Precision in Genetic Testing: High-definition for more accurate results and better outcomesRuslan Dorfman, PhD, MBA
Rapid advances in DNA technology now allow us the opportunity to peak inside our genes, glimpsing information that reaches beyond what is outward apparent in eye colour, height, or the ability to form blood clots.
A plethora of genetic testing companies have sprung up, offering services that predict everything from the percentage of Neanderthal DNA we contain to our ability to enjoy Cilantro (delicious herb or foul soapy-tasting weed?) to our risk of developing heart disease. Whether or not it is useful to find out that you are distantly related to the King of Spain is a matter of personal opinion. Medically, genetic tests screen for cancer, developmental abnormalities in fetuses, and how we process prescription medications.
To gain useful information, a genetic test must look at many genes or one gene in great detail. The exception is rare diseases, but that’s a different story.
A gene is a sequence of DNA. This sequence is composed of the four letters of DNA: A, T, G, and C. These letters repeat in unique combinations to form the genes that determine everything from hair colour to our ability to metabolize the alcohol in a glass of Pinot Grigio. Of course these are not regular alphabetical “letters” but a short form of the chemical molecule that each letter actually represents (called a nucleotide). But let’s keep it simple: the combination of A, T, G, or C in a gene instructs our cells how to build the 2 million different types of proteins of the human organism. Mutations, or changes in the letters at specific locations, account for the diversity in humans. These mutations are why some people have red hair and others brown or black or blonde. Red heads usually have a rare T mutation in the gene called Melanocortin 1 Receptor (MC1R) – the gene responsible for the amount of dark pigment produced.
Now mutation is not a nice word. It makes us think of grotesque creatures and other unpleasant things rather than the common changes in our genes that make each individual unique. Instead of mutation, let’s use the proper scientific term: Single Nucleotide Polymorphisms; or SNPs for short.
SNPs are what genetic testing companies examine in order to give us information about ourselves.
How useful is the information from a SNP?
A genetic test will examine a chosen collection of SNPs. Since SNPs cannot be patented (they belong to humanity), different companies can test the same SNPs. Often a single SNP in a single gene will be used to predict something like how well you tolerate caffeine or what type of exercise you should be doing. This can be problematic. Many thousands of interconnected chemical reactions occur in our cells to extract energy from sugar, build muscle, or get headache relief from a Tylenol. This involves a lot of genes working together. And the more complex the process, the more genes and SNPs involved. Testing a small number of SNPs becomes much less useful for determining something like how we respond to prescription medications.
Measuring haplotypes gives more useful information
To predict something complex, such as how rapidly the liver converts the drug Codeine into morphine (which can be toxic or even fatal if your liver is really, really fast at this!), we need to look at a “team” of SNPs that work together for this process. This team of SNPs is called a haplotype. Each person will have a unique haplotype depending on their combination of SNPs. The more SNPs we include, the more accurate the haplotype, which means higher-definition genetic testing. These high-definition haplotypes then determine if someone is really good at converting Codeine into morphine.
Pillcheck offers high-definition genetic testing
Pillcheck tests 168 individual SNPs. Some competitor companies test as little as 25. The increased resolution of 168 SNPs not only means more accurate haplotypes but also that rarer mutations are included. This increases the sensitivity of the test. Higher test sensitivity means a greater proportion of people can receive accurate haplotype results. In an ethnically diverse population such as in Canada, this is important. Rare mutations that are common in Native Canadians, Blacks, East Asians, Arabs, and Ashkenazi Jews are often excluded from low-definition genetic tests that focus on the mutations commonly found in populations with Northern European ancestry.
More SNPs in Pillcheck also means more medications are included in your report. Presently 115 (and counting) commonly prescribed medications are included in Pillcheck. Think of this as a high-definition television compared to an old technology. Why watch television on a standard-definition (SDTV) (576i) when you can have a crystal-clear picture? In this case the difference can be lifesaving, and why compromise quality when it comes to your health?
User considerations in assessing pharmacogenomic tests and their clinical support tools https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133969/
23ANDME IS OFFERING PHARMACOGENETIC TESTING, BUT IS IT ANY GOOD? https://www.precisionmedicineadvisors.com/precisionmedicine-blog/2019/1/16/23andme-is-offering-pharmacogenetic-testing-but-is-it-any-good
Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology https://jmd.amjpathol.org/article/S1525-1578(17)30519-6/pdf