Author
Andrew J Knights
Other affiliations: Babraham Institute
Bio: Andrew J Knights is an academic researcher from Wellcome Trust Sanger Institute. The author has contributed to research in topics: Gene expression & Chromatin. The author has an hindex of 19, co-authored 32 publications receiving 5137 citations. Previous affiliations of Andrew J Knights include Babraham Institute.
Papers
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Wellcome Trust Sanger Institute1, Seattle Biomed2, Katholieke Universiteit Leuven3, GATC Biotech4, Max Planck Society5, Washington University in St. Louis6, University of Trieste7, International Centre for Genetic Engineering and Biotechnology8, European Bioinformatics Institute9, University of São Paulo10, National Scientific and Technical Research Council11, Université catholique de Louvain12, University of London13, University of Edinburgh14, University of Glasgow15, University of Wisconsin-Madison16, University of York17, University of Cambridge18, University of Washington19
TL;DR: The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Tritryp genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling.
Abstract: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
1,357 citations
University of Cologne1, Laboratory of Molecular Biology2, Wellcome Trust Sanger Institute3, Baylor College of Medicine4, University of California, San Diego5, Northwestern University6, University of Tsukuba7, Ludwig Maximilian University of Munich8, University of Cambridge9, Hokkaido University10, Pasteur Institute11, University of York12, National Institute of Genetics13, University of Tokyo14, Princeton University15, University of Dundee16
TL;DR: A proteome-based phylogeny shows that the amoebozoa diverged from the animal–fungal lineage after the plant–animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
Abstract: The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
1,289 citations
TL;DR: This analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome.
Abstract: The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
1,102 citations
TL;DR: The sequence of chromosomes 1, 3–9 and 13 of P. falciparum clone 3D7 is reported—these chromosomes account for approximately 55% of the total genome, and a highly conserved sequence element is identified in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
Abstract: Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
273 citations
TL;DR: The finished sequence and biological annotation of human chromosome 1 is reported, which reveals patterns of sequence variation that reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident.
Abstract: The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
249 citations
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TL;DR: The genome sequence of P. falciparum clone 3D7 is reported, which is the most (A + T)-rich genome sequenced to date and is being exploited in the search for new drugs and vaccines to fight malaria.
Abstract: The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.
4,312 citations
TL;DR: In this paper, the authors characterized Cpf1, a putative class 2 CRISPR effector, which is a single RNA-guided endonuclease lacking tracrRNA and utilizes a T-rich protospacer-adjacent motif.
3,436 citations
University of California, Los Angeles1, United States Department of Energy2, University of Paris3, Duke University4, University of Massachusetts Medical School5, University of California, Berkeley6, Centre national de la recherche scientifique7, University of California, San Francisco8, Sun Yat-sen University9, University of Tennessee Health Science Center10, University of Minnesota11, Iowa State University12, Genetic Information Research Institute13, Salk Institute for Biological Studies14, Stanford University15, University of Liège16, University of Nebraska–Lincoln17, University of Cambridge18, Washington University in St. Louis19, University of Córdoba (Spain)20, Kyoto University21, Carnegie Institution for Science22, National Autonomous University of Mexico23, University of Münster24, École Normale Supérieure25, University of Melbourne26, University of Paris-Sud27, University of Mainz28, Scripps Research Institute29, Ohio State University30, University of Chicago31, University of Jena32, University of Arizona33, Louisiana State University34, University of New Brunswick35, University College London36, University of Potsdam37, Delaware Biotechnology Institute38, Boyce Thompson Institute for Plant Research39, Macquarie University40, Oklahoma State University Center for Health Sciences41, İzmir University of Economics42, Academy of Sciences of the Czech Republic43, Charles University in Prague44, St. Edward's University45, University of Puget Sound46, Hokkaido University47, Tsinghua University48, Washington State University49, Appalachian State University50, Marquette University51
TL;DR: Analyses of the Chlamydomonas genome advance the understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
2,554 citations
TL;DR: It is proposed that gene regulatory networks are sufficiently interconnected such that all genes expressed in disease-relevant cells are liable to affect the functions of core disease-related genes and that most heritability can be explained by effects on genes outside core pathways.
2,257 citations
TL;DR: All of the major steps in RNA-seq data analysis are reviewed, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping.
Abstract: RNA-sequencing (RNA-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping. We highlight the challenges associated with each step. We discuss the analysis of small RNAs and the integration of RNA-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics.
1,963 citations