RESUMEN
High-throughput sequencing of miRNAs has revealed the diversity and variability of mature and functional short noncoding RNAs, including their genomic origins, biogenesis pathways, sequence variability, and newly identified products such as miRNA-offset RNAs (moRs). Here we review known cases of alternative mature miRNA-like RNA fragments and propose a revised definition of miRNAs to encompass this diversity. We then review nomenclature guidelines for miRNAs and propose to extend nomenclature conventions to align with those for protein-coding genes established by international consortia. Finally, we suggest a system to encompass the full complexity of sequence variations (i.e., isomiRs) in the analysis of small RNA sequencing experiments.
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Vías Biosintéticas/genética , Variación Genética , MicroARNs/clasificación , MicroARNs/genética , Terminología como Asunto , Animales , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Regulación de la Expresión Génica , Humanos , Ratones , MicroARNs/metabolismo , ARN Citoplasmático Pequeño/genética , ARN Citoplasmático Pequeño/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ribonucleasa III/genética , Ribonucleasa III/metabolismo , Análisis de Secuencia de ARN , Transcriptoma , Pez CebraRESUMEN
The mouse is a prime organism of choice for modelling human disease. Over 450 inbred strains of mice have been described, providing a wealth of different genotypes and phenotypes for genetic and other studies. As new strains are generated and others become extinct, it is useful to review periodically what strains are available and how they are related to each other, particularly in the light of available DNA polymorphism data from microsatellite and other markers. We describe the origins and relationships of inbred mouse strains, 90 years after the generation of the first inbred strain. Given the large collection of inbred strains available, and that published information on these strains is incomplete, we propose that all genealogical and genetic data on inbred strains be submitted to a common electronic database to ensure this valuable information resource is preserved and used efficiently.
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Ratones Endogámicos/genética , Animales , Bases de Datos Factuales , Modelos Animales de Enfermedad , Humanos , Internet , Ratones , FenotipoRESUMEN
The Mouse Tumor Biology Database (MTB) is designed to provide an electronic data storage, search, and analysis system for information on mouse models of human cancer. The MTB includes data on tumor frequency and latency, strain, germ line, and somatic genetics, pathologic notations, and photomicrographs. The MTB collects data from the primary literature, other public databases, and direct submissions from the scientific community. The MTB is a community resource that provides integrated access to mouse tumor data from different scientific research areas and facilitates integration of molecular, genetic, and pathologic data. Current status of MTB, search capabilities, data types, and future enhancements are described in this article.
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Bases de Datos Factuales , Almacenamiento y Recuperación de la Información , Neoplasias Experimentales/patología , Neoplasias/patología , Animales , Biología Computacional , Modelos Animales de Enfermedad , Humanos , Internet , Ratones , Neoplasias/genética , Neoplasias Experimentales/genética , Interfaz Usuario-ComputadorRESUMEN
Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.
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Mapeo Cromosómico , Genoma , Ratones/genética , Muridae/genética , Animales , Evolución Biológica , Clonación Molecular , Cruzamientos Genéticos , Femenino , Marcadores Genéticos , Proyecto Genoma Humano , Humanos , Masculino , Familia de Multigenes , Mutación , Neoplasias/genéticaRESUMEN
Comparative maps display the chromosomal location of homologous genes in different species and highlight genetic segments that are conserved in evolution. These maps are used to study chromosomal changes that occurred during the divergence of mammalian lineages, to identify candidates for hereditary disease genes, and to facilitate mapping in other species. Recently, physical mapping in regions of known conserved linkage has revealed previously undetected chromosomal changes that may provide clues to understanding chromosomal structure and function and evolutionary processes. The availability of these data in electronically accessible formats is critical to the growth and analysis of comparative maps.
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Mapeo Cromosómico , Mamíferos/genética , Animales , Cromosomas , Bases de Datos Factuales , Enfermedad , Humanos , Hibridación Fluorescente in Situ , FenotipoRESUMEN
Chromosomal rearrangements such as inversions and translocations have played an important role in defining genome organization in existing mammals. The number of rearrangements that have occurred since divergence from the 'primordial' mammal has been modest and the distribution of these rearrangements among chromosomes seems to be random. As a result, each mammalian species has a unique arrangement of conserved and disrupted chromosomal segments as compared to other mammalian species. Genes are excellent markers for these chromosomal segments because homologies can be detected in highly divergent species. By comparing the chromosomal location of homologous genes in different species, maps of conserved chromosomal segments can be obtained. These comparative maps can be used to predict gene locations in other species, identify candidate disease genes, characterize the genetic basis for complex traits, and find modulators of disease susceptibility. Equally important is the use of comparative maps for addressing questions about genome organization and evolution.
