Chip-based DNA testing wrong more than right for very rare variants





The kind of chips utilized in some shopper DNA checks struggles to separate uncommon mutations from experimental noise, and a optimistic outcome for a uncommon cancer-causing gene variant is extra prone to be unsuitable than proper. Outcomes for frequent variants are higher, although.

Single-nucleotide polymorphism (SNP) chips are a less expensive option to map genomes than full genetic sequencing. Utilizing grids of tons of of hundreds of beads that react to particular gene variants by glowing in several colors, these chips can map whichever elements of the entire genome their designers select. They’re correct for frequent gene variants of the sort that may hint ancestry or which are tied to the chance of kind 2 diabetes, however with rarer gene variants, it turns into far tougher to separate information from noise.

Caroline Wright on the College of Exeter, UK, and her colleagues have now proven that SNP chips can pinpoint frequent variants of two genes linked to most cancers referred to as BRCA1 and BRCA2 with 99 per cent accuracy. However with rarer variants it was extra prone to present a false optimistic or false unfavourable than be correct.


The groups’s examine used information from the UK Biobank, which started gathering DNA samples for analysis from 500,000 individuals in 2006. All of these samples are processed with SNP chips, however Wright’s group checked out a subset of just about 50,000 individuals (55 per cent of whom have been feminine) who had additionally been examined with full genetic sequencing.

Variants within the BRCA genes will be handed down from both mum or dad and dozens are linked to most cancers. Folks incorrectly advised they’ve cancer-causing variants face further screening and doubtlessly pointless surgical procedure. These incorrectly advised that they don’t have the gene variants might miss out on preventative interventions.


The group discovered that solely 17 per cent of the 189 individuals who had acquired a optimistic BRCA outcome from SNP checks have been proven to have these variants by genome sequencing. Of the 45,678 individuals given an all-clear by SNP, 65 have been proven to really be optimistic. An additional 70 individuals who had unfavourable outcomes from the SNP information have been revealed by sequencing to have a number of of 43 cancer-causing variants.

The group additionally investigated uncommon variants amongst individuals who had submitted their very own DNA testing outcomes from numerous sources to the Private Genome Undertaking UK for open analysis. Solely 21 topics had submitted each SNP and sequencing information, however all of them had been incorrectly labelled by the SNP chips in regard to BRCA.

Wright says that the info reveals SNP chips to be “extraordinarily poor” for detecting uncommon gene variants. The truth is, for a person particular person, a optimistic outcome for a really uncommon pathogenic variant is extra prone to be unsuitable than proper.

She warns that anybody receiving a unfavourable outcome for cancer-causing variants from a shopper DNA take a look at shouldn’t be reassured that their threat of hereditary most cancers is low. Nor ought to they search medical interventions after a optimistic outcome with out having the info validated by sequencing by their physician. “It simply will not be the correct know-how for the job,” she says.

Most shopper DNA testing depends on SNP chips, though those used now have benefitted from a number of years of further analysis and improvement in contrast with these checked out within the UK Biobank information by this examine. Many corporations promote that their checks can display for BRCA variants however usually search for solely a small variety of the extra prevalent mutations.

Journal reference: BMJ, DOI: 10.1136/bmj.n214

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