Guidelines For Understanding Results

Introduction

This section presents a description of a detailed OMIM entry, describing the location and types of data returned from a simple or complex OMIM query. For this example, OMIM *163890 (alpha synuclein) will be discussed.

The OMIM Accession Number and Header

Each OMIM entry is assigned a unique MIM number. The numbering system uses the first number to indicate the mode of inheritance of the disorder as described in Table 1.2.3.

The distinction between 1 or 2 and 6 is that entries catalogued before May 1994 were assigned a 6 regardless of whether the mode of inheritance was dominant or recessive. An asterisk (*) preceding an MIM number indicates that the phenotype caused by the gene at this locus is not influenced by genes at other loci; however, the disorder itself may be caused by mutations at multiple loci. No asterisk before an entry number means that the mode of inheritance has not been determined.

A number symbol (#) before an entry number means that the phenotype can be caused by a mutation in two or more genes. Entries that have been deleted or superseded by other OMIM entries are preceded by a caret (A).

The MIM number in the current example is *163890, so the mode of inheritance of this gene has been established as autosomal dominant, and the phenotype is a result of just this gene and not a combination of genes. The leading number 1 indicates to the user that this is an autosomal dominant phenotype.

The next line under the OMIM number gives the protein name and gene name (Fig. 1.2.2). Directly below are Alternative titles or Symbols, listing other names for the same protein that may have been used in the literature.

Hyperlinks

Along the upper right are a series of hyperlinks (Nucleotide, Related

Entries, PubMed, LinkOut) that take the user out of OMIM to relevant information on this gene; this is similar to what was displayed on the previous page, illustrated in Figure 1.2.1. In addition to the links seen on the previous page, there is now an additional link called LinkOut. LinkOut provides a list of third-party Web sites and resources relating to the OMIM entry being viewed, such as external genome browsers and sites dedicated to the disease of interest (see Basic Protocol).

The links shown in the top of the left-hand panel of Figure 1.2.2 can be used to jump to each section within the OMIM document being examined. As before, not all links may appear for each individual entry, only those links relevant to a particular entry are shown.

Description

This section provides a brief description of the protein, what diseases are associated with that gene product, and any information about the protein family to which this protein belongs.

Cloning

This section contains descriptions of the process used to isolate the protein. In the cloning section there is usually a light-bulb symbol at the end of the paragraph. This link brings the user to records in PubMed that most closely match the text of the preceding paragraph.

Gene function

This section contains a summary of the literature describing the function of this gene product. Each paragraph contains a brief description of one or more journal articles, as well as PubMed links to the primary literature from which the summary was developed.

Mapping

The Mapping section contains descriptions of the methods used to map the protein to the cytogenetic location that is referenced in the OMIM Gene Map. This section contains many hyperlinks to take the user to the original research paper in PubMed for further analysis.

Molecular genetics

This section provides a description of any molecular studies on the gene and its corresponding protein.

Animal model

The Animal Model section describes any animal-based testing of the gene or gene product, along with any relevant results. The data that appear in this section will include phenotypic analysis of animals where the gene has been altered or removed. There is usually an effort to tie the animal studies and their related results to the human disorder.

Allelic variants

This section is one of the more useful parts of the OMIM entry, since it describes the actual mutations in the gene or protein and the phenotype resulting from these mutations. Each allelic variant carries a ten-digit number; the first six digits are those of the parent OMIM entry, followed by a decimal point and a sequentially assigned four digit variant number. Among the criteria used for inclusion are: whether this was the first mutation to be discovered, high population frequency, distinctive phenotype or phenotypes, 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).

Figure 1.2.9 shows the allelic variants for SNCA, both of which cause Parkinson's Disease. The first one is caused by a change in the alanine at position 53 to threonine (represented as [snca, ala53thr] in the first line of the description). The second one is caused by a change in the alanine at position 30 to proline (shown as [snca, ala30prc>]). The corresponding text for each entry gives all known information about the genetics and clinical implications of that particular mutation.

References

The references section cites the authors, journal and publication date for each paper cited within the OMIM entry.

OMIM gene map link

This link is discussed in detail below. Gene Map and Morbid Map

Selecting the Gene map locus link returns a table (Fig. 1.2.3) that consists of a number of columns, each of which is described below.

Chromosomal location

The cytogenetic location is displayed as the chromosome number, chromosome arm (p for short arm and q for long arm), and band number. When the user follows the hyperlinked chromosomal location, they are taken to the Entrez Map Viewer.

Symbol

This column shows all alternative symbols that have been used in the literature to represent the gene.

Title

The name (and sometimes a short description) of the gene at this locus is given here. Using the example, the Title column shows the name of the gene as synuclein, alpha with a description of non-A4 component of amyloid precursor.

MIM number

This is the unique identifier for the entry, as described above. Disorder

The Disorder column will contain an entry if a disorder has been associated with that gene. There are mapped genes that do not have a disorder associated with them, and those spaces will then be left blank. There may be a link to the OMIM entry for the disorder itself in this column.

Comments

Any relevant remarks about the gene at this position that does not fall into one of the other columns is given here.

Method

This column gives the method by which the gene was placed on the map. The methods are given in shorthand; clicking on the Method hyperlink at the top of the column gives a list of all of the mapping methods and the abbreviation for each one.

Mouse

This column gives information on mouse orthologs on the mouse genome informatics site at the Jackson Laboratory. The link here will display the chromosome the mouse ortholog is found on, its position in centimorgans, the gene symbol, and the gene name.

Morbid map

An alternative view of the data can be found by accessing the OMIM Morbid Map; a link to the Morbid Map is found at the top of every Gene Map page. The basic feature that differentiates the Morbid Map from the Gene Map is that the Morbid Map presents all listed genes in alphabetical rather than in chromosomal order.

From Current Protocols in Bioinformatics Online Copyright © 2002 John Wiley & Sons, Inc. All rights reserved.

CURRENT PROTOCOLS IN BIOINFORMATICS CHAPTER 1 USING BIOLOGICAL DATABASES UNIT 1.2 Searching Online Mendelian Inheritance in Man (OMIM) for Information for Genetic Loci Involved in Human Disease COMMENTARY

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