammals, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, Molecular Sequence Annotation, Exons, Sequence Analysis, DNA, 3. Good health, Health, RNA, Human genome, Mobile genetic elements, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

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., National Human Genome Research Institute (U.S.), National Institute of General Medical Sciences (U.S.) (Grant number GM82901), National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968), National Science Foundation (U.S.). Career (0644282), National Institutes of Health (U.S.) (R01-HG004037), Alfred P. Sloan Foundation., Austrian Science Fund. Erwin Schrodinger Fellowship

Published
2011
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17. Full-length transcriptome assembly from RNA-Seq data without a reference genome

Author

Kerstin Lindblad-Toh, Bruce W. Birren, Moran Yassour, Andreas Gnirke, Evan Mauceli, Aviv Regev, Chad Nusbaum, Raktima Raychowdhury, Nir Hacohen, Manfred Grabherr, Brian J. Haas, Joshua Z. Levin, Nicholas Rhind, Nir Friedman, Qiandong Zeng, Ido Amit, Xian Adiconis, Federica Di Palma, Lin Fan, Zehua Chen, and Dawn Thompson

Subjects
0106 biological sciences, Molecular Sequence Data, De novo transcriptome assembly, Biomedical Engineering, Sequence assembly, UniGene, Bioengineering, RNA-Seq, Computational biology, Biology, 01 natural sciences, Applied Microbiology and Biotechnology, Genome, Article, Transcriptome, 03 medical and health sciences, Reference Values, 030304 developmental biology, Genetics, 0303 health sciences, Base Sequence, Assembly software, Sequence Analysis, RNA, Gene Expression Profiling, RNA, Molecular Medicine, Algorithms, 010606 plant biology & botany, Biotechnology, Reference genome
Abstract

Massively parallel sequencing of cDNA has enabled deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here we present the Trinity method for de novo assembly of full-length transcripts and evaluate it on samples from fission yeast, mouse and whitefly, whose reference genome is not yet available. By efficiently constructing and analyzing sets of de Bruijn graphs, Trinity fully reconstructs a large fraction of transcripts, including alternatively spliced isoforms and transcripts from recently duplicated genes. Compared with other de novo transcriptome assemblers, Trinity recovers more full-length transcripts across a broad range of expression levels, with a sensitivity similar to methods that rely on genome alignments. Our approach provides a unified solution for transcriptome reconstruction in any sample, especially in the absence of a reference genome.

Published
2011
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18. Abstract 3416: Customizable gene panels overcome challenges associated with targeted resequencing

Author

Charles Elfe, Cynthia L. Hendrickson, Theodore B. Davis, Amy B. Emerman, Fiona A. Stewart, Kruti M. Patel, Eileen T. Dimalanta, Salvatore Russello, Sarah K. Bowman, Scott M. Adams, Andrew Barry, and Evan Mauceli

Subjects
Cancer Research, Oncology, Computer science, Gene panel, Computational biology
Abstract

Efficient utilization of targeted gene panels for clinical research is challenged by the wide variation in gene constituents specific to a given study. While focused gene panels efficiently provide the necessary depth of coverage for low-frequency variant detection, the high costs and technical requirements associated with panel design present obstacles to delivering assays that are focused on the specific targets of interest. The NEBNext DirectTM technology utilizes a novel approach to selectively enrich nucleic acid targets ranging from a single gene to several hundred genes, without sacrificing specificity. The approach rapidly hybridizes both strands of genomic DNA with biotinylated probes prior to streptavidin bead capture, enzymatic removal of off-target sequences, and conversion of captured molecules into sequence-ready libraries. This results in an exceptionally uniform coverage profile for a given target. Unlike alternative hybridization methods, this 1-day workflow does not necessitate upfront library preparation, and instead converts the captured molecules into libraries compatible with Illumina sequencing. We have designed and optimized baits specific to the full exonic content of >800 genes associated with cancer as well as a variety of other disease areas. These are designed, balanced, and pooled on a per gene basis, and can be readily combined into customized panels, allowing rapid turnaround of specific custom gene subsets. Here, we present the ability to rapidly deploy custom gene panels across a variety of panel sizes and content, while maintaining high specificity, uniformity of coverage across target content, and sensitivity to detect nucleic acid variants from clinically relevant samples. Citation Format: Andrew John Barry, Kruti M. Patel, Amy B. Emerman, Scott Adams, Sarah Bowman, Evan Mauceli, Fiona Stewart, Eileen Dimalanta, Salvatore Russello, Charles Elfe, Theodore Davis, Cynthia Hendrickson. Customizable gene panels overcome challenges associated with targeted resequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3416.

Published
2018
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19. Abstract 1421: Flexible tools for the development and performance verification of customized target enrichment panels

Author

Bharathi Anekella, Cynthia L. Hendrickson, Kruti M. Patel, Evan Mauceli, Andrew Barry, Catherine Huang, and Scott V. Adams

Subjects
Flexibility (engineering), Cancer Research, Identification (information), Oncology, Computer science, Relevance (information retrieval), Software verification and validation, Computational biology, Indel, Precision medicine, Target enrichment, DNA sequencing
Abstract

Implementation of next generation sequencing for variant identification and discovery presents difficulties both in the selection of genomic loci for inclusion in a panel, as well as the ability to effectively verify the performance of the assay based on the content selected. Balancing the relevance of genomic content with the practical hurdles of developing specific assays necessitates new approaches for the application of next generation sequencing toward precision medicine that are aimed at providing the flexibility of content to efficiently provide data capable of testing fundamental biological hypotheses. NEBNext Direct Custom Ready Panels overcome these obstacles by enabling the rapid development and deployment of customized target enrichment panels. This offering allows researchers to select from a large library of genes for which baits have been developed and optimized to produce sequencing data with extremely high specificity and coverage uniformity. These panels are effective in targeting a wide range of content, from highly focused, single-gene panels, to comprehensive panels comprised of hundreds of genes. In a similar approach for the verification and validation of new panels, SeraCare has developed the VariantFlex™ system, which is comprised of a broad library of mutations to develop custom controls and reference materials for NGS-based assays. These biosynthetic constructs contain variants such as SNVs, indel, frameshift and fusion variants that can be used to formulate controls across a range of variant allele frequencies, providing the necessary content and flexibility to verify assay performance. Here we will present data demonstrating the combined utility of these offerings to assess target enrichment panel performance with a range of genomic content, panel sizes and variant allele frequencies. Citation Format: Cynthia L. Hendrickson, Evan Mauceli, Andrew Barry, Kruti Patel, Catherine Huang, Scott Adams, Bharathi Anekella. Flexible tools for the development and performance verification of customized target enrichment panels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1421.

Published
2018
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20. Abstract 1422: NEBNext Direct® Custom Ready myeloid genes for NGS target enrichment

Author

Sarah K. Bowman, Cynthia L. Hendrickson, Scott M. Adams, Theodore B. Davis, Andrew Barry, Charles Elfe, Evan Mauceli, Amy B. Emerman, and Kruti M. Patel

Subjects
Cancer Research, Myeloid, medicine.anatomical_structure, Oncology, medicine, Computational biology, Biology, Target enrichment, Gene
Abstract

Comprehensive genetic evaluation of patients with blood cancer can be imperative for identifying and classifying myeloid malignancies in a patient. Since liquid tumors comprise of highly variable percentages of normal cells or multiple tumor clones, this type of screening is critical for early stage disease patients where a cytogenetic profile informs diagnosis or disease stratification, prognosis, and treatment options. For patients with late-stage disease, genetic testing can assist in choosing options for alternative treatments, including targeted therapies. Thus, next generation sequencing technologies are needed that can provide the sensitivity and specificity to identify these genetic complexities. Here we introduce a selection of over 50 genes from the NEBNext Direct® Custom Ready gene catalog that are known to be involved in myeloid malignancies. The NEBNext Direct® technology uses a novel approach to selectively enrich nucleic acid targets, and rapid customized panels can be generated by combining one to several hundred genes from the Custom Ready catalog. Unlike alternative hybridization methods, NEBNext Direct® does not require upfront library preparation. The approach rapidly hybridizes both strands of genomic DNA to biotinylated baits, captures the targets on streptavidin beads, enzymatically removes off-target sequence, and directly converts captured molecules into Illumina-compatible sequencing libraries in a single day protocol. A 12-base unique molecular identifier (UMI) tags each individual molecule prior to the final PCR amplification to enable identification of PCR duplicates, and an 8-base barcode is added to each library during PCR for high-throughput pooling. With 100ng of DNA input the panel provides highly uniform coverage and approximately 95% of sequence reads map to the targeted myeloid genes. The NEBNext Direct® Custom Ready myeloid genes demonstrate a high-throughput and cost-effective approach for the rapid and sensitive analysis of exon coding regions (~200kb) for over 50 oncogenic genes important in the pathogenesis of these types of blood disorders. These gene mutations are powerful prognostic markers that can be used as a guide for effective patient management. Citation Format: Scott M. Adams, Kruti M. Patel, Amy B. Emerman, Sarah K. Bowman, Charles D. Elfe, Evan Mauceli, Andrew Barry, Theodore Davis, Cynthia L. Hendrickson. NEBNext Direct® Custom Ready myeloid genes for NGS target enrichment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1422.

Published
2018
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21. Genome-wide association identifies a deletion in the 3′ untranslated region of Striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy

Author

Kerstin Lindblad-Toh, Stephen N. White, Evan Mauceli, Sunshine Lahmers, Gregory M. Acland, and Kathryn M. Meurs

Subjects
Genetics, Candidate gene, biology, Desmoplakin, Plakoglobin, Autosomal dominant trait, medicine.disease, Penetrance, Right ventricular cardiomyopathy, Arrhythmogenic right ventricular dysplasia, Chromosome 17 (human), biology.protein, medicine, Genetics (clinical)
Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease characterized by ventricular arrhythmias and sudden cardiac death. It is most frequently inherited as an autosomal dominant trait with incomplete and age-related penetrance and variable clinical expression. The human disease is most commonly associated with a causative mutation in one of several genes encoding desmosomal proteins. We have previously described a spontaneous canine model of ARVC in the boxer dog. We phenotyped adult boxer dogs for ARVC by performing physical examination, echocardiogram and ambulatory electrocardiogram. Genome-wide association using the canine 50k SNP array identified several regions of association, of which the strongest resided on chromosome 17. Fine mapping and direct DNA sequencing identified an 8-bp deletion in the 3' untranslated region (UTR) of the Striatin gene on chromosome 17 in association with ARVC in the boxer dog. Evaluation of the secondary structure of the 3' UTR demonstrated that the deletion affects a stem loop structure of the mRNA and expression analysis identified a reduction in Striatin mRNA. Dogs that were homozygous for the deletion had a more severe form of disease based on a significantly higher number of ventricular premature complexes. Immunofluorescence studies localized Striatin to the intercalated disc region of the cardiac myocyte and co-localized it to three desmosomal proteins, Plakophilin-2, Plakoglobin and Desmoplakin, all involved in the pathogenesis of ARVC in human beings. We suggest that Striatin may serve as a novel candidate gene for human ARVC.

