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• W1968820591 abstract "A recurring motto from the Tony Blair government in the UK was “Education, Education, Education.” An appropriate exhortation for the biomedical sciences would be “Standardization, Standardization, Standardization.” Inevitably, the two go hand in hand, and the challenge we face is how to encourage researchers to comply with existing or emerging standard terminologies and nomenclatures. This is both an educational and a regulatory task, one in which it is vital to succeed if we are to efficiently and accurately share and use the huge volume of data emerging in the biosciences. A recurring motto from the Tony Blair government in the UK was “Education, Education, Education.” An appropriate exhortation for the biomedical sciences would be “Standardization, Standardization, Standardization.” Inevitably, the two go hand in hand, and the challenge we face is how to encourage researchers to comply with existing or emerging standard terminologies and nomenclatures. This is both an educational and a regulatory task, one in which it is vital to succeed if we are to efficiently and accurately share and use the huge volume of data emerging in the biosciences. Investigators in the fields of medicine and biomedical research communicate effectively, primarily through the use of specialized and defined standard terminology (Becker, 1959Becker S.W. Dermatological nomenclature.Arch Derm. 1959; 80: 778-787Crossref PubMed Scopus (5) Google Scholar; Brown et al., 2007Brown S.J. Tilli C.M.L.J. Jackson B. Avilion A.A. MacLeod M.C. Maltais L.J. et al.Rodent Lce gene clusters; new nomenclature, gene organization, and divergence of human and rodent genes.J Invest Dermatol. 2007; 127: 1782-1786Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar; Friedman, 1955Friedman A.A. Medical nomenclature and dermatology.Va Med Mon (1918. 1955; 82: 516PubMed Google Scholar; Jackson, 2001Jackson R. What's in a name? Comments on the Dermatological Dictionary by Ledier, Rosenblum, and Carter.J Cutan Med Surg. 2001; 5: 505-507Crossref PubMed Scopus (2) Google Scholar; Porter, 2006Porter R.M. The new keratin nomenclature.J Invest Dermatol. 2006; 126: 2366-2368Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar; Taylor, 2006Taylor S. As simple as black and white?.J Am Acad Dermatol. 2006; 54: 1070-1071Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar). It has remained fluid over time to accommodate new discoveries and technological innovations but remains the key to denoting advances in science. Within the field of dermatology, a committee has functioned for decades to standardize nomenclature (Becker, 1959Becker S.W. Dermatological nomenclature.Arch Derm. 1959; 80: 778-787Crossref PubMed Scopus (5) Google Scholar). The Journal of Investigative Dermatology and other publications in the field should insist on strict adherence to the most current dermatological nomenclature to maintain the high esteem of members in the field. 1The Jackson Laboratory, Bar Harbor, Maine, USA and 2Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK Similar efforts for standardization of nomenclature are currently under way concerning the pathology of the laboratory mouse, now the preeminent model system for human disease (Rosenthal and Brown, 2007Rosenthal N. Brown S. The mouse ascending: perspectives for human-disease models.Nat Cell Biol. 2007; 9: 993-999Crossref PubMed Scopus (241) Google Scholar). Because this complicated effort covers all organ systems and merges veterinary and human medical terminology, various panels have been formed to address this issue. For cancer, the National Cancer Institute's Mouse Models for Human Cancer Consortium created panels of specialists to review mouse models for human cancer by organ system to develop a consensus nomenclature (http://emice.nci.nih.gov/emice; Cardiff et al., 2000Cardiff R.D. Moghanaki D. Jensen R.A. Genetically engineered mouse models of mammary intraepithelial neoplasia.J Mammary Gland Biol Neoplasia. 2000; 5: 421-437Crossref PubMed Scopus (59) Google Scholar; Kogan et al., 2002Kogan S.C. Ward J.M. Anver M.R. Berman J.J. Brayton C. Cardiff R.D. et al.Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice.Blood. 2002; 100: 238-245Crossref PubMed Scopus (325) Google Scholar; Nikitin et al., 2004Nikitin A. Alcaraz A. Anver M.R. Bronson R.T. Cardiff R.D. Dixon D. et al.Classification of proliferative pulmonary lesions of the mouse: recommendations of the mouse models of human cancers consortium.Cancer Res. 2004; 64: 2307-2316Crossref PubMed Scopus (273) Google Scholar; Shappell et al., 2004Shappell S.B. Thomas G.V. Roberts R.L. Herbert R. Ittmann M.M. Rubin M.A. et al.Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.Cancer Res. 2004; 64: 2270-2305Crossref PubMed Scopus (444) Google Scholar). A more extensive website, the Mouse Tumor Biology Database (http://tumor.informatics.jax.org), incorporates the mouse genetic literature with images of all types of cancer arising either spontaneously in mice of inbred strains or as a consequence of genetic engineering (Bult et al., 2006Bult C.J. Krupke D.M. Vincent M.J. Allio T. Sundberg J.P. Mikaelian I. et al.The Mouse Tumor Biology Database: an online resource for mouse models of human cancer. In: Nagel S (ed.Cancer Bioinformatics: From Therapy Design to Treatment. Wiley, West Sussex, UK2006: 143-153Crossref Scopus (1) Google Scholar; Naf et al., 2002Naf D. Krupke D.M. Sundberg J.P. Eppig J.T. Bult C.J. The mouse tumor biology database: a public resource for cancer genetics and pathology of the mouse.Cancer Res. 2002; 62: 1235-1240PubMed Google Scholar). For general mouse pathology, an international consortium was formed to develop MPATH, an evolving and expanding ontology of mouse pathology terms. The consortium is linked to a large image database (http://www.Pathbase.net). These online resources are supplemented by highly specialized residential training courses and internship programs (Sundberg et al., 2007Sundberg J.P. Hackman R.C. HogenEsch H. Nikitin A.Y. Ward J.M. Training mouse pathologists: Five years of Pathology of Mouse Models of Human Disease Workshops.Toxicol Pathol. 2007; 35: 447-448Crossref PubMed Scopus (10) Google Scholar), but even with these opportunities, a significant gap remains between demand and availability of appropriately trained pathologists (Schofield et al., 2009Schofield P.N. Brown S.D. Sundberg J.P. Arends M. Warren M.V. Dubus P. et al.PRIME importance of pathology expertise.Nat Biotechnol. 2009; 27: 24-25Crossref PubMed Scopus (15) Google Scholar). The second annual meeting of Coordination and Sustainability of Inter-national Mouse Informatics Resources (http://www.casimir.org.uk), held at the Nobel Forum, Stockholm, Sweden, 2–3 December 2008, focused on the topic “One Medicine, One Pathology,” with the goal of coordinating data collection, nomenclature, and comparative pathology among various disciplines (Sundberg and SchofieldSundberg and Schofield Sundberg JP Schofield PN (in press) One medicine, one pathology, one health concept J Am Vet Med AssocGoogle Scholar). These approaches refine existing nomenclature systems developed over the previous two centuries, with which all medically trained scientists are familiar. Researchers should use these online resources to double-check interpretations and standardize the results described in their publications. To that end, databases are now available that provide a “virtual second opinion” for mouse pathology nomenclature, with links to photomicrographs (http://research.jax.org/faculty/sundberg/index.html; Sundberg(in press) Sundberg BA Schofield PN Gruenberger M Sundberg JP A data capture tool for mouse pathology phenotyping. Vet PatholGoogle Scholar; Sundberg et al., 2008Sundberg J.P. Sundberg B.A. Schofield P.N. Integrating mouse anatomy and pathology ontologies into a diagnostic/phenotyping database: tools for record keeping and teaching.Mammalian Genome. 2008; 19: 413-419Crossref PubMed Scopus (35) Google Scholar). A larger and far more serious nomenclature issue involves genetic terminology, an area in which few have been trained. Rules for genetic nomenclature were devised in 1919, when the American Society of Naturalists appointed a Committee on Genetic Form and Nomenclature, with CC Little as chairman (Little, 1921Little C.C. Report of the Committee on Genetic Form and Nomenclature.Am Nat. 1921; 55: 175Crossref Google Scholar). As they applied to the mouse, these rules were published in 1940 by Dunn, Grueneberg, and Snell (Dunn et al., 1940Dunn L.C. Grüneberg H. Snell G.D. Report on the committee of mouse genetics nomenclature.J Hered. 1940; 31: 505-506Google Scholar). Subsequently, the International Committee for Standardized Genetic Nomenclature in Mice (Green et al., 1963Green M.C. Grueneberg H. Hertwig P. Heston W.E. Lyon M.F. Medvedev N.N. et al.A revision of the standardized genetic nomenclature for mice.J Hered. 1963; 54: 159-162Crossref PubMed Scopus (28) Google Scholar) was formed to standardize nomenclature for inbred, congenic, and recombinant inbred strains as well as mutant locus/gene symbols. Investigators proposed new names for mutant mouse strains and stocks (and later for genes) to this committee, and unique names and symbols were assigned to prevent ambiguity. Unfortunately, journal editors have been slow to require authors to adhere to this system, creating major problems. Today, with the advent of genetic engineering and large-scale mutagenesis projects, multiple allelic mutations (both spontaneous or chemical/radiation-induced “remutations” and multiple constructs of targeted mutations involving the same gene), often with very different phenotypes, are available. Strain and mutation symbols, when used correctly, are critical to the materials and methods section of any manuscript, and they help reviewers determine which allelic mutation is under investigation, enabling them to determine the validity of the work being reported. Mouse (International Committee on