DOCSLIB.ORG

Designating Eukaryotic Orthology Via Processed Transcription Units Meng-Ru Ho1,2,3, Wen-Jung Jang2,3,4, Chun-Houh Chen5, Lan-Yang Ch’Ang3 and Wen-Chang Lin1,3,*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

3436–3442 Nucleic Acids Research, 2008, Vol. 36, No. 10 Published online 29 April 2008 doi:10.1093/nar/gkn227 Designating eukaryotic orthology via processed transcription units Meng-Ru Ho1,2,3, Wen-Jung Jang2,3,4, Chun-houh Chen5, Lan-Yang Ch’ang3 and Wen-chang Lin1,3,* 1Institute of Biomedical Informatics, National Yang-Ming University, 2Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, 3Institute of Biomedical Sciences, Academia Sinica, Taipei, 4Institute of Bioinformatics, National Chiao-Tung University, Hsinchu and 5Institute of Statistical Sciences, Academia Sinica, Taipei, Taiwan Received January 4, 2008; Revised April 8, 2008; Accepted April 11, 2008 ABSTRACT functional annotations. Orthologs are defined as genes in different species that originated from a single gene locus in Orthology is a widely used concept in comparative the last common ancestor (1–3). Therefore, orthology is and evolutionary genomics. In addition to prokar- a strong indicator of functional conservation, allows yotic orthology, delineating eukaryotic orthology has genome annotation based on information available from provided insight into the evolution of higher organ- other species, provides raw material for evolutionary anal- isms. Indeed, many eukaryotic ortholog databases ysis and comparative genomics and identifies taxonomi- have been established for this purpose. However, cally restricted sequences. However, computer-generated unlike prokaryotes, alternative splicing (AS) has ortholog designation is complicated because it demands hampered eukaryotic orthology assignments. There- knowledge of the ancestral state of genes and requires fore, existing databases likely contain ambiguous knowledge of complete gene repertoires. It is particularly eukaryotic ortholog relationships and possibly challenging with respect to complex eukaryotic genomes due to gene duplication, conversion to pseudogenes, and misclassify alternatively spliced protein isoforms gene loss and fusion. as in-paralogs, which are duplicated genes that There are several approaches for delineating ortho- arise following speciation. Here, we propose a new logous genes. The phylogenetic tree-based methods approach for designating eukaryotic orthology using HOVERGEN (4) and TreeFam (5) provide good accuracy, processed transcription units, and we present an but because the trees are constructed by multiple sequence orthology database prototype using the human and alignments or are corrected by experts, they provide mouse genomes. Currently existing programs cover limited comprehensiveness, homogeneity of quality and less than 69% of the human reference sequences expandability to new species. Alternatively, the Best- when assigning human/mouse orthologs. In con- Reciprocal-Hits (BRHs) method clusters orthologous trast, our method encompasses up to 80% of the genes based on their whole-length protein sequence human reference sequences. Moreover, the ortholog similarities and was first introduced by the Cluster of database presented herein is more than 92% con- Orthologous Groups (6) database. Phylogenetically, BRHs could be interpreted as genes from different species sistent with the existing databases. In addition to having the shortest connecting path over the distance- managing AS, this approach is capable of identifying based tree. The identification of BRHs is widely adopted orthologs of embedded genes and fusion genes in comparative genomics for its simplicity and feasibil- using syntenic evidence. In summary, this new ity of application to large-scale data. For example, approach is sensitive, specific and can generate a Ensembl Compara (7) (http://www.ensembl.org/biomart/ more comprehensive and accurate compilation of martview/) identifies orthologous genes by searching eukaryotic orthologs. BRHs between paired species. This notion has also been extended and applied to other approaches. Guided by a sequence similarity-based tree, HomoloGene (http:// www.ncbi.nlm.nih.gov/sites/entrez?db=homologene) uses INTRODUCTION a blastp program to group proteins from input organisms The rapidly growing number of available complete and to restrict the molecular distance to prevent unlikely genome sequences attests to the insistent need for orthologs from being grouped together. Inparanoid (8,9) *To whom correspondence should be addressed. Tel: +(886) 2 2652 3967; Fax: +(886) 2 2782 7654; Email: [email protected] ß 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Nucleic Acids Research, 2008, Vol. 36, No. 10 3437 (http://inparanoid.sbc.su.se/cgi-bin/index.cgi) assigns the (http://www.ncbi.nlm.nih.gov/RefSeq/), (http://www.ncbi. orthologous pair having the shortest distance among nlm.nih.gov/Genomes/). There were 40 814 coding the BRHs of a given ortholog group as the anchor, and sequences (NM_ and XM_) among the 41 677 human identifies other additional co-orthologs as in-paralogs. reference sequences and 48 797 (NM_ and XM_) coding Allowing ortholog designations among multiple genomes, sequences among the 50 481 mouse reference sequences. OrthoMCL (10,11) utilizes the Markov Cluster algorithm, This study focused only on the coding sequences. The a probabilistic model that groups (putative) orthologs and detailed genomic locations of human reference sequences paralogs. were obtained and downloaded from the NCBI ftp site: All currently available databases mentioned above are (ftp://ftp.ncbi.nlm.nih.gov/refseq/H_sapiens/H_sapiens/ based on protein sequence alignments and do not take mapview/). This information is used as the gold standard alternative splicing (AS) events into full consideration. for further dataset comparison and examination. In AS in eukaryotic genomes plays an important role in comparison of various datasets, we did find some incon- augmenting biological complexity (12) such that a single sistent coordinates of annotated genes from different gene can result in the generation of multiple proteins with data sources, which could be resulted from different high similarity. However, these proteins are isoforms and genomic mapping processes or distinct genome assembly should not be annotated as in-paralogs or orthologs. versions. We then performed subsequent re-alignment Unfortunately, the current eukaryotic ortholog databases process to ensure the genomic transcription locations and all discard AS by utilizing an all-against-all protein to extract genomic sequences in order to perform comparison that cannot exclude isoforms, which results orthologous gene database comparison on the identical in aberrant assignment of orthologs and in-paralogs. For version of genome build. example, the gene SORBS2 has two NM entries for human and several dozen XM entries in the transitory The gene-oriented ortholog database mouse annotation of May 2006 at our initial data exam- Human and mouse genomes were used to demonstrate ination (Supplementary Table 1). Identifying the ortholog the ortholog assignment capability of our program, and of SORBS2 between human and mouse without taking the resulting data are presented as the Gene Oriented AS into account would be a challenging task. Thanking Ortholog Database (GOOD). Figure 1A illustrates the the continuous efforts of the reference gene curation at basic methodology used to designate orthologs based on National Center for Biotechnology Information (NCBI) the processed transcription units of gene-oriented genomic and of the MGI (mouse genome informatics) project, this regions. We utilized 36 018 human reference sequences gene now has a single NM entry in the current mouse and 41 815 mouse reference sequences to identify 21 544 annotation. Therefore, taking the BRH of human iso- human and 22 511 mouse transcription regions. Among forms as the only annotated ortholog at the beginning of these transcription regions, we identified 17 214 orthologs. this study would derive incomplete ortholog annotations. This serves as an example that such issues could create Identifying genomic transcription regions assignment inconsistencies among different databases with separated update schedules. Alternatively, isoforms might To define transcription regions within genomic sequences, be misclassified as in-paralogs by methods such as we used the Blast-like alignment tool (BLAT) (15) Inparanoid, which assigns an anchor pair based on the program to determine the genome locations of reference best alignment score and leaves the rest as in-paralogs. sequences. Several of the human and mouse reference Therefore, including AS in orthologous gene identification sequences from NCBI have poly-A tails of varying is crucial for accuracy. lengths. These poly-A tails reduce the apparent sequence In this study, we propose a new approach for delineat- identities calculated by BLAT in subsequent analyses. ing orthologs among species that are somewhat related. Therefore, we removed all poly-A tails from the reference We utilized processed transcription units rather than sequences to increase the accuracy of the BLAT results. protein sequences as the BRHs input. This accounts for Because BLAT provides all possible alignment results for AS by recognizing gene-oriented genome regions, but it each sequence, we needed to define a threshold to maintains the advantages provided by sequence align-
Recommended publications
  • Adaptin, a Component of Clathrin-Coated Vesicles Associated with the Golgi Apparatus

