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Genome
About: Genome is a research topic. Over the lifetime, 74231 publications have been published within this topic receiving 3819713 citations.
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TL;DR: A high-resolution genetic map of the human genome is presented, based on statistical analyses of genetic variation data, and more than 25,000 recombination hotspots are identified, together with motifs and sequence contexts that play a role in hotspot activity.
Abstract: Genetic maps, which document the way in which recombination rates vary over a genome, are an essential tool for many genetic analyses. We present a high-resolution genetic map of the human genome, based on statistical analyses of genetic variation data, and identify more than 25,000 recombination hotspots, together with motifs and sequence contexts that play a role in hotspot activity. Differences between the behavior of recombination rates over large (megabase) and small (kilobase) scales lead us to suggest a two-stage model for recombination in which hotspots are stochastic features, within a framework in which large-scale rates are constrained.
1,134 citations
Broad Institute1, Mayo Clinic2, Harvard University3, Multiple Myeloma Research Foundation4, Translational Genomics Research Institute5, Howard Hughes Medical Institute6, Weizmann Institute of Science7, Ohio State University8, Catholic Medical Center9, University of Michigan10, City of Hope National Medical Center11, Emory University12, Rutgers University13, Washington University in St. Louis14, University of Chicago15, Massachusetts Institute of Technology16
TL;DR: In this paper, a massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs was reported, and several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set.
Abstract: Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.
1,134 citations
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TL;DR: A phylogeny of chloroplast genomes inferred from 41 proteins and 8,303 amino acids sites indicates that at least two independent secondary endosymbiotic events have occurred involving red algae and that amino acid composition bias in chloropleft proteins strongly affects plastid genome phylogeny.
Abstract: Chloroplasts were once free-living cyanobacteria that became endosymbionts, but the genomes of contemporary plastids encode only ≈5–10% as many genes as those of their free-living cousins, indicating that many genes were either lost from plastids or transferred to the nucleus during the course of plant evolution. Previous estimates have suggested that between 800 and perhaps as many as 2,000 genes in the Arabidopsis genome might come from cyanobacteria, but genome-wide phylogenetic surveys that could provide direct estimates of this number are lacking. We compared 24,990 proteins encoded in the Arabidopsis genome to the proteins from three cyanobacterial genomes, 16 other prokaryotic reference genomes, and yeast. Of 9,368 Arabidopsis proteins sufficiently conserved for primary sequence comparison, 866 detected homologues only among cyanobacteria and 834 other branched with cyanobacterial homologues in phylogenetic trees. Extrapolating from these conserved proteins to the whole genome, the data suggest that ≈4,500 of Arabidopsis protein-coding genes (≈18% of the total) were acquired from the cyanobacterial ancestor of plastids. These proteins encompass all functional classes, and the majority of them are targeted to cell compartments other than the chloroplast. Analysis of 15 sequenced chloroplast genomes revealed 117 nuclear-encoded proteins that are also still present in at least one chloroplast genome. A phylogeny of chloroplast genomes inferred from 41 proteins and 8,303 amino acids sites indicates that at least two independent secondary endosymbiotic events have occurred involving red algae and that amino acid composition bias in chloroplast proteins strongly affects plastid genome phylogeny.
1,134 citations
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Broad Institute1, Harvard University2, Howard Hughes Medical Institute3, University of California, Berkeley4, University of California, Los Angeles5, Chinese Academy of Sciences6, Max Planck Society7, Columbia University8, Massachusetts Institute of Technology9, Cayetano Heredia University10, University of Pennsylvania11, University College London12, University of Bern13, Leiden University14, Nanyang Technological University15, University of Chicago16, Estonian Biocentre17, National University of La Plata18, University of Oxford19, University of Bergen20, Novosibirsk State University21, Moscow Institute of Physics and Technology22, Sofia Medical University23, Armenian National Academy of Sciences24, Wellcome Trust Sanger Institute25, Raja Isteri Pengiran Anak Saleha Hospital26, Case Western Reserve University27, University of Tartu28, Estonian Academy of Sciences29, Stony Brook University30, Illumina31, Gladstone Institutes32, University of Helsinki33, University of Washington34, Bashkir State University35, Jaramogi Oginga Odinga University of Science and Technology36, Pompeu Fabra University37, University of Arizona38, University of Cambridge39, Leidos40, Université de Montréal41, University of Utah42, Altai State University43, Council of Scientific and Industrial Research44
TL;DR: It is demonstrated that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Abstract: Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
1,133 citations
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TL;DR: MUMmer4 is described, a substantially improved version of MUMmer that addresses genome size constraints by changing the 32-bit suffix tree data structure at the core of Mummer to a 48- bit suffix array, and that offers improved speed through parallel processing of input query sequences.
Abstract: The MUMmer system and the genome sequence aligner nucmer included within it are among the most widely used alignment packages in genomics. Since the last major release of MUMmer version 3 in 2004, it has been applied to many types of problems including aligning whole genome sequences, aligning reads to a reference genome, and comparing different assemblies of the same genome. Despite its broad utility, MUMmer3 has limitations that can make it difficult to use for large genomes and for the very large sequence data sets that are common today. In this paper we describe MUMmer4, a substantially improved version of MUMmer that addresses genome size constraints by changing the 32-bit suffix tree data structure at the core of MUMmer to a 48-bit suffix array, and that offers improved speed through parallel processing of input query sequences. With a theoretical limit on the input size of 141Tbp, MUMmer4 can now work with input sequences of any biologically realistic length. We show that as a result of these enhancements, the nucmer program in MUMmer4 is easily able to handle alignments of large genomes; we illustrate this with an alignment of the human and chimpanzee genomes, which allows us to compute that the two species are 98% identical across 96% of their length. With the enhancements described here, MUMmer4 can also be used to efficiently align reads to reference genomes, although it is less sensitive and accurate than the dedicated read aligners. The nucmer aligner in MUMmer4 can now be called from scripting languages such as Perl, Python and Ruby. These improvements make MUMer4 one the most versatile genome alignment packages available.
1,131 citations