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Finding the Best DNA Test: Should I Genotype or Sequence?

Genes Mentioned
If you’ve arrived here you’re probably somewhat aware of the various consumer genotyping kits available for people wanting to check their ancestry and more recently (at least in an official sense) their health. By the end of this year, estimates predict that 100 million consumers will have taken some form of home DNA test. With the surge in interest, more genetic testing providers have popped up to meet demand. And consumers are the one’s who benefit, especially as the FDA has eased some restrictions on health reporting. For example, 23andme can now tell its customers whether they have a version of the APOE gene that is associated with an increased risk for Alzheimer’s disease. 23andMe is by far the most well known of these companies, as they were the first to identify the niche in the market for consumer focused genomics, all the way back in November 2007. While, the technology wasn’t especially cutting edge, the way the data was packaged and presented was ground breaking, with Time Magazine accordingly naming their service the “Invention of the Year” in 2008 However, even though over 2,000,000 people have been genotyped by 23andMe (and many more by their competitors) there is still a lot of misunderstanding about what exactly these services offer, and how individuals can use this data. Before diving in it’s worth looking at our genetics 101 primer so you’re familiar with some of the terminology that follows. Note: at Gene Food, we use the raw data from genetic testing services to craft custom nutrition plans for our clients.

Genotyping vs Whole Genome Sequencing

The first thing to understand is the difference between genotyping and sequencing. All the major players you’ve likely heard of, from to 23andme, are all genotyping companies. As we explore below, they report on a tiny fraction of your overall DNA. Below, I list the three basic ways you can have your DNA tested.

Whole genome – all your DNA

Whole Genome Sequencing (“WGS”) is exactly that. Every single base from all of your chromosomes is determined. Interestingly only about 2% of your genome is known as “coding DNA” that is DNA which codes for the proteins which make up all our cells and allow us to function as the unique humans we are. The rest, known as “non-coding DNA,” was long thought of as junk DNA, but as we understand more about our genetics we now know these regions play a hugely important role in regulating the coding portions of our DNA. Our understanding of these regions and their interactions is relatively poor compared to our knowledge of the DNA coding regions. To use a highway analogy, WGS represents every inch of the highway, including stretches of scrubland along the side of the road, far away from any exits or towns.

Exome Sequencing – just coding DNA

Whole Exome Sequencing (WES) sequences only the regions of DNA which code for proteins. This accounts for approximately 2% of the whole genome. On the DNA highway, WES represents every known exit and town, even ones that are not thought of as important, or are as yet still unknown.

Genotyping – curated DNA

Then onto genotyping. Here information for a carefully selected number of bases is captured. These bases are usually selected because they represent locations where particular sequences associate with characteristics. But there are huge regions of the exome, let alone the genome which aren’t covered. Genotyping picks up just the important stops on the highway that have activity. Approximate regions covered by whole genome sequencing (WGS), whole exome sequencing (WES) and consumer genotyping. 23andMe, and most other services are all genotyping companies. They look at select points of interest in your DNA, and look for variations (polymorphisms) giving rise to the term Single Nucleotide Polymorphism (SNP). But as you can see the amount of the genome they cover is tiny, approximately 0.03%!

Which genotyping service is best?

How long is a piece of string? A bit of a blasé answer, but there really isn’t much to separate the major players, a fact which is summed up really nicely by this table (which I also summarise below). There will be some differences in how the data is presented to you within their site, and their particular focus i.e. may be more relevant for those trying to trace relatives and construct a family tree, whereas 23andMe provides more “health” based information. – best for family tree searches

As the name suggests, beats 23and me for those trying to construct a family tree, or find a distant relative. The company boasts a database of over 5 million from which users can “connect dots” with those who may be related. To be clear, this is an interface win, rather than a data advantage, because as we will see, both services are very comparable.

