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Christina A Cuomo,
Ulrich Güldener,
Jin-Rong Xu,
Frances Trail,
B Gillian Turgeon,
Antonio Di Pietro,
Jonathan D Walton,
Li-Jun Ma,
Scott E Baker,
Martijn Rep, [......],
Hadi Quesneville,
M Isabel G Roncero,
Kye-Yong Seong,
Igor V Tetko,
Martin Urban,
Cees Waalwijk,
Todd J Ward,
Jiqiang Yao,
Bruce W Birren,
H Corby Kistler
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Christina A Cuomo,
Ulrich Güldener,
Jin-Rong Xu,
Frances Trail,
B Gillian Turgeon,
Antonio Di Pietro,
Jonathan D Walton,
Li-Jun Ma,
Scott E Baker,
Martijn Rep, [......],
Hadi Quesneville,
M Isabel G Roncero,
Kye-Yong Seong,
Igor V Tetko,
Martin Urban,
Cees Waalwijk,
Todd J Ward,
Jiqiang Yao,
Bruce W Birren,
H Corby Kistler
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Christina A Cuomo,
Christopher A Desjardins,
Malina A Bakowski,
Jonathan Goldberg,
Amy T Ma,
James J Becnel,
Elizabeth S Didier,
Lin Fan,
David I Heiman,
Joshua Z Levin,
Sarah Young,
Qiandong Zeng,
Emily R Troemel
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ABSTRACT: Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites.
Genome Research 07/2012; · 13.61 Impact Factor
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ABSTRACT: Fungal genome annotation is the starting point for analysis of genome content. This generally involves the application of diverse methods to identify features on a genome assembly such as protein-coding and non-coding genes, repeats and transposable elements, and pseudogenes. Here we describe tools and methods leveraged for eukaryotic genome annotation with a focus on the annotation of fungal nuclear and mitochondrial genomes. We highlight the application of the latest technologies and tools to improve the quality of predicted gene sets. The Broad Institute eukaryotic genome annotation pipeline is described as one example of how such methods and tools are integrated into a sequencing center's production genome annotation environment.
Mycology. 10/2011; 2(3):118-141.
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Christopher A Desjardins,
Mia D Champion,
Jason W Holder,
Anna Muszewska,
Jonathan Goldberg,
Alexandre M Bailão,
Marcelo Macedo Brigido,
Márcia Eliana da Silva Ferreira,
Ana Maria Garcia,
Marcin Grynberg, [......],
Maria Sueli Felipe,
Gustavo H Goldman,
Brian J Haas,
Juan G McEwen,
Gustavo Nino-Vega,
Rosana Puccia,
Gioconda San-Blas,
Celia Maria de Almeida Soares,
Bruce W Birren, Christina A Cuomo
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ABSTRACT: Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.
PLoS Genetics 10/2011; 7(10):e1002345. · 8.69 Impact Factor
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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, [......],
Catherine Sirven,
Darren M Soanes,
Nicholas J Talbot,
Matt Templeton,
Chandri Yandava,
Oded Yarden,
Qiandong Zeng,
Jeffrey A Rollins,
Marc-Henri Lebrun,
Marty Dickman
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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 <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea-specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.
PLoS Genetics 08/2011; 7(8):e1002230. · 8.69 Impact Factor
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Steven J Klosterman,
Krishna V Subbarao,
Seogchan Kang,
Paola Veronese,
Scott E Gold,
Bart P H J Thomma,
Zehua Chen,
Bernard Henrissat,
Yong-Hwan Lee,
Jongsun Park, [......],
Patrik Inderbitzin,
Ryan J Hayes,
David I Heiman,
Sarah Young,
Qiandong Zeng,
Reinhard Engels,
James Galagan, Christina A Cuomo,
Katherine F Dobinson,
Li-Jun Ma
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ABSTRACT: The vascular wilt fungi Verticillium dahliae and V. albo-atrum infect over 200 plant species, causing billions of dollars in annual crop losses. The characteristic wilt symptoms are a result of colonization and proliferation of the pathogens in the xylem vessels, which undergo fluctuations in osmolarity. To gain insights into the mechanisms that confer the organisms' pathogenicity and enable them to proliferate in the unique ecological niche of the plant vascular system, we sequenced the genomes of V. dahliae and V. albo-atrum and compared them to each other, and to the genome of Fusarium oxysporum, another fungal wilt pathogen. Our analyses identified a set of proteins that are shared among all three wilt pathogens, and present in few other fungal species. One of these is a homolog of a bacterial glucosyltransferase that synthesizes virulence-related osmoregulated periplasmic glucans in bacteria. Pathogenicity tests of the corresponding V. dahliae glucosyltransferase gene deletion mutants indicate that the gene is required for full virulence in the Australian tobacco species Nicotiana benthamiana. Compared to other fungi, the two sequenced Verticillium genomes encode more pectin-degrading enzymes and other carbohydrate-active enzymes, suggesting an extraordinary capacity to degrade plant pectin barricades. The high level of synteny between the two Verticillium assemblies highlighted four flexible genomic islands in V. dahliae that are enriched for transposable elements, and contain duplicated genes and genes that are important in signaling/transcriptional regulation and iron/lipid metabolism. Coupled with an enhanced capacity to degrade plant materials, these genomic islands may contribute to the expanded genetic diversity and virulence of V. dahliae, the primary causal agent of Verticillium wilts. Significantly, our study reveals insights into the genetic mechanisms of niche adaptation of fungal wilt pathogens, advances our understanding of the evolution and development of their pathogenesis, and sheds light on potential avenues for the development of novel disease management strategies to combat destructive wilt diseases.