Published
2010
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22. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

Author

Frances Letendre, Vasilia Magnisalis, Helen Vassiliev, Rebecca Reyes, Maura Costello, St Christophe Acer, Pen MacDonald, Geneva Young, Katherine Thompson, Iain MacCallum, Tarjei S. Mikkelsen, Andy Vo, Eva Markiewicz, Yeshi Lokyitsang, Sharon Stavropoulos, Rachel Mittelman, Xiaohui Xie, Diallo Ferguson, James Cuff, Terence P. Speed, Catherine Stone, Tanya Mihova, Janine E. Deakin, Aaron M. Berlin, David A. Ray, David D. Pollock, Ben Kanga, Kunsang Gyaltsen, Scott Anderson, Gary Gearin, Nabil Hafez, Lisa Chuda, Marco A. Marra, David B. Jaffe, Leonid Boguslavskiy, Asha Kamat, Jonathan Butler, Alicia Franke, Lynne Aftuck, Sheridon Channer, Rosie Levine, Kerstin Lindblad-Toh, Birhane Hagos, Imane Bourzgui, Monika D. Huard, Tamrat Negash, Jamal Abdulkadir, Tsering Wangchuk, Georgius De Haan, Sheila Fisher, Justin Abreu, Abderrahim Farina, Kebede Maru, M. Erii Husby, Peter Kisner, Kunsang Dorjee, Jacob L. Glass, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Christina R. Gearin, Otero L. Oyono, Atanas Mihalev, Yama Thoulutsang, Katie D'Aco, Choe Norbu, Christopher Strader, Edda Koina, Allen Alexander, Barry O'Neill, William Brockman, Wanjun Gu, Richard Elong, Keenan Ross, Shailendra Yadav, Alan Dupes, Seva Kashin, James Meldrim, Dmitry Khazanovich, Passang Dorje, Adal Abebe, April Cook, Matthew Breen, Randy L. Jirtle, Shangtao Liu, Jean L. Chang, Patrick Cahill, Claire M. Wade, Chee Whye Chin, Dennis C. Friedrich, Tina Goode, Cecil Rise, Robert D. Nicholls, Peter Rogov, Adam Brown, Oana Mihai, Sujaa Raghuraman, Adam Wilson, Marcia Lara, Chelsea D. Foley, Susan Faro, Sampath Settipalli, Thu Nguyen, Matthew Wakefield, Xiaohong Liu, Anna Montmayeur, Jerzy Jurka, Ngawang Sherpa, Riza M. Daza, Evan Mauceli, Senait Tesfaye, Sharleen Grewal, Susan McDonough, Leo Goodstadt, Manuel Garber, John M. Greally, Valentine Mlenga, Manfred Grabherr, Charles Matthews, Andrew Zimmer, Teena Mehta, Harindra Arachi, Mark A. Batzer, Rakela Lubonja, Margaret Priest, Diana Shih, Joseph Graham, Panayiotis V. Benos, Lance S. Davidow, Alex Lipovsky, Stephen M. J. Searle, Andreas Heger, Timothy A. Hore, Patrick Cooke, Leonidas Mulrain, Tsering Wangdi, Jennifer A. Marshall Graves, Sante Gnerre, Michelle L. Baker, Jacqueline E. Schein, Michael Weiand, Jessica Spaulding, Charlotte Henson, Jane Wilkinson, Terry Shea, Shannon E. Duke, William McCusker, Kerri Topham, Jerome Naylor, Lu Shi, Fritz Pierre, Claude Bonnet, Shaun Mahony, Michele Clamp, Katherine Belov, John L. VandeBerg, Nicole Stange-Thomann, Annie Lui, Radhika Das, Pema Phunkhang, Andrew J. Gentles, Elizabeth P. Ryan, Erica Anderson, Jill Falk, Bronwen Aken, Robert Nicol, Ted Sharpe, Sahal Osman, Missole Doricent, Michael Kleber, Jeannie T. Lee, Paul D. Waters, Melissa Fazzari, Jinlei Liu, Loryn Gadbois, Lisa Zembek, Daniel Bessette, Pasang Bachantsang, Adam Navidi, Caleb Webber, Tashi Bayul, Brikti Abera, Mayumi Oda, Gavin A. Huttley, Jennifer L. Hall, Chris P. Ponting, Michael Kamal, Kimberly Dooley, Mieke Citroen, Tsamla Tsamla, Ira Topping, Eric S. Lander, Edward Grandbois, Christopher Patti, Louis Meneus, Tracey Honan, Zuly E. Parra, Nga Nguyen, Todd Sparrow, Dawa Thoulutsang, Leanne Hughes, Yama Cheshatsang, Qing Yu, Niall J. Lennon, Nathaniel Novod, Christina Demaso, Anthony T. Papenfuss, Paul B. Samollow, Toby Bloom, Andrew Hollinger, Boris Boukhgalter, Talene Thomson, Zac Zwirko, Georgia Giannoukos, Michael C. Zody, Danni Zhong, Jason Blye, Stuart DeGray, Marc Azer, Robert D. Miller, Amr Abdouelleil, Brian Hurhula, Filip Rege, John Stalker, Andrew Barry, Pablo Alvarez, Norbu Dhargay, Krista Lance, Chris T. Amemiya, Jerilyn A. Walker, Jennifer R. Weidman, Peter An, Erin E. Dooley, William Lee, and Alville Collymore

Subjects
Genetics, Base Composition, Genome evolution, Genome, Multidisciplinary, Genomics, Opossums, Biology, biology.organism_classification, Polymorphism, Single Nucleotide, Synteny, Monodelphis domestica, Evolution, Molecular, X Chromosome Inactivation, Opossum, Molecular evolution, Protein Biosynthesis, DNA Transposable Elements, Animals, Humans, Gene family, Gene conversion, Conserved Sequence
Abstract

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

Published
2007
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23. A genome-wide map of diversity in Plasmodium falciparum

Author

Danny A. Milner, David DeCaprio, Daniel E. Neafsey, Manoj T. Duraisingh, James E. Galagan, S. Mboup, Eric S. Lander, Nicole Stange-Thomann, Ousmane Sarr, Evan Mauceli, Amanda K. Lukens, Sante Gnerre, Stephen F. Schaffner, Alan Derr, David B. Jaffe, Roger C. Wiegand, Dyann F. Wirth, Daouda Ndiaye, Joanne Zainoun, Pardis C. Sabeti, Bruce W. Birren, Liuda Ziaugra, Daniel L. Hartl, Robert C. Onofrio, Sarah K. Volkman, Skye G. Waggoner, Omar Ndir, and Johanna P. Daily

Subjects
Genetics, Linkage disequilibrium, Genetic diversity, Genetic variation, Population genetics, Single-nucleotide polymorphism, Plasmodium falciparum, Biology, biology.organism_classification, Genotyping, Genome
Abstract

Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite.

Published
2006
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24. DNA sequence and analysis of human chromosome 18

Author

Chad, Nusbaum, Michael C, Zody, Mark L, Borowsky, Michael, Kamal, Chinnappa D, Kodira, Todd D, Taylor, Charles A, Whittaker, Jean L, Chang, Christina A, Cuomo, Ken, Dewar, Michael G, FitzGerald, Xiaoping, Yang, Amr, Abouelleil, Nicole R, Allen, Scott, Anderson, Toby, Bloom, Boris, Bugalter, Jonathan, Butler, April, Cook, David, DeCaprio, Reinhard, Engels, Manuel, Garber, Andreas, Gnirke, Nabil, Hafez, Jennifer L, Hall, Catherine Hosage, Norman, Takehiko, Itoh, David B, Jaffe, Yoko, Kuroki, Jessica, Lehoczky, Annie, Lui, Pendexter, Macdonald, Evan, Mauceli, Tarjei S, Mikkelsen, Jerome W, Naylor, Robert, Nicol, Cindy, Nguyen, Hideki, Noguchi, Sinéad B, O'Leary, Keith, O'Neill, Bruno, Piqani, Cherylyn L, Smith, Jessica A, Talamas, Kerri, Topham, Yasushi, Totoki, Atsushi, Toyoda, Hester M, Wain, Sarah K, Young, Qiandong, Zeng, Andrew R, Zimmer, Asao, Fujiyama, Masahira, Hattori, Bruce W, Birren, Yoshiyuki, Sakaki, and Eric S, Lander

Subjects
Expressed Sequence Tags, Multidisciplinary, Genome, Human, Molecular Sequence Data, DNA, Exons, Sequence Analysis, DNA, Aneuploidy, Synteny, Introns, Genes, Animals, Humans, CpG Islands, Chromosomes, Human, Pair 18, Conserved Sequence
Abstract

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.

Published
2005

25. The genome sequence of the filamentous fungus Neurospora crassa

Author

Matthew G. Endrizzi, Li-Jun Ma, Ian T. Paulsen, Gregory O. Kothe, David B. Jaffe, David E. A. Catcheside, Edward M. Marcotte, Jonathan Butler, Giuseppe Macino, Matthew S. Sachs, David D. Perkins, Jerome Naylor, Oded Yarden, Nick O. Read, Shunguang Wang, Sarah E. Calvo, Reinhard Engels, J. Andrew Berglund, Nicole Stange-Thomann, Robert L. Metzenberg, Stephan Seiler, Scott Kroken, Seth Purcell, Dmitrij Frishman, Ulrich Schulte, Bruce W. Birren, Dayong Qui, Manolis Kamvysselis, Edward L. Braun, Gregory Jedd, Rodolfo Aramayo, Mary Anne Nelson, Sante Gnerre, Carlo Cogoni, Deborah Bell-Pedersen, Rodger B. Voelker, Chad Nusbaum, David Greenberg, Robert J. Pratt, Gertrud Mannhaupt, Bushra Rehman, Carolyn G. Rasmussen, Colin P.C. DeSouza, Michael Plamann, Weixi Li, Evan Mauceli, Daniel J. Ebbole, Katherine A. Borkovich, William Fitzhugh, Svetlana Krystofova, Peter Ianakiev, Claude P. Selitrennikoff, Stephen A. Osmani, Marc J. Orbach, Alice Roy, Jay C. Dunlap, Donald O. Natvig, Robert Barrett, Stephen Rudd, Louise Glass, James E. Galagan, Cord Bielke, Karen Foley, Alan Radford, John A. Kinsey, Michael Freitag, Chuck Staben, Lisa A. Alex, Alex Zelter, Cydney B. Nielsen, Margaret Werner-Washburne, Serge Smirnov, Timothy Elkins, Michael Kamal, Werner Mewes, Eric S. Lander, and Eric U. Selker

Subjects
Genome evolution, Genes, Fungal, Receptors, Cell Surface, Biology, Genome, Neurospora crassa, Evolution, Molecular, Multienzyme Complexes, Gene Duplication, Gene density, Calcium Signaling, Genome size, Plant Diseases, Repetitive Sequences, Nucleic Acid, Genetics, Multidisciplinary, fungi, Sequence Analysis, DNA, Genome project, DNA Methylation, biology.organism_classification, Heterotrimeric GTP-Binding Proteins, Mutagenesis, RNA, Ribosomal, Multigene Family, Schizosaccharomyces pombe, RNA Interference, Minimal genome, Diterpenes, Genome, Fungal, Signal Transduction
Abstract

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes—more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca21 signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.

Published
2003
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26. Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

Author

Jong Hyuk Kim, Lisa G. Barber, Chieko Azuma, Christina L. Williams, Sarah Fryc, Michele Koltookian, Evan Mauceli, Aaron L. Sarver, Daisuke Ito, Kristine Burgess, Cédric Howald, Tara Biagi, Rachael Thomas, Elinor K. Karlsson, Eric S. Lander, Jaime F. Modiano, Ross Swofford, Kate Megquier, Noriko Tonomura, Kerstin Lindblad-Toh, Aric M. Frantz, Anne C. Avery, Matthew Breen, Maja Louise Arendt, Jason Turner-Maier, Ingegerd Elvers, Hyun Ji Noh, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.

