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.
