52–55 Nucleic Acids Research, 2002, Vol. 30, No. 1 © 2002 Oxford University Press Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders Ada Hamosh*, Alan F. Scott, Joanna Amberger, Carol Bocchini, David Valle and Victor A. McKusick 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 ABSTRACT Online Mendelian Inheritance in Man (OMIM™) is a comprehensive, authoritative and timely knowledge- base 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 pheno- type 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 Figure 1. Growth of the database in terms of numbers of entries in each edition straightforward portal to the burgeoning information of MIM and in OMIM on October 1, 2001. in human genetics. INTRODUCTION Medicine (NLM). Funding is provided by the National Human Genome Research Institute (NHGRI) through a contract Mendelian Inheritance in Man (MIM), which has been administered by the NLM (NO1-LM-9-3511). Maintenance of published in 12 print editions since 1966 (1), is a compendium OMIM is also supported by a licensing fee associated with the of information on genetic disorders and genes. Its electronic commercial license agreement between Johns Hopkins counterpart, Online Mendelian Inheritance in Man (OMIM™), University and DoubleTwist Inc. is updated daily and is freely available on the World Wide Web OMIM has been generally available online since 1987, first (http://www.ncbi.nlm.nih.gov/omim/). OMIM is an authoritative full-text overview of genes and genetic phenotypes that can be from Johns Hopkins and since 1995 from the NCBI. The used by students, researchers and clinicians. Curation of the content, Mendelian Inheritance in Man, has been computerized database and editorial decisions take place at Johns Hopkins since 1964 and periodically published, first in 1966 and the University School of Medicine. Authors are located at Johns twelfth edition in 1998 (1). The print editions began as ‘catalogs Hopkins and around the world. Distribution of OMIM and of autosomal dominant, autosomal recessive and X-linked software development are provided by the National Center for phenotypes’; since 1992 the subtitle of MIM has been ‘catalogs of Biotechnology Information (NCBI) at the National Library of human genes and genetic disorders’. Figure 1 illustrates the *To whom correspondence should be addressed. Tel: +1 410 614 3313; Fax: +1 410 955 4999; Email: [email protected] Nucleic Acids Research, 2002, Vol. 30, No. 1 53 growth of the database in terms of numbers of entries in each differ in phenotype and gene entries. For example, the entry for edition of the book and in OMIM through October 1, 2001. cystic fibrosis (Fig. 2A) contains links to the cystic fibrosis OMIM averages at least 6000 unique users and 50 000 queries locus-specific mutation database (CFMDB) and the list of CF per day. 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 SEARCHING OMIM directly to the CFTR link within the other databases. Mutation OMIM can be searched from its homepage or from any page in database and cell repository database links are also accessible the NCBI Entrez suite of databases. The OMIM database can from the gene entry. be searched by MIM number, disorder or gene name and/or An OMIM entry includes the primary title and symbol, symbol, or plain English (e.g. ‘cryptorchidism webbed neck’). alternative titles and symbols, and ‘included’ titles (i.e. related The limits function may be used to perform a restricted search. but not synonymous information that is not addressed in Regardless of the method used, the search engine ranks the another entry). The gene map locus displays the cytogenetic entries that match the query so that the entry(ies) that are most location of the gene or disorder. This information is derived relevant to the question will be in the top 10 retrievals. from the OMIM gene map. Multiple map locations may be Each OMIM entry is assigned a unique six-digit number given if a disease is known to be genetically heterogeneous. whose first digit indicates whether its inheritance is autosomal, The light bulb icons located at the end of every paragraph link X-linked, Y-linked, or mitochondrial: 1, autosomal dominant to the NCBI’s ‘neighboring’ feature. This feature takes (entries created before May 15, 1994); 2, autosomal recessive keywords from the paragraph preceding the lightbulb and (entries created before May 15, 1994); 3, X-linked loci or searches PubMed to create a list of related articles. References phenotypes; 4, Y-linked loci or phenotypes; 5, mitochondrial within an OMIM entry are linked to the complete citation at the loci or phenotypes; 6, autosomal loci or phenotypes (created end of the entry. The PubMed ID is linked to the PubMed after May 15, 1994). Most MIM numbers are preceded by a abstract and in some instances the full text of the article if the symbol: an asterisk (*) indicates a separate locus and a proven journal is online. Following the references is a list of credits mode of inheritance (in the judgment of the authors and and edit history: the Creation Date lists the date the entry was editors); a hash sign (#) indicates a descriptive entry of a created and the name of the author; authors who subsequently phenotype or gene family and that the discussion of the gene(s) contribute additions or changes to the entry are given credit in reside in another entry(ies) as described in the first paragraph the Contributors field; changes made by the editorial staff are of the # entry. The absence of a symbol before an entry number documented in the Edit History field. means that the mode of inheritance has not been proven or that Allelic Variants with functional significance are maintained the distinction between this locus and another is uncertain. 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 HOME PAGE gene loci, only selected mutations are included as specific From the OMIM home page, one can review OMIM Statistics subentries. Criteria for inclusion include the first mutation to including the current count of the number of entries in OMIM be discovered, high population frequency, distinctive pheno- (13 005 on October 1, 2001) organized by catalog (autosomal, type, historic significance, unusual mechanism of mutation, X-linked, Y-linked and mitochondrial) as well as a count by unusual pathogenetic mechanism and distinctive inheritance chromosome of OMIM’s Synopsis of the Human Gene Map (e.g. dominant with some mutations, recessive with other (7432 loci on October 1, 2001). The Update Log allows a quick mutations in the same gene). Most of the allelic variants check of the latest additions and changes to OMIM. About represent disease-producing mutations. A few polymorphisms 100 new entries are created and 550 updated each month. are included, mainly those that show statistical association Restrictions on Use informs the user that OMIM is copyrighted with particular common disorders. As of October 1, 2001, by the Johns Hopkins University and is made available to the OMIM listed 9426 allelic variants in 1219 entries. 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 THE OMIM GENE MAP 600 genetic support groups. 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 WITHIN AN ENTRY form, the OMIM Synopsis of the Human Gene Map lists, for Within an OMIM entry, the blue bar along the left side each gene, the chromosomal location, gene symbols, method(s) of provides a menu for direct access to subheadings in the entry mapping and disorder(s) related to the specific gene. Links to (Fig. 2A and B). In addition there are links to resources both the human/mouse homology maps are also provided. The within and outside OMIM. MiniMIM takes the user to an Morbid Map is an alphabetical tabular listing of all mapped abridged (but not continuously updated) version of the larger disorders. As of October 1, 2001, there were at least 2610 OMIM entry. These have been created by Dr Clarke Fraser for disorders spread across 2011 loci. In 1631 of these disorders, several hundred of the longest entries. Clinical Synopsis takes the molecular basis has been identified at the DNA level. one to a listing of the clinical features of the disorder. There are These 1631 disorders of known molecular basis are distributed over 4300 clinical synopses in OMIM.