Genetic testing aims to find altered genes that could lead to a disease, and give doctors a head start in finding the best treatment. However, new research now suggest that finding these potentially ill-fated genes may not be such a big deal.
Researchers from Cambridge and Cardiff universities found that a normal person typically has about 400 DNA mutations in potentially important sites in the genome. But the researchers also found that people carrying these disease-causing mutations usually, and who represent about 10% of all the people carrying these mutations, have a very mild version of the genetic disease, or do not develop it until later in life. The research, published online on December 7, in the American Journal of Human Genetics, casts some doubt on the wisdom of treating someone for a genetic disease solely due to their genetic footprint, and also raises ethical questions about discussing individual results from clinical tests where results are not tied to a particular participant.
The study measured mutations found in the genomes of 179 people who donated samples to the 1000 Genomes Pilot Project, which collected data from healthy individuals. The study also used data from the Human Gene Mutation Database, which catalogues mutations reported in various scientific studies. Neither of these data sets matches an individual to a specific genome.
In most of the cases the scientists discovered that mutations ocurred on "recessive" genes, which meant that the defective gene was masked by a healthy version (humans always have two versions of any gene). A recessive gene will cause a disease only if both recessive versions are present. The 10% of people who had disease-causing variants and developed a disease either had two recessive genes, or a mutated, dominant gene.
While classical genetics would say that these 10 percent are doomed to illness, Dr. David Cooper, one of the lead author of the study, says not quite. "We now know that 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."
One problem is that data libraries like the Gene Mutation Database do not yet have complete profiles for every genetic disease in existence, which means they are only as good as the studies they include. The more studies and genomes are studied, the more accurate the database becomes. So, what should we be telling healthy people with "bad" genes? Maybe nothing. The researches strongly suggests an ethical problem stemming from warning people about diseases they might not contract, despite their genetic makeup, as Dr. Chris Tyler-Smith explains, "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".