dbSNP
short tandem repeats (STRs), (4) multinucleotide polymorphisms (MNPs), (5) heterozygous sequences, and (6) named variants.[2] The dbSNP accepts apparently neutral polymorphisms, polymorphisms corresponding to known phenotypes, and regions of no variation. It was created in September 1998 to supplement GenBank, NCBI’s collection of publicly available nucleic acid and protein sequences.[2]
In 2017, NCBI stopped support for all non-human organisms in dbSNP. PurposedbSNP is an online resource implemented to aid biology researchers. Its goal is to act as a single database that contains all identified genetic variation, which can be used to investigate a wide variety of genetically based natural phenomena. Specifically, access to the molecular variation cataloged within dbSNP aids basic research such as physical mapping, population genetics, investigations into evolutionary relationships, as well as being able to quickly and easily quantify the amount of variation at a given site of interest. In addition, dbSNP guides applied research in pharmacogenomics and the association of genetic variation with phenotypic traits.[4] According to the NCBI website, “The long-term investment in such novel and exciting research [dbSNP] promises not only to advance human biology but to revolutionise the practice of modern medicine.” Submission1. SourceOriginally, dbSNP accepts submissions for any HapMap, etc.), and private businesses.[5] On September 1, 2017, dbSNP stopped accepting non-human variant data submissions and two months later, its interactive websites and related NCBI services stopped presenting non-human variant data. Now dbSNP only accepts and presents human variant data.
2. Types of recordsEvery submitted variation receives a submitted SNP ID number (“ss#”).[5] This accession number is a stable and unique identifier for that submission. Unique submitted SNP records also receive a reference SNP ID number (“rs#”; "refSNP cluster"). However, more than one record of a variation will likely be submitted to dbSNP, especially for clinically relevant variations. To accommodate this, dbSNP routinely assembles identical submitted SNP records into a single reference SNP record, which is also a unique and stable identifier (see below).[4] 3. How to submit To submit variations to dbSNP, one must first acquire a submitter handle, which identifies the laboratory responsible for the submission.
ReleaseNew information obtained by dbSNP becomes available to the public periodically in a series of “builds” (i.e. revisions and releases of data).[4] There is no schedule for releasing new builds; instead, builds are usually released when a new genome build becomes available, assuming that the genome has some cataloged variation associated with it.[6] This occurs approximately every 3–4 months. Genome sequences may be improved over time so reference SNPs (“refSNP”) from previous builds, as well as new submitted SNPs, are re-mapped to the newly available genome sequence. Multiple submitted SNPs, if mapping to the same location, are clustered into one refSNP cluster and are assigned a reference SNP ID number. However, if two refSNP cluster records are found to map to the same location (i.e. are identical), dbSNP will also merge those records. In this case, the smaller refSNP number ID (i.e. the earliest record) would now represent both records, and the larger refSNP number IDs would become obsolete. These obsolete refSNP number IDs and are not used again for new records. When a merger of two refSNP records occurs, the change is tracked, and the former refSNP number IDs can still be used as a search query. This process of merging identical records reduces redundancy within dbSNP.[6] There are two exceptions to the above merging criteria. First, variation of different classes (e.g. a SNP and a DIP) are not merged. Secondly, clinically important refSNPs that have been cited in the literature are termed “precious”; a merger that would eliminate such a refSNP is never performed, since it could later cause confusion.[6] Retrieval1. How toThe dbSNP can be searched using the Entrez SNP search tool. A variety of queries can be used for searching: an ss number ID, a refSNP number ID, a gene name, an experimental method, a population class, a population detail, a publication, a marker, an allele, a chromosome, a base position, a heterozygosity range, or a build number.[6][7] In addition, many results can be retrieved simultaneously using batch queries.[6] Searches return refSNP number IDs that match the query term and a summary of the available information for that refSNP cluster. 2. Tools/DataThe information available for a refSNP cluster includes the basic information from each of the individual submissions (see “Submission”) as well as information available from combining the data from multiple submissions (e.g. heterozygosity, genotype frequencies). Many tools are available to examine a refSNP cluster in greater depth. Map view shows the position of the variation in the genome and other nearby variations. Another tool, gene view reports the location of the variation within a gene (if it is in a gene), the old and new codon, the amino acids encoded by both, and whether the change is synonymous or non-synonymous. Sequence viewer shows the position of the variant in relation to exons , and other distant and close variants. 3D structure mapping, which shows 3D images of the encoded protein is also available.
The dbSNP is also linked to many other NCBI resources including the OMIM , and UniGene.
3. Validation statusThe validation status list the categories of evidence that support a variant. These include: (1) multiple independent submissions; (2) frequency or genotype data; (3) submitter confirmation; (4) observation of all alleles in at least two chromosomes; (5) genotyped by HapMap; and (6) sequenced in the 1000 Genomes Project.[6]
Problems With Data QualityThe quality of the data found on dbSNP has been questioned by many research groups, Errors in the dbSNP can hamper candidate gene association studies[14] and haplotype-based investigations.[15] Errors may also increase false conclusions in association studies:[8] increasing the number of SNPs that are tested by testing false SNPs requires more hypothesis tests. However, these false SNPs cannot actually be associated with traits, so the alpha level is decreased more than is necessary for a rigorous test if only the true SNPs were tested and the false negative rate will increase. Musemeci et al. (2010)[8] suggested that authors of negative association studies inspect their previous studies for false SNPs (SNDs), which could be removed from analysis. How to cite data from dbSNPIndividual sequences can be referred to by their refSNP cluster ID numbers (e.g. rs206437). dbSNP should be referenced using the 2001 Sherry et al. paper: Sherry, S.T., Ward, M.H., Kholodov, M., Baker, J., Phan, L., Smigielski, E.M., Sirotkin, K. (2001). dbSNP: the NCBI database of genetic variation. Nucleic Acids Research, 29: 308-311.[5] See alsoReferences
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