Standardized Genetic Nomenclature for Mice: http://www.informatics.jax.org/mgihome/nomen/strains.shtml), human (HU GO Gene Nomenclature Committee: http://www.genenames.org), and rat (Rat Gene Nomenclature Committee: http://rgnc.gen.gu.se/RGNChem.html) nomenclature rules are available online. For laboratory mice, names of inbred strains are in all capital letters. After a forward slash (/) following the strain name, and equally important, are the laboratory (investigator) and institutional codes that designate substrains. For example, NOD/ShiLtSzJ designates a subline of the nonobese diabetic strain originally inbred at Shionogi (Shi), in Japan, and later maintained by Edward Leiter (Lt), from whose colony a subline was initiated by Leonard Shultz (Sz). The strain is maintained and distributed by The Jackson Laboratory (J). Abbreviations for commonly used inbred strains are also standardized. C57BL/6J is abbreviated B6, which is also used to refer to mixed or unknown/unspecified C57BL/6 substrains. B6ByJ refers to C57BL/6ByJ and B6EiJ to C57BL/6JEi, which, like many other substrains, carry unique mutations. In contrast, the BALB/cJ inbred strain is abbreviated C, and BALB/cByJ mice are CBy. Mixed inbred or incipient congenic strains, in which a mutated gene is being transferred from one strain background onto another strain, are designated by a semicolon between the strain abbreviations (e.g., B6;129), followed by a hyphen and the mutant gene symbol. This nomenclature, indicating a segregating background, is in sharp contrast to congenic strain names, in which the semicolon is replaced by a period to indicate that the congenic procedure has been completed (10 backcrosses, N10, onto the new strain, e.g., B6.129). Six backcross generations (N6; incipient congenic) are commonly accepted by many journals as adequate, and many mouse distributors use congenic nomenclature at N5; however, speed congenic technology has demonstrated that this is not optimal (Markel et al., 1997Markel P. Shu P. Ebeling C. Carlson G.A. Nagle D.L. Smutko J.S. et al.Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains.Nat Genet. 1997; 17: 280-284Crossref PubMed Scopus (338) Google Scholar). Mouse gene symbols are shown in italics with only the first letter capitalized. Symbols for dominant or semidominant spontaneous or chemical/radiation-induced mutations of unidentified genes are written in the same manner as gene symbols. Recessive allelic mutations appear entirely in lowercase. Once the previously unknown gene has been identified, the allele (mutation) symbol is superscripted, appearing immediately after the gene symbol. For example, the mouse hairless and rhino Jackson mutations are written Hrhr and Hrrh7J, respectively. To differentiate them from mouse genes, human gene symbols are presented in all capital letters; e.g., the human hairless gene symbol is HR. For both mice and humans, gene and allele names (as opposed to symbols) are written entirely in lowercase unless they include a proper noun, as with Alstrom syndrome I. Whereas gene symbols are italicized, symbols for their respective proteins are not. The symbols for both mouse and human proteins are printed entirely in capital letters.Use of standardized genetic nomenclature is absolutely essential Specific nomenclature guidance for strains, genes, alleles/mutations, and chromosomal aberrations can be found on the Mouse Genome Informatics website via links from the Nomenclature Home Page (http://www.informatics.jax.org/mgihome/nomen/gene.shtml). Strict adherence to these nomenclature standards will allow work to be compared fairly and, more important, reviewed accurately. The power of informatics to integrate and analyze phenotype and genotype data within and across species is continually increasing, although it is still outstripped by the volume of emerging data, particularly from the analysis of mouse mutants. It is essential that the way in which alleles are expressed and disease descriptions are captured be semantically unambiguous and standardized to allow computational analysis. Nonstandard nomenclature is a serious barrier to the analysis of large historical datasets in which local nomenclature and data structure are idiosyncratic. In addition, it is becoming a rate-limiting step in the analysis of new data, particularly data published only in the printed literature and not uploaded to databases, because failure to use standardized terminology results in ambiguity and inaccuracy, which confound text-mining tools, resulting in the need for laborious and expensive extraction of the data by professional curators. We thank Beverly Richards-Smith for her constructive comments and verification of nomenclature issues raised in the manuscript. This work was supported by grants from the National Institutes of Health (CA34196, CA089713, and RR17436) and the Commission of the European Community, Framework Programme 6 Contract LSHG-CT-2006-037811, CASIMIR." @default.
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