In a major development for genetics, a complete map of how human DNA from two parents mixes in offspring has now been revealed through the work of deCODE genetics/Amgen scientists, with major ramifications for our genetic future.
Understanding how DNA combines is a huge leap forward in understanding genetic diversity and its relation to human health and fertility. For the first time, scientists have successfully incorporated elusive non-crossover grandparent DNA recombinations into their research, challenging the long-held belief that such mutations are primarily a male phenomenon.
Studying How DNA Evolves
deCODE Genetics has been at the forefront of research into genetic diversity, health, and disease research for over 25 years. Since its founding in 1996, the company has published seven major studies on gene recombination. While the Human Genome Project, completed in 2003, mapped our DNA, many questions about how human genetics evolves over generations remain unanswered.
“When the genome is passed from one generation to the next, there are a bunch of alterations in the sequence that happen. There is a generational new sequence diversity that is necessary for the human beings to continue to evolve and adjust to new environments, and the new sequence diversity is generated through two kinds of mechanisms,” deCODE CEO Kári Stefánsson explained to The Debrief.
“One is recombination that we are describing in this paper, and the other is mutation. There is hardly any biological process that is more important than the generation in the sequence of the human kingdom,” Stefánsson said. “So, we are mapping the way in which we are empowered to continue to survive as a species.”
The Challenge of Non-Crossover Recombination
One of deCODE’s biggest breakthroughs involved uncovering the elusive process of non-crossover DNA recombination. When a new organism is formed, DNA from the parents recombines in one of two ways. In crossover recombination, chromosomes from each parent exchange small segments of DNA. In non-crossover events, however, one chromosome incorporates a piece of the other without reciprocation, making these exchanges much harder to detect.
“They can be very difficult to find, and you need very large amounts of material to be able to do so. We overcame the difficulties of doing that. This is the reason we can now, for the first time, [create] a recombination map for the human genome that includes both the crossover and the non-crossover,” Stefánsson said.
New Insights into DNA Recombination
Previous studies have demonstrated that mutations and recombination exhibit sex-based differences. Traditionally, men were seen as more likely to exhibit mutations, while women contributed to genetic diversity through recombination. However, deCODE’s research reveals an unexpected connection between these processes.
“What we have shown clearly, clearly is that recombinations, they predispose to be no mutations,” Stefánsson commented. “So these two fundamental phenomena that generate new diversity in the sequence of our genomes, they are not independent. They are actually closely correlated, which is very, very interesting. I mean, when it comes to the knowing mutations that are passed from mother to child, about 11% of them are directly consequence of recombination.”
The Real-World Impact of Recombination
While understanding humanity’s genetic evolution is critical on a broader scale, DNA recombination also has immediate and profound implications for individual health and reproduction.
“You see, about 50% of all spontaneous abortion seems to be a consequence of abnormalities in recombination,” Stefánsson explained. “You find in 50% of spontaneously aborted fetuses, where you find chromosomal abnormalities, but only in about 1% of live-born children.”
The consequences of recombination failures, Stefánsson says, play a significant role in terms of whether fetuses survive. “And it’s interesting that in this generation of new sequence diversity through recombinations and in mutations that are necessary for our species to survive, that there is a small percentage of the population that pays the price for it,” he added.
Recombination errors not only affect fetal survival but are also linked to a range of genetic conditions, such as Down syndrome. “This is in no way trivial when it comes to the way in which it impacts our health and our ability to reproduce,” Stefánsson added.
The Future of DNA Research
Looking ahead, Stefánsson envisions the next phase of DNA recombination research focusing on pinpointing the root causes of recombination failures. He describes the next challenge as identifying what fundamentally prevents genetic viability “to try to figure out what it is that truly prevents survival, and that is what I believe is going to be our next contribution.”
Current studies largely rely on DNA from living humans. Stefánsson suggests that future research should examine the DNA of non-surviving fetuses to understand where recombination becomes non-viable. By addressing these issues at the earliest stages, researchers may find ways to improve genetic health overall, as well as reduce reproductive challenges going forward.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.