Showing papers by "Bruce W. Birren published in 2007"
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TL;DR: The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.
Abstract: We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.
4,565 citations
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Pardis C. Sabeti1, Pardis C. Sabeti2, Patrick Varilly1, Patrick Varilly2 +255 more•Institutions (50)
TL;DR: ‘Long-range haplotype’ methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population are developed.
Abstract: With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.
1,778 citations
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J. Craig Venter Institute1, Broad Institute2, Virginia Tech3, Johns Hopkins University4, University of Notre Dame5, Harvard University6, Colorado State University7, Northwestern University8, University of California, Riverside9, University of Oxford10, Purdue University11, Pasteur Institute12, University of São Paulo13, University of Geneva14, University of Massachusetts Amherst15, Instituto Butantan16, University of A Coruña17, University of Göttingen18
TL;DR: A draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genomes of the malaria vector Anopheles gambiae was presented in this paper.
Abstract: We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 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 approximately 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 approximately 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.
1,107 citations
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Massachusetts Institute of Technology1, Purdue University2, Michigan State University3, Cornell University4, University of Córdoba (Spain)5, Broad Institute6, Pacific Northwest National Laboratory7, University of Amsterdam8, University of Natural Resources and Life Sciences, Vienna9, Rothamsted Research10, University of Minnesota11, University of Ottawa12, United States Department of Agriculture13, Saint Louis University14, University of Arizona15, University of Tennessee Health Science Center16, National Center for Agricultural Utilization Research17, National Academy of Sciences of Ukraine18, Wageningen University and Research Centre19
TL;DR: The genome of the filamentous fungus Fusarium graminearum, a major pathogen of cultivated cereals, was sequenced and annotated and many highly polymorphic regions contained sets of genes implicated in plant-fungus interactions and were unusually divergent, with higher rates of recombination.
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.
822 citations
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TL;DR: An initial survey of genetic variation across the P. falciparum genome is described and its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite is demonstrated.
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.
309 citations
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TL;DR: Statistical analysis shows that transcripts encoding proteins involved in protein synthesis and in the production of extracellular proteases, cellulases, and xylanases predominate in the infection library, suggesting that the fungus is dependant on the degradation of wheat macromolecular constituents to provide the carbon skeletons and energy for the synthesis of proteins and other components destined for the developing pycnidiospores.
Abstract: Stagonospora nodorum is a major necrotrophic fungal pathogen of wheat (Triticum aestivum) and a member of the Dothideomycetes, a large fungal taxon that includes many important plant pathogens affecting all major crop plant families. Here, we report the acquisition and initial analysis of a draft genome sequence for this fungus. The assembly comprises 37,164,227 bp of nuclear DNA contained in 107 scaffolds. The circular mitochondrial genome comprises 49,761 bp encoding 46 genes, including four that are intron encoded. The nuclear genome assembly contains 26 classes of repetitive DNA, comprising 4.5% of the genome. Some of the repeats show evidence of repeat-induced point mutations consistent with a frequent sexual cycle. ESTs and gene prediction models support a minimum of 10,762 nuclear genes. Extensive orthology was found between the polyketide synthase family in S. nodorum and Cochliobolus heterostrophus, suggesting an ancient origin and conserved functions for these genes. A striking feature of the gene catalog was the large number of genes predicted to encode secreted proteins; the majority has no meaningful similarity to any other known genes. It is likely that genes for host-specific toxins, in addition to ToxA, will be found among this group. ESTs obtained from axenic mycelium grown on oleate (chosen to mimic early infection) and late-stage lesions sporulating on wheat leaves were obtained. Statistical analysis shows that transcripts encoding proteins involved in protein synthesis and in the production of extracellular proteases, cellulases, and xylanases predominate in the infection library. This suggests that the fungus is dependant on the degradation of wheat macromolecular constituents to provide the carbon skeletons and energy for the synthesis of proteins and other components destined for the developing pycnidiospores.
275 citations
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TL;DR: CDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts, and drive the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes.
Abstract: A consortium of investigators is engaged in a functional genomics project centered on the filamentous fungus Neurospora, with an eye to opening up the functional genomic analysis of all the filamentous fungi. The overall goal of the four interdependent projects in this effort is to acccomplish functional genomics, annotation, and expression analyses of Neurospora crassa, a filamentous fungus that is an established model for the assemblage of over 250,000 species of nonyeast fungi. Building from the completely sequenced 43-Mb Neurospora genome, Project 1 is pursuing the systematic disruption of genes through targeted gene replacements, phenotypic analysis of mutant strains, and their distribution to the scientific community at large. Project 2, through a primary focus in Annotation and Bioinformatics, has developed a platform for electronically capturing community feedback and data about the existing annotation, while building and maintaining a database to capture and display information about phenotypes. Oligonucleotide-based microarrays created in Project 3 are being used to collect baseline expression data for the nearly 11,000 distinguishable transcripts in Neurospora under various conditions of growth and development, and eventually to begin to analyze the global effects of loss of novel genes in strains created by Project 1. cDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts. In addition, these studies have driven the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes.
201 citations
01 Jan 2007
TL;DR: An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An.
Abstract: Vishvanath Nene,* Jennifer R. Wortman, Daniel Lawson, Brian Haas, Chinnappa Kodira, Zhijian (Jake) Tu, Brendan Loftus, Zhiyong Xi, Karyn Megy, Manfred Grabherr, Quinghu Ren, Evgeny M. Zdobnov, Neil F. Lobo, Kathryn S. Campbell, Susan E. Brown, Maria F. Bonaldo, Jingsong Zhu, Steven P. Sinkins, David G. Hogenkamp, Paolo Amedo, Peter Arensburger, Peter W. Atkinson, Shelby Bidwell, Jim Biedler, Ewan Birney, Robert V. Bruggner, Javier Costas, Monique R. Coy, Jonathan Crabtree, Matt Crawford, Becky deBruyn, David DeCaprio, Karin Eiglmeier, Eric Eisenstadt, Hamza El-Dorry, William M. Gelbart, Suely L. Gomes, Martin Hammond, Linda I. Hannick, James R. Hogan, Michael H. Holmes, David Jaffe, J. Spencer Johnston, Ryan C. Kennedy, Hean Koo, Saul Kravitz, Evgenia V. Kriventseva, David Kulp, Kurt LaButti, Eduardo Lee, Song Li, Diane D. Lovin, Chunhong Mao, Evan Mauceli, Carlos F. M. Menck, Jason R. Miller, Philip Montgomery, Akio Mori, Ana L. Nascimento, Horacio F. Naveira, Chad Nusbaum, Sinead O’Leary, Joshua Orvis, Mihaela Pertea, Hadi Quesneville, Kyanne R. Reidenbach, Yu-Hui Rogers, Charles W. Roth, Jennifer R. Schneider, Michael Schatz, Martin Shumway, Mario Stanke, Eric O. Stinson, Jose M. C. Tubio, Janice P. VanZee, Sergio VerjovskiAlmeida, Doreen Werner, Owen White, Stefan Wyder, Qiandong Zeng, Qi Zhao, Yongmei Zhao, Catherine A. Hill, Alexander S. Raikhel, Marcelo B. Soares, Dennis L. Knudson, Norman H. Lee, James Galagan, Steven L. Salzberg, Ian T. Paulsen, George Dimopoulos, Frank H. Collins, Bruce Birren, Claire M. Fraser-Liggett, David W. Severson*
95 citations