A better way to read the genome

UConn researchers have sequenced the RNA of the most complicated gene known in nature, using a hand-held sequencer no bigger than a cell phone.

Genomicists from the UConn Institute of Systems Genomics teamed up with UK-based Oxford Nanopore Technologies to show that the company's MinION nanopore sequencer can sequence genes faster, better, and at a much lower cost than the standard technology.

If your genome was a library and each gene was a book, some genes would be straightforward reads - but some would be more like a "Choose Your Own Adventure" novel. Researchers often want to know which version of the gene is actually expressed in the body, but for complicated choose-your-own-adventure genes, that has been impossible.

Brentom Graveley and his colleagues chose the most complex choose-your-own-adventure gene known, Down Syndrome cell adhesion molecule 1 (Dscam1), which controls the wiring of the brain in fruit flies. Dscam1 has the potential of making 38,016 possible isoforms, and every fruit fly has the potential to make every one of them, yet how many of these versions are actually made remains unknown.

Researchers took a fruit fly brain, extracted the RNA, converted it into DNA, isolated the DNA copies of the Dscam1 RNAs, and then ran them through the MinION's nanopores. In this one experiment, they not only found 7,899 of the 38,016 possible isoforms of Dscam1 were expressed but also that many more, if not all versions are likely to be expressed.

"A lot of people said 'The MinION will never work,'" Graveley says, "but we showed it works using the most complicated gene known."