Super fast genomes move a step closer to reality

Thursday, November 20, 2008

The first Asian and African human genomes have been deciphered using a technique originally invented by Professors Shankar Balasubramanian and David Klenerman at the University of Cambridge’s Department of Chemistry and developed by the spin-out Solexa.

The genome sequence of three individuals, from China, Nigeria and a cancer patient, are only the third, fourth and fifth complete genomes to be decoded and the first using Solexa sequencing on the Illumina Genome Analyzer (Illumina purchased Solexa in 2007).

Their completion amounts to a major step to the goal of tailor-made profiles of individual genomes.

Each of the sequences cost a fraction of the first human genome sequenced by the Human Genome Project which finished in 2004 at a cost of $300 million. Each of these genomes cost less than $250,000.

This is the first time that the technology has been used to sequence an entire DNA sequence of a human. Next year Illumina expects the cost to fall to around $10,000.

This technology overcomes the limitations that have held back previous attempts to sequence a complete human genome. Previous sequencing approaches could only read 10 to 100 bases per step/cycle. This technique can sequence more than 10 million bases at a time.

The phenomenal increase in the number of bases that can be read is because of the novel technology used - reverse terminator chemistry. Human DNA is randomly cut up into small pieces and immobilized to a surface. Each molecule of DNA is copied 100s of times so that a forest of sequences builds up from each original sequence. It is then possible to process more than 10 million samples at a time.

With all the molecules attached to a surface, an enzyme attaches colored blocks to the first base of the sequence. Each of the four bases of DNA (A,T,C,G) has a colored fluorescent block that equates to it; red, green, blue and green. With the colored blocks attached an image is taken of the surface and the base at the first position is determined. To ensure that only one colored block is incorporated at a time, a protecting group blocks incorporation of any more fluorescent blocks.

A process then clips off the color block and the blocking group at that position, hence reversible terminator sequencing. Using the same process, each base in the sequence is read to provide a color coded sequence. This assembled color sequence can then be translated to provide the DNA sequence.

The process builds up a picture of the sequence using short reads of 35 base pairs for each cut segment. Although each read is very short, the sheer number of molecules allows the sequences to be stitched together to form the complete genome sequence.

The three anonymous genomes join those of the distinguished geneticists James Watson and Craig Venter as the only people to have their personal genome made publicly available.

When Professors Shankar Balasubramanian and David Klenerman began their research into DNA sequencing 10 years ago, the Human Genome Project was less than half way through when they had the lofty goal of generating over a billion bases of DNA sequence at a time. In a decade that work has surpassed their original expectations, and the resulting spin out company, Solexa.

Commenting on this successful application of research, Dr Richard Jennings, Director of Technology Transfer & Consultancy Services, Cambridge Enterprise said:

"This remarkable technology which started as a researchers conversation and a sketch on a whiteboard, shows how the University of Cambridge and its inventors can help translate the results of fundamental research into applications with outstanding societal benefits."

Recent work by Illumina has increased the number of bases that the technique can read to more than 100 bases at a time and it can process up to 20 billion bases per run. This research takes another step towards the aim of the $1,000 genome that could allow each of us to discover our unique genome that could lead to tailor made treatments for a wide range of diseases.

This year it is anticipated that many more human genomes will be sequenced using this technique.

Since its commercial release in 2007, more than 130 original research projects have been published in peer reviewed journals using the Illumina Genome Analyzer.

The process has been used to analyze genetic variation between individuals. It has also been used assemble miRNA profiles in cancers that could lead to diagnostic and therapeutic benefits.

Source: University of Cambridge

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Time Stamp: 11/20/2008 at 4:43:35 PM UTC