Genetic studies using SNPs may not pick up genes affected by copy number variation.

The human population is genetically remarkably similar. The major source of variation has been assumed to be single letter changes in DNA code – single nucleotide polymorphisms, or SNPs.

In 2006, however, an international collaboration led by researchers at the Wellcome Trust Sanger Institute found that so-called copy number variation (CNV) – the duplication or deletion of chunks of DNA – was surprisingly common. Now, the team has discovered that SNP analysis will not necessarily pick up CNV.

The researchers compared the activity of 14 000 genes in 210 unrelated individuals from four major population groups. They then looked for SNPs or CNVs that were associated with differences in gene activity between individuals.

In all, SNPs accounted for 83.6 per cent of genetic variation linked to altered gene activity, the remaining 17.7 per cent being due to CNV. Significantly, there was very little overlap between the two – variation in a gene's activity was generally linked to SNPs or CNV but rarely both.

The results suggest that traditional methods of gene detection, using SNPs, may miss effects caused by CNV. To uncover all relevant genetic variation, researchers should therefore assess CNV as well as single nucleotide changes.

Image: Coloured points illustrating SNP-associated levels of gene activity; courtesy of Matt Hurles

External links

• Stranger BE et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 2007;315(5813):848–53.