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Human genome Tuesday, 30 May, 2000, 17:28 GMT 18:28 UK
How the code was cracked
DOE Human Genome Program/Affymetrix.
Techniques will allow gene mutations to be found
Some of the bitterest arguments sparked by the quest to unravel the human genome have been over the merits of the different approaches to decoding the DNA.

The publicly funded Human Genome Project (HGP) has taken a slower, more methodical approach. The entire DNA blueprint for humans is contained on 24 chromosomes.

Time to assemble 12,000 bases
Today - one minute
Three years ago - 20 minutes
20 years ago - over a year
So they mapped out the major signposts and then chopped up specific sections for investigation. They are now filling in these details.

This is rather like making a road map of the UK by starting with the motorways and then driving around, filling in the A roads and B roads.

Craig Venter's company Celera started their effort eight years after the HGP, when computers were much faster and more powerful. Their approach simply chops up the whole genome for sequencing and then uses supercomputers to reassemble all the data.

Humans and flies

This is like making a roadmap of the UK by taking millions of aerial photographs and hoping that you will be able to recognise enough overlaps to put it all back together.
Genome jigsaws
Celera sequencing
60 million overlapping fragments
Each 2,000 to 10,000 bases long
HGP sequencing
22,000 fragments
Each 100,000 to 300,000 bases long

Sceptics said that Celera's method could only work for the relatively small genomes of bacteria and viruses.

But the sequencing of 120 million bases of the fruit fly genome, Drosophila melanogaster, proved those sceptics wrong. Humans share 60% of the 13,600 fruit fly genes.

So whose data is better? The HGP argue that because they have repeated the sequencing four or five times for their draft, as opposed to Celera's three, their data has fewer inaccuracies.

However, Dr Venter counters that the HGP could have an accurate sequence, but that they do not know where exactly on the chromosome each sequence is positioned.

Free access

"That's important because we can't define the genes until it's assembled in the proper order, as well as being highly accurate."

The tit-for-tat continues with the HGP's Dr John Sulston saying: "Celera has got to sell its product and it must convince people that its product is best." The HGP also point out that Celera can use all of its data, freely available on the internet, but they have no access to Celera's work.

The actual DNA used by the HGP came from 12 anonymous volunteers - Celera used six volunteers.

Such numbers of volunteers may seem too small to be representative of humanity, but the difference in DNA between everyone on Earth is just 0.1%.

One difference in a thousand separates a Chinese peasant from a US president. Differences of just 1.5% of the genome accounts for the creation of a chimpanzee rather than a human.

Gold standard

However, the data being produced by either of the two sequencing efforts is not as comprehensive or reliable as is often suggested.

The first drafts will consist of 90% of the human genome to an accuracy of 99.9%. That is an error rate of 0.1% which, theoretically, could obliterate the entire diversity of the human race.

The groups believe this level of precision can be achieved by repeating their work four or five times. But the "gold standard" of reliability set by the Human Genome Project, 99.99%, will require tenfold duplication - another two or three years work.

And even then, as much as 10% of the genome will remain intractable to current technology. Much of this missing data will be short, repetitive sequences of bases that jam up the current DNA processing technique. These repeats are unlikely to hold important instructions.

However, bacteria are used to multiply the chopped up human DNA and there may be sequences that prevent the microbes from copying the fragments. These pieces could contain active regions.

By BBC News Online's Dr Damian Carrington





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See also:

19 May 00 | Science/Nature
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