Ancestry genetic testing is a great introduction to genetics for many consumers. Direct-to-consumer ancestry tests can predict how much Neanderthal DNA you’ve inherited or that your eyes are blue rather than brown. These tests are entertaining, affordable and have changed the relationship we have with our DNA. However, ancestry tests are not a substitute for more specialized genetic testing or medical tests.
Customers who order ancestry tests, such as those offered by 23andme and Ancestry.com, have the option to download their genetic data. This data can then be further analyzed using web-based tools, such as Promethease. Yet it is important to keep in mind that these tests are not always accurate. A recent study published in the journal Genetics in Medicine, found that some of this downloaded data can be wrong 40% of the time. Using an ancestry genetic test to predict your probability of developing a disease, or how you respond to prescription medications, can be further problematic since ancestry tests are not specialized for this purpose.
In general, a genetic test looks for differences in DNA. Human DNA is 99.5% identical between individuals. The remaining 0.5% contains differences that vary from human to human. These DNA differences, which occur in thousands of regions throughout the genome, are called variants. Variants are responsible for some of our traits, such as height or how fast you metabolize certain drugs.
There are roughly 10 million variants in the human genome. Many variants are ‘silent’ and have little or no influence on traits. Other variants determine traits like the colour of your hair or how you respond to medications.
The variants included in a genetic test depends on the genetic testing company and the goals of the test. Different technologies are also used to measure variants. These technologies can vary immensely in the resolution used to read your DNA. Think of this in terms of a microscope: you can decrease the resolution to observe a very large area with less detail; or you can increase the resolution to see a smaller, more specific region with far greater detail.
DNA-reading technologies tends to fall into two broad categories: Sequencing and Genotyping.
Sequencing reads each letter of your DNA molecule-by-molecule, and produces long stretches of the exact genetic code your cells use as instructions to build the proteins of the human body. Sequencing is more detailed than genotyping. The higher resolution of sequencing means it is better at finding very rare variants that can cause disease. Medical or clinical genetic testing will often use sequencing for this reason.
Sequencing your entire genome – all 23 pairs of chromosomes – is considered the holy grail of genetic testing, but can be very expensive. A decade ago, sequencing a human genome cost $300,000. In 2011, Steve Jobs paid $100,000 for his genome sequence. As sequencing technologies rapidly advance, costs have decreased. Today, you can have your genome sequenced for as little as $1000-$2000 depending on your desired level of quality. Another option is to only sequence smaller, more select parts of your genome – this is called Exome or Targeted Sequencing.
Genotyping technology works differently from sequencing and costs less. Most ancestry genetic tests use some form of genotyping. Instead of reading your exact DNA sequence, genotyping looks at pre-selected variants in specific locations across your genome. These selected variants can be located close together, with many variants in one gene (higher resolution); or variants can be scattered across the genome, hitting many different genes (lower resolution). Some clinical genetic tests use high-resolution genotyping to look closely at a disease-causing gene.
Ancestry genetic testing measures variants that tend to be spread-out across many genes. At 23andMe, a genotyping DNA chip scans 600,000 or so variants. The goal is to hit as many different genes as possible to get the “big-picture” rather focus on specific genes, such as those involved in predicting your response to medications. Ancestry tests also tend to overlook some of the rarer genetic variants that impact medication response.
23andMe does not measure one of the most important genes for predicting medication response, (called CYP2D6), in a way that gives us the information necessary to report on 30% of the medications covered by Pillcheck. For some drug response genes (such as CYP2D6), measuring the number of gene copies is important. 23andMe does not provide CYP2D6 gene copy numbers. This is one of the reasons why 23andMe data cannot be used to construct an accurate Pillcheck report. 23andme recognizes this problem and no longer reports on medications affected by CYP2D6.
Pillcheck focuses directly on the genes that impact drug response, with many variants often covered per gene. A Pillcheck genetic test includes rare, ethnicity-specific variants that are sometimes missed by other tests.
Currently, Pillcheck tests 88 carefully selected variants that predict drug response. This means your Pillcheck report includes more drugs, with 200 (and counting) common medications covered. Pillcheck reports are continuously updated as more scientific research becomes available.