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Evolución Biológica , Mapeo Cromosómico , Genoma , Mamíferos/genética , Animales , Aberraciones Cromosómicas , Cromosomas Humanos Par 11 , Enfermedades Genéticas Congénitas/genética , Ligamiento Genético , Genoma Humano , Humanos , Translocación Genética , Cromosoma XRESUMEN
The Mouse Genome Database (MGD) is the community database resource for the laboratory mouse, a key model organism for interpreting the human genome and for understanding human biology and disease (http://www.informatics.jax.org). MGD provides standard nomenclature and consensus map positions for mouse genes and genetic markers; it provides a curated set of mammalian homology records, user-defined chromosomal maps, experimental data sets and the definitive mouse 'gene to sequence' reference set for the research community. The integration and standardization of these data sets facilitates the transition between mouse DNA sequence, gene and phenotype annotations. A recent focus on allele and phenotype representations enhances the ability of MGD to organize and present data for exploring the relationship between genotype and phenotype. This link between the genome and the biology of the mouse is especially important as phenotype information grows from large mutagenesis projects and genotype information grows from large-scale sequencing projects.
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Bases de Datos Factuales , Genoma , Ratones/genética , Alelos , Animales , Marcadores Genéticos , Internet , Ratones Endogámicos , Alineación de SecuenciaRESUMEN
The Mouse Tumor Biology (MTB) Database serves as a curated, integrated resource for information about tumor genetics and pathology in genetically defined strains of mice (i.e., inbred, transgenic and targeted mutation strains). Sources of information for the database include the published scientific literature and direct data submissions by the scientific community. Researchers access MTB using Web-based query forms and can use the database to answer such questions as 'What tumors have been reported in transgenic mice created on a C57BL/6J background?', 'What tumors in mice are associated with mutations in the Trp53 gene?' and 'What pathology images are available for tumors of the mammary gland regardless of genetic background?'. MTB has been available on the Web since 1998 from the Mouse Genome Informatics web site (http://www.informatics.jax.org). We have recently implemented a number of enhancements to MTB including new query options, redesigned query forms and results pages for pathology and genetic data, and the addition of an electronic data submission and annotation tool for pathology data.
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Neoplasias Experimentales/patología , Neoplasias/patología , Animales , Bases de Datos como Asunto , Modelos Animales de Enfermedad , Humanos , Servicios de Información , Internet , Ratones , Neoplasias/genética , Neoplasias Experimentales/genéticaRESUMEN
The Gene Expression Database (GXD) is a community resource of gene expression information for the laboratory mouse. By combining the different types of expression data, GXD aims to provide increasingly complete information about the expression profiles of genes in different mouse strains and mutants, thus enabling valuable insights into the molecular networks that underlie normal development and disease. GXD is integrated with the Mouse Genome Database (MGD). Extensive interconnections with sequence databases and with databases from other species, and the development and use of shared controlled vocabularies extend GXD's utility for the analysis of gene expression information. GXD is accessible through the Mouse Genome Informatics web site at http://www.informatics.jax.org/ or directly at http://www.informatics.jax.org/menus/expression_menu. shtml.
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Bases de Datos Factuales , Perfilación de la Expresión Génica , Ratones/genética , Animales , Servicios de Información , InternetRESUMEN
The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.