Subjects
Cancer Research, lcsh:QH426-470, 040301 veterinary sciences, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, 0403 veterinary science, 03 medical and health sciences, medicine, Genetics, Genetik, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Haplotype, 04 agricultural and veterinary sciences, medicine.disease, Canine Hemangiosarcoma, 3. Good health, Non-Hodgkin's lymphoma, Lymphoma, lcsh:Genetics, Hemangiosarcoma, Research Article
Abstract

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps thevesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers., Golden Retriever Foundation, Morris Animal Foundation (Grant D10CA-501), National Institutes of Health (U.S.) (P30CA077598 (MCC Core)), Land of PureGold Foundation, Inc., Uppsala University, American Kennel Club Canine Health Foundation, Inc. (Grant 422), American Kennel Club Canine Health Foundation, Inc. (Grant 615), American Kennel Club Canine Health Foundation, Inc. (Grant 2254), American Kennel Club Canine Health Foundation, Inc. (Grant 1131), American Kennel Club Canine Health Foundation, Inc. (Grant 593), American Kennel Club Canine Health Foundation, Inc. (Grant 1168), American Kennel Club Canine Health Foundation, Inc. (Grant 1169), National Institutes of Health (U.S.) (RO1CA112211), American Kennel Club Canine Health Foundation, Inc. (Grant 1147), American Kennel Club Canine Health Foundation, Inc. (Starlight Fund), National Institutes of Health (U.S.) (NIH Short-term Training Grant (T32 RR18267)), Swedish Medical Research Council, University of Minnesota, United States. Army Medical Research and Materiel Command (Training Grant (W81XWH-06-1-064)), European Research Council (ERC Young Investigator Award), European Science Foundation (European Young Investigator Award Program)

Published
2015

27. Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background

Author

Federica Di Palma, Jaime F. Modiano, Jessica Alföldi, Mara Rosenberg, Chip Stewart, Matthew Breen, Michele Koltookian, Ingegerd Elvers, Evan Mauceli, Kerstin Lindblad-Toh, Gad Getz, Jason Turner-Maier, Ross Swofford, Cheng-Zhong Zhang, Jeremy Johnson, Rameen Beroukhim, Steven E. Schumacher, and Rachael Thomas

Subjects
F-Box-WD Repeat-Containing Protein 7, Lymphoma, B-Cell, DNA Copy Number Variations, T-Lymphocytes, Ubiquitin-Protein Ligases, Telomere-Binding Proteins, Cell Cycle Proteins, Biology, Protein Serine-Threonine Kinases, medicine.disease_cause, Shelterin Complex, Germline mutation, Dogs, hemic and lymphatic diseases, Genetics, medicine, Animals, Humans, Exome, Gene, Genetics (clinical), Exome sequencing, Mutation, B-Lymphocytes, Cancer och onkologi, TNF Receptor-Associated Factor 3, F-Box Proteins, Research, Biochemistry and Molecular Biology, medicine.disease, Lymphoma, Leukemia, Disease Models, Animal, Cocker spaniel, Cancer and Oncology, Genetic Background, Sequence Alignment, Biokemi och molekylärbiologi
Abstract

Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options.

Published
2015

28. High-Throughput Gene Mapping in Caenorhabditis elegans

Author

Serafim Batzoglou, Jonathan Butler, Sante Gnerre, Jill P. Mesirov, Evan Mauceli, Bonnie Berger, Ken Stanley, Eric S. Lander, and David B. Jaffe

Subjects
Genetics, Whole genome sequencing, Contig, Shotgun sequencing, Molecular Sequence Data, Physical Chromosome Mapping, Chromosome Mapping, Computational biology, Biology, Polymorphism, Single Nucleotide, Genome, Contig Mapping, Gene Order, Methods, Animals, Phrap, Human genome, Caenorhabditis elegans, Genes, Helminth, Genetics (clinical)
Abstract

Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 ± 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.[The sequence data described in this paper have been submitted to the NCBI dbSNP data library under accession nos. 4388625–4389689 and GenBank dbSTS under accession nos. 973810–974874. The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: The C. elegans Sequencing Consortium and TheCaenorhabditis Genetics Center.]

Published
2002
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29. Whiteboard: a framework for the programmatic visualization of complex biological analyses

Author

Evan Mauceli, Manfred Grabherr, Neda Zamani, and Görel Sundström

Subjects
Statistics and Probability, Class (computer programming), Theoretical computer science, Databases, Factual, Computer science, Whiteboard, Computational Biology, Information Storage and Retrieval, Biochemistry, Computer Science Applications, Computational science, Visualization, Computational Mathematics, Computational Theory and Mathematics, Computer Graphics, Humans, Programming Languages, Molecular Biology, Software
Abstract

Summary: Whiteboard is a class library implemented in C++ that enables visualization to be tightly coupled with computation when analyzing large and complex datasets. Availability and implementation: the C++ source code, coding samples and documentation are freely available under the Lesser General Public License from http://whiteboard-class.sourceforge.net/. Contact: emauceli@parabasegenomics.com.

Published
2014

30. The fusarium graminearum genome reveals a link between localized polymorphism and pathogen specialization

Author

David R. Nelson, Hans-Werner Mewes, H. Corby Kistler, Weihong Qi, Kerry O'Donnell, John C. Kennell, Scott E. Baker, Liane R. Gale, Igor V. Tetko, Jon K. Magnuson, Gary J. Muehlbauer, Martin Münsterkötter, Martijn Rep, Karen Hilburn, Jiqiang Yao, B. Gillian Turgeon, Thérèse Ouellet, Hadi Quesneville, Li-Jun Ma, Todd J. Ward, Linda J. Harris, Gerhard Adam, Kim E. Hammond-Kosack, Sarah E. Calvo, Scott Kroken, M. Isabel G. Roncero, Kye Yong Seong, Jin-Rong Xu, Gertrud Mannhaupt, Yueh-Long Chang, Antonio Di Pietro, Ulrich Güldener, Christina A. Cuomo, Evan Mauceli, Rudolf Mitterbauer, John F. Antoniw, Rubella S. Goswami, David DeCaprio, Martin Urban, Cees Waalwijk, Jonathan D. Walton, Sante Gnerre, Frances Trail, Thomas K. Baldwin, Bruce W. Birren, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Bioinformatics (MIPS), GSF National Research Center for Environment and Health, Purdue University [West Lafayette], Michigan State University [East Lansing], Michigan State University System, Cornell University [New York], Universidad de Córdoba [Cordoba], Pacific Northwest National Laboratory (PNNL), University of Amsterdam [Amsterdam] (UvA), Universität für Bodenkultur Wien [Vienne, Autriche] (BOKU), Rothamsted Research, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Agriculture and Agri-Food [Ottawa] (AAFC), U.S. Department of Agriculture - Agricultural Research Service - Cereal Disease Laboratory (USDA), USDA-ARS : Agricultural Research Service, Saint Louis University (SLU), University of Arizona, University of Tennessee Memphis, The University of Tennessee Health Science Center [Memphis] (UTHSC), USDA ARS, National Center for Agricultural Utilization Research (USDA ARS,), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institute of Bioorganic Chemistry and Photochemistry, National Ukrainian Academy of Sciences, Institute Bioorganic Chemistry an Photochemistry, Plant Research International (PRI), Wageningen University and Research [Wageningen] (WUR), Molecular Plant Pathology (SILS, FNWI), Technische Universität München [München] (TUM), Cornell University, University of Minnesota [Twin Cities], and Wageningen University and Research Centre [Wageningen] (WUR)

Subjects
localized polymorphism, MESH: Sequence Analysis, DNA, neurospora, Sequence analysis, Molecular Sequence Data, Single-nucleotide polymorphism, Genomics, Gene mutation, Biology, dna, medicine.disease_cause, Genome, Polymorphism, Single Nucleotide, Evolution, Molecular, 03 medical and health sciences, MESH: Plant Diseases, Fusarium, MESH: Polymorphism, Genetic, medicine, Point Mutation, DNA, Fungal, Gene, MESH: Evolution, Molecular, 030304 developmental biology, Plant Diseases, MESH: Point Mutation, Genetics, 0303 health sciences, Mutation, MESH: Fusarium, Multidisciplinary, Polymorphism, Genetic, MESH: Molecular Sequence Data, Biointeracties and Plant Health, 030306 microbiology, Point mutation, MESH: Polymorphism, Single Nucleotide, food and beverages, Hordeum, Sequence Analysis, DNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: DNA, Fungal, MESH: Hordeum, MESH: Genome, Fungal, Fusarium graminearum genome, PRI Biointeractions en Plantgezondheid, Genome, Fungal, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract

We sequenced and annotated the genome of the filamentous fungus Fusarium graminearum , a major pathogen of cultivated cereals. Very few repetitive sequences were detected, and the process of repeat-induced point mutation, in which duplicated sequences are subject to extensive mutation, may partially account for the reduced repeat content and apparent low number of paralogous (ancestrally duplicated) genes. A second strain of F. graminearum contained more than 10,000 single-nucleotide polymorphisms, which were frequently located near telomeres and within other discrete chromosomal segments. Many highly polymorphic regions contained sets of genes implicated in plant-fungus interactions and were unusually divergent, with higher rates of recombination. These regions of genome innovation may result from selection due to interactions of F. graminearum with its plant hosts.

Published
2007
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31. Unsupervised genome-wide recognition of local relationship patterns

Author

Kerstin Lindblad-Toh, Patric Jern, Henrik Lantz, Manfred Grabherr, Nagarjun Vijay, Pamela Russell, Evan Mauceli, Jennifer R. S. Meadows, Federica Di Palma, Marc P. Hoeppner, and Neda Zamani

Subjects
Primates, 0106 biological sciences, Genomics, Bioinformatik och systembiologi, Biology, 010603 evolutionary biology, 01 natural sciences, Genome, Disease Outbreaks, Coalescent theory, 03 medical and health sciences, Species Specificity, Phylogenetics, Genetics, Animals, Humans, Genome size, Phylogeny, 030304 developmental biology, Bioinformatics (Computational Biology), 0303 health sciences, Models, Genetic, Bioinformatics and Systems Biology, Phylogenetic tree, Immunity, Dengue Virus, Markov Chains, Evolutionary biology, Horizontal gene transfer, Bioinformatik (beräkningsbiologi), DNA microarray, Software, Algorithms, Biotechnology
Abstract

Background Phenomena such as incomplete lineage sorting, horizontal gene transfer, gene duplication and subsequent sub- and neo-functionalisation can result in distinct local phylogenetic relationships that are discordant with species phylogeny. In order to assess the possible biological roles for these subdivisions, they must first be identified and characterised, preferably on a large scale and in an automated fashion. Results We developed Saguaro, a combination of a Hidden Markov Model (HMM) and a Self Organising Map (SOM), to characterise local phylogenetic relationships among aligned sequences using cacti, matrices of pair-wise distance measures. While the HMM determines the genomic boundaries from aligned sequences, the SOM hypothesises new cacti in an unsupervised and iterative fashion based on the regions that were modelled least well by existing cacti. After testing the software on simulated data, we demonstrate the utility of Saguaro by testing two different data sets: (i) 181 Dengue virus strains, and (ii) 5 primate genomes. Saguaro identifies regions under lineage-specific constraint for the first set, and genomic segments that we attribute to incomplete lineage sorting in the second dataset. Intriguingly for the primate data, Saguaro also classified an additional ~3% of the genome as most incompatible with the expected species phylogeny. A substantial fraction of these regions was found to overlap genes associated with both the innate and adaptive immune systems. Conclusions Saguaro detects distinct cacti describing local phylogenetic relationships without requiring any a priori hypotheses. We have successfully demonstrated Saguaro’s utility with two contrasting data sets, one containing many members with short sequences (Dengue viral strains: n = 181, genome size = 10,700 nt), and the other with few members but complex genomes (related primate species: n = 5, genome size = 3 Gb), suggesting that the software is applicable to a wide variety of experimental populations. Saguaro is written in C++, runs on the Linux operating system, and can be downloaded from http://saguarogw.sourceforge.net/.

Published
2013
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32. The genomic basis of adaptive evolution in threespine sticklebacks

Author

Ross Swofford, Eric S. Lander, Jeremy Schmutz, Jane Grimwood, Timothy R. Howes, Mono Pirun, Anne K. Knecht, Evan Mauceli, Manfred Grabherr, Kerstin Lindblad-Toh, Haili Zhang, Brian R. Summers, Michael C. Zody, Richard M. Myers, Felicity C. Jones, Stephen M. J. Searle, Ewan Birney, Federica Di Palma, Simon D. M. White, Jeremy Johnson, Chris T. Amemiya, David M. Kingsley, Shannon D. Brady, Alex A. Pollen, Mark Dickson, Yingguang Frank Chan, Craig Miller, Pamela Russell, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.

