Genome-wide sequencing: beware of mistakes!
How reliable is medical DNA sequencing?
Kirill Stasevich, CompulentaDNA analysis can tell a lot about what diseases threaten a person.
Although not all possible mutations are known and studied, we still have enough knowledge to assess the risk of a particular type of malignant tumor or, say, diabetes. Of course, the manifestation of the mutation depends on external factors, but hardly anyone will argue with the fact that a genetic defect, all other things being equal, still increases the likelihood of the disease.
But to find a mutation, DNA needs to be sequenced, read the sequence of nucleotides in it. That is, we need an analysis method by which we could disassemble DNA into letters and find out which letters turned out to be mutated. There are many methods of sequencing, and they are being improved with dizzying speed. Of course, because a huge part of scientific work begins with finding out the DNA sequence, and this is necessary not only in the molecular biological fields, but also when solving some evolutionary zoological problems. And that's not to mention medical needs.
One of the laboratory methods of DNA sequencing using radioactively or fluorescently labeled nucleotides,
the radiation of which is recorded by a sensitive film. (Photo by Michael Rosenfeld.)
But the DNA sequencing method is far from perfect – that is, simply put, it has some percentage of defects, errors in reading DNA. And in this case, by the "sequencing method" we mean all its modern variants; among them there are worse, there are better, but they do not give perfect 100% accuracy. Here, however, it is worth considering whether this accuracy is so critical for us?
Euan A. Ashley and Thomas Quertermous from the Center for Hereditary Cardiovascular Diseases at Stanford University (USA) together with colleagues decided to check how complete information about dangerous mutations will be given by two machines for DNA sequencing – production of Illumina and Complete Genomics (both USA). The study involved 12 healthy people, without any signs of genetic diseases. However, their DNA still carried bad mutations, ranging from two to six in number; moreover, one woman was found to have a mutation in the BRCA1 gene, which is closely related to ovarian or breast tumors. Although the subjects were healthy, awareness of problems in their own DNA could help them organize their lives so as not to provoke mutations, reduce the likelihood of triggering these genetic "mines".
These results undoubtedly spoke in favor of the method (more precisely, two of its variants presented by different technological solutions). However, as researchers write in the Journal of the American Medical Association (Dewey et al., Clinical Interpretation and Implications of Whole-Genome Sequencing), from 10 to 19% of genes associated with diseases were read unsatisfactorily by both aggregates. And this means that mutations in them can escape the attention of doctors. In addition, these two variants of the sequence often did not converge with each other regarding particularly dangerous mutations when an insert is inserted into a gene associated with a disease, or, conversely, when it loses a fragment of the sequence.
It is worth noting here that genome-wide sequencing, when absolutely all DNA is read and analyzed with the same care, is not yet widely used in modern medicine; usually only those genes that cause special suspicion in connection with some symptoms are analyzed. Genomic analysis, undoubtedly, could be a great help in medicine, but there are several problems here, one of which is still insufficient cheapness and availability of such systems, and the second is what we just talked about, that is, still not quite perfect accuracy. However, it is worth hoping that the accuracy will soon "reach" the desired level: after all, a complete genetic map made in advance with all the genetic risks would greatly help both doctors and their potential patients.
Prepared based on Nature News: Genome sequencing stumbles towards the clinic.
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