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Bases de Datos Genéticas , Genes , Terminología como Asunto , Animales , Bibliografías como Asunto , Correo Electrónico , Genómica , Humanos , Almacenamiento y Recuperación de la Información , Internet , Biología Molecular , Proteínas/clasificación , Proteínas/genética , Programas InformáticosRESUMEN
Murine ovarian teratomas were used to determine recombination percentages for gene-gene and centromere-gene intervals. Data were obtained utilizing a recombinant inbred strain, LTXBJ, and a number of newly developed LT/SvEi congenic strains.--Centromere-gene recombination was measured at 11.3 +/- 1.2% for the centromere of chromosome 7 - Gpi-1 interval and 15.8 +/- 2.4% for the centromere of chromosome 14 - Np-1 interval using the ovarian teratoma method. The centromere - Np-1 interval was measured at 26.5 +/- 3.6% using a standard backcross involving the Rb6Bnr Robertsonian translocation as a centromere marker.--To assess the accuracy of the ovarian teratoma mapping method, we compared the recombination frequency obtained for the Mpi-1-Mod-1 interval on chromosome 9 using the ovarian teratoma method to that obtained using a standard backcross. The recombination percentage was 22.9 +/- 5.4 using the ovarian teratoma method and 18.6 +/- 3.3 using the backcross method, indicating that the two methods produce equivalent estimates of recombination. In addition, for centromere-gene intervals known to be more than 30 cM in length, the ovarian teratoma method was consistent with classical recombination methods, yielding high recombination percentages. We conclude from these results that the ovarian teratoma mapping method is a reliable method for estimating recombination frequencies and the most accurate method available for estimating centromere-gene recombination frequency in the mouse.
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Mapeo Cromosómico , Ratones/genética , Neoplasias Ováricas/genética , Teratoma/genética , Animales , Centrómero , Femenino , Ligamiento Genético , Heterocigoto , Isoenzimas/genética , Ratones Endogámicos , Neoplasias Experimentales/genética , Recombinación GenéticaRESUMEN
Mice altered by transgenesis or gene targeting ("knockouts") have increasingly been employed as alternative effective tools in elucidating the genetic basis of neurophysiology and behavior. Standardization of specific behavioral paradigms and phenotyping strategies will ensure that these behavioral mouse mutants offer robust models for evaluating the efficacy of novel therapeutics in the treatment of hereditary neurological disorders. The Induced Mutant Resource (IMR) at The Jackson Laboratory (Bar Harbor, Maine, USA) imports, cryopreserves, develops, maintains, and distributes to the research community biomedically valuable stocks of transgenic and targeted mutant mice. Information on behavioral and neurological strains-including a phenotypic synopsis, husbandry requirements, strain availability, and genetic typing protocols-is available through the IMR database (http://www.jax.org/resources/documents/imr/). A current catalog of available strains is readily accessible via the JAX Mice Web site at http://jaxmice.jax.org/index.shtml. In addition, The Jackson Laboratory is now home to TBASE (http://tbase.jax.org/), a comprehensive, community database whose primary focus is on mouse knockouts. TBASE accommodates an exhaustive bibliographical resource for transgenic and knockout mice and provides a detailed phenotypic characterization of numerous behavioral knockouts that is primarily extracted from the literature. Concerted efforts to merge the two resources into a new, schematically reformed database are underway.
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Conducta Animal/fisiología , Ratones Noqueados/genética , Ratones Transgénicos/genética , Fenotipo , Animales , Encéfalo/fisiología , Catálogos como Asunto , Bases de Datos Genéticas , Genética , Internet , RatonesAsunto(s)
Bases de Datos Factuales , Cooperación Internacional , Internet , Ratones Endogámicos , Ratones Mutantes , Academias e Institutos , Animales , Bancos de Muestras Biológicas , Aberraciones Cromosómicas , Cromosomas , Inglaterra , Genes , Laboratorios , Maine , Ratones , Ratones Endogámicos/embriología , Ratones Endogámicos/genética , Ratones Mutantes/embriología , Ratones Mutantes/genética , MutaciónRESUMEN
For effectively annotated phenotypes for mouse, a number of detailed phenotypic classification systems are needed. The rapidly increasing number of phenotypically described characteristics of both normal and mutant mice are providing a rich data set for comparison and analysis. However, we cannot rely on text descriptions that are subject to the word-usage style of the writer if we are to do large-scale comparative analysis of traits and diseases. The rationale for developing vocabularies and examples of several vocabularies being developed are described. Finally, the critical nature of community participation in both building and applying phenotype vocabularies is discussed.
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Algoritmos , Ratones/genética , Mutación , Terminología como Asunto , Animales , Bases de Datos Factuales , Internet , FenotipoRESUMEN
A community-wide effort to establish baseline phenotypic data on commonly used and genetically diverse inbred mouse strains and to provide the information through a publicly accessible database.