Problem Summary:
Identify known variations in the MLH1
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| Sample User Question |
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What mutations in the MLH1 gene or protein have
been associated with colon cancer patients?
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| Analysis/Comments |
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Two Entrez databases contain information about sequence variations (polymorphisms):
Online Mendelian Inheritance in Man (OMIM), which contains information about Allelic
Variants in a subset of records, and the Database of Single Nucleotide Polymorphisms
(dbSNP).
Variatons within the human MLH1 gene can be identified by retrieving the RefSeq
protein record (NP_000240) and following the "SNP" link and/or "OMIM" links. Or, you
can search the Entrez dbSNP or OMIM databases directly. Our focus here will be on
OMIM.
The SNP link will retrieve records for variations submitted by individual labs to
dbSNP and aligned to the corresponding mRNA using the BLAST algorithm. A graphic
summary for each SNP indicates whether it is in a locus region, transcript, or coding
region and gives additional information about mapping consistency, heterozygosity,
validation status, and more.
An OMIM record, on the other hand, describes (if available) allelic variants that
have been reported in the literature and summarized by the OMIM editorial staff. For
example, one interesting mutation reported in MIM entry number 120436 is allelic
variant .0011 (Gly67Trp), in which the smallest amino acid has been substituted by
the largest amino acid. A corresponding structure record, as described in the
structure section of the colon cancer gene demo, can shed light on the possible
significance of that substitution.
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| Flow Chart |
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RESOURCE USED: Entrez (RefSeq protein record NP_000240), then link to OMIM.
Or search OMIM directly for
MLH1
FEATURES HIGHLIGHTED: look at the allelic variants section of the record MIM
# 120436. Note the allelic variant .0011 (Gly67Trp), in which the smallest amino acid
has been substituted by the largest amino acid.
NOTES: Can also follow links from NP_000240 to dbSNP, but those records might
be
confusing to the group, because they are so
detailed/technical, and look very different
from regular sequence records.
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| Additional Notes |
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This exercise is also narrated as part of Entrez tutorial:
- Geer RC, Sayers EW. 2003. Entrez: making use of its power.
Brief Bioinform., 4(2):179-84 (June). PMID: 12846398
The Entrez
Tutorial page provides a brief summary of the article and a link to the full text
*.pdf file.
Please note that the search results (number of hits) noted in
the article reflect the data that were available as of March 2003. The number of
search hits will change as the databases grow, but the general search concepts will
continue to apply.
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