The mouse genome will help us to understand our own DNA
New Scientist | (Nicola Jones) As the two parallel efforts to sequence the human genome enter their final stages, the geneticists who gathered in Vancouver for last week's meeting of the Human Genome Organisation are already looking ahead. Many think the key to finding the meaningful words in the three-billion-letter long sentence of our DNA is sequencing the genome of the humble lab mouse. "That will be the Rosetta Stone in terms of interpreting the human genome," says Steven Jones of the Genome Sequence Centre in Vancouver.
The company Celera Genomics, headed by Craig Venter, which is already setting the pace in unravelling the human genome, announced it would try to sequence the mouse genome earlier this month. Later this year, when the main publicly funded American sequencing centres are scaling down work on the human genome, they will start sequencing the mouse genome. The US's National Human Genome Research Institute estimates that it will take the ten public labs about three years to produce a working draft.
Despite appearances, mice and humans are remarkably similar when it comes to their DNA. Both genomes have about three billion bases, only about 3 per cent of which codes for functional genes--the other 97 per cent being "junk DNA". In the many millions of years since mice and humans diverged from a common ancestor, much of the important DNA has been conserved, while the "junk" has mutated freely and is now very different. That means that simply comparing the two genomes will be an efficient way of identifying vital stretches of DNA, including genes and sequences that regulate gene expression.
Even better, by "knocking out" selected genes in lab mice, we get a good idea of what they do. The equivalent genes in humans should have very similar functions. And that is the first step on the long road to finding useful applications for all this genetic information. "When it comes to drug development, this is crucial," says Lap-Chee Tsui, president of the Human Genome Organisation (HUGO).
Vancouver's Genome Sequence Centre, part of the British Columbia Cancer Research Centre, is starting the public sequencing effort by making a physical map of the mouse genome--a low-resolution chart that orders known sections of DNA and helps locate important areas of each chromosome. With that map, the centre can decide which stretches of DNA need to be sequenced to get good coverage of the mouse genome without unnecessary duplication. Sometime this autumn the Vancouver lab will deal out the cards saying who should sequence what--including data about which segments might be of the greatest medical importance.
Celera uses a different method, known as the "shotgun technique", in which the whole genome is randomly broken into fragments. The fragments are then sequenced and researchers use heavyweight computer power to spot overlapping fragments which allow reassembly. Although potentially less accurate than traditional "directed" sequencing along the chromosome, the shotgun approach is considerably faster. "Ultimately it will accelerate the progress and the public availability of information," says HUGO's senior vice-president Gert-Jan van Ommen about Venter's work.