New Single-Cell Genome Sequencing Technique Promises Unprecedented Details

Scientists have made a leap forward when it comes to genome sequencing. They've generated the most complete genome sequences from single E. coli cells and individual neurons from the human brain with a new technique that confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters.

"Our preliminary data suggest that individual neurons from the same brain have different genetic compositions," said Kun Zhang, one of the researchers, in a news release. "This is a relatively new idea, and our approach will enable researchers to look at genomic differences between single cells with much finer detail."

The new sequencing approach identified gains or loss of single copy DNA as small as one million base pairs, the highest resolution to date for single-cell sequencing approaches.  In addition, the 12 nanoliter volume microwells in which amplification takes place are some of the smallest volume wells to be used in published protocols for single-cell genome sequencing.

"By reducing amplification reaction volumes 100-fold to nanoliter levels in thousands of microwells, we increased the effective concentration of the template genome, leading to improved amplification uniformity and reduced DNA contamination," said Jeff Gole, one of the researchers, in a news release.

In fact, compared to the most completely previously published single E. coli genome data set, the new approach recovered 50 percent more of the E. coli genome with 3 to 13-fold less sequencing data.

"We now have the wonderful opportunity to take a higher-resolution look at genomes within single cells, extending our understanding of genomic mosaicism within the brain to the level of DNA sequence, which here revealed new somatic changes to the neuronal genome," said Jerold Chun, one of the researchers, in a news release. "This could provide new insights into the normal as well as abnormal brain, such as occurs in Alzheimer's and Parkinson's disease or Schizophrenia."

The findings are published in the journal Nature Biotechnology.