Researchers identify seventh and eighth bases of DNA

Researchers from the University of North Carolina (UNC) School of Medicine have identified the seventh and eighth bases of DNA.

For decades, scientists have known that DNA consists of four basic units — adenine, guanine, thymine, and cytosine. In recent history, scientists have expanded that list from four to six.

Much is known about the “fifth base,” 5-methylcytosine, which arises when a chemical tag or methyl group is tacked onto a cytosine. This methylation is associated with gene silencing, since it causes the DNA’s double helix to fold even tighter upon itself. Last year, the researchers found that Tet proteins can convert 5 methylC (the fifth base) to 5 hydroxymethylC (the sixth base) in the first of a four-step reaction leading back to cytosine.

However, the researchers could not continue the reaction on to the seventh and eighth bases, called 5 formylC and 5 carboxyC. The problem was that their experimental assay wasn’t sensitive enough. They redesigned it and were able to detect the seventh and eighth bases — called 5-formylcytosine (5fC) and 5 carboxylcytosine (5caC) — which are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming.

The researchers then examined embryonic stem cells as well as mouse organs and found that both bases can be detected in genomic DNA.

Their findings could have important implications for stem cell research, since it could provide researchers with new tools to erase previous methylation patterns to reprogram adult cells. It could also inform cancer research by giving scientists the opportunity to reactivate tumor suppressor genes that had been silenced by DNA methylation.

Your genome in minutes

Scientists from Imperial College London are developing technology that could ultimately sequence a person’s genome in mere minutes, at a fraction of the cost of current commercial techniques.

The researchers have patented an early prototype technology that they believe could lead to an ultrafast commercial DNA sequencing tool within ten years. Their work is described in a study published this month in the journal Nano Letters and it is supported by the Wellcome Trust Translational Award and the Corrigan Foundation.

The research suggests that scientists could eventually sequence an entire genome in a single lab procedure, whereas at present it can only be sequenced after being broken into pieces in a highly complex and time-consuming process. Fast and inexpensive genome sequencing could allow ordinary people to unlock the secrets of their own DNA, revealing their personal susceptibility to diseases such as Alzheimer’s, diabetes and cancer. Medical professionals are already using genome sequencing to understand population-wide health issues and research ways to tailor individualised treatments or preventions.

Dr Joshua Edel, one of the authors on the study from the Department of Chemistry at Imperial College London, said: “Compared with current technology, this device could lead to much cheaper sequencing: just a few dollars, compared with $1m to sequence an entire genome in 2007. We haven’t tried it on a whole genome yet but our initial experiments suggest that you could theoretically do a complete scan of the 3,165 million bases in the human genome within minutes, providing huge benefits for medical tests, or DNA profiles for police and security work. It should be significantly faster and more reliable, and would be easy to scale up to create a device with the capacity to read up to 10 million bases per second, versus the typical 10 bases per second you get with the present day single molecule real-time techniques.”