Genetics is about much more than DNA

Regular listeners of Conversations in Science will know that I have a wide breadth of knowledge within the realm of science. Let’s face it, I’m a science geek. However, there are some areas of science where I’m just as much in the dark as those around me. That’s when it’s time to bring in an expert. On this month’s show, I did exactly that.

It was such a pleasure to invite Dan Koboldt to join Jessie and me as we talked about the field of genetics and the genome project. I did have to rein in Jessie’s bizarre questions (something the two of us still laugh about), but I had no idea that the field had progressed to the point it had. It’s not often that I’m left speechless, but Dan succeeded.

Take a listen as Dan explains what a geneticist really does and how our understanding of the human genome had led to amazing advancements in cancer research.

Conversations in Science looks at Genetics
(First aired on KLRNRadio, Monday, March 6, 2017)

While Dan Koboldt might moonlight as a writer of science-fiction and fantasy published with Harper Voyager, by day, Dan is a genetics researcher with a major children’s hospital where he spends countless hours examining how our genetic material can contribute to what we look like, how we get disease and any component that we could potentially inherit for our parents and ancestors.

We started with the basics: DNA. DNA stands for deoxyribonucleic acid. It’s a molecule that is in every cell of our bodies and contains the instructions for making a human being. All of us have very similar DNA with slight differences. However, the study of genetics is about much more than DNA. As Dan pointed out, environmental factors play a role too. The field of genetics is about understanding how genetic factors are influenced by a variety of sources.

Dan works with what is called “Next Generation DNA Sequencing” where geneticists take full advantage of current technology to examine the human genome. The term genome refers to everything that is in your DNA. The human genome is approximately 3.2 billion base pairs long — super long. However, 99.99% of the genome is the same from person to person. It’s the 0.01% difference that geneticist are interested in. That might not seem like a lot of difference, but when you look at the numbers, that’s still roughly 320,000 base pairs.

The Human Genome Project was an initiative that set out to map the human genome, effectively coming up with a blue print for making a human being. The original models are actually a composite of the DNA structures from 10 – 20 people. Each of the 24 chromosomes (1-22, X and Y) was analysed in detail, working out the exact sequences of base pairs in each chromosome. The first genome model took 13 years to generate, declared as complete in 2003. Today, mapping the human genome takes a fraction of that time and a fraction of the cost. The original reference has been expanded, refining the model as we gain a better understanding and more measurements. This includes the identification of certain sequences that in reality only occur in a small portion of the human population that the original genome project just happened to capture among their small sample set.

We have now mapped major components of the genome, however, our knowledge is still limited by our current level of technology. A sample of DNA might contain only a few hundred base pairs, perhaps a few thousand. Remember that I said there was 3.2 billion base pairs? So to map the full DNA sequence, we’re forced to analyse it in pieces. The real issue within the field of genetics is trying to understand exactly how the sequences fit together. There are most definitely gaps within our current knowledge, particularly in highly repetitive regions.

For forensics, we are only interested in approximately 15 different specific places of random repeats within the full sequence that vary from one person to the next. By the time you have looked at approximately 10 – 12 of these sections, you’ve built up a DNA fingerprint that is highly likely to belong to a single person. This is the information that is stored in the CODIS directory, making DNA for forensics reasonably quick (depending on the paperwork and the backlog of work within forensic labs).

When looking at hereditary illnesses, geneticists will commonly look at the DNA of twins. As identical twins have near identical DNA, the progression of diseases can be possibly attributed to environmental factors. However, there are some rare diseases that can attributed to recessive genes, where you inherit a defective copy of one gene from mom and another defective gene from dad; the two mix together and the child has the disease. There are also mutations that could occur during early fetal development that result in disease.

Your DNA could change over time, resulting in somatic mutations (somatic meaning within a single cell). Exposure to certain carcinogens could increase the chance of developing these somatic mutations and could lead to cancer.

This is a gross simplification of the whole process and Dan explained it so much better than I ever could during the show, talking about how some geneticist study blood to track the progression of somatic mutations in bone marrow. (In truth, it was one aspect that just blew my mind away. I think I’ll be listening to the episode over and over just to get my head around it.)

To quote Dan:

“Every type of cancer is fundamentally a genetic disease. It arises due to a genetic change in your cells—that’s sort-of the unifying premise. Now, how that particular change arose and where it arose can affect what type of cancer you get and what happens with it. But basically a tumor that is inside someone has a slightly different genetic makeup than the rest of their healthy cells.”

Cancer research really did benefit in a big way from the human genome project and the improvement of DNA technologies. One of the tools now at the disposal of oncologists is the ability to examine the DNA of a tumor, comparing it to the DNA from say blood. Areas that are different in the two samples can be identified and the results could lead to ideas on how to treat a patient. This DNA comparative analysis is now becoming standard practice during the diagnosis and on-going treatment of cancer.

Of course, I just had to ask if it was possible that we could manipulate DNA to the level that we could create a Khan. (Sorry, Star Trek fan here. I just had to ask, because those story lines were all about genetic modifications.) It was an interesting question, but one not easily answered.

There are definitely new and improved technologies available for the genetic modification of living cells, targeting specific base pairs. Dan introduced us to the concept behind CRISPR/Cas, a system that evolved from the way bacteria defends itself, chopping up the DNA of attacking viruses. A template of DNA is recorded then changes are made on a cellular level. (Again, this is a gross simplification and Dan explained it so much better.)

Currently, these technologies are used within plant and food production (leading to the arguments on genetically modified foods), but several years ago a consortium of nations met to discuss these technologies. Many agreed to not apply them to living human cells until we had a better understanding of the implications. China was one nation that declined to take part in this agreement. A year and half ago, some Chinese scientists released a paper showing how they applied this technology to living human embryos, revealing how it was possible to alter a known disease-causing mutation and replace it with a normal, healthy sequence.

It’s still not a perfect technology — it’s not point and click and off it goes — but there are so many things to think about. This is a really tough situation with massive implications and ethical issues. Let’s face it, this technology could lead to wonderful things for the human race, eliminating certain genetic diseases entirely and possibly providing the ultimate answers on curing cancer. But this technology could go the other way too, leading to Khan and Botany Bay.

The technology is a long way off yet. The human genome is incredibly complex and it’s difficult to say what one small change would do across the lifetime of a human, but the potential is there.

I should point out that most geneticists are ultimately trying to improve lives, helping others. They don’t do this because they want to create designer babies. They’re in this particular field because the answers to so many diseases and health conditions lie within our understanding of DNA and the human genome. Just look at the progress they have made so far and how it has already had a positive impact on our lives.

Like so many scientists, geneticists rely on public and government funding. Keep that in mind the next time you are asked to vote about these issues.

Thank you so much, Dan, for helping me understand the basics on this field of science and why it's so important.

Dan Koboldt is a genetics researcher and fantasy/science fiction author. He has co-authored more than 60 publications in Nature, Science, The New England Journal of Medicine, and other scientific journals. Dan is also an avid deer hunter and outdoorsman. He lives with his wife and children in Ohio, where the deer take their revenge by eating the flowers in his backyard.

His debut novel, The Rogue Retrieval, was published by Harper Voyager in 2016, and will soon followed by two other novels following the antics of a Las Vegas magician through a world of mystery and intrigue.

You can find out more about Dan's various activities on his website ( Alternatively, you can catch him on Twitter (@DanKoboldt).

P.S. I'd love to meet you on Twitter or Facebook.

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© Copyright, Judy L Mohr 2017

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