We always knew that the spellings of our genetic code differed slightly, but new research published this month shows that it's not only single letters but sentences, paragraphs and even whole pages that can be missing or duplicated.

An international team has now produced a map of such changes – copy number variations - using copies of the genetic code of 270 people, revealing new routes for finding genes involved in disease. The research has been published in Nature.

The Human Genome Project produced a reference sequence for the human genome. Studies such as the HapMap Project mapped single-letter differences (called single nucleotide polymorphisms or SNPs) between individuals and compared them to the human reference DNA sequence.

While these SNP maps are invaluable, most larger regions absent from or duplicated in different individuals (copy number variations) are missed by these maps.

The team found that ten per cent of disease-related genes are associated with copy number variations. One striking example is resistance to infection by HIV, which is determined in part by multiple copies of the gene CCL3L1, and is essentially invisible to SNP-based maps.

The copy number variation map is transforming medical research in four areas. The first and major area is in studies hunting genes underlying common diseases, which have not looked at copy number variations to date. Second, the copy number variation map is being used in the study of familial genetic conditions. Third, there are thousands of severe developmental defects caused by chromosomal rearrangements. The copy number variation map is being used to exclude variation found in unaffected individuals, helping researchers to target the region that might be involved. Finally, as with HIV, it will be possible to find variants that protect against other infectious diseases, such as malaria.

This map is freely available for researchers worldwide. The Wellcome Trust Sanger Institute and its partners have developed a copy number variation database called DECIPHER, allowing researchers around the world to submit clinical information of patients with copy number variation details using the internet. This patient information is then mapped onto the human genome in the public Ensembl browser, which enables collaborative investigations of these rare disorders. In this way, DECIPHER has already helped in the identification of new syndromes with subsequent improvements in care and genetic advice for affected individuals and families.

See also

• Research resources (access Wellcome Trust-funded resources to support biomedical research)
• The Human Genome website

External links

• Press release
• DECIPHER database
• Ensembl Genome Browser