While searching for an article to explain pleiotropy and how it interacts with epigenetics, I came across an article about the proposed ideas of the genetics behind Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder. This article caught my attention as it shows a current example of how genes affect our phenotypes and the types of research being undertaken in order to understand what the source of many diseases are. There is some mention of pleiotropy in the article, but I will go into more detail on that subject next week. For this week, I will try to explain what was found in the study of the Disrupted in Schizophrenia 1 (DISC1) gene.
Hodgkinson et al. (2004) believe that Schizophrenia and Bipolar Disorder are inherited and that there is a specific gene locus responsible for these psychiatric diseases. Specifically, the DISC1 gene is thought to undergo recombination causing a change in expression (Hodgkinson et al., 2004). The DISC1 protein is involved with many other proteins which causes this single gene to play a role in cellular processes that regulate neuronal signals and gene expression (Hodgkinson et al., 2004). Any alteration to the function of this gene is believed to have a pleiotropic effect on the individual. Depending on how the gene function is altered, there could be many different associations with the other proteins that DISC1 interacts with (Hodgkinson et al., 2004). The result of such a shift may be observed through different phenotypes seen in people with Schizophrenia, Bipolar Disorder, or Schizoaffective Disorder. These disorders may be a result of single-gene pleiotropy where there are different changes in the sequence of a gene or they may be from single-locus pleiotropy where there is a common change in the sequence (Hodgkinson et al., 2004). The type of alteration leads to different phenotypes which can be observed in the various symptoms experienced by individuals affected by these disorders. Hodgkinson et al. (2004) also found that reduced activity of the DISC1 gene between exons 1 and 9, coupled with environmental conditions may also be a source of the psychiatric disorders discussed in the article. The recombination of DISC1 gene was not found to be the key factor in these disorders, although evidence demonstrated that it did result in depression (Hodgkinson et al., 2004). Hodgkinson et al. (2004) did find that an amino acid substitution in the haplotype causes a change in protein structure that seems likely to result in Schizoaffective Disorder. They also believe that such changes may cause a decrease in transcription of the DISC1 gene that could also result in a psychiatric disorder (Hodgkinson et al., 2004). Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder are believed to be linked by the DISC1 gene, and the variation of changes to this gene are the cause of the different phenotypes associated with each of the diseases (Hodgkinson et al., 2004). These disorders are still under study, but it appears that genetics play a major role in each of these cases.
From the limited reading I've done on the subject, my understanding is that in many disorders and diseases that are likely to be inherited, it's very unusual that one gene is responsible. The BRCA1 and 2 breast cancer genes come to mind, but they don't seem to account for all inherited breast cancer risk. Do you know if there are any other genes that may play a part in developing schizophrenia? The DISC1 gene, with its multiple protein interactions, does seem to be quite critical, though! Very interesting post.
ReplyDeleteThe article I looked at also mentioned the DISC2 gene as playing a role in these disorders, however the main focus was on DISC1. There is still a lot of information unknown about these disorders, and I'm sure that more research will lead to the discovery of other linked genes.
DeleteVery interesting. It’s fascinating to think that these disorders may be genetically inherited, and that they may also be genetically linked. Do you think that epigenetics could play a significant role in differential expression of the gene, which could possibly be why different phenotypes result? Great post!
ReplyDeleteI definitely think epigenetics plays a role in differential expression of the gene which probably leads to different phenotypes. I wonder if this also contributes to the varying degrees of psychiatric disorders people possess.
DeleteInteresting read. Do you know if any tests can be done in the fetal stage to test for such changes to the DISC1 gene and if it could be 'treated'?
ReplyDeleteI don't know of any tests currently being done to the fetal stage to test for changes to the DISC1 gene. The study I looked at was just trying to find the connection between the gene and disease in a population of people that expressed the disorders. I bet that once there is more evidence of how the genes correlate to these disorders that researchers will look into tests for preventative measures.
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