Groundbreaking study reveals hidden complexity in human genetics

Amazing stuff!

Unfortunately, this article lacks a reference to the research paper! Using Google Scholar, I was not able to find this paper!

"... the key was to account for variant combinations in a gene, also called epistasis. They measured functional effects of variant combinations in the DNA of a key enzyme, argininosuccinate lyase (ASL), a lack of which results in urea cycle disorder, a rare but devastating condition.  

The researchers tested thousands of variant combinations that resulted in no enzyme activity when on their own and found that a significant portion of them had high levels of enzyme activity when in combination with each other. In other words, two defective variants, when combined, can recover function. ...

[Francis] Crick, who shared the Nobel Prize in Physiology or Medicine 1962 with James Dewey Watson and Maurice Wilkins for their discoveries concerning the molecular structure of DNA, had hypothesized this could happen.

“Crick had a fancy word for it—variant sequestration,” ... “But until [now], no one had demonstrated it.” ..."

Groundbreaking study reveals hidden complexity in human genetics | George Mason University "Sometimes, in genetics, two wrongs do make a right. A research team recently showed that two harmful genetic variants, when occurring together in a gene, can restore function—proving a decades-old hypothesis originally proposed by Nobel laureate Francis Crick. Their study ... not only experimentally validated this theory but also introduced a powerful artificial intelligence (AI)-driven approach to genetic interpretation ..."