Nucleic Acids Research, 2002, Vol. 30, No. 1 52-55
© 2002 Oxford University Press
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders
McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1007, Baltimore, MD 21287-4922, USA
Received October 3, 2001; Accepted October 10, 2001.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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Online Mendelian Inheritance in Man (OMIMTM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support research and education in human genomics and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (www.ncbi.nlm.nih.gov/omim) is now distributed electronically by the National Center for Biotechnology Information (NCBI), where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, approved gene nomenclature, and the highly detailed mapviewer, as well as patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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Mendelian Inheritance in Man (MIM), which has been published in 12 print editions since 1966 (1), is a compendium of information on genetic disorders and genes. Its electronic counterpart, Online Mendelian Inheritance in Man (OMIMTM), is updated daily and is freely available on the World Wide Web (http://www.ncbi.nlm.nih.gov/omim/). OMIM is an authoritative full-text overview of genes and genetic phenotypes that can be used by students, researchers and clinicians. Curation of the database and editorial decisions take place at Johns Hopkins University School of Medicine. Authors are located at Johns Hopkins and around the world. Distribution of OMIM and software development are provided by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM). Funding is provided by the National Human Genome Research Institute (NHGRI) through a contract administered by the NLM (NO1-LM-9-3511). Maintenance of OMIM is also supported by a licensing fee associated with the commercial license agreement between Johns Hopkins University and DoubleTwist Inc.
OMIM has been generally available online since 1987, first from Johns Hopkins and since 1995 from the NCBI. The content, Mendelian Inheritance in Man, has been computerized since 1964 and periodically published, first in 1966 and the twelfth edition in 1998 (1). The print editions began as ‘catalogs of autosomal dominant, autosomal recessive and X-linked phenotypes’; since 1992 the subtitle of MIM has been ‘catalogs of human genes and genetic disorders’. Figure 1 illustrates the growth of the database in terms of numbers of entries in each edition of the book and in OMIM through October 1, 2001. OMIM averages at least 6000 unique users and 50 000 queries per day.
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SEARCHING OMIM |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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OMIM can be searched from its homepage or from any page in the NCBI Entrez suite of databases. The OMIM database can be searched by MIM number, disorder or gene name and/or symbol, or plain English (e.g. ‘cryptorchidism webbed neck’). The limits function may be used to perform a restricted search. Regardless of the method used, the search engine ranks the entries that match the query so that the entry(ies) that are most relevant to the question will be in the top 10 retrievals.
Each OMIM entry is assigned a unique six-digit number whose first digit indicates whether its inheritance is autosomal, X-linked, Y-linked, or mitochondrial: 1, autosomal dominant (entries created before May 15, 1994); 2, autosomal recessive (entries created before May 15, 1994); 3, X-linked loci or phenotypes; 4, Y-linked loci or phenotypes; 5, mitochondrial loci or phenotypes; 6, autosomal loci or phenotypes (created after May 15, 1994). Most MIM numbers are preceded by a symbol: an asterisk (*) indicates a separate locus and a proven mode of inheritance (in the judgment of the authors and editors); a hash sign (#) indicates a descriptive entry of a phenotype or gene family and that the discussion of the gene(s) reside in another entry(ies) as described in the first paragraph of the # entry. The absence of a symbol before an entry number means that the mode of inheritance has not been proven or that the distinction between this locus and another is uncertain.
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HOME PAGE |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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From the OMIM home page, one can review OMIM Statistics including the current count of the number of entries in OMIM (13 005 on October 1, 2001) organized by catalog (autosomal, X-linked, Y-linked and mitochondrial) as well as a count by chromosome of OMIM’s Synopsis of the Human Gene Map (7432 loci on October 1, 2001). The Update Log allows a quick check of the latest additions and changes to OMIM. About 100 new entries are created and 550 updated each month. Restrictions on Use informs the user that OMIM is copyrighted by the Johns Hopkins University and is made available to the general public subject to certain restrictions. Finally, the OMIM home page maintains links to many useful genetic resources including the Genetic Alliance, an umbrella organization of over 600 genetic support groups.
