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Why nobody is perfect

18 December 2012

DNA helix

Researchers at Cardiff and Cambridge Universities have found that a healthy person carries, on average, approximately 400 potentially damaging DNA variants and two variants known to be associated directly with disease. The study, published in the American Journal of Human Genetics, shows that as many as one in ten people is likely to develop a genetic condition as a consequence of carrying these variants.

It has been known for decades that everyone carries some damaging genetic variants that appear to cause little or no ill effect. However, this is the first time that researchers have been able to quantify how many such variants each of us has, and to list them. This was made possible by using the Human Gene Mutation Database (HGMD), developed over the last 15 years by Professor David Cooper and his team of researchers at the University's Institute of Medical Genetics. HGMD constitutes a comprehensive collection of published data on gene mutations underlying or associated with human inherited disease.

To perform the analysis, scientists at the Wellcome Trust Sanger Institute, led by Dr Chris Tyler-Smith, cross-compared the HGMD dataset with whole genome sequences derived from 179 people enrolled in the 1000 Genomes Pilot Project. This allowed a detailed catalogue of human disease-causing mutations to be drawn up. Samples for this study were taken from individuals who at the time of sampling were unlikely to have any overt genetic disease.

The average figure of 400 potentially damaging DNA variants is predicted to increase as more and more powerful genetic studies discover rare genetic variants more efficiently. However, such research also brings to the fore ethical questions surrounding anonymous studies and what to do with incidental findings.

"In the majority of people we found to have a potential disease-causing mutation, the genetic condition is actually quite mild, or would only become apparent in the later decades of life," says Professor David Cooper, lead author of the study from Cardiff University. "We now know that normal healthy people can possess many damaged or even completely inactivated proteins without any noticeable impact on their health. It is extremely difficult to be able to predict the clinical consequences of a given genetic variant. So databases such as HGMD promise to come into their own as we enter the new era of personalized medicine."