December 7, 2012
Nobody Is Perfect: Study Shows People Have 400 Genetic Flaws In DNA
Lawrence LeBlond for redOrbit.com - Your Universe Online
Perfection is something that all humans strive for at one time or another, be it scoring a perfect 100 on a test, making the perfect soufflÃ©, having the perfect play in basketball, or even landing the perfect job. For others, perfection is a state of well-being–as in being perfectly healthy. While achieving perfect health may be plausible in sense of how one feels, new research shows that, at the genetic level, nobody will ever be perfect.
Scientists have long known that all people carry some harmful genetic variants, but this is the first time researchers have been able to quantify how many variants each person has on average, and also list them. The study authors said this figure is likely to increase as more powerful genetic studies discover rare genetic variants more efficiently.
While most of these genetic variants are considered “silent” mutations and do not affect health, the team said they can cause problems as they pass down through generations. Some of the more harmful genetic variants found were linked to cancer and heart disease.
Dr. Yali Xue, lead author of the research from Wellcome Trust Sanger Institute at Cambridge, said: “For over half a century, medical geneticists have wanted to establish the magnitude of the damage caused by harmful variants in our genomes. Our study finally brings us closer to understanding the extent of these damaging mutations.”
The evidence comes from the 1,000 Genomes Pilot Project, which has been mapping normal human genetic differences, from tiny changes in DNA to major mutations. The researchers also gleaned data “from the Human Gene Mutation Database (HGMD), a detailed catalogue of human disease-causing mutations that have been reported in scientific literature,” said Xue.
Xue and his colleagues compared the genomes of 179 participants, who were healthy at the time their DNA was sampled, with a database of human mutations compiled at Cardiff University. The research found that along with the 400 average variations, most people also have two DNA changes known to be associated with disease.
“Ordinary people carry disease-causing mutations without them having any obvious effect,” said Dr. Chris Tyler-Smith, a lead researcher on the study from Wellcome. “In a population there will be variants that have consequences for their own health.”
This research gives insight into the “flaws that make us all different, sometimes with different expertise and different abilities, but also different predispositions in diseases,” study coauthor Prof. David Cooper of Cardiff, said in an interview with the BBC´s Helen Briggs.
“Not all human genomes have perfect sequences,” he said in the interview. “The human genome is packed with pervasive, architectural flaws.”
"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," Cooper said in a separate statement. "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 predict the clinical consequences of a given genetic variant, but databases such as HGMD promise to come into their own as we enter the new era of personalized medicine."
The work to catalog disease-causing variants has been ongoing for more than two decades, yet the work is still far from complete. Disease variants are extremely rare for the most part and comprehensive searches for such mutations have so far only scratched the surface.
But as DNA sequencing becomes more common in humans, geneticists must determine ethical ways to go about handling sensitive data. For this latest study, researchers anonymized the samples so as not to offer participants any information as to whether or not they may be at risk for a particular genetic disorder.
Tyler-Smith said currently there is no clear answer for what is ethical and what is not when it comes to sharing genetic variation data and potential incidental findings with volunteers in their study.
"All of our genomes contain flaws; some of us will carry deleterious variants but will not be at risk of acquiring the associated disease for one reason or another. For others, there will be health consequences, and early warning could be useful, but might still come as an unwelcome surprise to the participant," he concluded.
This study is published in the American Journal of Human Genetics.