PLoS Pathogens 07/2011; 7(7):e1002137. · 9.13 Impact Factor
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Sébastien Duplessis, Christina A Cuomo,
Yao-Cheng Lin,
Andrea Aerts,
Emilie Tisserant,
Claire Veneault-Fourrey,
David L Joly,
Stéphane Hacquard,
Joëlle Amselem,
Brandi L Cantarel, [......],
Yves Van de Peer,
Pierre Rouzé,
Jeffrey G Ellis,
Peter N Dodds,
Jacqueline E Schein,
Shaobin Zhong,
Richard C Hamelin,
Igor V Grigoriev,
Les J Szabo,
Francis Martin
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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.
Proceedings of the National Academy of Sciences 05/2011; 108(22):9166-71. · 9.68 Impact Factor
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Li-Jun Ma,
H Charlotte van der Does,
Katherine A Borkovich,
Jeffrey J Coleman,
Marie-Josée Daboussi,
Antonio Di Pietro,
Marie Dufresne,
Michael Freitag,
Manfred Grabherr,
Bernard Henrissat, [......],
B Gillian Turgeon,
Ilan Wapinski,
Olen Yoder,
Sarah Young,
Qiandong Zeng,
Shiguo Zhou,
James Galagan, Christina A Cuomo,
H Corby Kistler,
Martijn Rep
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ABSTRACT: Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
Nature 03/2010; 464(7287):367-73. · 36.28 Impact Factor
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ABSTRACT: The sequence of Saccharomyces cerevisiae enabled systematic genome-wide experimental approaches, demonstrating the power of having the complete genome of an organism. The rapid impact of these methods on research in yeast mobilized an effort to expand genomic resources for other fungi. The "fungal genome initiative" represents an organized genome sequencing effort to promote comparative and evolutionary studies across the fungal kingdom. Through such an approach, scientists can not only better understand specific organisms but also illuminate the shared and unique aspects of fungal biology that underlie the importance of fungi in biomedical research, health, food production, and industry. To date, assembled genomes for over 100 fungi are available in public databases, and many more sequencing projects are underway. Here, we discuss both examples of findings from comparative analysis of fungal sequences, with a specific emphasis on yeast genomes, and on the analytical approaches taken to mine fungal genomes. New sequencing methods are accelerating comparative studies of fungi by reducing the cost and difficulty of sequencing. This has driven more common use of sequencing applications, such as to study genome-wide variation in populations or to deeply profile RNA transcripts. These and further technological innovations will continue to be piloted in yeasts and other fungi, and will expand the applications of sequencing to study fungal biology.
Methods in enzymology 01/2010; 470:833-55. · 1.90 Impact Factor
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Li-Jun Ma,
Ashraf S Ibrahim,
Christopher Skory,
Manfred G Grabherr,
Gertraud Burger,
Margi Butler,
Marek Elias,
Alexander Idnurm,
B Franz Lang,
Teruo Sone, [......],
Lucila Ortiz-Castellanos,
Russell Poulter,
Julio Rodriguez-Romero,
José Ruiz-Herrera,
Yao-Qing Shen,
Qiandong Zeng,
James Galagan,
Bruce W Birren, Christina A Cuomo,
Brian L Wickes
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ABSTRACT: Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called "zygomycetes," R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99-880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin-proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14alpha-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments.
PLoS Genetics 08/2009; 5(7):e1000549. · 8.69 Impact Factor
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Geraldine Butler,
Matthew D Rasmussen,
Michael F Lin,
Manuel A S Santos,
Sharadha Sakthikumar,
Carol A Munro,
Esther Rheinbay,
Manfred Grabherr,
Anja Forche,
Jennifer L Reedy, [......],
Thyagarajan Srikantha,
Qiandong Zeng,
Judith Berman,
Matthew Berriman,
Joseph Heitman,
Neil A R Gow,
Michael C Lorenz,
Bruce W Birren,
Manolis Kellis, Christina A Cuomo
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ABSTRACT: Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
Nature 07/2009; 459(7247):657-62. · 36.28 Impact Factor
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ABSTRACT: High-throughput MS/MS was used to identify proteins secreted by Fusarium graminearum (Gibberella zeae) during growth on 13 media in vitro and in planta during infection of wheat heads. In vitro secreted proteins were collected from the culture filtrates, and in planta proteins were collected by vacuum infiltration. A total of 289 proteins (229 in vitro and 120 in planta) were identified with high statistical confidence. Forty-nine of the in planta proteins were not found in any of the in vitro conditions. The majority (91-100%) of the in vitro proteins had predicted signal peptides, but only 56% of the in planta proteins. At least 13 of the nonsecreted proteins found only in planta were single-copy housekeeping enzymes, including enolase, triose phosphate isomerase, phosphoglucomutase, calmodulin, aconitase, and malate dehydrogenase. The presence of these proteins in the in planta but not in vitro secretome might indicate that significant fungal lysis occurs during pathogenesis. On the other hand, several of the proteins lacking signal peptides that were found in planta have been reported to be potent immunogens secreted by animal pathogenic fungi, and therefore could be important in the interaction between F. graminearum and its host plants.
