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Annotation

Zhou X, Chen Q, Schaukowitch K, Kelsoe JR, Geyer MA. Insoluble DISC1-Boymaw fusion proteins generated by DISC1 translocation. Mol Psychiatry . 2010 Jul 1 ; 15(7):669-72. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Carsten Korth, SRF Advisor
Submitted 5 July 2010 Posted 5 July 2010

The study proposes an alternative mechanism of how the chromosomal translocation in the Scottish pedigree reported by Millar et al. (2000) could cause a behavioral phenotype. I think this is exactly the point: In the Scottish family, can such transcripts and fusion proteins be identified? Do they really exist? If they do, this paper certainly would help to identify them. I understand that it is very difficult to obtain material that could prove this, and I would like to hear Kirsty Millar's or David Porteous's comment on this.

Regarding the data on the solubility assays of the fusion transcripts, I would have liked to see more controls, like those of the DISC1 fragments only (i.e., without Boymaw domains) and whole lysate controls, since the paper reads as if insolubility would be a specific phenotype of the DISC1-Boymaw fusion protein. From our experience, I guess it isn't; we see insolubility with N-terminal, as well as C-terminal, DISC1 fragments, with expression time being a critical variable to consider.

Altogether, I...  Read more


View all comments by Carsten Korth

Comment by:  Xianjin Zhou
Submitted 11 July 2010 Posted 11 July 2010

I would like to explain a little more on the protein expression from the two fusion transcripts. After we identified the brain-specific Boymaw mRNA, we generated the two fusion transcripts between the Boymaw and DISC1 genes. Because the DISC1 gene is expressed in human brain, it is likely that the ORF (Open Reading Frame) of DISC1-Boymaw fusion transcripts would be recognized for translation. However, it is unclear whether the Boymaw-DISC1 fusion transcripts will be translated because there are several small ORFs upstream of the long internal ORF of the DISC1 gene. These small ORFs in the long 5 UTR (about 520 bp) could interfere with the translation of the C-terminal DISC1.

To examine whether the C-terminal DISC1 protein could be produced from the Boymaw-DISC1 fusion transcripts, we conducted the transfection experiments by using the DISC1-Boymaw fusion transcript as a positive control. Abundant C-terminal DISC1 proteins were produced from the Boymaw-DISC1 fusion transcripts. Surprisingly, the expression of DISC1-Boymaw fusion proteins is very low and can only be...  Read more


View all comments by Xianjin Zhou

Comment by:  Akira Sawa, SRF Advisor
Submitted 14 July 2010 Posted 14 July 2010

The paper by Dr. Zhou and colleagues, describing insoluble DISC1-Boymaw fusion proteins generated by DISC1 translocation, may be one of the most important accomplishments in the field of DISC1 research since the pioneer of this field, Dr. St. Clair, identified the Scottish pedigree associated with major mental illnesses (St. Clair et al., 1990). Although the gene coding for DISC1 is disrupted in the Scottish pedigree, it has been totally unclear how the disruption may lead to psychiatric conditions in some (but not all) of the family members with this disruption.

If a putative truncated protein is generated, it seems to function as a dominant-negative protein (Kamiya et al., 2005). In lymphoblasts from some patients with this chromosomal abnormality in the pedigree, immunoreactivity of DISC1 fails to be observed (Millar et al., 2005). These two observations may not be contradictory, as both scenarios can result in an overall loss of...  Read more


View all comments by Akira Sawa

Comment by:  Aaron Marley
Submitted 19 July 2010 Posted 19 July 2010

Since the translocation event deletes portions of the CHORDC1 and DISC1 genes, is it possible that CHORDC1 and not DISC1 is a causative factor in the psychiatric phenotype?

View all comments by Aaron Marley

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