The Mind Power Times

The capacity to track and change genetic mutations to the level of a single letter could drastically enhance the capacity to understand genetic diseases, and lead the way to their correction.

“Advances in human genetics have led to the discovery of hundreds of genetic changes linked to disease, but until now we’ve lacked an efficient means of studying them,” explained Gladstone Institutes’ Dr Bruce Conklin, “We must have the capability to engineer the human genome, one letter at a time, with tools that are efficient, robust, and accurate. And the method that we outline in our study does just that.” Conklin and his colleagues announced the first demonstration of their technique in Nature Methods.

Many genetic diseases involve very rare variations in the text of our genes, sometimes just a single “letter” where one of the four nucleobase that spell out our genetic code is replaced by another. Such changes can produce no noticeable effect, devastating diseases and everything in between. Finding a single variation that exists in only a fraction of cells invites comparisons with needles and haystacks.

“For our method to work, we needed to find a way to efficiently identify a single mutation in a cell among hundreds of normal, healthy cells,” explained lead author Dr Yuichiro Miyaoka, PhD, also of Gladstone Institutes. “So we designed a special fluorescent probe that would distinguish the mutated sequence from the original sequences. We were then able to sort through both sets of sequences and detect mutant cells—even when they made up as little one in every thousand cells. This is a level of sensitivity more than one hundred times greater than traditional methods.”

Methods of editing genetic code exist, but until now they have either left damage to the genome, with dangers for future generations of cells, or work on only a fraction of the cells to which they are applied.

The Gladstone team introduced mutations into the genome of induced pluripotent stem cells, cells that are capable of turning into a variety of the body’s cell types, using existing techniques. They then demonstrated that their new technique could, in Conklin’s words, “capture and amplify specific mutations that are normally exceedingly rare.”

Finding mutated genes would make the identification of genetic disease much easier, but the ultimate goal is to be able to correct such slips. “We are hopeful that our technique, by treating the human genome like lines of computer code, could one day be used to reverse these harmful mutations, and essentially repair the damaged code,” said Conklin.