New gene map reveals details of copy number variations
9 October 2009
In the study, reported in the journal 'Nature', researchers studied copy number variations (CNVs), a type of genetic variation where relatively long sections of DNA are gained or lost in one individual relative to another.
"This study is more than ten times as powerful as our first map, published three years ago," explains Dr Matt Hurles from the Wellcome Trust Sanger Institute, and a leader on the project. "Importantly, we have also assigned the CNVs to a specific genetic background so that they can be readily examined in disease studies carried out by others, such as the Wellcome Trust Case Control Consortium."
For this study, the team scanned 42 million locations on the genomes of 40 people, half of European ancestry and half of West African ancestry. The scale of the method meant they could detect CNVs as small as 450 bases occurring in one in 20 individuals.
One aim of the study was to find if CNVs are likely to explain what researchers call 'missing heritability'. This refers to the fact that, while genetic studies looking at single-base changes in the DNA sequence have been useful for understanding why diseases cluster in families, the majority of this clustering is not explained. It was thought that CNVs might be responsible.
However, the researchers conclude that although CNVs might explain some of the existing disease associations, it is highly unlikely that they explain a significant proportion.
The results show that any two genomes differ by more than 1000 CNVs, or around 0.8 per cent of a person's genome sequence. Most of these CNVs are DNA deletions, others are duplications. The researchers found that 75 regions had jumped around in the genomes of the samples studied.
They have also produced the first measure of the rate of CNV mutation: at least one in 17 children will have a new CNV. In many cases, a new CNV will have no obvious clinical consequences. However, for some the effects are severe.
"CNV studies have made huge advances in the past few years, but we are still looking only at the most common CNVs," explains Dr Steve Scherer of the Hospital for Sick Children in Toronto, an author on the paper. "We suspect that there are many CNVs that have real clinical consequences that occur in perhaps one in 50 or one in 100 people - below the level we have detected."
"Success in the hunt for the missing genetic causes of common disease has become possible in the last few years and we expect to find more as higher-resolution searches become possible."
Dr Matt Hurles profile [PDF 572KB]
Image: Distribution of 58 out of 75 putative inter-chromosomal duplications, coloured according to their chromosome of origin. Credit: Courtesy of Jan Aerts, Wellcome Trust Sanger Institute.
Reference
Conrad DF et al. Copy number variation in the human genome: mechanism, selection and disease. Nature 2009 [Epub ahead of print]