23andme – best for health research

23andme wins out on how they present health data to customers (although it’s important to point out that the Health plus Ancestry version of 23andme is more expensive). For example, 23andme users can access a “Genetic health risk” section which outlines the genetic risk for conditions like late onset Alzheimer’s and Age-related macular degeneration. The company has even included a new report providing risk factors for celiac disease.

True value of genotype data is the raw data file

But the true power of your genotype data (at least for us with a health focus) comes with the raw data file, which can be analyzed by third party providers (Genetic Genie, Promehease, Livewello, and now Gene Food with the launch of our custom nutrition plan) with a much clearer health focus. For example, if you’re curious about your MTHFR status, you will need to use the raw data to find if a mutation in that gene is present. As both 23andMe and provide access to this raw data there is very little difference between the two. Even the number of SNPs analyzed is remarkably similar with the most recent 23andMe kit analyzing ~670,000 SNPs and covering ~700,000 SNPs.
Major FocusPhysical and behavioral traits, and some information about genetic disorders.Geographic interpretation of genome with advanced ancestry matching.
Health InformationSome, limited.n/a
Ancestry InformationPaternal and maternal information. Geographic analysis. Some simple genealogy tools.Geographic analysis.
Advanced genealogy and DNA matching tools for family tree building and ancestry matching.
SNPs Tested670,000700,000
Estimated Turnaround3-4 weeks4-weeks
Access to Raw DataYesYes

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So what about sequencing?

Personal sequencing is the next big step in personalised medicine. While the genotyping services described above are powerful, they are only looking at a fraction of the exome (the coding region of the genome) and a minuscule fraction of the entire genome. Theoretically therefore getting access to your WGS or even WES would open up many more more doors. And there are services available which offer this. Two major players are Veritas Genetics and Gene by Gene; however, each is only available to researchers or clinicians, not consumers.

Direct to consumer WGS options

Moving, on I was able to find three companies who offer direct to consumer WGS. FullGenomes, Dante Labs and Guardiome (who seem to be in the process of starting up). All three offer WGS and will supply your raw data, for actually quite reasonable prices. Interpretation of this raw data however will be very limited. While all three services offer curated analysis, this seems limited to the same information covered by the much cheaper genotyping companies. Additionally, automated analysis of the raw data using services such as Livewello is currently not supported. So unless you’re a practicing bioinformatician who can analyze these huge datasets, you will be paying for further analysis, and this is where the costs can ramp up significantly.

Whole exome sequencing? Is Helix a good value?

Are things better with WES? Remember, the whole exome sequencers provide your coding DNA. One option here is a recently opened startup called Helix, which is approaching WES in a different way. With a low initial price of $80 they will perform WES, you can then access a variety of analysis packs through their store. Sounds great? $80 is a steal compared to the genotyping companies, let alone the other WGS and WES offerings… UPDATE: Data export is now available for an optional $499, which is in line with what you may expect to pay for a WES service. It also appears that Helix is headed away from a consumer application model and moving more towards products for medical providers. Another good reason to avoid Helix.

Why we don’t recommend Helix

I’m sure you’ve spotted the rub however. Helix don’t provide your raw data, so in effect you’re locked into their system forever. For some this will be fine, but for me personally I struggle to see the benefit… By the time you’ve performed the same sorts of analyses offered by the genotyping companies you’ll have spent many times more and you won’t have access to a single byte of your raw data. For me this one is a definite avoid. Based on the ability to download your data now this is somewhat more appealing. I would still recommend genotyping for most individuals based on the cost and evidence available right now. However, if the cost listed isn’t prohibitive to you this service will provide you everything genotyping does, and future proof you as well.