    Adaptin, a Component of Clathrin-Coated Vesicles Associated with the Golgi Apparatus

    Cloning and Expression of -Adaptin, a Component of Clathrin-coated Vesicles Associated with the Golgi Apparatus Margaret S. Robinson Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR England Abstract. Adaptins are the major components of all. Weaker homology was seen between ~/- and adaptors, the protein complexes that link clathrin to /~-adaptins. Like both a- and #-adaptins, 3,-adaptin has transmembrane proteins (e.g., receptors) in coated pits a proline and glycine-rich hinge region, dividing it and vesicles. The plasma membrane adaptor contains into NH2- and COOH-terminal domains. A chimeric an ot-adaptin subunit and a/~-adaptin subunit, while 3,-adaptin was constructed from the mouse and bovine the Golgi adaptor contains a 3,-adaptin subunit and a cDNAs and transfected into Rat 1 fibroblasts. Im- /~'-adaptin subunit. A partial cDNA clone encoding munofluorescence microscopy was carded out using an 3,-adaptin was isolated from a bovine brain expression mAb which recognizes an epitope present on the chi- library by screening with antibodies, and was used to mera but not found on the rodent protein. The con- obtain a cDNA clone from a mouse brain library con- struct was found to have a distribution typical of en- taining the full coding sequence. The identity of the dogenous "¥-adaptin. Using this transfection system, it clones was confirmed by protein sequencing. The should now be possible to exchange domains between deduced amino acid sequence of 3,-adaptin was found or- and "r-adaptins, to try to find out how adaptors are to be homologous to that of c~-adaptin, with several targeted to the appropriate membrane compartment of stretches of identical amino acids or conservative sub- the cell, and how they recruit the appropriate recep- stitutions in the first *70 kD, and 25 % identity over- tors into the coated vesicle.
  • CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells With

    CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells With

    + CD29 identifies IFN-γ–producing human CD8 T cells with an increased cytotoxic potential Benoît P. Nicoleta,b, Aurélie Guislaina,b, Floris P. J. van Alphenc, Raquel Gomez-Eerlandd, Ton N. M. Schumacherd, Maartje van den Biggelaarc,e, and Monika C. Wolkersa,b,1 aDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; bLandsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cDepartment of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands; dDivision of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; and eDepartment of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019) Cytotoxic CD8+ T cells can effectively kill target cells by producing therefore developed a protocol that allowed for efficient iso- cytokines, chemokines, and granzymes. Expression of these effector lation of RNA and protein from fluorescence-activated cell molecules is however highly divergent, and tools that identify and sorting (FACS)-sorted fixed T cells after intracellular cytokine + preselect CD8 T cells with a cytotoxic expression profile are lacking. staining. With this top-down approach, we performed an un- + Human CD8 T cells can be divided into IFN-γ– and IL-2–producing biased RNA-sequencing (RNA-seq) and mass spectrometry cells. Unbiased transcriptomics and proteomics analysis on cytokine- γ– – + + (MS) analyses on IFN- and IL-2 producing primary human producing fixed CD8 T cells revealed that IL-2 cells produce helper + + + CD8 Tcells.
  • And Thermo-Adaptation in Hyperthermophilic Archaea: Identification of Compatible Solutes, Accumulation Profiles, and Biosynthetic Routes in Archaeoglobus Spp

    And Thermo-Adaptation in Hyperthermophilic Archaea: Identification of Compatible Solutes, Accumulation Profiles, and Biosynthetic Routes in Archaeoglobus Spp