PROTEOMICS 10/2007; 7(17):3171-83. · 4.51 Impact Factor
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Christina A Cuomo,
Ulrich Güldener,
Jin-Rong Xu,
Frances Trail,
B Gillian Turgeon,
Antonio Di Pietro,
Jonathan D Walton,
Li-Jun Ma,
Scott E Baker,
Martijn Rep, [......],
Hadi Quesneville,
M Isabel G Roncero,
Kye-Yong Seong,
Igor V Tetko,
Martin Urban,
Cees Waalwijk,
Todd J Ward,
Jiqiang Yao,
Bruce W Birren,
H Corby Kistler
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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.
Science 10/2007; 317(5843):1400-2. · 31.20 Impact Factor
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Michael C. Zody,
Manuel Garber,
David J. Adams,
Ted Sharpe,
Jennifer Harrow,
James R. Lupski,
Christine Nicholson,
Steven M. Searle,
Laurens Wilming,
Sarah K. Young, [......],
Vijay Venkataraman,
Charles A. Whittaker,
Xiaoping Yang,
Andrew R. Zimmer,
Allan Bradley,
Tim Hubbard,
Bruce W. Birren,
Jane Rogers,
Eric S. Lander,
Chad Nusbaum
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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.
Nature 04/2006; 440(7087):1045-1049. · 36.28 Impact Factor
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Michael C Zody,
Manuel Garber,
Ted Sharpe,
Sarah K Young,
Lee Rowen,
Keith O'Neill,
Charles A Whittaker,
Michael Kamal,
Jean L Chang, Christina A Cuomo, [......],
Carrie Sougnez,
Sabrina M Stone,
Kerri Topham,
Dascena Vincent,
Shunguang Wang,
Andrew R Zimmer,
Bruce W Birren,
Leroy Hood,
Eric S Lander,
Chad Nusbaum
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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.
Nature 04/2006; 440(7084):671-5. · 36.28 Impact Factor
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Todd D Taylor,
Hideki Noguchi,
Yasushi Totoki,
Atsushi Toyoda,
Yoko Kuroki,
Ken Dewar,
Christine Lloyd,
Takehiko Itoh,
Tadayuki Takeda,
Dae-Won Kim, [......],
Xiaoping Yang,
Andrew R Zimmer,
Michael C Zody,
Bruce W Birren,
Chad Nusbaum,
Asao Fujiyama,
Masahira Hattori,
Jane Rogers,
Eric S Lander,
Yoshiyuki Sakaki
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ABSTRACT: Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856 olfactory receptor genes in the human genome, more than 40% are located in 28 single- and multi-gene clusters along this chromosome. Out of the 171 disorders currently attributed to the chromosome, 86 remain for which the underlying molecular basis is not yet known, including several mendelian traits, cancer and susceptibility loci. The high-quality data presented here--nearly 134.5 million base pairs representing 99.8% coverage of the euchromatic sequence--provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena.
Nature 04/2006; 440(7083):497-500. · 36.28 Impact Factor
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Michael C. Zody,
Manuel Garber,
Ted Sharpe,
Sarah K. Young,
Lee Rowen,
Keith O'Neill,
Charles A. Whittaker,
Michael Kamal,
Jean L. Chang, Christina A. Cuomo, [......],
Carrie Sougnez,
Sabrina M. Stone,
Kerri Topham,
Dascena Vincent,
Shunguang Wang,
Andrew R. Zimmer,
Bruce W. Birren,
Leroy Hood,
Eric S. Lander,
Chad Nusbaum
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[hide abstract]
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
Nature 03/2006; 440(7084):671-675. · 36.28 Impact Factor
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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, [......],
Gaiping Wen,
Satoru Yamazaki,
Sarah K Young,
Qiandong Zeng,
Andrew R Zimmer,
Andre Rosenthal,
Bruce W Birren,
Matthias Platzer,
Nobuyoshi Shimizu,
Eric S Lander
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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.
Nature 02/2006; 439(7074):331-5. · 36.28 Impact Factor
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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, [......],
Gaiping Wen,
Satoru Yamazaki,
Sarah K. Young,
Qiandong Zeng,
Andrew R. Zimmer,
Andre Rosenthal,
Bruce W. Birren,
Matthias Platzer,
Nobuyoshi Shimizu,
Eric S. Lander
[show abstract]
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ABSTRACT: The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome
Nature 01/2006; 439(7074):331-335. · 36.28 Impact Factor
