In the comments on Dante Labs is a scam, there has been some discussion on pricing of whole-genome sequencing. There are a lot of companies out there with different business models, different pricing schemes, and subtly different offerings—all of which is undoubtedly confusing to consumers. I’ve been trying to collect pricing information for the past year, and I’m still often confused by the offerings.
Consumers buy sequencing for two main purposes: to find out about their ancestry and to find out about the genetic risks to their health.
For ancestry, there is no real need for sequencing—the information from DNA microarrays (as used by companies like 23andme or ancestry.com) is more than sufficient, and those companies have big proprietary databases that allow more precise ancestry information than the public databases accessible to companies that do full sequencing. The microarray approach is currently far cheaper than sequencing, though the difference is shrinking.
The major, well-documented risk factors for health are also covered by the DNA microarrays, but there are thousands of risk factors being discovered and published every year, and the DNA microarray tests need to redesigned and rerun on a regular basis to keep up. If whole-genome sequencing is done, almost all of the data needed for analysis is collected at once, and only analysis needs to be redone. (This is not quite true—long-read sequencing is beginning to provide information about structural rearrangements of the genome that are not visible in the older short-read technologies, and some of these structural rearrangements are clinically significant, though usually only in cancer tumors, not in the germ line.)
For most consumers mildly interested in ancestry and genetic risks, the 23andme $200 package is all they need. If they are just interested in ancestry, there are even cheaper options ($100 from 23andme or ancestry.com—I have no idea which is better).
My interest in my genome is to try to figure out the genetics of my inherited low heart rate. It is not a common condition, and it seems to be beneficial rather than harmful (at any rate, my ancestors who had it were mostly long-lived), so the microarrays are not looking for variants that might be responsible. Whole genome sequencing would give me a much larger pool of variants to examine to try to track down the cause. To get high probability of seeing every variant, I would need 30× sequencing of my whole genome. If I thought that the problem was in a protein-coding gene, I could get 100× exome sequencing instead.
The problem with whole-genome sequencing is that everybody has about a million variants, almost all of which are irrelevant to any specific health question. The variants that have already been studied and well documented are not too hard to deal with, but most of them are already in the DNA microarrays, so whole-genome sequencing doesn’t offer much more on them. Looking for a rare variant that has not been well studied is much harder—which of the millions of base changes matters?
The popular, and expensive, approach in recent genomics literature is to do genome-wide association studies (GWAS). These take a large population of people with and without the phenotype of interest, then looks for variants that reliably separate the groups. If there are many possible hypotheses (generally in the thousands or millions), a huge population is needed to separate out the real signal from random noise. Many of the early GWAS papers were later shown to have bogus results, because the researchers did not have a proper appreciation of how easy it was to fool themselves.
Earlier studies focussed on families, where there is a lot of common genetic background, and each additional person in the study cuts the candidate hypothesis pool almost in half. To narrow down from a million candidate variants to only one would take a little over 20 closely related people (assuming that the phenotype was caused by just a single variant—always a dangerous assumption). I can probably get 4 or 5 of my relatives to participate in a study like this, but probably not 20. I don’t think I want to pay for 20 whole-genome sequencing runs out of my own pocket anyway.
I have some hope of working with a smaller number of samples, though, as there has been an open-access paper on inherited bradycardia implicating about 16 genes. If I have variants in those genes or their promoters, they are likely to be the interesting variants, even if no one has previously seen or studied the variants. Of course, the size of the region means I’m likely to have about 80 variants in those regions just by chance, so I’ll still need to have some of my relatives’ genomes to narrow down the possibilities, but 8 or 9 relatives may be enough to get a solid conjecture. (Proving that the variant is responsible would be more difficult—I’d either need a much larger cohort or someone would have to do genetic experiments in animal models.)
How expensive is the whole-genome sequencing anyway? It can be hard to tell, as different labs offer different packages and many require more than the advertised price.
A university research lab like UC Davis will do the DNA library prep and 30× sequencing for about $1000, but not the extraction of the DNA from a spit kit or cheek swabs. That is a fairly cheap procedure (about $50, I think), but arranging for one lab to do the extraction and ship to another lab increased the complexity of the logistics, to the point where I don’t think I’d ever get around to doing it. Storing the sequencing results (FASTQ files), doing the mapping of the reads to a reference genome to get BAM files, and calling variants to get VCF files adds to the cost, though cloud-based systems are available that make this reasonably cheap (I think about $50 a year for storage and about $50 for the analysis). Interpreting the VCF files can be aided by using Promethease for $12 to find relevant entries in SNPedia.
Fullgenomes.com offers packages from $545 to $2900, with an extra $250 for analysis. The most relevant package for what I want would be the 30× sequencing package for $1295, probably without their $250 analysis, which I suspect is not much more than consumer-friendly rewrite of the results from Promethease (which can be very hard to read, so most consumers would need the rewrite). Their pricing is a little weird, as the 15× sequencing is less than half the price of 30×, while the underlying technology should make the 30× cheaper per base. I’ll have to check on exactly what is included in the $1295 package, as that is looking like the best deal I can find right now.
BGI advertises bulk whole-genome sequencing at low prices for researchers, but never responded to my email (from my university account) trying to get actual prices. A lot of other companies (like Novogene) also have “request a quote” buttons. My usual reaction to that is that if you have to ask the price, you can’t afford it. Secret pricing is almost always ridiculously high pricing, and I prefer not to deal with companies that have secret pricing.
Dante Labs advertises very low prices, but does not deliver results—they seem to be a scam.
Veritas Genetics offers a low price ($999), but that does not include giving you back your data—they want to hang onto it and sell you additional “tests” that cost ridiculously large amounts. I believe they will sell the VCF file (but not the BAM or FASTQ files it is based on) for an additional fee.
Most of the other companies I’ve seen have 30× whole-genome sequencing priced at over $2000, which is a little out of my price range.