    Universidade Nova de Lisboa Osmo- andInstituto thermo de Tecnologia-adaptation Química e Biológica in hyperthermophilic Archaea: Subtitle Subtitle Luís Pedro Gafeira Gonçalves Osmo- and thermo-adaptation in hyperthermophilic Archaea: identification of compatible solutes, accumulation profiles, and biosynthetic routes in Archaeoglobus spp. OH OH OH CDP c c c - CMP O O - PPi O3P P CTP O O O OH OH OH OH OH OH O- C C C O P O O P i Dissertation presented to obtain the Ph.D degree in BiochemistryO O- Instituto de Tecnologia Química e Biológica | Universidade Nova de LisboaP OH O O OH OH OH Oeiras, Luís Pedro Gafeira Gonçalves January, 2008 2008 Universidade Nova de Lisboa Instituto de Tecnologia Química e Biológica Osmo- and thermo-adaptation in hyperthermophilic Archaea: identification of compatible solutes, accumulation profiles, and biosynthetic routes in Archaeoglobus spp. This dissertation was presented to obtain a Ph. D. degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. By Luís Pedro Gafeira Gonçalves Supervised by Prof. Dr. Helena Santos Oeiras, January, 2008 Apoio financeiro da Fundação para a Ciência e Tecnologia (POCI 2010 – Formação Avançada para a Ciência – Medida IV.3) e FSE no âmbito do Quadro Comunitário de apoio, Bolsa de Doutoramento com a referência SFRH / BD / 5076 / 2001. ii ACKNOWNLEDGMENTS The work presented in this thesis, would not have been possible without the help, in terms of time and knowledge, of many people, to whom I am extremely grateful. Firstly and mostly, I need to thank my supervisor, Prof. Helena Santos, for her way of thinking science, her knowledge, her rigorous criticism, and her commitment to science.
  • A Yeast Phenomic Model for the Influence of Warburg Metabolism on Genetic Buffering of Doxorubicin Sean M

    A Yeast Phenomic Model for the Influence of Warburg Metabolism on Genetic Buffering of Doxorubicin Sean M

    Santos and Hartman Cancer & Metabolism (2019) 7:9 https://doi.org/10.1186/s40170-019-0201-3 RESEARCH Open Access A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin Sean M. Santos and John L. Hartman IV* Abstract Background: The influence of the Warburg phenomenon on chemotherapy response is unknown. Saccharomyces cerevisiae mimics the Warburg effect, repressing respiration in the presence of adequate glucose. Yeast phenomic experiments were conducted to assess potential influences of Warburg metabolism on gene-drug interaction underlying the cellular response to doxorubicin. Homologous genes from yeast phenomic and cancer pharmacogenomics data were analyzed to infer evolutionary conservation of gene-drug interaction and predict therapeutic relevance. Methods: Cell proliferation phenotypes (CPPs) of the yeast gene knockout/knockdown library were measured by quantitative high-throughput cell array phenotyping (Q-HTCP), treating with escalating doxorubicin concentrations under conditions of respiratory or glycolytic metabolism. Doxorubicin-gene interaction was quantified by departure of CPPs observed for the doxorubicin-treated mutant strain from that expected based on an interaction model. Recursive expectation-maximization clustering (REMc) and Gene Ontology (GO)-based analyses of interactions identified functional biological modules that differentially buffer or promote doxorubicin cytotoxicity with respect to Warburg metabolism. Yeast phenomic and cancer pharmacogenomics data were integrated to predict differential gene expression causally influencing doxorubicin anti-tumor efficacy. Results: Yeast compromised for genes functioning in chromatin organization, and several other cellular processes are more resistant to doxorubicin under glycolytic conditions. Thus, the Warburg transition appears to alleviate requirements for cellular functions that buffer doxorubicin cytotoxicity in a respiratory context.
  • CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells with an Increased Cytotoxic Potential

    CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells with an Increased Cytotoxic Potential

