Doctor’s Note: What’s in My DNA?

What’s in my DNA? An increasing number of Americans have not only asked this question; they’ve sought out an answer. A 2022 Health Information National Trends Survey showed that 40 percent of Americans reported taking at least one genetic test. What are the reasons for getting DNA testing, and how reliable is it?

Let’s start with basic facts. Deoxyribonucleic acid (DNA) is the genetic code for all complex life on Earth. Each human cell contains 3.2 billion DNA base pairs organized into a genome of two pairs of 23 chromosomes. These chromosomes are numbered 1-22 and XX or XY, with the latter sex chromosomes determining our genetic sex. About 1.5 percent of our genome is made up of genes that encode a protein, with approximately 20,000 genes total. The rest of our genome is non-coding DNA that may control how genes are expressed, or may serve other functions.

Unless you have an identical twin, no one has exactly the same DNA sequence as you, but we’re all very close. Roughly 99.9 percent of DNA is the same in every typical human, leaving ~0.1 percent to account for the huge variation in human forms that we see. Many of our genes are shared with other animals, as we have ~99 percent similarity with chimpanzees and ~60 percent with fruit flies.

These similarity numbers may sound confusing if you’ve ever heard the expression that you’re 50 percent identical to your mother or brother. Does this mean that you’re closer to a fruit fly than to dear old Mom? Of course not! We’re measuring on different scales. Out of the ~0.1 percent of your DNA that differs from an unrelated human, 50 percent of those base pairs will be identical to your brother or mother. That means you’re ~99.95 percent similar to your mom.

Direct-to-consumer (DTC) genetic testing is done outside of the medical insurance system, akin to over-the-counter drugs or pregnancy tests. Most DTC gene tests are affordable, often $99 or less. Popular DTC companies include 23andMe, Ancestry.com, MyHeritage, FamilyTreeDNA, and LivingDNA.

The most common type of DTC testing is ancestry testing. Consumer-grade DNA testing is highly accurate for determining close blood relatives, and fairly accurate for continental ancestral origin (“North African,” “East Asian,” etc.). It is less reliable for determining specific country or ethnicity of origin, as this is often a social rather than biological distinction. The greatest risk of ancestry testing is that you might uncover a painful family secret – the “not parent expected” (NPE) event which could prove infidelity, rape, or incest.

In addition to ancestry, some DTC services include health/wellness testing. These genetic markers are linked to disease risks, reaction to foods and medications, even athletic capabilities. However, the most common DTC testing technique is notoriously error-prone when it comes to predicting medical outcomes. This is because these tests don’t actually sequence any genes; they just measure a whole bunch of gene markers in a technique known as SNP genotyping.

Imagine that your genome is a library filled with tens of thousands of books. SNP genotyping does the equivalent of reading the spine of each book. In scanning through a library in this manner, you could easily tell the difference between an elementary school library, a law school library, and a comics shop. But an individual copy of To Kill a Mockingbird could have a misprint, torn pages, or water damage, and you’d never know. To figure that out you’d have to read the book cover-to-cover.

Clinical/professional DNA tests do exactly this, sequencing DNA with a high level of accuracy. Depending on which test you order, it could sequence a single gene, a panel of genes, or the entire genome. Most clinical DNA testing is ordered by a doctor or genetic counselor, and is covered by health insurance. Like most blood tests, you could always pay for clinical DNA testing out-of-pocket without a prescription, but it may set you back anywhere from a few hundred to many thousands of dollars. Clinical DNA testing companies include GeneDx, Myriad, and Invitae.

Professional-grade DNA testing can establish a formal diagnosis of genetic disease. For example, inherited BRCA mutations cause many breast, ovarian, and prostate cancers. People who test positive for this mutation could qualify for screening exams, medications, or even surgical treatments that could lower cancer risk and improve overall lifespan.

Some DNA tests are designed to detect if your bloodstream has more than one genome, a situation that commonly happens during pregnancy (fetal DNA) and in some cancers (tumor DNA). It is possible to read DNA sequences from the secondary genome, but this is far less accurate than sequencing the primary genome. For this reason, exams such as cell-free DNA testing for fetal abnormalities, which requires a blood draw, are not considered definitive tests. An abnormal genetic screen must be followed by confirmatory testing such as amniocentesis or chorionic villis sampling to obtain a diagnosis.

So, is DNA testing something you should do?

In my opinion, DTC testing for ancestry and/or health is something that can be done for educational purposes, but should not be relied upon to make important lifestyle or healthcare decisions. It can be fun to see who you’re related to, and fun to see an algorithm spit out recommendations like “you’re better at sprinting than at distance running.” However, given the inherent limits of DTC testing, these should be treated more like zodiac signs than medical diagnostics, at least for now.

Clinical testing is a highly technical field with many different tests that should be ordered by a healthcare professional. If you have a strong family history of any specific disease, talk to your primary care provider about genetic testing options.