Subjects
0106 biological sciences, Aquatic Organisms, General Science & Technology, Physiological, Molecular Sequence Data, Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team, Zoology, Genomics, Fresh Water, 010603 evolutionary biology, 01 natural sciences, Genome, Article, Chromosomes, 03 medical and health sciences, Genetic variation, Genetics, Animals, Seawater, 14. Life underwater, Adaptation, Conserved Sequence, 030304 developmental biology, Ecotype, 0303 health sciences, Multidisciplinary, biology, Human Genome, Stickleback, Genetic Variation, Reproductive isolation, Sequence Analysis, DNA, DNA, biology.organism_classification, Adaptation, Physiological, Biological Evolution, 6. Clean water, Smegmamorpha, Chromosome Inversion, Female, Sequence Analysis, Alaska, Reference genome
Abstract

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine–freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine–freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature., National Human Genome Research Institute (U.S.), National Human Genome Research Institute (U.S.) (NHGRI CEGS Grant P50-HG002568)

Published
2012

33. Mutation discovery in mice by whole exome sequencing

Author

Frank J. Probst, Federica Di Palma, Wenhui Huang, Joel E. Richardson, Rebecca R. Corrigan, Yueming Ding, Laura G. Reinholdt, Heather Fairfield, Stephen A. Murray, Michelle Curtain, Mary Barter, Daniel J. Gerhardt, Jay Shendure, Jeffrey A. Jeddeloh, Carol J. Bult, Kerstin Lindblad-Toh, Leah Rae Donahue, Todd Richmond, David E. Bergstrom, Mona S. Spector, Snaevar Sigurdsson, Chao He, Griffith J Gilbert, Evan Mauceli, Jorg Hager, Mark D'Ascenzo, Benjamin T. Kile, Lucy B. Rowe, Ivo Glynne Gut, Scott W. Lowe, Timothy C. Cox, Michael L. Cunningham, Thomas J. Albert, and Monica J. Justice

Subjects
Genotype, Mutant, DNA Mutational Analysis, Method, Genomics, Mice, Inbred Strains, Biology, medicine.disease_cause, 03 medical and health sciences, Mice, 0302 clinical medicine, Inbred strain, Gene Frequency, INDEL Mutation, medicine, Animals, Exome, Collagen Type II, Exome sequencing, 030304 developmental biology, Genetics, 0303 health sciences, Mutation, Chromosome Mapping, Exons, MAP Kinase Kinase Kinases, Chromosomes, Mammalian, Human genetics, 3. Good health, Phenotype, Indicators and Reagents, 030217 neurology & neurosurgery
Abstract

We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.

Published
2011

34. Genome Sequencing and Assembly

Author

Li-Jun Ma, Evan Mauceli, and Manfred Grabherr

Subjects
Comparative genomics, Whole genome sequencing, Genetics, Sequence assembly, DNA sequencing theory, Genomics, Computational biology, Biology, DNA sequencing, Personal genomics
Abstract

Decoding the genome sequence is becoming a fundamental tool for molecular, genetic, and genomic studies. This chapter reviews the history of DNA sequencing and technical principles of different sequencing platforms, and compares the strengths and weaknesses of different techniques for high-throughput genome sequencing applications are compared. It also covers brief descriptions on genome assembly and its validation.

Published
2011
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35. Obligate biotrophy features unraveled by the genomic analysis of rust fungi

Author

Richard C. Hamelin, Jacqueline E. Schein, Brandi L. Cantarel, Bernard Henrissat, Peter N. Dodds, Robert F. Park, Rohit Mago, Ursula Kües, Pedro M. Coutinho, Stéphane Hacquard, Joelle Amselem, Philippe Tanguay, Nicolas Feau, Claire Veneault-Fourrey, Annegret Kohler, Claude Murat, Chinnappa D. Kodira, Sébastien Duplessis, Erika Lindquist, Pierre Rouzé, Readman Chiu, Christina A. Cuomo, Emmanuelle Morin, Jonathan M. Goldberg, Nicolas Rouhier, Jasmyn Pangilinan, Manfred Grabherr, Yves Van de Peer, Matthew Pearson, Andrea Aerts, Igor V. Grigoriev, Susan Lucas, Shaobin Zhong, Benjamin Selles, Gerald A. Tuskan, Eric Gelhaye, Asaf Salamov, Jeremy Schmutz, Yao-Cheng Lin, Jeffrey G. Ellis, Harris Shapiro, Emilie Tisserant, David L. Joly, Sharadha Sakthikumar, Hadi Quesneville, Evan Mauceli, Matthew A. Field, Pascal Frey, Les J. Szabo, Francis Martin, Interactions Arbres-Microorganismes (IAM), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Institute of Massachuetts Institute of technology and harward university, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of plant systems biology, Flanders Institute for Biotechnology, Joint Genome institute, United States Department of Energy, BIOlogie et GEstion des Risques en agriculture (BIOGER), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Genome sciences, BC Cancer Agency (BCCRC), Division of molecular wood biotechnology and technical mycology - Büsgen-Institute, Bûsgenweg, Georg-August-Universität Göttingen, Plant Industry, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Plant breeding institute Cobbitty, The University of Sydney, Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Department of plant pathology, University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, Cereal diseases laboratory US D epartment of agriculture, Agricultural Research Service, Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Georg-August-University = Georg-August-Universität Göttingen, University of Minnesota [Twin Cities] (UMN), USDA-ARS : Agricultural Research Service, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Georg-August-University [Göttingen], Duplessis, Sébastien, Cuomo, Christina A, Szabo, Les J, and Martin, Francis

Subjects
puccinia graminis tritici, 0106 biological sciences, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Rust (fungus), champignon phytopathogène, Stem rust, 01 natural sciences, Genome, Haustorium, Triticum, Phylogeny, Oligonucleotide Array Sequence Analysis, 2. Zero hunger, Genetics, 0303 health sciences, Multidisciplinary, biology, Sulfates, food and beverages, Melampsora, Biological Sciences, Plants, Adaptation, Physiological, rouille, melampsora larici populina, séquençage du génome, Genome, Fungal, RUST EVOLUTION, COMPARATIVE GENOMICS, Genes, Fungal, champignon biotrophique, Genes, Plant, Models, Biological, 03 medical and health sciences, PLANT PATHOGEN, BASIDIOMYCETE, EVOLUTION, Commentaries, Symbiosis, Plant Diseases, 030304 developmental biology, Comparative genomics, Puccinia, Nitrates, Models, Genetic, Obligate, Basidiomycota, Gene Expression Profiling, fungi, Fungi, Sequence Analysis, DNA, biology.organism_classification, Plant Leaves, Immune System, 010606 plant biology & botany
Abstract

Rust fungi are some of the most devastating pathogens of crop plants. They are obligate biotrophs, which extract nutrients only from living plant tissues and cannot grow apart from their hosts. Their lifestyle has slowed the dissection of molecular mechanisms underlying host invasion and avoidance or suppression of plant innate immunity. We sequenced the 101-Mb genome of Melampsora larici - populina , the causal agent of poplar leaf rust, and the 89-Mb genome of Puccinia graminis f. sp. tritici , the causal agent of wheat and barley stem rust. We then compared the 16,399 predicted proteins of M. larici-populina with the 17,773 predicted proteins of P. graminis f. sp tritici . Genomic features related to their obligate biotrophic lifestyle include expanded lineage-specific gene families, a large repertoire of effector-like small secreted proteins, impaired nitrogen and sulfur assimilation pathways, and expanded families of amino acid and oligopeptide membrane transporters. The dramatic up-regulation of transcripts coding for small secreted proteins, secreted hydrolytic enzymes, and transporters in planta suggests that they play a role in host infection and nutrient acquisition. Some of these genomic hallmarks are mirrored in the genomes of other microbial eukaryotes that have independently evolved to infect plants, indicating convergent adaptation to a biotrophic existence inside plant cells.

Published
2011
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36. High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5

Author

Lishuang Shen, John C. Schimenti, Joyanna F Gilmour, Robert J. Munroe, Kerry J. Schimenti, Patrick J. Stover, James Y Shou, Tanya P Harris, Kerstin Lindblad-Toh, David L Rogal, Frederica diPalma, Yunhai Luo, John L. McElwee, Yung-Hao Ching, Jennifer L. Moran, Hyo K Park, Evan Mauceli, Mami Shindo, Weipeng Mu, Anna K. Barker, Lindsay M Abcunas, Erin K. Stenson, Susan L. Kloet, and Timothy Fennell

Subjects
Male, lcsh:QH426-470, Positional cloning, DNA Mutational Analysis, Mutant, Embryonic Development, Mutagenesis (molecular biology technique), Biology, medicine.disease_cause, Chromosomes, Mice, 03 medical and health sciences, 0302 clinical medicine, Gene mapping, Genetics, medicine, Animals, Genetics(clinical), Cloning, Molecular, Spermatogenesis, Gene, Genetics (clinical), Sequence Deletion, 030304 developmental biology, 0303 health sciences, Mutation, Genetic Complementation Test, Chromosome Mapping, Mice, Inbred C57BL, lcsh:Genetics, Ethylnitrosourea, Genes, Lethal, Homeotic gene, 030217 neurology & neurosurgery, Research Article, Genetic screen
Abstract

Background Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a ~50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals. Results We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis. Conclusion This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.

Published
2010
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37. Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses

Author

Claire M. Wade, Kerstin Lindblad-Toh, Sheila Archer, Freyja Imsland, Tosso Leeb, Lynne S. Sandmeyer, Snaevar Sigurdsson, George W. Forsyth, Martina Engensteiner, Rebecca R. Bellone, Evan Mauceli, Ernest Bailey, and Bruce H. Grahn

Subjects
Candidate gene, DNA Mutational Analysis, Molecular Sequence Data, TRPM Cation Channels, Single-nucleotide polymorphism, Biology, Biochemistry, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Gene mapping, Night Blindness, Night vision, Genotype, Genetics, Animals, Genetic Predisposition to Disease, Horses, Promoter Regions, Genetic, Molecular Biology, TRPM1, 030304 developmental biology, 0303 health sciences, Base Sequence, Haplotype, Chromosome Mapping, General Medicine, Exons, Genetic marker, Horse Diseases, 030217 neurology & neurosurgery
Abstract

Leopard Complex spotting occurs in several breeds of horses and is caused by an incompletely dominant allele (LP). Homozygosity for LP is also associated with congenital stationary night blindness (CSNB) in Appaloosa horses. Previously, LP was mapped to a 6 cm region on ECA1 containing the candidate gene TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) and decreased expression of this gene, measured by qRT-PCR, was identified as the likely cause of both spotting and ocular phenotypes. This study describes investigations for a mutation causing or associated with the Leopard Complex and CSNB phenotype in horses. Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs. Most of the SNPs did not have a predictive value for the presence of LP. However, one SNP (ECA1:108,249,293 C>T) found within intron 11 had a strong (P < 0.0005), but not complete, association with LP and CSNB and thus is a good marker but unlikely to be causative. To further localize the association, 70 SNPs spanning over two Mb including the TRPM1 gene were genotyped in 192 horses from three different breeds segregating for LP. A single 173 kb haplotype associated with LP and CSNB (ECA1: 108,197,355- 108,370,150) was identified. Illumina sequencing of 300 kb surrounding this haplotype revealed 57 SNP variants. Based on their localization within expressed sequences or regions of high sequence conservation across mammals, six of these SNPs were considered to be the most likely candidate mutations. While the precise function of TRPM1 remains to be elucidated, this work solidifies its functional role in both pigmentation and night vision. Further, this work has identified several potential regulatory elements of the TRPM1 gene that should be investigated further in this and other species.