    + CD29 identifies IFN-γ–producing human CD8 T cells with an increased cytotoxic potential Benoît P. Nicoleta,b, Aurélie Guislaina,b, Floris P. J. van Alphenc, Raquel Gomez-Eerlandd, Ton N. M. Schumacherd, Maartje van den Biggelaarc,e, and Monika C. Wolkersa,b,1 aDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; bLandsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cDepartment of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands; dDivision of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; and eDepartment of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019) Cytotoxic CD8+ T cells can effectively kill target cells by producing therefore developed a protocol that allowed for efficient iso- cytokines, chemokines, and granzymes. Expression of these effector lation of RNA and protein from fluorescence-activated cell molecules is however highly divergent, and tools that identify and sorting (FACS)-sorted fixed T cells after intracellular cytokine + preselect CD8 T cells with a cytotoxic expression profile are lacking. staining. With this top-down approach, we performed an un- + Human CD8 T cells can be divided into IFN-γ– and IL-2–producing biased RNA-sequencing (RNA-seq) and mass spectrometry cells. Unbiased transcriptomics and proteomics analysis on cytokine- γ– – + + (MS) analyses on IFN- and IL-2 producing primary human producing fixed CD8 T cells revealed that IL-2 cells produce helper + + + CD8 Tcells.
  • Characterization of Chronic Lymphocytic Leukemia by Acgh/MLPA

    Characterization of Chronic Lymphocytic Leukemia by Acgh/MLPA

    UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS DEPARTAMENTO DE BIOLOGIA VEGETAL Characterization of Chronic Lymphocytic Leukemia by aCGH/MLPA Diana Cristina Antunes Candeias Adão Mestrado em Biologia Molecular e Genética Dissertação orientada por: Professora Doutora Isabel Maria Marques Carreira Professor Doutor Manuel Carmo Gomes 2018 Agradecimentos Começo por agradecer ao CIMAGO e à ACIMAGO por todo o apoio prestado no âmbito do desenvolvimento deste trabalho, tanto a nível logístico como financeiro. Agradeço também ao Laboratório de Citogenética e Genómica e ao Laboratório de Oncologia e Hematologia da FMUC, pelo fornecimento dos equipamentos e bens necessários à realização deste projeto. À Professora Doutora Isabel Marques Carreira, muito obrigada por me permitir desenvolver o meu projeto de tese de mestrado no Laboratório de Citogenética e Genómica da FMUC e por orientar este trabalho. Agradeço tudo o que me ensinou, o apoio e, acima de tudo, o exemplo que é como profissional na área da Genética Humana, que em muito contribuiu para o meu desenvolvimento e crescimento a nível académico e profissional. Ao Professor Doutor Manuel Carmo Gomes, pela sempre célere e incondicional orientação durante este ano. Mostrou-se sempre disponível para responder às minhas dúvidas e questões, e por isso demonstro o meu agradecimento. À Professora Doutora Ana Bela Sarmento Ribeiro, pela proposta que me apresentou para trabalhar no âmbito da Leucemia Linfocítica Crónica, pelo apoio nas correções necessárias, e pela possibilidade que me deu de realizar alguns passos do meu trabalho nas instalações do Laboratório de Oncologia e Hematologia da FMUC. Ao Miguel Pires, por todos os ensinamentos ao nível do trabalho laboratorial, pela enorme disponibilidade e apoio na realização desta tese, bem como pela amizade e conselhos que me deu.
  • Genome-Wide Association Meta-Analysis Using a Recessive Model Illuminates Genetic Architecture of Type 2 Diabetes Mark J

    Genome-Wide Association Meta-Analysis Using a Recessive Model Illuminates Genetic Architecture of Type 2 Diabetes Mark J

    medRxiv preprint doi: https://doi.org/10.1101/2021.07.08.21258700; this version posted July 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Genome-Wide Association Meta-Analysis Using a Recessive Model Illuminates Genetic Architecture of Type 2 Diabetes Mark J. O’Connor 1, 2, 3, 4, 5, Alicia Huerta-Chagoya 6, Paula Cortés-Sánchez 7, Silvía Bonàs-Guarch 7, Joanne B. Cole 4, 5, 8, 9, David Torrents 7, 10, Kumar Veerapen 8, 11, 12, Niels Grarup 13, Mitja Kurki 8, 11, 12, Carsten F. Rundsten 13, Oluf Pedersen 13, Ivan Brandslund 14, 15, Allan Linneberg 16, 17, Torben Hansen 13, Aaron Leong 1, 2, 3, 4, 5, 8, 18,#, Jose C. Florez 1, 2, 3, 4, 5, 8,#, Josep M. Mercader 3, 4, 5, 8,# 1. Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. 2. Endocrine Division, Massachusetts General Hospital, Boston, MA, USA. 3. Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. 4. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. 5. Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. 6. Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 7. Barcelona Supercomputing Center (BSC), Barcelona, Spain. 8. Department of Medicine, Harvard Medical School, Boston, MA, USA. 9.
  • The Disruption Ofcelf6, a Gene Identified by Translational Profiling

