Expression of the DISC1 Gene
Gene expression is the process of converting genetic information encoded in the brain into a final product (a protein or RNA). Uncovering where a given gene's protein is most commonly expressed in the body can yield vital clues as to the purpose of that gene. DISC1 expression has been traced to neurons in a number of areas in the brain, particularly the hippocampus. It is associated with synaptic function, suggesting that one of its adult functions may be synaptic plasticity, a process that underlines learning and memory.
So one of the first things that you want to do when you find a new protein is to ask "well, where is that protein expressed?" So you can use probes derived from the gene, and antibodies raised against the protein, to ask in which cells at what time in development do you see it expressed. Now DISC1 is quite unusual in that it is actually expressed in a large number of different tissues, but at quite low levels. Itâ€™s expressed in blood cells, and itâ€™s expressed in the heart, but very importantly it is also expressed in the brain. Not just anywhere in the brain, but in the regions of the brain that we most commonly associate with the most likely site of the problem in schizophrenia â€“ and that is called the hippocampus. So we get very strong staining in regions of this particular specialized part of the brain that we think is important in schizophrenia. Now, thatâ€™s just telling us about the general landscape of expression. Whatâ€™s also important is to ask "where in the cell is this gene expressed, where does the protein reside?" And cells are complicated structures that have various sub-compartments that carry out a variety of different specialized functions, and we were very interested to find that the DISC1 protein was in a number of different compartments. [We were] particularly interested in the fact that it was expressed in the mitochondria, which are the energy centers of the cell.
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Disrupted in Schizophrenia 1 (DISC1) is a candidate gene for schizophrenia.
Professor David Porteous describes how his group is trying to uncover the function of the DISC1 gene.
An interactive chromosome map of the genes and loci associated with schizophrenia.
Professor David Porteous describes how his group was first alerted to the DISC1 gene, which was found in a family with a pedigree of schizophrenia and psychoses.
Professor David Lewis discusses how the diversity of symptoms in schizophrenia is reflected in the diversity of genetic and neural causes of the disorder.
Professor David Porteous discusses how his group discovered the DISC1 gene, which is a balanced translocation between chromosomes 1 and 11.
Professor David Porteous discusses genes for schizophrenia and points out that susceptibility likely aligns to a combination of genetic variants.
Discs, large homolog 3 (DLG3) is a gene associated with learning and memory. DLG3 encodes synapse-associated protein 102 (SAP102).
Discs, large homolog 4 (DLG4) is a gene associated with learning and memory. The human DLG4 protein is 99% identical to the rat and mouse PSD-95 proteins.
An overview of schizophrenia-related content on Genes to Cognition Online.