Post by Sarah Witherington, genetic counselor extraordinaire…
One of the common questions I am asked by patients and other medical professionals is: “Why does it take so long for genetic tests results to come back?”
Most doctors and patients are used to receiving blood test results within 48 hours. So why on earth would genetic testing take so much longer when it is also done on blood?
Let’s back it up to high school science class again and my last post where I spoke about DNA and mutations. Let me put the size of the human genome, which remember is the instructional manual for body and its functions, into perspective for you. In 1990, we first started trying to read and copy the entire human genome, it took us until 2003 before we had the entire human instruction manual mapped. That is 13 years of scientists, the best minds in the world, working around the clock to try and complete this project. And it cost us a total of $2.7 billion dollars. That’s Billion with a “B”, which by today’s inflated standards many not seem like much, but that was back in the 90’s when a tank of gas cost you $1.10 per gallon. No joke.
So now let’s think about the size of the genome in another way. Remember when I talked about DNA being the instruction manual for the human body? Then there must be “words” in our instruction manual, those “words” are what we call genes. And the “words” are written in chemical letters, some of you may remember this from biology as A, T, G, and C. Those are the only four letters that make up the words within our instruction manual. The human genome project allowed us to count the number of letters that make up our DNA instruction manual; they came up with the total of 3.3 billion letters (that’s another Billion with a “B”) per strand of DNA and you just happen to have 2 strands of DNA, so let’s make that number a round 6.6 billion. And that’s not 6.6 billion letters per person, that’s 6.6 billion letters per cell. According to my Google search the average book has about 500,000 letters in it. That means that each cell in your body contains about 13,200 books worth of information. Think about the enormity of that for a second. One square inch of your skin contains 9.5 million cells and each one of those cells contains the equivalent of 13,200 books. Yikes!
Ok, ok, I’ve harped on it enough, you’ve got the idea. The human genome is huge! So imagine what all we have to do in the lab to make sure we are doing a test correctly and interpreting our science correctly. So let’s go back to the tube of blood your doctor drew. That tube of blood gets packaged up and shipped to any number of genetic laboratories, which usually takes 24-48 hours, so there goes our 48 hour results window automatically! Once it reaches us we have to get your DNA instruction manual ready to be read. That means we have to carefully destroy the cells holding the DNA without destroying the DNA itself. Don’t worry labs have become very good at this, you and your kids (or big kids at heart!) can practice a simple version of this concept at home using strawberry DNA. http://www.genome.gov/pages/education/modules/strawberryextractioninstructions.pdf
Once we have the DNA outside of your cells what do we do next? Well right now it’s just one long big tangled mess inside of a tube, you can’t see it of course since it was just inside of a cell that is so small we measure it in micrometers. We clean it up and break it down into smaller pieces that are easy for the machines to read. No one can read 13,200 books all at once, so we have to make it into paragraph size chunks instead.
Your DNA is now nice, clean, and in a readable size so that it can be put on the sequencing machines. There are currently two major types of DNA sequencing methods used in genetics right now for patient testing. When we talk about sequencing DNA, all that means is that we are reading every single letter, copying it into the computer, and then checking the DNA for spelling errors, basically. Obviously, there are a lot of complicated chemical reactions that go into this process and each of these sequencing machines costs hundreds of thousands of dollars. The first type of sequencing is called Sanger sequencing and it is the “gold standard” of genetic testing. It was of course named after the guy who developed it, Dr. Sanger, because the best way to be remembered in science is to name something after yourself of course! (Sorry, Dr. Sanger.) So now why is it called the gold standard? Well that’s because it’s the way we have been sequencing things since 1977. Yep, there weren’t any major break throughs in genetics on how to more efficiently read DNA in 30 years. So imagine the excitement in 2007 when the second major type of sequencing came out, this is called Next Generation Sequencing. Clever name right? There is obviously a much more scientific name for it but pretty much everyone in the genetics world calls it Next-Gen for short.
Back on topic! Most labs are using Next-Gen sequencers and confirming any spelling errors using Sanger sequencing methods, just to be doubly sure. But the hard part about being doubly sure about something, is that it usually takes double the amount of time at least. So now that we have read your DNA and put it into the computer, we have to look for misspellings. “But”, you may ask, “you said that everyone’s DNA instruction manual is the same! How can I have a misspelling?” That’s a great question! I also mentioned that everyone has somewhere around 60 new misspellings compared to their parents and that most people are carriers for something like 10 genetic diseases. Not to mention, that if our instruction manual was all EXACTLY the same then all of us would look EXACTLY the same. Everyone has very slight variations in their DNA that makes them unique and that means it can be really, really difficult to tell if a “misspelling” is actually normal or if it is disease causing.
Labs spend a lot of time making sure that we are reading your DNA correctly but we also spend a lot of time looking at the letters for misspellings and trying to determine if they could really cause disease. This is a time intensive process and takes scientists from many different backgrounds. There are a lot of things we still don’t know about genetics, in fact we really only know what about 4,000 of the genes out of the 24,000 genes in your DNA instruction manual do. And sometimes we won’t know what these “misspellings” or changes of a letter really mean for you even when we see thousands and thousands of patients. Because the reality is no lab knows everything, science doesn’t know everything yet, and we know that you, as a patient, are making decisions off of these genetic testing results.
We may see billions of letters of genetic code from thousands of patients but at the end of the day we treat each sample very carefully and weigh all the scientific evidence we have. Because we know if we mess up in anyway, it’s your medical management and potentially your life on the line. So if you are one of those patients who gets an “uncertain” or “inconclusive” result, don’t look at that result as a bad thing, look at that result and realize that as a lab we are working our hardest to get you an answer. We aren’t going to give you a yes or a no in these cases because if we are wrong there can be dire consequences.
After reviewing all the evidence the scientists at the lab write your individual report, some labs even include all the scientific evidence available with the report. We then send the report to your doctor or genetic counselor so they can contact you.
Depending on what test your physician or genetic counselor orders for you, this whole process can take anywhere from a week to 3 months. Three months may seem like a really long time to wait for a blood test right? But remember how much data we have to sort through? Somewhere around 13,200 books worth of genetic information and then we have to search all of those words for misspellings that may or may not mean anything all trying to find an answer. It’s not an easy feat. So when you hear your doctor or genetic counselor say a test will take up to 3 months, please try to be understanding. The doctor, genetic counselor, and the lab know you are anxious and worried about these results. We are too. We want to find you an answer and we want to get it right. If we can do it faster, we will, but not at the expense of being wrong. So be kind to doctor or genetic counselor, I promise they are doing all they can.
If you should have more questions about genetic testing and genetic counseling, please check out the National Society of Genetic Counselors website at www.NSGC.org
Thanks all for taking the time to read this blog! If you have suggestions please send them our way!
As always, you can email Georgia at firstname.lastname@example.org and me at email@example.com.
You may as follow me on Twitter: https://twitter.com/twitherington and G at: https://twitter.com/ShewithLynch!
Sarah Witherington grew up in Dallas, Texas and received her bachelor’s degree in Biochemical sciences from Louisiana State University in Shreveport, Louisiana. While studying at LSU, she worked in several research labs studying the genetics of subtropical ferns and Alzheimer’s disease. After graduation she worked in a molecular pathology and cytogenetics lab before attending Northwestern University where she received her Master’s degree in Genetic Counseling. Sarah is a board certified genetic counselor for Ambry Genetics with research interests in pediatric cancers, pheochromocytomas, paragangliomas, and whole exome sequencing. In what little spare time she has she reads fantasy fiction incessantly, shops online, and is recovering from cliff diving in Jamaica.
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