    The Disruption Ofcelf6, a Gene Identified by Translational Profiling

    2732 • The Journal of Neuroscience, February 13, 2013 • 33(7):2732–2753 Neurobiology of Disease The Disruption of Celf6, a Gene Identified by Translational Profiling of Serotonergic Neurons, Results in Autism-Related Behaviors Joseph D. Dougherty,1,2 Susan E. Maloney,1,2 David F. Wozniak,2 Michael A. Rieger,1,2 Lisa Sonnenblick,3,4,5 Giovanni Coppola,4 Nathaniel G. Mahieu,1 Juliet Zhang,6 Jinlu Cai,8 Gary J. Patti,1 Brett S. Abrahams,8 Daniel H. Geschwind,3,4,5 and Nathaniel Heintz6,7 Departments of 1Genetics and 2Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, 3UCLA Center for Autism Research and Treatment, Semel Institute for Neuroscience and Behavior, 4Program in Neurogenetics, Department of Neurology, and 5Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, 6Laboratory of Molecular Biology, Howard Hughes Medical Institute, and 7The GENSAT Project, Rockefeller University, New York, New York 10065, and 8Departments of Genetics and Neuroscience, Albert Einstein College of Medicine, New York, New York 10461 The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons.
  • Suppression of the Pelo Protein by Wolbachia and Its Effect on Dengue Virus in Aedes Aegypti

    Suppression of the Pelo Protein by Wolbachia and Its Effect on Dengue Virus in Aedes Aegypti

    RESEARCH ARTICLE Suppression of the pelo protein by Wolbachia and its effect on dengue virus in Aedes aegypti Sultan Asad1, Mazhar Hussain1¤, Leon Hugo2, Solomon Osei-Amo1, Guangmei Zhang1, Daniel Watterson3, Sassan Asgari1* 1 Australian Infectious Disease Research Centre, School of Biological Sciences, The University of Queensland, Brisbane Australia, 2 QIMR Berghofer Medical Research Institute, Herston, Australia, 3 School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane Australia ¤ Current address: School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, QIMR Berghofer Medical Research Institute, Herston Australia a1111111111 * [email protected] a1111111111 a1111111111 a1111111111 Abstract a1111111111 The endosymbiont Wolbachia is known to block replication of several important arboviruses, including dengue virus (DENV), in the mosquito vector Aedes aegypti. So far, the exact mechanism of this viral inhibition is not fully understood. A recent study in Drosophila mela- OPEN ACCESS nogaster has demonstrated an interaction between the pelo gene and Drosophila C virus. In Citation: Asad S, Hussain M, Hugo L, Osei-Amo S, this study, we explored the possible involvement of the pelo protein, that is involved in pro- Zhang G, Watterson D, et al. (2018) Suppression of tein translation, in Wolbachia-mediated antiviral response and mosquito-DENV interaction. the pelo protein by Wolbachia and its effect on We found that pelo is upregulated during DENV replication and its silencing leads to reduced dengue virus in Aedes aegypti. PLoS Negl Trop Dis DENV virion production suggesting that it facilities DENV replication. However, in the pres- 12(4): e0006405. https://doi.org/10.1371/journal.
  • Supplementary Tables S1-S3

