14 Mar 2012

Gene Mutation Resources

Genes carry instructions for building proteins, molecules that do most of the body's work. Certain variations in a gene's nucleotide sequence can affect the resulting protein's function by altering amino acid sequence and protein structure. The inability of some variant proteins to function properly can cause genetic disorders or other distinctive phenotypes.

Indication: OMIM records for many genes include an Allelic Variants section that summarizes published research concerning selected allelic variants or mutations, many of which cause disorders. Some criteria for selecting allelic variants for inclusion in OMIM are first mutation discovered, high population frequency, distinctive phenotype, and unusual disease-causing mechanism. Each variant is assigned a ten-digit number made up of the gene's six-digit OMIM number, followed by a period and four digits unique to the variant. For more information about this database, see the OMIM entry above in the Learning about Genes and Their Products section.

Indication: The Human Genome Variation database (HGVbase) is a database of annotated records for known sequence variations in the human genome. This database was designed as a tool to help scientists understand how common genome sequence variations, such as single nucleotide polymorphisms, result in complex phenotypes such as disease susceptibility and reactions to drugs. Each HGVbase record features data extracted from publicly available genome databases or published literature that has been subjected to manual review and enhanced with annotations. HGVbase shares data with NCBI's dbSNP, and currently incorporates about 40% of dbSNP's records into its database. HGVbase is funded by the Karolinska Institute Center for Genomics and Bioinformatics in Sweden, the European Bioinformatics Institute, and the European Molecular Biology Laboratory (EMBL).

Examination Tips: HGVbase provides text search and sequence search options for its users. In addition to the quick search box available on the HGVbase home page, there are links to four different search tools: Text Search, Text+ Search, Sequence Search, and Regional Search. The Text and Text+ search forms allow users to search for records by text strings that can be targeted to particular fields of a record. The Regional Search lets users search for SNPs by chromosomal location.

Since some characterized genes may lack standardized names, HGVbase recommends sequence searching over text-based searching. To search by sequence, simply paste DNA or RNA sequence data (in any format) into the Sequence Search form and click "Run." For more information about searching HGVbase see the "How to search" page available from the navigation menu on the left or click the "Help" link in the upper right corner of each search form.

Info provided: Some features included in each record are: The variant type, accession numbers that link to sequences that contain the variant, portions of the sequence that flank the variant, alleles or possible nucleotides at the site of the polymorphism, associated gene names and symbols, the region of the gene where the variant is found (e.G., exon, intron, etc.) and citations to source literature. For more information about the various fields of each HGVbase record see the Data Structure Record.

Indication: Human Gene Mutation Database (HGMD) is a collection of published gene lesions associated with human hereditary disorders. This database is maintained by the Institute for Medical Genetics at University of Wales College of Medicine. HGMD collaborates with Celera Genomics and is supported by Genome Database (GDB) and several biotechnology companies. The home page links to a useful overview of mutation nomenclature.

Examination Tips: HGMD provides a simple search interface for querying its database by disease, gene name, and gene symbol. All punctuation marks (e.G., slashes, plus signs, double quotes, commas, and dashes) are ignored. Truncation using an asterisk (*) is supported. For more information on using HGMD, see the Help file.

Info Provided: Each search will pull up a list of gene symbols corresponding to search terms. Clicking on a gene symbol will access a record summarizing mutations and phenotypes and the number of entries associated with each mutation type and phenotype. Clicking on a mutation type will show the accession number, location, and associated phenotype and link to a reference citation for each mutation. The record for each gene also links to a mutation map, the gene's cDNA sequence, and gene-specific records in other databases.

Indication: One of the most common types of DNA sequence variation is the single nucleotide polymorphism (SNP), in which a single nucleotide base (A, C, T, or G) is substituted for another. NCBI's Database of Single Nucleotide Polymorphism (dbSNP) serves as a public repository for sequence variations such as small-scale insertions or deletions, polymorphic repetitive elements, and microsatellite variation, in addition to SNPs. Data can come from any part of a genome in any species. Sequence variations are submitted to the database by members of the scientific community. This database is separate from GenBank but is cross-linked to records in other NCBI resources such as GenBank, LocusLink, and PubMed.

For more about SNPs and why they are important to biomedical research, see the SNP Fact Sheet and NCBI's SNPs: Variation on a Theme.

Examination Tips: Users can search dbSNP directly or access the database through other NCBI resources. One way to access SNP data mapped to a particular gene is to use NCBI LocusLink. Once you have found a gene's LocusLink record, clicking on the purple V or VAR link (if available) will open a list of SNPs mapped to that locus. Records in NCBI's sequence databases also may link to SNP data.

To search dbSNP directly, use Entrez SNP or dbSNP's Easy Search Form. DbSNP also provides a BLAST search option that compares the query sequence with sequence data contained in each SNP record. The BLAST option will generate a list of SNPs that can be found within the query sequence. See the Entrez SNP main page for descriptions of the different fields that can be used for searching the database.

NCBI will soon feature a quick how-to guide called GETTING STARTED. This guide should help novice users learn how to use and design search strategies for dbSNP. To learn more about dbSNP, see the FAQs page.

Info Provided: From LocusLink, after clicking on the purple V or VAR link, the SNP's linked from LocusLink page will open. This page provides Gene Model information with links to associated contig, mRNA, and protein sequence records. Each SNP is included in the graphic gene model and color-coded based on where the SNP is located (intron, exon, or untranslated region) and whether the change is synonymous or non-synonomous. For each SNP that occurs in an exon, the associated nucleotide, codon position, and amino acid residue are given.

Each SNP is assigned an identification number called a cluster id or rs number. The record for each cluster id is referred to as a cluster report and includes source organism, variation type (e.G., SNP (single nucleotide polymorphism) or DIP (deletion/insertion polymorphism)), the nucleotide sequence flanking the SNP in FASTA format, a LocusLink Analysis map depicting where the SNP is found within the gene, and links to other NCBI resources related to the particular SNP. Submitter records for each cluster provide one or more links to more detailed descriptions for each SNP submission.

Indication: This Web site is a collection of different types of mutation databases such as locus specific, disease-centered, national and ethnic, and non human. Locus-specific databases are arranged alphabetically by gene symbol. Links to other related databases and educational resources also are provided.

Indication: This resource, from the UK Human Genome Mapping Project Resource Centre, is a collection of links to general mutation and locus-specific databases. A brief description of each database is found below the list of links.

View-Article-Sources : http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/geneguide.shtml#mutation

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