Genome reaches two billion letters

Published November 4, 2003

LONDON: Fifty years after the discovery of the structure of the genetic code, UK scientists at Cambridge have set a new world record. They have decoded two billion letters of the alphabet of life, and delivered them freely to researchers of 135 countries.

The first of the two billion was G — it stands for the base chemical guanine — from the DNA double helix of a tiny nematode worm called Caenorhabditis elegans. It was entered into a database set up by what is now the Wellcome Trust Sanger Institute on May 4 1991. The two-billionth was T, for the base thymine, from a laboratory mouse, and it was placed in the public domain on October 30, 2003.

In between came an avalanche of the letters GTAC — the other two stand for adenine and cytosine — which together spell the code for the proteins from which all living things are assembled.

Between the first letter of the worm and the latest letter of the laboratory mouse came the entire genetic codes for yeast, the worm itself, a representative human being, and 25 microbes, including some of the world’s most dangerous: the malaria parasite, the tuberculosis bacillus, leprosy and meningitis.

DNA is a fine filament of molecules coiled like a spiral staircase into the chromosomes in almost every cell in every living creature. The two billion letters sequenced by the Cambridge team would — if scaled up to the size of a real spiral staircase — stretch from the Earth to the moon. If read aloud at the rate of a letter a second, the sequence would take more than 60 years to recite.

The achievement has lead to new sciences — genomics and proteomics — and the identification of a startling array of genes linked to things as diverse as longevity, limb formation and chronic myelogenous leukaemia.

Researchers are racing to complete the DNA sequences of chimpanzees, bananas, farm animals and commercially valuable microbes, and universities and pharmaceutical companies are collecting the millions of genetic variations which make some people more prone to particular diseases or less able to metabolise certain drugs.

All of them use a technique devised in 1977 by the Cambridge double Nobel prizewinner Fred Sanger. What has taken the Sanger Institute team to the top of the league tables is an emphasis on accuracy. By international agreement, a “finished” gene sequence will be accurate to one in 10,000. The Sanger Institute is confident of an accuracy of one in 100,000.

To get to those levels of certainty the scientists used sophisticated robotics, state-of-the-art computing power and experienced human oversight to examine up to an estimated 20 billion bases of DNA.

Over the next 25 years the research will complete a revolution in medical science. Until recent times all drugs were devised by trial and error. Doctor sifted through treatments that would destroy a tumour or poison a pathogen without actually killing the patient as well. Now, equipped with the complete maker’s manual of both disease and patient, researchers have begun the hunt for a new generation of drugs to provide effective treatment of cardiovascular diseases, viral and bacterial infections, neurodegenerative disorders, inherited conditions, and cancers, all with the fewest side-effects.—Dawn/The Guardian News Service.

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