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WITHIN AN ENTRY |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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Within an OMIM entry, the blue bar along the left side provides a menu for direct access to subheadings in the entry (Fig. 2A and B). In addition there are links to resources both within and outside OMIM. MiniMIM takes the user to an abridged (but not continuously updated) version of the larger OMIM entry. These have been created by Dr Clarke Fraser for several hundred of the longest entries. Clinical Synopsis takes one to a listing of the clinical features of the disorder. There are over 4300 clinical synopses in OMIM. Genemap takes the user to OMIM’s Synopsis of the Human Gene Map. The links will differ in phenotype and gene entries. For example, the entry for cystic fibrosis (Fig. 2A) contains links to the cystic fibrosis locus-specific mutation database (CFMDB) and the list of CF cell lines available for research (Coriell). Figure 2B shows an example of links from the CFTR entry to Nomenclature, RefSeq, GenBank, Protein and UniGene databases. These links take one directly to the CFTR link within the other databases. Mutation database and cell repository database links are also accessible from the gene entry.
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An OMIM entry includes the primary title and symbol, alternative titles and symbols, and ‘included’ titles (i.e. related but not synonymous information that is not addressed in another entry). The gene map locus displays the cytogenetic location of the gene or disorder. This information is derived from the OMIM gene map. Multiple map locations may be given if a disease is known to be genetically heterogeneous. The light bulb icons located at the end of every paragraph link to the NCBI’s ‘neighboring’ feature. This feature takes keywords from the paragraph preceding the lightbulb and searches PubMed to create a list of related articles. References within an OMIM entry are linked to the complete citation at the end of the entry. The PubMed ID is linked to the PubMed abstract and in some instances the full text of the article if the journal is online. Following the references is a list of credits and edit history: the Creation Date lists the date the entry was created and the name of the author; authors who subsequently contribute additions or changes to the entry are given credit in the Contributors field; changes made by the editorial staff are documented in the Edit History field.
Allelic Variants with functional significance are maintained within the relevant gene entry. Allelic variants are given a 10-digit number: the six-digit number of the parent locus followed by a decimal point and a unique four-digit variant number. For most gene loci, only selected mutations are included as specific subentries. Criteria for inclusion include the first mutation to be discovered, high population frequency, distinctive phenotype, historic significance, unusual mechanism of mutation, unusual pathogenetic mechanism and distinctive inheritance (e.g. dominant with some mutations, recessive with other mutations in the same gene). Most of the allelic variants represent disease-producing mutations. A few polymorphisms are included, mainly those that show statistical association with particular common disorders. As of October 1, 2001, OMIM listed 9426 allelic variants in 1219 entries.
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THE OMIM GENE MAP |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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OMIM’s Synopsis of the Human Gene Map is maintained as a convenience to users and focuses on the ‘Morbid Map’, i.e. the mapping of disorders. In chromosome-by-chromosome tabular form, the OMIM Synopsis of the Human Gene Map lists, for each gene, the chromosomal location, gene symbols, method(s) of mapping and disorder(s) related to the specific gene. Links to the human/mouse homology maps are also provided. The Morbid Map is an alphabetical tabular listing of all mapped disorders. As of October 1, 2001, there were at least 2610 disorders spread across 2011 loci. In 1631 of these disorders, the molecular basis has been identified at the DNA level. These 1631 disorders of known molecular basis are distributed over the 1219 loci with at least one allelic variant; many loci (genes) are the site of more than one mutation causing phenotypically distinct disorders (e.g. cystic fibrosis and congenital bilateral absence of the vas deferens caused by different mutations in CFTR). The Morbid Map may be displayed from within NCBI’s MapViewer program to allow integration with finer physical and sequence-based maps of the human genome.
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FUTURE DIRECTIONS |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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As a continuously updated repository of intersecting data on genes and disorders, OMIM offers help to clinicians, students and researchers in unraveling the complex relationships between genes and disease. This task will undoubtedly become even more difficult and interesting as the Mendelian disorders are completely characterized and knowledge of the genes underlying complex traits and common diseases is gathered.
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FOOTNOTES |
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* To whom correspondence should be addressed. Tel: +1 410 614 3313; Fax: +1 410 955 4999; Email: ahamosh@mail.jhmi.edu
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSEARCHING OMIMHOME PAGEWITHIN AN ENTRYTHE OMIM GENE MAPFUTURE DIRECTIONSREFERENCES |
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1 McKusick,V.A. (1998) Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders, 12th edn. Johns Hopkins University Press, Baltimore, MD.
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