Personal genomics is a rapidly evolving game, with a clear end goal in sight: offering consumers an accurate, affordable and complete genome sequence, and providing them with tools to dig out the useful nuggets of information contained therein. That goal remains out of reach, and while DNA sequencing technology continues to mature companies in the personal genomics space are offering products at various points on the trade-off curve between information content and cost.
At the low-information/low-cost end, companies such as 23andMe and deCODEme offer cheap (sub-$1000) genome scans looking at between 500,000 and a million sites of common variation throughout the genome. These provide insight into a small fraction of your genome, but include the variants we know the most about (due to the recent explosion of genome-wide association studies, which look for common genetic variants associated with complex disease risk).
Meanwhile, at the other end of the spectrum we have the boutique service offered by Knome – sequencing of the entire human genome, or at least the 85-90% of it that can be reached with current short-read technologies, for the princely sum of close to $100,000. It’s difficult to justify this cost given the interpretable information currently obtainable from a genome sequence, but a full genome sequence does offer the possibility of getting insight into rare, severe disease-causing variants lurking in your genome that are largely invisible to genome scans.
Now Knome has launched a new product that provides a substantial chunk of the information value of a whole genome sequence at a quarter of the cost, by focusing exclusively on the 2-3% of the genome that codes for proteins:
Unlike low-priced SNP-based genotyping, which captures genetic changes
known as common variants by taking a sample of less than 0.05% of the
genome, comprehensive gene sequencing captures the entire coding region
of an individual’s genes, collectively known as the exome, enabling the
detection of rare variants – mutations that many scientists believe
account for the majority of the genetic burden of disease.
That last claim is pretty optimistic – it’s now clear from genome-wide association studies that the majority of the common variants associated with common diseases are actually found outside protein-coding regions. However, it’s also true that more rare, severe disease-causing mutations do tend to cluster within and around protein-coding regions.
Perhaps more importantly, there is a sound pragmatic reason for focusing on this fraction of the genome: it’s simply much easier to interpret a mutation in a protein-coding region than outside it. Right now, our dismal ability to predict the functional impact of variants in non-coding regions means that sequencing the majority of the genome falling outside protein-coding genes actually adds very little in terms of health prediction. For the moment, combining a cheap genome scan (to pick up genome-wide patterns of common variation) with exome sequencing (to detect any rare, clearly pathogenic mutations) would give you pretty much everything you’d be likely to get from a whole genome sequence.
Knome plans to offer the service for $24,500 for individuals, or $19,500 per person for couples and families. That’s still well and truly in the boutique price range – but you should see this as yet another waypoint on the road towards affordable, complete genome sequencing.