OMIM.org: leveraging knowledge across phenotype-gene relationships

Abstract

For over 50 years Mendelian Inheritance in Man has chronicled the collective knowledge of the field of medical genetics. It initially cataloged the known X-linked, autosomal recessive and autosomal dominant inherited disorders, but grew to be the primary repository of curated information on both genes and genetic phenotypes and the relationships between them. Each phenotype and gene is given a separate entry assigned a stable, unique identifier. The entries contain structured summaries of new and important information based on expert review of the biomedical literature. OMIM.org provides interactive access to the knowledge repository, including genomic coordinate searches of the gene map, views of genetic heterogeneity of phenotypes in Phenotypic Series, and side-by-side comparisons of clinical synopses. OMIM.org also supports computational queries via a robust API. All entries have extensive targeted links to other genomic resources and additional references. Updates to OMIM can be found on the update list or followed through the MIMmatch service. Updated user guides and tutorials are available on the website. As of September 2018, OMIM had over 24,600 entries, and the OMIM Morbid Map Scorecard had 6,259 molecularized phenotypes connected to 3,961 genes.

Figure 1.

The pace of disease gene discovery as cataloged by the OMIM Morbid Map Scorecard. The current scorecard is available from https://omim.org/statistics/geneMap. As of 29 September 2018, there were over 6259 disorders spread across 3961 genes.

Figure 2.

OMIM clinical synopses can be selected and viewed side-by-side to enable quick review of the similarities and differences of clinical features between and among synopses. Anatomical headings can be toggled open or closed to aid in feature comparison.

Figure 3.

Leveraging clinical naming across molecular biology. OMIM’s approach to naming enhances analysis of the relationship between phenotypes and their molecular basis and provides new avenues of research through increased molecular understanding. Grouping of similar phenotypes into a Phenotypic Series facilitates the collection of genes underlying related clinical conditions. (A) Variation in the MSX1 gene can cause 3 clinically distinct disorders, each of which is part of separate Phenotypic Series. Each series lists various forms of the same phenotype caused by distinct genes (numbers in gray). (B) Ehlers-Danlos syndrome has been classified into 13 different clinical subtypes. The mutated gene(s) in one subtype, hypermobile, has not been found. Some of the subtypes have been found to be genetically heterogeneous, with a total of 21 different EDS syndromes. The grouping of the subtypes with their causative genes provides a unique focus for biological research.