Monday, December 17, 2012

SNPedia’s Nightmare Before Christmas

rs17602729 is the "most prevalent genetic disease mutation" in Caucasians according to PMID 11331279 as it appears to cause muscle pain after exercise for some people. Despite this relatively minor medical impact, it represents SNPedia’s ‘Nightmare before Christmas’.

As our understanding of the genome improves, the scientific community occasionally updates the reference standards. In August 23andMe updated from human reference genome build 36 to build 37.3. If you downloaded your raw data in July, this snp was at position 115037580 but after August it was at 115236057.  SNPedia made similar changes back in 2010, but in 2012 we discovered that this snp hadn’t just changed position, it had also changed it's orientation. With this newest assembly, dbSNP flipped the SNP to the opposite strand of DNA, changing the normal G and variant A into normal C and variant T.

Confused? You’re not alone. ClinVar is the new NIH database of variation which affects human health. If you download their raw data and search for rs176027291 you will see that it shows all 4 alleles, with the G as normal. This is probably an artifact of the orientation change, but its likely that someone out there does have each allele. And each one of these nucleotide changes causes a different change to the amino. Since the most common variant is a premature stop codon, the altered aminos are probably viable with subtly different effects. Getting this SNP 
- and others that are similar challenges - straightened out in 2012 would take a Christmas miracle.

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