Published
2010

38. Genome sequence, comparative analysis and population genetics of the domestic horse

Author

Elisa Magnani, Sarah Fryc, Teri L. Lear, James R. Mickelson, Evan Mauceli, Loren C. Skow, Tosso Leeb, Emmeline W. Hill, Ann-Christine Syvänen, Joy M. Raison, Snaevar Sigurdsson, S. Searle, J. Vogel, Leif Andersson, Robert C. Onofrio, Helmut Blöcker, Bhanu P. Chowdhary, Eric S. Lander, Teruaki Tozaki, Kerstin Lindblad-Toh, Ottmar Distl, Mariano Rocchi, Matthew M. Binns, Ted Sharpe, Claire M. Wade, Solomon G. Nergadze, Tara Biagi, Manuel Garber, T. Hasegawa, Sante Gnerre, Freyja Imsland, Anna Kiialainen, Maria Cecilia T. Penedo, Robert C. Edgar, M. F. Piras, Oliver A. Ryder, David L. Adelson, G. Della Valle, James N. MacLeod, Jerzy Jurka, Elena Giulotto, Gabriella Lindgren, June E Swinburne, K. H. Røed, James D. Murray, S. Pedroni, Terje Raudsepp, Jared White, S.J. Coleman, Monica Zoli, Michael C. Zody, Douglas F. Antczak, Jinze Liu, Mark Vaudin, Rebecca R. Bellone, Ernest Bailey, Gérard Guérin, Stephanie J. Valberg, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Faculty of Veterinary Sciences, The University of Sydney, Dipartimento di Genetica e Microbiologia, Università di Pavia, Department of Medical Biochemistry and Microbiology, Uppsala University, Dipartimento di Biologia, Alma Mater Studiorum University of Bologna (UNIBO), Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, University of Adelaide, University of Tampa, Helmholtz Centre for Infection Research (HZI), Institute of Animal Breeding and Genetics, University of Veterinary Medecine Hannover, 45 Monterey Drive, Institute of Genetics, University of Bern, Veterinary Genetics Laboratory, University of California, The Wellcome Trust Sanger Institute [Cambridge], Cornell University, Royal Veterinary College, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Equine Research Institute, Japan Racing Association, Animal Genomics Laboratory, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin [Dublin] (UCD), Genetic Information Research Institute, Department of Medical Sciences, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Department of Computer Science, College of Veterinary Medecine, University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, Population Health and Reproduction, School of Veterinary Medicine, Department of Genetics and Microbiology, Università degli studi di Bari, San Diego Zoo's Institute for Conservation Research, College of Veterinary Medicine, Texas A&M University System, Animal Health Trust (AHT), Department of Molecular Genetics, Laboratory of Racing Chemistry, Department of Biology, Massachusetts Institute of Technology (MIT)-Howard Hugues Medical Institute, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Howard Hugues Medical Institute-Massachusetts Institute of Technology (MIT), Università degli Studi di Pavia, Cornell University [New York], Department of Animal Bredding and Genetics, University of Minnesota [Twin Cities] (UMN), Università degli studi di Bari Aldo Moro (UNIBA), and Howard Hughes Medical Institute (HHMI)-Massachusetts Institute of Technology (MIT)

Subjects
Genetics, Whole genome sequencing, 0303 health sciences, Multidisciplinary, 040301 veterinary sciences, [SDV]Life Sciences [q-bio], Haplotype, complete genome, Chromosome, 04 agricultural and veterinary sciences, sequencing, Biology, Genome, horse, 0403 veterinary science, 03 medical and health sciences, Horse genome, Evolutionary biology, Centromere, evolution, 030304 developmental biology, Segmental duplication, Synteny
Abstract

A Horse Is a Horse, of Course The history of horse domestication is closely tied to the history of the human society. Wade et al. (p. 865 ) report on the sequencing and provide a single nucleotide polymorphism map of the horse ( Equus caballus ) genome. Horses are a member of the order perissodactyla (odd-toed animals with hooves). The analysis reveals an evolutionarily new centromere on equine chromosome 11 that displays properties of an immature but fully functioning centromere and is devoid of centromeric satellite sequence. The findings clarify the nature of genetic diversity within and across horse breeds and suggest that the horse was domesticated from a relatively large number of females, but few males.

Published
2009
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39. Evolution of genes and genomes on the Drosophila phylogeny

Author

Adam M. Phillippy, Edward Grandbois, Pen MacDonald, Iain MacCallum, Laura K. Reed, Wojciech Makalowski, Tracey Honan, Tania Tassinari Rieger, Melissa J. Hubisz, Josep M. Comeron, Douglas Smith, Jennifer Godfrey, Sebastian Strempel, Amr Abdouelleil, Brenton Gravely, Harindra Arachi, Albert J. Vilella, Marc Azer, Sarah A. Teichmann, Roger A. Hoskins, Corbin D. Jones, Keenan Ross, Derek Wilson, Stuart J. Newfeld, John Stalker, Thomas D. Watts, Dennis C. Friedrich, Therese A. Markow, Michael U. Mollenhauer, Tina Goode, Geneva Young, Terry Shea, Krista Lance, Karin A. Remington, Kevin A. Edwards, Lynne Aftuck, Cecil Rise, Sheridon Channer, Matthew D. Rasmussen, Nicole Stange-Thomann, Annie Lui, Robert A. Reenan, Todd Sparrow, Dave Begun, Tamrat Negash, Laura K. Sirot, Adrianne Brand, Adam Brown, Daisuke Yamamoto, Pema Phunkhang, Justin Abreu, Russell Schwartz, Ana Llopart, Abderrahim Farina, Kebede Maru, Chung-I Wu, Allen Alexander, Scott Anderson, So Jeong Lee, Jason Blye, Gary H. Karpen, Wilfried Haerty, Daniel A. Barbash, Peter Rogov, Barry O'Neill, Rachel Mittelman, Jakob Skou Pedersen, Leanne Hughes, Robert K. Bradley, Graziano Pesole, Wyatt W. Anderson, Anthony J. Greenberg, Alejandro Sánchez-Gracia, Julio Rozas, Stephen W. Schaeffer, Yama Thoulutsang, Roger K. Butlin, David H. Ardell, Stuart DeGray, Chris P. Ponting, Deborah E. Stage, Corrado Caggese, Montserrat Aguadé, Casey M. Bergman, Diallo Ferguson, Peili Zhang, Jeffrey R. Powell, Hajime Sato, Xiaohong Liu, Marta Sabariego Puig, Michael Parisi, Passang Dorje, Yoshihiko Tomimura, Adal Abebe, Carlo G. Artieri, Brian Hurhula, Filip Rege, Peter D. Keightley, Andrew Barry, Pablo Alvarez, Tsamla Tsamla, Marvin Wasserman, Santosh Jagadeeshan, Daniel L. Halligan, Chelsea D. Foley, Kim D. Delehaunty, Manfred Grabherr, Sourav Chatterji, Angela N. Brooks, James C. Costello, Mieke Citroen, James A. Yorke, Hsiao Pei Yang, Charles Chapple, Jian Lu, Carlos A. Machado, Norbu Dhargay, Tsering Wangchuk, Anat Caspi, Patrick Cahill, Tashi Bayul, Lisa Levesque, Otero L. Oyono, Atanas Mihalev, Dawa Thoulutsang, Dawn N. Abt, Sujaa Raghuraman, Manyuan Long, Maria Mendez-Lago, Charles Matthews, Kimberly Dooley, Alex Wong, Melanie A. Huntley, William R. Jeck, Ira Topping, Ben Kanga, José P. Abad, Ana Cristina Lauer Garcia, Brikti Abera, Kunsang Gyaltsen, Jonathan Butler, Alicia Franke, Michael C. Schatz, Cheewhye Chin, Charles F. Aquadro, Justin Johnson, Bryant F. McAllister, Georgia Giannoukos, M. Erii Husby, Rod A. Wing, Shangtao Liu, Jean L. Chang, Jennifer Daub, Eiko Kataoka, Leopold Parts, Rakela Lubonja, Margaret Priest, Yoshiko N. Tobari, Teena Mehta, Evgeny M. Zdobnov, Yeshi Lokyitsang, Richard Elong, Matthew J. Parisi, Louis Meneus, Eric S. Lander, Alan Filipski, Gary Gearin, Nabil Hafez, Nicholas Sisneros, David B. Jaffe, Ian Holmes, Marina Sirota, Leonid Boguslavskiy, Lisa Chuda, LaDeana W. Hillier, Meizhong Luo, Phil Batterham, Michael Kleber, Richard K. Wilson, Yama Cheshatsang, Qing Yu, Rebecca Reyes, Matthew W. Hahn, Andreas Heger, Mar Marzo, Patrick Minx, Kerstin Lindblad-Toh, Vera L. S. Valente, Adam Wilson, William C. Jordan, Mohamed A. F. Noor, Chiao-Feng Lin, Asha Kamat, Heather Ebling, Mihai Pop, Frances Letendre, Mariana F. Wolfner, Don Gilbert, Ngawang Sherpa, Riza M. Daza, Oana Mihai, Gabriel C. Wu, Aaron M. Berlin, Ewen F. Kirkness, Monika D. Huard, Robert S. Fulton, Randall H. Brown, Danni Zhong, Sharon Stavropoulos, Venky N. Iyer, Xu Mu, Christina R. Gearin, David M. Rand, Jerry A. Coyne, Dan Hultmark, Jill Falk, Christopher Patti, Montserrat Papaceit, James Meldrim, Valentine Mlenga, Muneo Matsuda, Sven Findeiß, Todd A. Schlenke, Kevin McKernan, Brian P. Walenz, Timothy B. Sackton, Leonardo Koerich, Peter An, Robert Nicol, Chuong B. Do, Dmitry Khazanovich, Carmen Segarra, Maura Costello, St Christophe Acer, Claudia Rohde, Serafim Batzoglou, Hadi Quesneville, Evan Mauceli, Andy Vo, Luciano M. Matzkin, Susan E. Celniker, Patrick M. O’Grady, William M. Gelbart, Lloyd Low, Jamal Abdulkadir, Jessica Spaulding, Brian R. Calvi, Charlotte Henson, Robert David, Jennifer L. Hall, Andrew G. Clark, Anastasia Gardiner, Susan M. Russo, Birhane Hagos, Kerri Topham, Amy Denise Reily, Eli Venter, Jerome Naylor, Sandra W. Clifton, Valer Gotea, Samuel R. Gross, Manolis Kellis, Claude Bonnet, Christopher Strader, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Stephen M. Mount, Robert L. Strausberg, Shailendra Yadav, Kristipati Ravi Ram, Steven L. Salzberg, Erik Gustafson, David A. Garfield, Eva Freyhult, Arthur L. Delcher, Enrico Blanco, Granger G. Sutton, Jason M. Tsolas, Charles Robin, Angie S. Hinrichs, Christopher D. Smith, Jane Wilkinson, Brendan McKernan, Fritz Pierre, William McCusker, Brian Oliver, Barry E. Garvin, Sudhir Kumar, Peter Kisner, Kunsang Dorjee, A. Bernardo Carvalho, Anna Montmayeur, Andrew Zimmer, Diana Shih, Wei Tao, Shiaw Pyng Yang, Sante Gnerre, Sampath Settipalli, Thu Nguyen, Paolo Barsanti, Brian P. Lazzaro, Sonja J. Prohaska, J. Craig Venter, Senait Tesfaye, Susan McDonough, Kim D. Pruitt, Alexander Stark, Sergio Castrezana, Lucinda Fulton, Richard T. Lapoint, Greg Gibson, John Spieth, Boris Adryan, Georgius De Haan, Sheila Fisher, Daniel A. Pollard, Seva Kashin, Rob J. Kulathinal, Michael B. Eisen, Nathaniel Novod, Christina Demaso, Alan Dupes, Amanda M. Larracuente, Toby Bloom, Alfredo Villasante, Charles H. Langley, Rama S. Singh, Niall J. Lennon, Kristi L. Montooth, Daniel Barker, Wolfgang Stephan, David Sturgill, Ruiqiang Li, Andrew Hollinger, Boris Boukhgalter, Talene Thomson, Patrick Cooke, Zac Zwirko, Nadia D. Singh, Michael Weiand, Lior Pachter, Roderic Guigó, Yu Zhang, Jay D. Evans, Stephanie Bosak, Rosie Levine, Lu Shi, Kiyohito Yoshida, Carolyn S. McBride, Pouya Kheradpour, William Brockman, Alberto Civetta, Hiroshi Akashi, Marcia Lara, Susan Faro, Sam Griffiths-Jones, Michael R. Brent, Thomas H. Eickbush, Gane Ka-Shu Wong, Elizabeth P. Ryan, Erica Anderson, Roberta Kwok, Asif T. Chinwalla, Sahal Osman, Nga Nguyen, Damiano Porcelli, Missole Doricent, Saverio Vicario, Marc Rubenfield, Bárbara Negre, Gillian M. Halter, Erin E. Dooley, Elena R. Lozovsky, William Lee, Alville Collymore, Catherine Stone, Tanya Mihova, Jun Wang, Karsten Kristiansen, Imane Bourzgui, Michael F. Lin, Katie D'Aco, Filipe G. Vieira, Choe Norbu, Yu-Hui Rogers, Aaron L. Halpern, Eugene W. Myers, Sharleen Grewal, Robert T. Good, Alfredo Ruiz, Dave Kudrna, Joseph Graham, Alex Lipovsky, Leonidas Mulrain, Tsering Wangdi, Roman Arguello, Mira V. Han, Arjun Bhutkar, Rasmus Nielsen, David J. Saranga, Aleksey V. Zimin, Vasilia Magnisalis, Helen Vassiliev, Thomas C. Kaufman, Eva Markiewicz, Temple F. Smith, Jinlei Liu, Loryn Gadbois, Michael G. Ritchie, Lisa Zembek, Daniel Bessette, Pasang Bachantsang, Adam Navidi, Department of Molecular Biology and Genetics, Cornell University [New York], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), University of California [Berkeley], University of California, Agencourt Bioscience Corporation, Partenaires INRAE, Faculty of Life Science, University of Manchester [Manchester], Laboratory of Cellular and Developmental Biology (LCDB), NIDDK, NIH, Department of Ecology and Evolutionary Biology, University of Arizona, Department of Biology, Indiana University [Bloomington], Indiana University System-Indiana University System, Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Brown University, Laboratory of Molecular Biology, Medical Research Council, Departament de Genetica, Universitat de Barcelona (UB), Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Genetics, University of Georgia [USA], Uppsala University, Department of Ecology and Evolution [Lausanne], Université de Lausanne (UNIL), McMaster University, School of Biology, IE University, Università degli Studi di Bari Aldo Moro, University of Melbourne, Stanford University, University of California [Davis] (UC Davis), Boston University [Boston] (BU), Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Washington University in Saint Louis (WUSTL), University of Sheffield, Syracuse University, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Department of Bioengineering, Beihang University (BUAA), Tucson Stock Center, Genome Center, University of California-University of California, Genome Sequencing Center, University of Washington School of Medicine, University of Winnipeg, Iowa State University (ISU), Indiana University System, The Wellcome Trust Sanger Institute [Cambridge], Center for Bioinformatics and Computational Biology, University of Delaware [Newark], Illinois State University, University of Rochester [USA], United States Department of Agriculture (USDA), Arizona State University [Tempe] (ASU), Leipzig University, Universidade Federal do Rio Grande do Sul (UFRGS), Duke University, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of Connecticut (UCONN), Computer Science Département, Université Saint-Esprit de Kaslik (USEK), Mc Master University, Indiana University, Institute of Evolutionary Biology, University of Edinburgh, J. Craig Venter Institute [La Jolla, USA] (JCVI), University of Oxford [Oxford], Center for Biomolecular Science and Engineering, Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), and Zdobnov, Evgeny

