The purpose of genetic testing is to find altered genes that could cause disease. Then, people could be treated, or prospective parents can make decisions about having children. However, scientists are finding that having a gene that causes disease doesn’t necessarily cause that disease.
Researchers at Cambridge and Cardiff universities found that a normal person typically has about 400 DNA mutations, and that 10 percent of people who have these variants will probably come down with the genetically prescribed disease. But the researchers also found that people carrying these disease-causing mutations usually have a very mild version of the genetic disease, or do not develop it until later in life.
The research, published in the Dec. 6 edition of the American Journal of Human Genetics, casts some doubt of the wisdom of treating someone for a genetic disease solely due to a genetic test, and also raises ethical questions about discussing individual results in a clinical test in which results were not tied to any participant.
The study measured mutations in the genomes of 179 people who donated samples to the 1000 Genomes Pilot Project, which collected data from healthy individuals, as well as data from the Human Gene Mutation Database, which catalogues mutations reported in various scientific studies. Neither of these products matches an individual to a specific genome.
In most of the cases the scientists uncovered, the mutation was a “recessive” gene—in this case, 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 one-tenth of people who had disease-causing variants either had two recessive genes, or a mutated, dominant gene.
While classical genetics would say that these 10 percent are doomed to illness, David Cooper, the leader author of the study from Cardiff, 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 provide complete profiles of every genetic disease in existence; they are only as good as the studies that are included. The more studies and genomes are studied, the more accurate the database becomes.
But until that moment occurs, what should we be telling healthy people with “bad” genes?
Xue, Y., Chen, Y., Ayub, Q., Huang, N., Ball, E., Mort, M., Phillips, A., Shaw, K., Stenson, P., Cooper, D., & Tyler-Smith, C. (2012). Deleterious- and Disease-Allele Prevalence in Healthy Individuals: Insights from Current Predictions, Mutation Databases, and Population-Scale Resequencing The American Journal of Human Genetics, 91 (6), 1022-1032 DOI: 10.1016/j.ajhg.2012.10.015