How Good Are Genetic Screening Tests?

Genetic Screening Tests
Want a difficult read? Leaf through your genome (Courtesy: Unsplash.com)

Think of your genome — all the DNA in your body — as a big book. Twenty-three chapters long, containing hundreds of thousands of letters and tens of thousands of words, all telling your story. If you alter a paragraph, a sentence or even a letter in a word in your book, will it read differently? Maybe, or maybe not. Depends on lots of things including exactly which words are altered, where they are located and who is reading the book. The point is that your genome is complicated precisely because there are so many layers to it. And that makes direct-to-consumer genetic tests an equally complex proposition.

A Tale of Two Chromosomes

Here’s a real-life example. Fifteen years ago, we published a paper about infertile couples with male factor issues due to azoospermia. They were all missing the vas deferens, an unfixable condition called congenital absence of the vas deferens. It’s not that uncommon, occurring in 1 in 500 men. Men with this condition can’t conceive naturally but can conceive with sperm retrieval and IVF.

There’s more though: These men have an 80% chance of carrying a mutation in the cystic fibrosis (CF) gene. They don’t have CF, but their children could, depending on how the genetic cards fall. And CF is a very serious and debilitating disease.

One of the study couples was tested for CF gene mutations to get an idea of the risk of having an affected child. Unexpectedly, the man showed no mutations, nor did his partner. So, they were under the impression that the risk of having an affected child was very low and they were ready to have a baby. But the test they took only examined 32 of the most common mutations (among 1,600 known at that time) found in Caucasians. And they were both of Asian descent. So, we retested them for all known CF mutations by essentially cloning their genes, and, sure enough, they both shared a rarer mutation. That brought the risk of their child having CF to 25%, a scenario much different from what they previously thought they were facing.

But there’s good news: Using preimplantation testing of embryos to avoid CF, they now have a healthy child. The fact is that their genetic testing created a false sense of security that “all was clear” in transmitting a serious disease to offspring.

It Does Not Compute

Very recently, two studies warned that direct-to-consumer genetic testing should not be used in isolation to make medical decisions. Both the U.S. and European studies found that over-the-counter genetic testing for BRCA1 and BRCA2 tests (for breast and ovarian cancer risk) missed risk detection in 80-99% of ethnically diverse populations, a situation reminiscent of that faced by our infertile couple. The researchers involved in the studies warned that testing that suggests increased genetic “risk” does not necessarily mean that a disease or problem will occur. And, as occurred with our infertile couple, reassuring results that suggest lower risk or being “all clear” might be unreliable or even outright wrong.

Realize that your genomic book is one of the most complex readings imaginable and requires enormous expertise to understand and properly interpret. Off-the-cuff evaluations just don’t cut it.

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