Roche software points to disease-causing genes

Researchers at Roche have designed a computer program that could speed up the search for disease-causing genes and hasten the discovery of new drugs to treat genetic illnesses. The software, called Digital Disease, may replace a painstaking process that often requires months of laboratory trial and error

‘The beauty of our software is that it runs in under a second on a computer instead of taking months to years in a lab,’ said Jonathan Usuka, a graduate student in chemistry who developed Digital Disease in collaboration with colleagues at the Roche pharmaceutical company.

The software scans databases containing computerised maps of DNA molecules, then instantly locates irregularities in genes that might be responsible for cancer, diabetes and other ailments.

Instead of searching through maps of the human genome, Digital Disease scans the DNA of mice, which are genetically similar to people.

‘Human genes and mouse genes are about 80 percent identical,’ said Usuka, ‘so if you can identify a genetic mutation in mice, you can easily locate the same mutation in humans.’

Genes are located on chromosomes, which are molecules of DNA. Each gene, in turn, is made up of thousands of chemical subunits – called nucleotides – strung together in a specific sequence.

Every nucleotide contains one of four chemicals known by the abbreviations A, T, C and G. The order in which the four nucleotides occur determines how a gene functions and its ultimate effect on the physical makeup of both people and mice.

Human and mouse genomes contain roughly the same number of nucleotides – 3.1 billion. Digital Disease scans the mouse genome for locations in the DNA where a single nucleotide has been altered from the norm. These locations are called single nucleotide polymorphisms – or SNPs.

Scientists estimate that a SNP occurs about once every 1,000 nucleotides, which means that each person — and each mouse – may carry some 3 million SNPs in their DNA. Most are harmless aberrations, but some have been linked to genetic illnesses, such as breast cancer.

Usuka said the primary application of Digital Disease is to hunt down SNPs that are potentially harmful to mice – and therefore to people.

Statistically, a mouse with an inherited illness is likely to have SNPs that are different from disease-free mice. Digital Disease instantly recognises those unique SNPs, allowing researchers to zero in on specific chromosome segments where disease-causing genes may be located.

Finding the precise location of disease-causing genes will require additional lab work, Usuka pointed out, but the new software should give medical researchers a tremendous head start.

The new software is described in a study in the June 8 issue of the journal Science.

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