Copy number Variants is a type of variation in the genome of two individuals. Whole genes or big chunks of DNA may get deleted or duplicated in individuals leading to CNVs. It is important to stress that each individual has two copies of a gene. Now it might happen that the whole gene from one of the parents gets deleted leaving the individual with only one functional gene. It may also happen that one of the DNA strands, instead of having a single gene sequence, has multiple such sequences leading to duplication. These sort of duplications and deletions can also have deleterious effects. this type of variation between genomes of individuals is as opposed to the Single Nucleotide Polyphormism (SNPs) in which normally only a single base changes and this may or may not lead to change in amino acid being transcribed. The two variants of genes that differ by such a single base change are referred to alleles and we have dominant or recessive genetic disorders based on whether both genes have to be of the same deviant mutation to confer susceptibility to disease.
CNVs on the other hand present a different model of disease. One can have one or more types of CNVs (deletions, duplications, multiple duplications etc) associated with the same genetic code sequence and this in my view would lead to spectrum like diseases where one may find variations along a continuum on a particular trait- based on how many copies of the genetic sequence one has. One would remember that I adhere to a spectrum based view of schizophrenia/psychosis and also a spectrum based view of Autism. Moreover I believe that Schizophrenia and Autism are the opposite ends of the spectrum, whose middle is normalcy and that the appropriate traits may have to do with social brain, creativity etc.
now as it happen previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.
One of the readers of this blog, ‘concerned heart’, in a comment on an earlier post ,though has taken the new finding to imply that autism and Schizophrenia (especially childhood onset schizophrenia) is one and the same. Nothing could be farther from the truth. They are the same spectrum conditions and both are due to deficits in the same brain circuit/ mind module. Yet the deficits in one are the reverse of that found in the other and they are opposite ends of the spectrum. The mere fact that both involve CNVs and that too near the same chromosomal region, is not sufficient to warrant that they are the same. It would be akin to saying that because both sickle cell anemia and Huntington disease are due to SNPs , they are the same disorder. Nothing could be farther from the truth. I’m stretching the analogy too far, but this is just to stress that the role of CNVs in both the diseases do not imply that both diseases are same. However, some overlap , or even the same gene, could be involved in both Autism and Schizophrenia as they indeed are opposite ends of a spectrum. It may be like a gene for height (although life is not so simple that there is only one gene for height) —one sort of disruption of the gene may lead to dwarfism ; while the other may lead to an unusually high height.
However, I do not claim to fully understand the significance of CNVs or how they can have deleterious effects; but it is heartening to note that CNV mechanism may be a viable alternative to multiple genes coming together additively to bring about complex effects. If I understand correctly rare de novo CNV is equivalent to shearing of a single gene and could lead to deleterious effects on the scale of complex symptomatology like that of autism or schizophrenia. I’ll be watching this CNV business quite keenly, but meanwhile I stand by my position that this in no way proves that Autism and schizophrenia are the same condition.If at all it juts bolsters the argument that they are opposite disorders of the same gene/ loci/ trait/ brain system.