A New Face and New Challenges for Online Mendelian
Inheritance in Man (OMIMs)
Joanna Amberger, Carol Bocchini, and Ada Hamosh?
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland
For the HVP Bioinformatics Special Issue
Received 10 December 2010; accepted revised manuscript 19 January 2011.
Published online 5 April 2011 in Wiley Online Library (www.wiley.com/humanmutation). DOI: 10.1002/humu.21466
ABSTRACT: OMIM’s task of cataloging the association
between human phenotypes and their causative genes (the
Morbid Map of the Genome) and classifying and naming
newly recognized disorders is growing rapidly. Establishing
the relationship between genotype and phenotype has
become increasingly complex. New technologies such as
genome-wide association studies (GWAS) and array
comparative genomic hybridization (aCGH) define ‘‘risk
alleles’’ that are inherently prone to substantial interpreta-
tion and modification. In addition, whole exome and
genome sequencing are expected to result in many reports
of new mendelian disorders and their causative genes. In
preparation for the onslaught of new information, we have
launched a new Website to allow a more comprehensive
and structured view of the contents of OMIM and to
improve interconnectivity with complementary clinical and
basic science genetics resources. This article focuses on the
content of OMIM, the process and intent of disease
classification and nosology, and anticipated improvements
in our new Website (http://www.omim.org).
Hum Mutat 32:564–567, 2011. & 2011 Wiley-Liss, Inc.
KEY WORDS: OMIM; nosology; disease classification;
For over 40 years, OMIM has cataloged human mendelian disease
and has focused on the relationship between genes and their
molecular variants and associated phenotypes [McKusick, 2007].
The exponential growth of the database reflects the growth of
knowledge in the field of medical genetics. As of 29 November 2010,
OMIM had over 20,267 entries describing 13,606 genes and over
7,000 disorders. OMIM continues to add new gene descriptions to
the database, with priority for creation given to genes with clinical
relevance and functional significance. The phenotype entries in
OMIM primarily describe single gene mendelian disorders, for
example, sickle cell anemia (MIM# 603903), which is caused by
mutation in the hemoglobin beta gene (HBB; MIM# 141900), and
achondroplasia (MIM# 100800), which is caused by mutation in the
fibroblast growth factor receptor 3 gene (FGFR3; MIM# 134934).
Other phenotype entries describe complex traits for which variation
in a single gene results in significant contribution to the phenotype,
for example, macular degeneration (see MIM# 603075), skin/hair/
eye pigment variation (see MIM# 227220), and inflammatory bowel
disease (see MIM# 266600). A number of inherited disorders
previously thought to be single gene disorders, such as Williams-
Beuren syndrome (MIM# 194050), Smith-Magenis syndrome
(MIM# 182290), and DiGeorge/velocardiofacial syndrome (e.g.,
MIM# 188400), have been shown to be contiguous gene deletion or
duplication syndromes. Recent advances in chromosome microarray
technology have allowed for rapid discovery of new members in this
class of inherited genetic disease. This expanding category of copy
number variation (CNV) disorders are now included in OMIM.
In OMIM, mutations known to cause a phenotype are cataloged in
the allelic variants section of the causative gene entry. Only selected
mutations are included, based on the following criteria: the first
mutation to be discovered, a distinctive phenotype, an unusual type of
mutation for a specific phenotype, an unusual pathogenetic mechan-
ism, high population frequency, a distinctive inheritance (e.g.,
dominant with some mutations and recessive with others in the same
gene), and historically important mutations. Most of the allelic
variants represent disease-producing mutations; however, a few
polymorphisms are included, many of which show a positive statistical
correlation with particular common d isorders. As of 29 November
2010, OMIM had over 18,000 allelic variants distributed among 2,494
genes and associated with 4,218 different disorders or susceptibilities
(Fig. 1). A tabular view of the allelic variant information is available
from the ‘‘Table View’’ link under the Allelic Variant heading in gene
entries and in the ‘‘Table View’’ link in the Table of Contents menu
bar in gene entries. In addition, a summary of the gene phenotype
relationships (the Morbid Anatomy of the Human Genome) is
presented at the top of each entry (Fig. 2).
The naming and classification of mendelian phenotypes is
essential to our understanding of biologic variation, and MIM has
played a central role in this nosology. The process of disease
classification involves defining recognizable patterns of features
and highlighting those that allow one condition to be distin-
guished from another. Classifying disease is an evolving process
that is affected by diagnostic modalities, medical intervention,
molecular understanding, and community consensus. Sound
nosologic practices will aid clinicians in diagnosis, prognosis,
counseling, and management, and will aid researchers in
elucidation of disease etiology.
& 2011 WILEY-LISS, INC.
Contract grant sponsor: NHGRI; Contract grant number: 3UO1HG004438 (for OMIM
curation and updating).
?Correspondence to: Ada Hamosh, McKusick-Nathans Institute of Genetic
Medicine, Johns Hopkins University, Baltimore, MD 21287.