Genetically speaking, humans are almost identical. But those differences that do exist can affect our health. With the sequencing of the human genome and global efforts to map genetic variation, many surprising findings have emerged – not least the importance of copy number variation.

Copy number variation refers to blocks of DNA throughout the genome, which can be anything from 1000 to 5 million nucleotides long; the number of copies at a given location in the genome can vary from zero to tens or even hundreds. These variations have been implicated in several human genetic diseases, and are known to affect susceptibility to HIV and malaria infection.

Now, a multinational team, including Dr Matthew Hurles and colleagues from the Wellcome Trust Sanger Institute, has constructed the first map of copy number variation across the entire human genome. Surprisingly, it affects 12 per cent of the genome – much more than suspected. Affected areas spanned known genes and disease loci, emphasising the importance of copy number variation in both disease and genetic diversity.

Dr Nigel Carter's group, also at the Sanger Institute, is one of several teams that have identified specific copy number variations on chromosome 17 as causes of a mental retardation syndrome. The deletion affects two genes, CRHR1 and MAPT, which are likely candidates for the syndrome, as they are active in the brain and known to be involved in degenerative disorders.

In other research (funded by the Wellcome Trust and others), Professor Tim Aitman of Imperial College and others discovered that a low copy number of the Fcgr3 gene increased susceptibility to a kidney disease, glomerulonephritis, in rats and humans.

Copy number variations are mutations that are likely to have a profound impact on phenotypic differences between individuals. The whole-genome map will greatly aid studies exploring the impact of genetic variation on health.

Image: Young children; Fiona Pragoff

External links

• Redon R et al. Global variation in copy number in the human genome. Nature. 2006 Nov 23;444(7118):444-54.
• Shaw-Smith C et al. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat Genet 2006;38(9):1032–7.
• Aitman TJ et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 2006;439(7078):851–5.
• Database of Genomic Variants