Subjects
melanogaster genome, 0106 biological sciences, RNA, Untranslated, [SDV]Life Sciences [q-bio], Genome, Insect, RNA, Untranslated/genetics, Genes, Insect, 01 natural sciences, Genome, Genome, Insect/ genetics, Gene Order, Genome, Mitochondrial/genetics, Drosophila Proteins, Phylogeny, ddc:616, Genetics, 0303 health sciences, Multidisciplinary, biology, Reproduction, Genomics, Multigene Family/genetics, Reproduction/genetics, DNA Transposable Elements/genetics, Genes, Insect/ genetics, Multigene Family, dosage compensation, Drosophila, amino-acid substitution, Drosophila Protein, Drosophila Proteins/genetics, Synteny/genetics, fruit-fly, 010603 evolutionary biology, Synteny, Drosophila sechellia, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, Molecular evolution, Codon/genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Animals, adaptive protein evolution, Codon, 030304 developmental biology, Gene Order/genetics, molecular evolution, fungi, Immunity, synonymous codon usage, Sequence Analysis, DNA, Immunity/genetics, biology.organism_classification, Drosophila mojavensis, Evolutionary biology, Genome, Mitochondrial, DNA Transposable Elements, maximum-likelihood, noncoding dna, Drosophila/ classification/ genetics/immunology/metabolism, Sequence Alignment, natural-selection, Drosophila yakuba
Abstract

Affiliations des auteurs : cf page 216 de l'article; International audience; Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Published
2007
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40. Integrated cytogenetic BAC map of the genome of the gray, short-tailed opossum, Monodelphis domestica

Author

Kerstin Lindblad-Toh, Paul B. Samollow, Matthew Breen, Evan Mauceli, and Shannon E. Duke

Subjects
Comparative genomics, Genetics, Whole genome sequencing, Chromosomes, Artificial, Bacterial, Genome evolution, Genome, Base Sequence, Chromosome Mapping, Sequence assembly, Genomics, Computational biology, Genome project, Biology, biology.organism_classification, Monodelphis domestica, Monodelphis, Sequence-tagged site, Cytogenetics, Animals, In Situ Hybridization, Fluorescence
Abstract

The generation of high-quality genome assemblies for numerous species is advancing at a rapid pace. As the number of genome assemblies increases, so does our ability to investigate genome relationships and their contributions to unraveling complex biological, evolutionary, and biomedical processes. A key process in the generation of a genome assembly is to determine and verify the precise physical location and order of the large sequence blocks (scaffolds) that result from the assembly. For organisms of relatively recent common ancestry this process may be achieved largely through comparative sequence alignment. However, as the evolutionary distance between species lengthens, the use of comparative sequence alignment becomes increasingly less reliable. Simultaneous cytogenetic mapping, using multicolor fluorescence in-situ hybridization (FISH) analysis, offers an alternative means to define the cytogenetic location and relative order of DNA sequences, thereby anchoring the genome sequence to the karyotype. In this article we report the molecular cytogenetic locations of 415 bacterial artificial chromosome (BAC) clones that served to anchor sequence scaffolds of the gray, short-tailed opossum (Monodelphis domestica) to its karyotype, which enabled accurate integration of these regions into the genome assembly.

Published
2007
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41. Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Author

Claire M. Wade, Matt J. Cahill, Eric C.H. Ho, Plinio Guzmán, Bruce W. Birren, David DeCaprio, Li-Jun Ma, Gabi Friedrich, Jan Schirawski, Sarah Young, Gero Steinberg, Gertrud Mannhaupt, Heine J. Deelstra, Steven J. Klosterman, Patricia Sánchez-Alonso, Thomas Brefort, Karen M. Snetselaar, Candace Swimmer, Han A. B. Wösten, Christoph W. Basse, Jose Ruiz-Herrera, Dirk Haase, Jonathan Butler, Regine Kahmann, Michael P. McCann, Hans-Werner Mewes, Juan Manuel González-Prieto, Feng Chen, Martin Münsterkötter, Barry J. Saville, Chad Nusbaum, Evan Mauceli, Kylie J. Boyce, Jason E. Stajich, Miroslav Vranes, Scott E. Gold, Olaf Müller, Michael H. Perlin, John C. Kennell, Björn Sandrock, Volker Vincon, James W. Kronstad, Valentina Vysotskaia, Oliver Ladendorf, Michael Bölker, Andreas Gnirke, Peter Schreier, José Pérez-Martín, Matthias Oesterheld, Lazaro Molina, Isolde Häuser-Hahn, David B. Jaffe, Michael Feldbrügge, Shaowu Meng, Martin Vaupel, José I. Ibeas, Jörg Kämper, Darren Mark Platt, Cristina G. Reynaga-Peña, Jonathan Margolis, Jana Klose, Rafael Sentandreu, Karin Münch, Edda Koopmann, Ulrich Güldener, Mark L. Farman, Doris Greilinger, Uta Fuchs, Hartmut Voss, Flora Banuett, Lucila Ortiz-Castellanos, Thomas Schlüter, Artemio Mendoza-Mendoza, Mario Scherer, William K. Holloman, Weixi Li, Ronald P. de Vries, Sarah E. Calvo, Nicole Rössel, and James E. Galagan

Subjects
Corn smut, Genetics, Multidisciplinary, biology, Virulence, Ustilago, Gene Expression Profiling, Genes, Fungal, Fungal genetics, Genomics, biology.organism_classification, Genome, Zea mays, Fungal Proteins, Gene Expression Regulation, Fungal, Multigene Family, Gene family, Genome, Fungal, Gene, Pathogen
Abstract

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.

Published
2006

42. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage

Author

James R. Lupski, Xiaohong Liu, Sante Gnerre, Bruce W. Birren, Nicole R. Allen, James G. R. Gilbert, Pawel Stankiewicz, Tashi Lokyitsang, Jane E. Loveland, Amr Abouelleil, John E. Major, Manuel Garber, Steven A. McCarroll, April Cook, Mark L. Borowsky, Annie Lui, David C. Schwartz, Jonathan Butler, Christine Nicholson, Chad Nusbaum, Atanas Mihalev, Laurens G. Wilming, Catherine Hosage Norman, Daniel S. Hagopian, Jessica A. Lehoczky, Robert Nicol, David Swarbreck, Cindy Nguyen, Varsha K. Khodiyar, Ted Sharpe, Gavin K. Laird, Evan Mauceli, Russell J. Grocock, Jane Rogers, S. Searle, Charles Shaw-Smith, Michael C. Zody, Toby Bloom, Boris Bugalter, David B. Jaffe, Pieter J. de Jong, Jean L. Chang, Kazutoyo Osoegawa, Michael Kamal, Sinéad B. O'Leary, Steven A. Goldstein, David J. Adams, Richard Gibson, Jennifer Harrow, Sean Humphray, Chao-Kung Chen, Michael Fitzgerald, Allan Bradley, Ken Dewar, Charles A. Steward, Eric S. Lander, E. Hart, David DeCaprio, Nabil Hafez, Matthew C. Jones, Darren Grafham, Tim Hubbard, Vijay Venkataraman, Jonathan M. Mudge, Charles A. Whittaker, Kurt LaButti, Andrew Zimmer, Christina A. Cuomo, Xiaoping Yang, Benjamin Corum, Sarah Young, Pendexter Macdonald, Lucy Matthews, and Weimin Bi

Subjects
Genetics, Base Composition, Multidisciplinary, Sequence Analysis, DNA, Biology, Synteny, Article, Chromosome 17 (human), Evolution, Molecular, Mice, Chromosome 4, Chromosome 16, Long Interspersed Nucleotide Elements, Chromosome 19, Gene Duplication, Animals, Humans, Chromosome 21, Chromosome 22, Chromosomal inversion, Segmental duplication, Chromosomes, Human, Pair 17, Short Interspersed Nucleotide Elements
Abstract

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome1, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome2,3. It is also enriched in segmental duplications, ranking third in density among the autosomes4. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution5,6, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

