2017/10/25

Scientists need a human reference genome - Accurate DNA repair now possible

Lifestyle induced inheritable DNA mutations can be repaired on the atomic level


Excerpt: "Scientists at Harvard University and the Broad Institute of MIT and Harvard have developed a new class of genome editing tool. This new “base editor” can directly repair the type of single-letter changes in the human genome that account for approximately half of human disease-associated point mutations. These mutations are associated with disorders ranging from genetic blindness to sickle-cell anemia to metabolic disorders to cystic fibrosis.

The research team, led by David Liu, professor of chemistry and chemical biology at Harvard University, core institute member at the Broad Institute, and a Howard Hughes Medical Institute (HHMI) investigator, developed a molecular machine that can converts the DNA base pair A•T to G•C, without cutting the double helix, with high efficiency and virtually no undesired products. The development is an important addition to the growing suite of genome editing tools.

The new system is described in a paper published today in Nature. In addition to Liu, the study was led by Nicole Gaudelli, a postdoctoral fellow in Liu’s lab; Alexis Komor, a former postdoctoral fellow in Liu’s lab who is now an assistant professor at UCSD; graduate student Holly Rees; former graduate students Michael Packer and Ahmed Badran, and former postdoctoral fellow David Bryson.

The new system, dubbed Adenine Base Editor, or ABE, can be programmed to target a specific base pair in a genome using a guide RNA and a modified form of CRISPR-Cas9. It works by rearranging the atoms in a target adenine (A) — one of the four bases that make up DNA — to instead resemble guanine (G), and then tricking cells into fixing the other DNA strand to complete the base pair conversion, making the change permanent. As a result, what used to be an A•T base pair becomes a G•C base pair.

Not only is the system very efficient compared with other genome editing techniques for correcting point mutations, but there are virtually no detectable byproducts such as random insertions, deletions, translocations, or other base-to-base conversions.
 
Making this specific change is important because approximately half of the 32,000 disease-associated point mutations already identified by researchers are a change from G•C to A•T.

“We developed a new base editor — a molecular machine — that in a programmable, irreversible, efficient, and clean manner can correct these mutations in the genome of living cells,” said Liu, who is also the Richard Merkin Professor and Director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. “When targeted to certain sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease.”
 
ABE joins other base-editing systems pioneered in Liu’s lab, such as BE3 and its improved variant, BE4. Using these base editors, researchers can now correct all the so-called “transition” mutations — C to T, T to C, A to G, or G to A — that together account for almost two-thirds of all disease-causing point mutations, including many that cause serious illnesses for which there are no current treatments. Additional research is needed, Liu notes, to enable ABE to target as much of the genome as possible, as Liu and his students previously achieved through engineering variants of BE3."

My comment: The most common form of point mutations in the human DNA is CG > TA due to proclivity of methylated cytosine turning to thymine in circumstances where the DNA is exposed to oxidative stress, viral attacks or other disruptive contributors. Point mutations result in faulty gene sequences that are always critical and often harmful. They are the most common reason for disease-causing genetic mutations (total number 208,368 in October 2017. Annual growth was ~20,000) in the human DNA.

Because mutations are not resulting in evolution, but genetic degradation only, scientists need this kind of new technologies for being able to repair the human DNA and to restrain devolution from happening. However, scientists need a proper human reference genome. Will people then realize that the DNA genes are not determining human traits like height, intelligence, skin color etc.? And will they also realize that the theory of Evolution is a major lie?