DNA VARIETY GREATER THAN FIRST THOUGHT By Clive Cookson in London
Friday, November 24, 2006
People differ much more in their DNA than scientists previously realised. An international research team last night reported the discovery of a new dimension to genetic variation, with important implications for medicine and basic science.
Until now geneticists have focused on small differences between individuals. Looking at the human genome as a “book of life” they have mapped vast numbers of variations in letters or short words – but missed much larger deletions and duplications of pages or chapters.
The newly discovered differences, known as “copy number” variations or CNVs, have been mapped by an international consortium of 13 research centres. The results are published in today's issue of the journal Nature. They open up a new vista for genetics “with dramatic implications for disease studies”, said Matthew Hurles, one of the project's leaders at the Wellcome Trust Sanger Institute near Cambridge, England.
“Each one of us has a unique pattern of gains and losses of complete sections of DNA,” said Dr Hurles, “and one of the real surprises of these results was just how much of our DNA varies in copy number.”
Although the full implications of CNVs are not yet understood, they mean that genetic variation – between individuals and between species – is probably three times greater than scientists estimated when the Human Genome Project was completed five years ago.
Biologists had known for years that large changes in the human genome could cause disease – for example people with an extra copy of chromosome 21 have Down's Syndrome – but these were believed to be rare exceptions to the rule that variation normally occurred in single letters or short sequences of genetic code.
“The copy number variation that researchers had seen before was simply the tip of the iceberg, while the bulk lay submerged, undetected,” said Dr Hurles. “We now appreciate the immense contribution of this phenomenon to genetic differences between individuals.”
The true scale of copy number variation has been revealed only now because new techniques of genetic analysis – developed by companies such as Affymetrix of California – are enabling researchers for the first time to make large-scale comparisons between individual human genomes. Paradoxically, it has been far easier to map small variations.
Commentators, who had been stressing the unexpected genetic closeness between different species, may now have to change their tune. The previous estimate was that unrelated people had 99.9 per cent of DNA in common – the real figure is more like 99.7 per cent. Humans actually share 96 per cent or 97 per cent of their genome with chimpanzees, the most closely related living species, rather than 99 per cent.
The new CNV map – compiled from 270 individual genomes of people with African, Asian and European ancestry – will change the way in which scientists search for genes involved in disease.
“Many examples of diseases resulting from changes in copy number are emerging,” said Charles Lee, another project leader from Harvard Medical School in Boston. A striking example is resistance to infection by HIV, which is determined in part by multiple copies of a gene called CCL3L1. CNVs have been implicated in diseases of the nervous system, heart, skin and eyes.