Published
2006

43. Analysis of the DNA sequence and duplication history of human chromosome 15

Author

Sandra Stewart, Amardeep Kaur, Evan Mauceli, Kerri Topham, Harindra Arachchi, Brian Birditt, Jerome Naylor, Toby Bloom, Sarah Young, Anup Madan, Reinhard Engels, Manuel Garber, Sabrina M. Stone, Anuradha Madan, Amber L Ratcliffe, Ryan Nesbitt, Amr Abouelleil, Keith O'Neill, Scott Bloom, Katherine M. B. Sneddon, Dascena Vincent, Lester Dorris, Steven Rounsley, Jennifer L. Hall, Michael Fitzgerald, David B. Jaffe, Grace Hensley, Gary Gearin, Devin P. Locke, Asha Kamat, Ericka M. Johnson, Jonathan Butler, Sinéad B. O'Leary, Jeremy Burke, Lida Baradarani, Jean L. Chang, Kurt DeArellano, Michael Kamal, Andrew Zimmer, Annie Lui, Eric S. Lander, Charles A. Whittaker, Monica Dors, Chad Nusbaum, David DeCaprio, Chinnappa D. Kodira, Leroy Hood, Robert Nicol, Ted Sharpe, Evan E. Eichler, Nissa Abbasi, Christina A. Cuomo, Glen Munson, Mark L. Borowsky, Shunguang Wang, Michael C. Zody, Shizhen Qin, Charlien Jones, Peter Fleetwood, Xinwei She, Pendexter Macdonald, Ken Dewar, April Cook, Xiaoping Yang, Bruce W. Birren, Jessica Fahey, Cynthia Friedman, Carrie Sougnez, and Lee Rowen

Subjects
Molecular Sequence Data, Biology, Synteny, Evolution, Molecular, Chromosome 16, Chromosome 19, Gene Duplication, Animals, Humans, Conserved Sequence, Phylogeny, Segmental duplication, Genetics, Chromosome 7 (human), Chromosomes, Human, Pair 15, Multidisciplinary, Polymorphism, Genetic, Genome, Human, Sequence Analysis, DNA, Macaca mulatta, Chromosome 17 (human), Chromosome 4, Genes, Haplotypes, Multigene Family, Chromosome 21, Chromosome 22
Abstract

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

Published
2005

44. Genome sequence, comparative analysis and haplotype structure of the domestic dog

Author

Tsering Wangchuk, Mayank Kumar, Sharon Stavropoulos, James Cuff, Mostafa Benamara, David DeCaprio, Birhane Hagos, Nathaniel Novod, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Sabrina M. Stone, Catherine Stone, Geneva Young, Osebhajajeme Egbiremolen, Dawa Thoulutsang, Tanya Mihova, Lisa Kim, Julie Sahalie, Jan Macdonald, Amr Abouelleil, Toby Bloom, Yama Cheshatsang, Carolyne Bardeleben, Qing Yu, Berta Blitshteyn, Tuyen T. Nguyen, Tarjei S. Mikkelsen, Edward Grandbois, Claire M. Wade, John E. Major, Filip Rege, Cindy Nguyen, Andrew Barry, Tracey Honan, Pablo Alvarez, Andy Vo, Manuel Garber, Cristyn Kells, Rachel Mittelman, Lucien Oyono, Norbu Dhargay, Sean M. Sykes, Diallo Ferguson, Tyler Aldredge, Tenchoe Nyima, Todd Sparrow, Daniel S. Hagopian, Christophe Hitte, Andreas Heger, Jane E. Wilkinson, Verneda Ray, Peter Rogov, Ewen F. Kirkness, Jill Falk, Robert Nicol, Christopher Patti, Danielle Perrin, Ted Sharpe, Douglas Smith, Peter Olandt, Matthew Breen, Ali Aslam, Cherylyn Smith, Tara Biagi, Diane Gage, Jean L. Chang, Karen Hughes Miller, Valentine Mlenga, Andrea Horn, Jessie Sloan, Claire M. Healy, Adam Wilson, Ngawang Sherpa, Riza M. Daza, David B. Jaffe, Leonid Boguslavskiy, Jody Camarata, Peter Kisner, William H. Lee, Kunsang Dorjee, M. Husby, Sante Gnerre, Kunsang Gyaltsen, Asha Kamat, Jonathan Butler, Terrance Shea, Alicia Franke, Patrick Cooke, Rayale Rameau, Andrew Zimmer, Gary Gearin, Nabil Hafez, Kerri Topham, Kebede Maru, Chris P. Ponting, Jerome Naylor, Yama Thoulutsang, Keith O'Neill, Jinlei Liu, Manolis Kellis, Claude Bonnet, Claudel Antoine, Passang Dorje, Adal Abebe, Tsamla Tsamla, Michael Kleber, Michael Weiand, Audra Goyette, Rachael Thomas, Lisa Zembek, Atanas Mihalev, Daniel Bessette, Helen Vassiliev, Pasang Bachantsang, Adam Navidi, Kathleen Dooley, Caleb Webber, Pierre Tchuinga, Tashi Bayul, Michael Kamal, Heidi G. Parker, Ben Kanga, Kimberly Dooley, Nadia Calixte, Mostafa Ait-zahra, Niall J. Lennon, Ira Topping, Eric S. Lander, Pieter J. deJong, Nicole R. Allen, Peter An, Boris Boukhgalter, Richard Elong, Thomas E. Landers, Anthony Rachupka, Michael Fitzgerald, Lisa Leuper, William Brockman, Marcia Lara, Susan Faro, Elaine A. Ostrander, Joanne Zainoun, Leigh Anne Hunnicutt, Mark J. Daly, Leanne Hughes, April Cook, Patrick Cahill, Sujaa Raghuraman, Manfred Grabherr, Robert K. Wayne, Adam Brown, Xiaohong Liu, Charles Matthews, Scott Anderson, Margaret Priest, Shailendra Yadav, Evan Mauceli, Kerstin Lindblad-Toh, Patricia Ferreira, Yeshi Lokyitsang, Harindra Arachchi, Alexandre Melnikov, Christina Raymond, James Meldrim, Dmitry Khazanovich, Mieke Citroen, Aaron M. Berlin, Alix Chinh Kieu, John Stalker, Francis Galibert, Noah Duffey, Krista Lance, Louis Meneus, Jennifer Ruth Sadler Hall, Choe Norbu, Pema Tenzing, Richard Marabella, Chee-Wye Chin, Karen Foley, Xiaoping Yang, Nga Nguyen, Tenzin Dawoe, Ryan Hegarty, Julie Rogers, Joseph Graham, Chelsea D. Foley, Leonidas Mulrain, Tsering Wangdi, Karin Decktor, Sarah LeVine, Shuli Yang, Dennis C. Friedrich, Tina Goode, Cecil Rise, Teena Mehta, Laura Ayotte, Michele Clamp, Nicole Stange-Thomann, Annie Lui, Edward J. Kulbokas, Pema Phunkhang, Alan Dupes, Elinor K. Karlsson, Lynne Aftuck, Sahal Osman, Abderrahim Farina, Barry O'Neill, Diana M. Shih, Xiaohui Xie, Lester Dorris, Vijay Venkataraman, Benjamin Jester, Sampath Settipalli, Thu Nguyen, Alville Collymore, Klaus-Peter Koepfli, Senait Tesfaye, Nathan Houde, Susan McDonough, Leo Goodstadt, Glen Munson, Georgia Giannoukos, Jeffrey Chu, Nathan B. Sutter, Sheila A. Fisher, Charlien Jones, Michael C. Zody, Jianying Shi, John P. Pollinger, Mechele Sheehan, Stephen M. J. Searle, Fritz Pierre, Jason Blye, Jean-Pierre Leger, and Stuart DeGray

Subjects
Male, Genomics, Single-nucleotide polymorphism, Biology, Genome, Polymorphism, Single Nucleotide, Synteny, Conserved sequence, Evolution, Molecular, Mice, Dogs, Molecular evolution, Animals, Humans, Dog Diseases, Conserved Sequence, Short Interspersed Nucleotide Elements, Genetics, Whole genome sequencing, Multidisciplinary, Dog leukocyte antigen, Haplotype, Rats, Haplotypes, Mutagenesis, biology.protein, Hybridization, Genetic, Female
Abstract

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

Published
2005

45. DNA sequence and analysis of human chromosome 8

Author

Chad Nusbaum, Tarjei S. Mikkelsen, Michael C. Zody, Shuichi Asakawa, Stefan Taudien, Manuel Garber, Chinnappa D. Kodira, Mary G. Schueler, Atsushi Shimizu, Charles A. Whittaker, Jean L. Chang, Christina A. Cuomo, Ken Dewar, Michael G. FitzGerald, Xiaoping Yang, Nicole R. Allen, Scott Anderson, Teruyo Asakawa, Karin Blechschmidt, Toby Bloom, Mark L. Borowsky, Jonathan Butler, April Cook, Benjamin Corum, Kurt DeArellano, David DeCaprio, Kathleen T. Dooley, Lester Dorris, Reinhard Engels, Gernot Glöckner, Nabil Hafez, Daniel S. Hagopian, Jennifer L. Hall, Sabine K. Ishikawa, David B. Jaffe, Asha Kamat, Jun Kudoh, Rüdiger Lehmann, Tashi Lokitsang, Pendexter Macdonald, John E. Major, Charles D. Matthews, Evan Mauceli, Uwe Menzel, Atanas H. Mihalev, Shinsei Minoshima, Yuji Murayama, Jerome W. Naylor, Robert Nicol, Cindy Nguyen, Sinéad B. O'Leary, Keith O'Neill, Stephen C. J. Parker, Andreas Polley, Christina K. Raymond, Kathrin Reichwald, Joseph Rodriguez, Takashi Sasaki, Markus Schilhabel, Roman Siddiqui, Cherylyn L Smith, Tam P. Sneddon, Jessica A. Talamas, Pema Tenzin, Kerri Topham, Vijay Venkataraman, Gaiping Wen, Satoru Yamazaki, Sarah K. Young, Qiandong Zeng, Andrew R. Zimmer, Andre Rosenthal, Bruce W. Birren, Matthias Platzer, Nobuyoshi Shimizu, and Eric S. Lander

Subjects
Male, Multidisciplinary, Molecular Sequence Data, Sequence Analysis, DNA, DNA, Satellite, Immunity, Innate, Defensins, Euchromatin, Evolution, Molecular, Contig Mapping, Multigene Family, Animals, Humans, Female, Chromosomes, Human, Pair 8
Abstract

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.

Published
2005

46. Initial sequence of the chimpanzee genome and comparison with the human genome

Author

Xose S. Puente, Edward J. Kulbokasl, Tina Graves, Lucinda L. Fulton, Xiaoqiu Huang, Wolfgang Enard, Tracie L. Miner, Peer Bork, Arian F.A. Smit, Mario Ventura, Ge Liu, Eray Tüzün, Jean L. Chang, W. James Kent, Daniel J. Richter, Robert H. Waterston, Maryellen Ruvolo, Sante Gnerre, Toshiyuki Hayakawa, David B. Jaffe, Ines Hellmann, Svante Pääbo, Ajit Varki, Gloria Velasco, Carlos López-Otín, Asif T. Chinwalla, Orna Man, Gustavo Glusman, Catrina Fronick, Katherine S. Pollard, Tarjei S. Mikkelsen, Craig Pohl, Nick Patterson, Scott M. Smith, Kateryna D. Makova, Jonathan Butler, William E. Nash, Mariano Rocchi, Pieter J. de Jong, Ze Cheng, Evan E. Eichler, Hongkai Ji, Mikita Suyama, Tasha K. Altheide, Kerstin Lindblad-Toh, Yoav Gilad, Kay Prüfer, James E. Taylor, Karen E. Hayden, Joanne O. Nelson, Mary Claire King, Evan Mauceli, Michael C. Wendl, Ming K. Lee, David Reich, Richard K. Wilson, Eric S. Lander, Nicoletta Archidiacono, Kimberley D. Delehaunty, Shiaw-Pyng Yang, Kate R. Rosenbloom, LaDeana W. Hillier, Michael C. Zody, John W. Wallis, David Torrents, Stephen F. Schaffner, and Elaine R. Mardis

Subjects
Genome evolution, Time Factors, Pan troglodytes, Biology, ENCODE, Genome, Chimpanzee genome project, Evolution, Molecular, Alu Elements, biology.animal, Animals, Humans, Disease, Alleles, Phylogeny, Whole genome sequencing, Genetics, Recombination, Genetic, Base Composition, Multidisciplinary, Polymorphism, Genetic, Genome, Human, Computational Biology, Genome project, Genomics, Sequence Analysis, DNA, Telomere, Evolutionary biology, Mutagenesis, DNA Transposable Elements, Common chimpanzee, Reference genome
Abstract

Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.