    Supplementary Tables S1-S3

    Supplementary Table S1: Real time RT-PCR primers COX-2 Forward 5’- CCACTTCAAGGGAGTCTGGA -3’ Reverse 5’- AAGGGCCCTGGTGTAGTAGG -3’ Wnt5a Forward 5’- TGAATAACCCTGTTCAGATGTCA -3’ Reverse 5’- TGTACTGCATGTGGTCCTGA -3’ Spp1 Forward 5'- GACCCATCTCAGAAGCAGAA -3' Reverse 5'- TTCGTCAGATTCATCCGAGT -3' CUGBP2 Forward 5’- ATGCAACAGCTCAACACTGC -3’ Reverse 5’- CAGCGTTGCCAGATTCTGTA -3’ Supplementary Table S2: Genes synergistically regulated by oncogenic Ras and TGF-β AU-rich probe_id Gene Name Gene Symbol element Fold change RasV12 + TGF-β RasV12 TGF-β 1368519_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 42.22 5.53 75.28 1373000_at sushi-repeat-containing protein, X-linked 2 (predicted) Srpx2 19.24 25.59 73.63 1383486_at Transcribed locus --- ARE 5.93 27.94 52.85 1367581_a_at secreted phosphoprotein 1 Spp1 2.46 19.28 49.76 1368359_a_at VGF nerve growth factor inducible Vgf 3.11 4.61 48.10 1392618_at Transcribed locus --- ARE 3.48 24.30 45.76 1398302_at prolactin-like protein F Prlpf ARE 1.39 3.29 45.23 1392264_s_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 24.92 3.67 40.09 1391022_at laminin, beta 3 Lamb3 2.13 3.31 38.15 1384605_at Transcribed locus --- 2.94 14.57 37.91 1367973_at chemokine (C-C motif) ligand 2 Ccl2 ARE 5.47 17.28 37.90 1369249_at progressive ankylosis homolog (mouse) Ank ARE 3.12 8.33 33.58 1398479_at ryanodine receptor 3 Ryr3 ARE 1.42 9.28 29.65 1371194_at tumor necrosis factor alpha induced protein 6 Tnfaip6 ARE 2.95 7.90 29.24 1386344_at Progressive ankylosis homolog (mouse)
  • The Genome 10K Project: a Way Forward

    The Genome 10K Project: a Way Forward

    The Genome 10K Project: A Way Forward Klaus-Peter Koepfli,1 Benedict Paten,2 the Genome 10K Community of Scientists,Ã and Stephen J. O’Brien1,3 1Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, 199034 St. Petersburg, Russian Federation; email: [email protected] 2Department of Biomolecular Engineering, University of California, Santa Cruz, California 95064 3Oceanographic Center, Nova Southeastern University, Fort Lauderdale, Florida 33004 Annu. Rev. Anim. Biosci. 2015. 3:57–111 Keywords The Annual Review of Animal Biosciences is online mammal, amphibian, reptile, bird, fish, genome at animal.annualreviews.org This article’sdoi: Abstract 10.1146/annurev-animal-090414-014900 The Genome 10K Project was established in 2009 by a consortium of Copyright © 2015 by Annual Reviews. biologists and genome scientists determined to facilitate the sequencing All rights reserved and analysis of the complete genomes of10,000vertebratespecies.Since Access provided by Rockefeller University on 01/10/18. For personal use only. ÃContributing authors and affiliations are listed then the number of selected and initiated species has risen from ∼26 Annu. Rev. Anim. Biosci. 2015.3:57-111. Downloaded from www.annualreviews.org at the end of the article. An unabridged list of G10KCOS is available at the Genome 10K website: to 277 sequenced or ongoing with funding, an approximately tenfold http://genome10k.org. increase in five years. Here we summarize the advances and commit- ments that have occurred by mid-2014 and outline the achievements and present challenges of reaching the 10,000-species goal. We summarize the status of known vertebrate genome projects, recommend standards for pronouncing a genome as sequenced or completed, and provide our present and futurevision of the landscape of Genome 10K.
  • Chromosome 18 Gene Dosage Map 2.0

    Chromosome 18 Gene Dosage Map 2.0

    Human Genetics (2018) 137:961–970 https://doi.org/10.1007/s00439-018-1960-6 ORIGINAL INVESTIGATION Chromosome 18 gene dosage map 2.0 Jannine D. Cody1,2 · Patricia Heard1 · David Rupert1 · Minire Hasi‑Zogaj1 · Annice Hill1 · Courtney Sebold1 · Daniel E. Hale1,3 Received: 9 August 2018 / Accepted: 14 November 2018 / Published online: 17 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chro- mosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.