"[Whole genome sequencing] gives us the opportunity to be proactive and make decisions to optimize our lives, avoid disease and hopefully, achieve longevity.” — Keith A, MD, Veritas Customer
With so many genetic products on the market today, it’s hard to tell what exactly you’re getting. The truth is, not all tests are created equal, but what exactly are the differences?
There are two main technologies that are used in popular genetic products. One is genotyping, the other sequencing. Within sequencing there is Whole Exome Sequencing and Whole Genome Sequencing. Each method has a different approach to looking at DNA and also deals with a different amount of DNA. Let’s dive in.
Genotyping looks for specific variants in a relatively tiny fraction across your genome — usually less than 1% of the genome’s A’s, T’s, G’s, and C’s. It’s an effective method for identifying variants, however, it requires a pre-defined list of variants to search for, which limits analysis to those on the list. If you have a variant that is not on this list, it will not be picked up. Further analysis on genotyping data is unable to extract genetic variants from outside of the pre-defined list. For example, 23andMe, a popular test that utilizes genotyping technology, looks at less than half of 1% of your genome. While there are thousands of mutations in the BRCA genes, 23andMe only picks up three of these mutations.
Whole Exome Sequencing (WES)
Whole Exome Sequencing (WES) analyzes the exome, the portion of the genome consisting entirely of exons, which are the protein coding portions of the genome. Currently, WES covers about 20,000 protein coding genes, with research unlocking more every year. This method is cost-efficient and more robust than genotyping, however, WES still only analyzes less than 2% of the entire genome, leaving an extraordinary wealth of relevant information out of the picture.
For example, the products offered on the Helix platform are based on WES.
Whole Genome Sequencing (WGS)
Where the previously mentioned technologies deal with a very small percentage of your DNA, Whole Genome Sequencing (WGS) looks at over 99% of your genome. As we've written about previously, that's about 6.4 billion A's, T's, C's and G's. Why does this matter? Let's say you have a variant in an intron (the non-coding region of a DNA molecule) that increases your risk of heart attack. Unless there was a targeted probe designed by a lab, chances are that both genotyping and exome sequencing would miss this during routine testing. Whole genome sequencing, however, would identify the variant.
Here's a simpler way to look at it: If you think about your DNA as letters on a page, other tests might give you somewhere around 180 pages of data. Not bad, right? 180 pages can tell you a lot, for sure. But what if we told you that whole genome sequencing offers you close to 4,200 books — not merely pages — of personal genomic data? Would you rather make decisions on your health based on a few pages worth of information, or on the contents of an entire library?
By sequencing your whole genome — rather than just a piece of it — you’re getting the ‘master blueprint’, which doesn’t change over time. What does change is how much we understand about the human genome. We can return to your results as science uncovers more about genetics and give you updated information, or if you want to, we can dig deeper in concern areas — such cardiovascular or cancer.
Our mission is to give millions of people access to their genomes and support them make better decisions for their health. It's that mission that pushed us to break the $1,000 barrier for whole genome sequencing and interpretation — and keeps us looking for ways to drive the price down even further. While for now it comes with a higher price tag, whole genome sequencing is an invaluable investment for your health management — not just today, but for the rest of your life.