My opinion

While WGS and WES are going to be the future of personalized medicine, and are already providing great information to researchers and healthcare professionals, the framework just isn’t there for personal consumers… yet! But if you rewound the clock back to October 2007 you could say the same thing about consumer genotyping. So for me personally, I would still currently go for the genotyping option over either WES or WGS. However, if you’re comfortable paying more now for a similar level of curated analysis, while being happy holding onto your data ready for some clever company to unlock (or feel confident analyzing this yourself), then WGS is the way to go! So, bottom line, we recommend either having your whole genome sequenced, or going with one of the genotyping options, all of which are comparable.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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Leave Comment

  1. Roger Cappallo says:

    Nice article, thanks. FYI, your graphic comparing the different types of tests has the incorrect number (off by an order of magnitude) for WGS total base pairs. It should be 3 billion, not 300 million.

  2. Amy Napier says:

    Genome It All provides genetic testing that provides 700,000 SNPs on their raw data. The biggest benefit is that it comes with a VERY detailed custom report for each person on over 15,000 SNPs. It breaks down the results to make them easy to understand. It even explains what certain findings are defined, so that you don’t have to constantly look up what something means.

  3. Randy Harr says:

    Nice article and genetics 101 primer. Love the DNA single diagram and would love to reuse.
    Biggest clarification I would make is adding MyHeritage (based on FTDNA/Gene by Gene lab) and LivingDNA (reform of services available previously in the UK). Also ySeq for WGS services (started by CTO/CSO couple for FTDNA who left 4+ yrs ago and returned to Germany). Key also is 23andMe and LivingDNA use the new xxx machine from Illumina which has all new SNPs and hg reference model. The results are very difficult to compare with others without significant work to impute missing values from other tests / companies / Illumina genotyping machines. LivingDNA just announced they are going to switch to the old generation machines to be more compatible with the market. (Given up on making a match database.) MyHeritage just made available the tool to impute and compare results from both sources after considerable effort. They are the first and only to allow the apples to oranges comparison. (GEDMatch is still working on this in their Genesis “product”.) Overall, there is actually little overlap in the SNPs tested between many of these companies. ISOGG has just started looking into this and reporting it in their wiki. But tool / software / bioinformatic people have known this for 10+ years. See where an ad-hoc tool researcher put out a venn diagram of the SNP lack of overlap back in 2012! Something you all must be aware of if looking for specific SNPs for your reporting from the various sources.
    One small (for you, major for others) is there is variance in the WGS products. In reality, they do not do Full Sequencing. So the read length of the snippets that are sequenced and the depth read coverage of the chromosom are important metrics. DanteLabs and FGC basic products have minimal coverage (big gaps still). Y haplogroup projects have lots of info to compare from looking only at the Y chromosome.

  4. Steve Coker says:

    Good article. But, I think your comparison of 23andMe, Ancestry, and FamilyTreeDNA (FTDNA) ignores the genealogic perspective. I agree with you that they are good. But, for genetic genealogy, FTDNA is the winner.

    FTDNA offers deep Y-DNA and mtDNA testing. FTDNA has the largest Y-DNA haplotree on the planet. And the largest mtDNA haplotree using Full mtDNA Sequencing. FTDNA has thousands of project groups for sharing and comparing with group administrators to help group members.

  5. Marion says:

    Thank-you for a very informative and well illustrated article. You clarified the field of genetic testing for me.

  6. Craig says:

    There seems to be a significant error in your math. You list WGS as 300M bases and WES as 60M bases, identifying WGS as 100% of the genome and WES as 2% of the genome. However, 60M is 20% of 300M. Can you please correct whatever is wrong in these? Thanks,

  7. Nikki says:

    Hi Dr. Gardner,

    I was able to download my raw data for no extra charge actually through my genographic 2.0 account. I found this odd. Helix was the lab. I have all of this information though, and there appears to be nothing I can do with it. Any suggestions?

    • Hi Nikki,

      Sorry for the slow reply I missed the notification that you’d posted. You should be able to use the raw data in the same way you would use the data from 23andme or similar. I know that can deal with the data at a cost. It is also possible for you to manually interpret your data, you just need to find the SNP that you’re interested in amongst all the others.

      Do you know what sort of file format you have? I can point you in the direction of useful software then.


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