Notice that hemochromatosis
has more than one entry because there is more than one type of hemochromatosis,
each associated with a different gene. For example, the most common
form of hereditary hemochromatosis is associated with the HFE gene on
chromosome 6, while juvenile hemochromatosis is associated with the
HAMP gene on chromosome 19.
Although the most
common type of hereditary hemochromatosis is caused by a defect in a
single gene (HFE), most hereditary diseases are multigene disorders
(disorders caused by mutations in more than one gene). Colon cancer,
like other cancers, is a multigene disorder. When you search for colon
cancer in Morbid Map, there will be several different entries
for colon cancer where each entry corresponds to a different gene that
has been linked to the development of colon cancer.
It is important
to understand that just because a person has a variant form of a gene
that has been linked to the development of a genetic disorder does not
necessarily mean that that person will develop the disorder. Other genes,
as well as a variety of genetic and environmental factors are involved
in the development of most genetic disorders.
Searching by keyword
is the way most users find records in OMIM. OMIM provides three different
levels of searching: basic, advanced, and complex Boolean. Basic searching
is done by simply typing text into the search box at the top of the
OMIM home page. Advanced searching involves the use of Limits,
Preview/Index, and History options
available below the OMIM search box. With these options users can specify
which fields of an OMIM record to search, browse the index of a particular
field, or combine different searches.
The most powerful
option for searching OMIM is the complex Boolean option. Rather than
selecting search fields and other criteria from the Limits page, complex
Boolean searching involves the use of a command language to limit searches
to specific fields. By adding search field qualifiers in square brackets
to each search term and combining terms using Boolean operators (OR,
AND, or NOT), a user can execute a much more specific search in a single
step. See NCBI's Entrez
Help for more information about Boolean operators.
This section of
the tutorial will demonstrate how to use some of NCBI's search field
qualifiers to design more effective search strategies in OMIM.
from chromosome 6 of the Human Genome Landmarks poster has been selected
for use in this tutorial, the same steps can be followed for any disorder
listed on the poster. If you do not have a printed copy of the Human
Genome Landmarks poster, use the online
version to select another disorder of interest.
A common assumption
made by many Web users is that all they have to do to find the information
they need is type a few key words into the search box and click a
button to submit the search. Unfortunately, this does not always produce
the best results. Let's see how the results from basic term searching
differ from the results of a targeted search using field qualifiers.
into the search box at the top of the OMIM
home page, and click Go to submit your search.
This search returns
46 results. Which result is the one you want? By simply searching
for "hemochromatosis," OMIM returns all results that contain
"hemochromatosis" anywhere within a record. "Hemochromatosis"
could be in the record title or just mentioned briefly in the text
of a record.
Searching with field
All of the genes,
disorders and traits listed on the Human Genome Landmarks (HGL) poster
were taken from the title fields of OMIM records. The field qualifier
for the title field is [TI] or [TITL]. Since we selected our disorder
from the HGL poster, we also know that hemochromatosis is found on
chromosome 6. The field qualifier for specifying a particular chromosome
is [CH] or [CHR].
To use a field
qualifier in your search, simply add the qualifier to the end of your
search term. For example, to search for hemochromatosis on chromosome
6 enter hemochromatosis[TI] AND 6[CHR] as shown in
the screenshot below. Be sure to capitalize any Boolean operator (AND,
OR, and NOT) you use in your search statements. Click Go
to submit your search.
The search should
return only one result.
Clicking on the
MIM number *235200
opens the full OMIM record for hemochromatosis, which is examined
in the next section of this tutorial.
For more information
about searching with field qualifiers, see the search
fields section of OMIM Help.
an OMIM record
The OMIM record
for hemochromatosis should look like the screenshot below.
the record a little more closely.
- Each record
features a blue navigation menu on the left with quick links to
different sections within the record.
- Each OMIM record is
assigned a unique six-digit MIM number located at the top of each
on the MIM number link will open the record up in a simpler, frame-free
format that is more suitable for printing. For a description of
what the asterisk in the MIM number represents, see OMIM
- Below the MIM number,
you will find the disorder or gene name and the official gene symbol.
is a simple disorder caused by mutations in only one gene, the
official gene symbol is included with the disorder name at the
top of the record. For complex genetic disorders, such as breast
cancer, the official symbols of genes linked to the disorder
will be identified in the text of the record.
hemochromatosis, the gene is named for the disorder to which
it is linked. The gene that causes hemochromatosis is called
the "hemochromatosis gene." This is misleading because
it implies that the function of this gene is to cause hemochromatosis.
In fact, the disorder only develops if an individual has two
copies of a mutated version of this gene. The gene in its normal,
non-mutated form codes for a protein that is involved with cellular
uptake of iron.
gene symbol, which is HFE for hemochromatosis,
serves as a unique identifier for a gene. To be "official"
a gene symbol must have been approved by the HUGO
Gene Nomenclature Committee.
want to search OMIM by gene symbol use the Gene Name search
field [GN] or [GENE]. For example, an alternative method for
searching for the hemochromatosis gene by symbol would be to
enter HFE[GN] into the search box.
gene symbol is especially useful when searching other databases
(such as sequence, genome-mapping, and structure databases)
for gene-specific information.
- The gene map
locus describes where a gene can be found on a chromosome. For the
gene locus 6p21.3, 6 is the chromosome number,
p indicates the short arm of the chromosome, and 21.3 is the number
assigned to a particular band on a chromosome. The gene map locus
links to the OMIM's Gene Map.
- The amount
of text within an OMIM record varies depending upon what is known
about a particular gene, disorder, or trait. Since hemochromatosis
is well studied, there is a lot of information about this disorder
and its gene. Some of the different types of information that may
be included in an OMIM record are: disorder description, nomenclature,
clinical features, heterogeneity, mapping, biochemical features,
genotype/phenotype correlations, animal models, and several others.
- Although it
is not a part of every OMIM record, another important part of many
records is the ALLELIC VARIANTS section. This section
typically describes some of the most common mutations associated
with the development of disorders.
- Some other
features of each OMIM record are the references (with links to article
citations and abstracts in MEDLINE), a list of contributors, creation
date, and edit history (to see when the entry was last updated).
The length of each
OMIM record depends on how much information pertaining to a particular
gene or disorder has been published and how much has been reviewed by
OMIM staff. For example, the OMIM entry for the HFE gene is more than
50 printed pages long, while an OMIM entry for another condition that
researchers know little about may only be 1 or 2 pages long.
This concludes a
brief introduction to OMIM. To learn more about searching OMIM, see the
FAQs, or the Online
Mendelian Inheritance in Man (OMIM): A Directory of Human Genes and Genetic
Disorders, a chapter of the The
OMIM is just one
resource for finding general information about human genes and genetic
disorders. For other genetic disorder resources see our Guide
to Genetic Disorder Information on the Web.
For other databases
of gene-specific information see the resources for
Learning About Genes and Their Products in the Gene
and Protein Database Guide.
Source for screen
shots used in this tutorial:
Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore,
MD. MIM Number: 235200. Last Edited: April 30, 2003. <http://www.ncbi.nlm.nih.gov/omim/>
(June 2, 2003).
Continue with other
a gene on a chromosome map using NCBI Map Viewer
records in NCBI's sequence databases
similarity searching using NCBI BLAST
protein structures from the Protein Data Bank