Handheld device could bring genome sequencing into the maintstream

This is one conclusion from a study that used a pocket sized, portable DNA sequencer to sequence the complete human genome in fragments hundreds of times larger than usual.

The research, published in Nature Biotechnology, involved scientists from the University of Nottingham, University of Birmingham and the University of East Anglia in the UK in collaboration with researchers in the US and Canada.

The authors generated a new method for sequencing “ultra-long” sequences of DNA, more than a thousand times longer than the original ‘reads’ used to generate the human genome reference sequence in 2001.

The authors have used this method to generate the longest ever read sequenced at 1,204,840 base-pairs (an individual’s DNA code stored as a sequence of bound pairs of the organic bases adenine, guanine, cytosine and thymine) in length, or 8,000 times longer than a typical sequencing read.

The authors speculate that these reads and longer ones can be generated routinely in future, enabling human genomes as complete as the reference genome which was the subject of over 20 years of research and over $2bn of investment.

Prof Nick Loman, of the Institute of Microbiology and Infection at Birmingham University said: “One of the most important findings of this research was that, even though the human genome reference was completed or thought to have been completed a while ago, it still contains many missing pieces and we were able to close some of those gaps in the sequence by developing a new method for developing these extremely long reads using nanopore sequencing.”

As well as sequencing previously uncharacterised regions of the genome, the new analysis provided greater insight into regions of the genome that are responsible for functions such as immunity and tumour growth. This could potentially have an impact on clinical practice, such as detecting large genome rearrangements important in the development of cancer.

The ability to sequence using a portable device may put also personalised genome sequencing into the mainstream.

The international research effort used the Oxford Nanopore Technologies MinION sequencer. The sequencer, approximately the size of a mobile phone, sequences the DNA by detecting the change in current flow as single molecules of DNA pass through a nanopore in a membrane.

The MinION sequencer was developed in collaboration with Prof Loman and his PhD student Josh Quick, and the scientists recently used the technology in separate research in the field in Africa and the US to trace the spread of infectious diseases Ebola and the Zika virus.

Dr Andrew Beggs, of Birmingham University’s Institute of Cancer and Genomic Sciences, said: “The human genome is the body’s code that tells the body how to grow and develop and all the instructions in it are similar between people, but when the instructions go wrong that’s when disease develops.

“About 20 years ago, sequencing was a very difficult task which required huge machinery and took a very long time. With the nanopore system we could rapidly get a diagnosis for cancer based on the changes in the patient’s genetic code, within 24 hours.

“Thanks to advances using the nanopore system, I think in five to ten years we’ll be at the stage where genetic sequencing will be as ubiquitous as boiling a kettle or making a cup of tea. It will be available to us all and will lead to so-called ‘home brewed genetics’, where people will be able to take it into their own power to sequence their own genome.”