A central concept in modern biology has been that in any individual, all cells contain identical copies of the DNA that establishes the phenotype of that individual. This assumption seemed so critical to the life of the organism that it has never been routinely tested. Current research challenges this assumption.
There is a condition referred to as Long QT Syndrome (LQTS). The genetic form of this disease can result in life-threatening arrythmias of the heart. In spite of the genetic correlation, only 30 percent of the patients studied tested positive for the genetic markers associated with LQTS.
Stephen R. Quake and his colleagues at Stanford University performed a detailed mosaic DNA analysis of an infant with perinatal LQTS. As a result of this analysis, it was discovered that 8% of the heart cells were capable of arrythmia. To further study this intriguing result, 7500 patients presenting with LQTS were studied for mosaicism.
Somatic mosaicism represents the occurrence and subsequent proliferation of DNA variants in cell lineages resulting from differentiation after fertilization. It is now believed that this mosaicism may play a causal role in a variety of human ailments. Furthermore, in the case of LQTS, a variant in the sodium channel protein NA 1.5 that is encoded by the SCN5A gene located on chromosome 3 may be the causative factor.
According to the authors, “One report suggests that 6.5% of de novo mutations presumed to be germline in origin may instead have arisen from postzygotic mosaic mutation events, and recent genetic investigations directly interrogating diseased tissues in brain malformations, breast cancer, and atrial fibrillation have revealed postzygotic causal mutations absent from germline DNA. Pathogenic mosaic structural variation is also detectable in children with neurodevelopmental disorders. However, a consequential category of genetic variation has not been surveyed systematically in clinical or research studies of other human diseases.”
These surprising results not only challenge the accepted assumption regarding the homogeneity of genetic information in every cell of the individual, it also may have profound implications for the etiology and treatment of human disease.