- Genotyping vs Whole Genome Sequencing
- Which genotyping service is best?
- So what about sequencing?
- My opinion
Genotyping vs Whole Genome SequencingThe first thing to understand is the difference between genotyping and sequencing. All the major players you’ve likely heard of, from Ancestry.com 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 DNAWhole 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 DNAWhole 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 DNAThen 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, Ancestry.com 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. Ancestry.com may be more relevant for those trying to trace relatives and construct a family tree, whereas 23andMe provides more “health” based information.
Ancestry.com – best for family tree searchesAs the name suggests, Ancestry.com 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 research23andme 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 fileBut 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 Ancestry.com 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 Ancestry.com covering ~700,000 SNPs.
|Major Focus||Physical and behavioral traits, and some information about genetic disorders.||Geographic interpretation of genome with advanced ancestry matching.|
|Health Information||Some, limited.||n/a|
|Ancestry Information||Paternal and maternal information. Geographic analysis. Some simple genealogy tools.||Geographic analysis.|
Advanced genealogy and DNA matching tools for family tree building and ancestry matching.
|Estimated Turnaround||3-4 weeks||4-weeks|
|Access to Raw Data||Yes||Yes|