I received an email a while back from a reader wondering why his friend has had to submit multiple saliva samples to personal genomics company 23andMe without getting a result back. Customers in a similar position may be reassured by a lengthy explanation posted yesterday on 23andMe’s blog about their sample processing protocol, penned by the company’s Director of Operations.
(Other potential customers may also be reassured to hear that this type of failure is apparently “quite rare”, although 23andMe haven’t responded yet to my queries regarding the frequency of sample failures; and that sample repeats are provided free of charge to customers.)
There are several points at which a saliva sample can fail to yield high-quality genetic data. Firstly, the saliva sample may have been compromised, either by the collection tube leaking in transit or by a failure of the preservative solution to mix with the saliva after collection. Secondly, the saliva may not contain enough useful DNA (a point I’ll return to below), or the DNA may be too degraded to use. Finally, there might be a problem with the genotyping process that converts DNA into 580,000 pieces of genetic information.
High-throughput genotyping has become so routine now (thanks to massive genome-wide association studies) that the systems for sample processing are well-developed and robust, meaning that genotyping failures are likely to be extremely rare. That means that situations where a customer has to submit multiple samples are most likely to arise due to problems with the sample itself.
If the issue is with poor sample submission (not providing enough saliva, or failure to mix the saliva with the preservative in the tube) then that’s easily fixed. But there’s a more interesting potential problem: 23andMe notes that “[s]ome people seem to have less DNA in their spit, though almost everyone has enough for the purposes of our analysis.”
It strikes me that variation in saliva DNA content could be driven by a number of different factors (for instance: variation in saliva production and composition, epithelial cell shedding, or oral microflora), all of which are likely to be determined to some extent by genetic factors. What a delightful irony it would be if there were genetic variants associated with an inability to undergo a genome scan…
(If anyone working in the field can provide good estimates of the variation in DNA content in saliva between individuals, please comment below.)
One final note while I’m on the topic of 23andMe: several people have noted that the turnaround time for the company has increased considerably in recent months, with customers now receiving emails advising of an 8-10 week wait rather than the original 4-6 weeks (e.g. here). I gather this is due to a substantial surge in demand following the appearance of the 23andMe co-founders on Oprah – so new customers are (temporarily) paying the price of 23andMe’s success.