I’d like to mention a common misconception about dbSNP. “Polymorphism” (the P in dbSNP) is a misnomer — a true polymorphism is a variant that occurs normally in a population, as opposed to a new mutation or rare disease variant, etc. dbSNP contains polymorphisms *and* any other short variants that are submitted to it, including known disease-causing mutations from locus-specific databases (i.e. databases devoted to particular well studied disease genes).

dbSNP recently changed their banner text to “Short Genetic Variants”, which is more accurate, but perhaps too subtle to be widely noticed. Unfortunately it’s too late for them to change their acronym!

Why does it matter that dbSNP contains disease mutations in addition to polymorphisms? — because many groups use dbSNP as a filter to remove “boring” variants from the large number of variants that they get from sequencing somebody’s genome. Not all dbSNP variants are boring! Using the entire dbSNP as a filter may result in throwing out some babies with the bathwater.

When it came to our attention that many groups (including a member of our scientific advisory board and some of our UCSC neighbors) were assuming that all variants in dbSNP are nonfunctional polymorphisms, we started thinking about extracting a subset of dbSNP — the truly boring variants — that would make a better filter. We came up with two subsets, which we call Common SNPs and Mult. SNPs (see tracks of those names in the Browser’s Variation track group: http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&hgTracksConfigPage=configure+tracks+and+display#varRepGroup ). “Mult. SNPs” are variants whose flanking sequences map to multiple positions in the genome, which casts doubt on whether they are genetic variants — they might simply be slightly diverged duplications. By default, we now make those SNPs invisible in the All SNPs display. “Common SNPs” are uniquely mapped variants for which dbSNP has allele frequency data and whose minor allele frequency is at least 1%.

Out of 54,212,080 mappings in snp135, there are 3,538,479 multiple-mappers (snp135Mult) and 11,525,489 variants that match our criteria for “common” (snp135Common). That leaves a whopping 39 million uniquely mapping variants that might be rare or might simply be lacking allele frequency data. So filtering out our Mult. and Common subsets might be too weak of a filter, but in my personal opinion (not representing my employer here) that is still preferable to filtering out any variant that appears in dbSNP.

Last but not least, thanks to dbSNP for performing this gargantuan task and providing such a great resource!

The *shame*

However it might be worth mentioning the still nascent

http://www.ncbi.nlm.nih.gov/dbvar/

which is the NCBI equivalent of Database of Genomic Variants

http://snpedia.com/index.php/Rs332
http://snpedia.com/index.php/Rs333

A haplotype is something else entirely – it’s essentially a set of variants that tend to be inherited together because they’re physically linked on the same chromosome. See the HapMap Project’s nice overview of the Origins of Haplotypes.

How does it relate to a “haplotype”?