Published
2005

47. Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype

Author

Nicole Stange-Thomann, Michael Katinka, Michael Levy, Vincent Laudet, Olivier Jaillon, Cécile Fischer, Véronique de Berardinis, Zineb Skalli, Jill P. Mesirov, David M. Jaffe, Alain Bernot, Genís Parra, Simone Duprat, Claude Scarpelli, Daniel Kahn, Chad Nusbaum, Sophie Nicaud, Laurence Bouneau, Francis Quetier, Hugues Roest Crollius, Corinne Cruaud, Bruce W. Birren, Jérôme Gouzy, Kevin McKernan, Eric S. Lander, Nathalie Boudet, Vanina Castelli, Marc Robinson-Rechavi, Jean-Pierre Coutanceau, Béatrice Segurens, Michael C. Zody, Corinne Dasilva, Evan Mauceli, Paul A. McEwan, Manolis Kellis, Carole Dossat, Benoit Vacherie, Marcel Salanoubat, Roderic Guigó, Sheila Fisher, Christian Biémont, Stephanie Bosak, Jean Weissenbach, Véronique Anthouard, Jean-Nicolas Volff, William Saurin, Vincent Schächter, Julie Poulain, Catherine Ozouf-Costaz, Jean-Louis Petit, Laurence Cattolico, Guillaume Lardier, Charles Chapple, Sergi Castellano, Georges Lutfalla, Frédéric Brunet, Kerstin Lindblad-Toh, Philippe Brottier, Claire Jubin, Patrick Wincker, Jean-Marc Aury, Eléments transposables, évolution, populations, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Atmospheric and Environmental Chemistry [Bothell], University of Washington-Bothell, Bayer Cropscience, Centre d'étude spatiale des rayonnements (CESR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
Genome evolution, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Proteome, [SDV]Life Sciences [q-bio], Molecular Sequence Data, 2R hypothesis, Tetraodon nigroviridis, Fish Proteins, Synteny, Genome, Chromosomes, Evolution, Molecular, Gene Duplication, biology.animal, Animals, Chromosomes, Human, Humans, Urochordata, Tetraodon, Conserved Sequence, Mammals, Genetics, Base Composition, Multidisciplinary, Models, Genetic, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Fishes, Vertebrate, Sequence Analysis, DNA, Physical Chromosome Mapping, biology.organism_classification, Genes, Karyotyping, Vertebrates, Human genome
Abstract

International audience; Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests ∼900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype.

Published
2004
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48. Whole-genome sequence assembly for mammalian genomes: Arachne 2

Author

David B. Jaffe, Kerstin Lindblad-Toh, Evan Mauceli, Eric S. Lander, Michael C. Zody, Sante Gnerre, Jill P. Mesirov, and Jonathan Butler

Subjects
Genetics, Genome, Contig, Genome sequence assembly, Computational Biology, Computational biology, Biology, Contig Mapping, DNA sequencing, Mice, Simulated data, Methods, Animals, Humans, Genetics (clinical), Software
Abstract

We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal changes were simultaneously made and applied to the assembly of the mouse genome, during a six-month period of development: (1) Supercontigs (scaffolds) were iteratively broken and rejoined using several criteria, yielding a 64-fold increase in length (N50), and apparent elimination of all global misjoins; (2) gaps between contigs in supercontigs were filled (partially or completely) by insertion of reads, as suggested by pairing within the supercontig, increasing the N50 contig length by 50%; (3) memory usage was reduced fourfold. The outcome of this mouse assembly and its analysis are described in (Mouse Genome Sequencing Consortium 2002).

Published
2003

49. Initial sequencing and comparative analysis of the mouse genome

Author

Laura Elnitski, David B. Jaffe, Jia Li, Marina Alexandersson, Michael J. Morgan, Shiaw Pyng Yang, Robert Baertsch, Claire M. Wade, John Tromp, Michael C. Zody, Terrence S. Furey, Emma Overton-Larty, Stephen D. Brown, Scott Schwartz, Diane M. Dunn, J. P. Leger, Kris A. Wetterstrand, David Torrents, Ratna Shownkeen, Brian Schultz, Kim C. Worley, Richard D. Emes, John Mayer, Tom Landers, Beverley Meredith, Carol Scott, R. J. Weber, Sean R. Eddy, David Kulp, Jun Kawai, J Bailey, Fan Hsu, Diana L. Kolbe, Kirsten McLay, Marc Botcherby, Richard Mott, Tracie L. Miner, Jill P. Mesirov, Cristyn Kells, Michael A. Quail, Melanie M. Wall, Alistair G. Rust, Josep F. Abril, Ian F Korf, Peter An, Roderic Guigó, Abel Ureta-Vidal, Evan Mauceli, L. Steven Johnson, Arian F.A. Smit, Arkadiusz Kasprzyk, Michael C. Wendl, Deanna M. Church, Francis S. Collins, Wayne N. Frankel, Pallavi Eswara, Bin Ma, Robert H. Waterston, Stylianos E. Antonarakis, Edward M. Rubin, John Douglas Mcpherson, Andrew Sheridan, Megan McCarthy, Ming Li, Colin N. Dewey, Justin Deri, Rosie Levine, Matthew Jones, Sheila Dodge, Richard R. Copley, Leo Goodstadt, Shan Yang, Donna Maglott, Jamey Wierzbowski, Nick Goldman, Evgeny M. Zdobnov, Simon G. Gregory, C M Clee, Steven Leonard, Elaine R. Mardis, Simon C. Potter, Sarah Sims, Richard A. Gibbs, Mark S. Guyer, Francesca Chiaromonte, Susan Lucas, Mark Diekhans, Steve Searle, Rachel Ainscough, Jane Peterson, Emmanouil T. Dermitzakis, Robert Nicol, Lucy Matthews, Guy Slater, Adam Felsenfeld, Karen Foley, Lucinda Fulton, Tim Hubbard, Richard K. Wilson, Deana W. LaHillier, W. Richard McCombie, Johanna Thompson, Robert David, John Attwood, Anthony P. West, Jane Rogers, Evan Keibler, Lisa Cook, Raju Kucherlapati, Steven Seaman, William E. Nash, Ian J. Jackson, Jonathan Singer, Axin Hua, Tina Graves, Ted Sharpe, Dudley Wyman, Bruce W. Birren, Stuart McLaren, David Willey, A Joy, Douglas Smith, Alexandre Reymond, Paul Flicek, Simon Cawley, Richa Agarwala, Diane Gage, Evanne Trevaskis, Ginger A. Fewell, Michael R. Brent, Tracy C. Ponce, W. James Kent, Timothy Holzer, Eduardo Eyras, Michael J. O’Connor, Webb Miller, Donna M. Muzny, Andrew von Niederhausern, Inna Dubchak, Eitan E. Winter, Catherine Ucla, Arne Stabenau, Michael N. Nhan, Piero Carninci, Michele Clamp, Pavel A. Pevzner, James Meldrim, Tim Cutts, R. D. Campbell, Joy Davies, Wratko Hlavina, Elinor K. Karlsson, David Haussler, John Burton, Peer Bork, Nicole Stange-Thomann, Mikita Suyama, Mark J. Daly, Ewan Birney, Edward J. Kulbokas, Craig Pohl, James C. Mullikin, Chad Nusbaum, Genís Parra, Jade P. Vinson, Yoshihide Hayashizaki, Sante Gnerre, Eric Berry, Daniel G. Brown, Asif T. Chinwalla, Emmanuel Mongin, Robert B. Weiss, Raymond Wheeler, Andrew Kirby, Yasushi Okazaki, Lior Pachter, Ross C. Hardison, Brian Spencer, Carol J. Bult, Joanne O. Nelson, Pankaj K. Agarwal, Darren Grafham, Gustavo Glusman, Thomas A. Jones, Glenn Tesler, Simon Whelan, James Cuff, Robert S. Fulton, K F Barlow, Jörg Schultz, Matthias S. Schwartz, Alex Poliakov, Jonathan Butler, Bruce A. Roe, Angela S. Hinrichs, Alan Coulson, Kate Montgomery, Eric D. Green, Stephan Beck, Val Curwen, Krishna M. Roskin, Robert W. Plumb, Chris P. Ponting, Ralph Santos, Victor Sapojnikov, Nicolas Bray, Kymberlie H. Pepin, Charles W. Sugnet, Olivier Couronne, Ivica Letunic, Sophie Williams, Kimberly D. Delehaunty, Kerstin Lindblad-Toh, Zemin Ning, Karen Oliver, Toby Bloom, Michael Kamal, Nicholas J. Dickens, Eric S. Lander, Christine Lloyd, Donna Karolchik, Adrienne Hunt, Antonarakis, Stylianos, Couronne, Olivier, Dermitzakis, Emmanouil, and Zdobnov, Evgeny

Subjects
RNA, Untranslated, Proteome, Untranslated/genetics, Genome, Transgenic, Repetitive Sequences, Mice, Models, Neoplasms, Conserved Sequence, ddc:616, Genetics, Mice, Knockout, Base Composition, Multidisciplinary, Sex Chromosomes, Pseudogenes/genetics, Genomics, Multigene Family/genetics, Physical Chromosome Mapping, Neoplasms/genetics, CpG Islands/genetics, Proteome/genetics, Genetic Variation/genetics, Multigene Family, Mice/classification/ genetics, Models, Animal, Conserved Sequence/genetics, Sequence Analysis, Pseudogenes, Human, Genome evolution, Evolution, Sequence analysis, Knockout, Quantitative Trait Loci, Mice, Transgenic, Sex Chromosomes/genetics, Computational biology, Biology, Synteny, Chromosomes, Evolution, Molecular, Nucleic Acid/genetics, Genetic, Species Specificity, Mammalian/ genetics, Animals, Humans, Genes/genetics, Selection, Genetic, Selection, Repetitive Sequences, Nucleic Acid, Comparative genomics, Animal, Genome, Human, Molecular, Genetic Variation, DNA, Sequence Analysis, DNA, Chromosomes, Mammalian, Gene Expression Regulation, Genes, Mutagenesis, RNA, Human genome, CpG Islands, Quantitative Trait Loci/genetics, Reference genome
Abstract

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.

Published
2002

50. ARACHNE: a whole-genome shotgun assembler

Author

Serafim, Batzoglou, David B, Jaffe, Ken, Stanley, Jonathan, Butler, Sante, Gnerre, Evan, Mauceli, Bonnie, Berger, Jill P, Mesirov, and Eric S, Lander

Subjects
Genome, Genome, Human, Saccharomyces cerevisiae, Haemophilus influenzae, Contig Mapping, Drosophila melanogaster, Consensus Sequence, Methods, Animals, Humans, Genome, Fungal, Sequence Alignment, Algorithms, Genome, Bacterial, Software
Abstract

We describe a new computer system, called ARACHNE, for assembling genome sequence using paired-end whole-genome shotgun reads. ARACHNE has several key features, including an efficient and sensitive procedure for finding read overlaps, a procedure for scoring overlaps that achieves high accuracy by correcting errors before assembly, read merger based on forward-reverse links, and detection of repeat contigs by forward-reverse link inconsistency. To test ARACHNE, we created simulated reads providing approximately 10-fold coverage of the genomes of H. influenzae, S. cerevisiae, and D. melanogaster, as well as human chromosomes 21 and 22. The assemblies of these simulated reads yielded nearly complete coverage of the respective genomes, with a small number of contigs joined into a smaller number of supercontigs (or scaffolds). For example, analysis of the D. melanogaster genome yielded approximately 98% coverage with an N50 contig length of 324 kb and an N50 supercontig length of 5143 kb. The assembly accuracy was high, although not perfect: small errors occurred at a frequency of roughly 1 per 1 Mb (typically, deletion of approximately 1 kb in size), with a very small number of other misassemblies. The assembly was rapid: the Drosophila assembly required only 21 hours on a single 667 MHz processor and used 8.4 Gb of memory.

Published
2002

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