Review of Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Mukai, J et al. Proc. Natl. Acad. Sci. USA

BACKGROUND:

The brain and nervous system is very complicated the knowledge of how it works and functions to make animals think, behave and act is growing. Schizophrenia is a chronic and disabling psychosis - a disorder of thought and sense of self that affects the brain and nervous system. Patients may suffer from impairment of cognitive function, but schizophrenia is distinguished from other dementias where cognitive disturbance is primary. Numerous different genetic susceptibility points for schizophrenia have been found for this disease like 6p22.3 (Straub et al. 2002). A susceptibility point for schizophrenia was found on chromosome 22q11 (Karayiorgou, M et al. 1995) and there have been many susceptibility points on this chromosome where mutations could occur such as PRODH (Liu, H. et al. 2002), COMT (Aleman, A. et al. 2003) and ZDHHC8 (Liu, H. et al. 2002). The function of ZDHHC8 is still not known but there is some suspicion that it plays a role at the synapse and in glutamatergic transmission.

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There are also other proteins that play a part in glutamatergic transmission that when not expressed properly could be a potential susceptibility point for schizophrenia. It is predicted that the expressed ZDHHC8 has four transmembrane domains. It also has a cysteine-rich domain including a Cys4 zinc finger-like metal binding site. Previous research and knowledge has brought the researchers to create this study to show a stronger link between ZDHHC8 on 22q11 as a susceptibility point for schizophrenia.

AIMS:

This study was performed to show that SNP rs175174 regulates the level of fully functional transcript by modulating the retention of intron 4 in the gene ZDHHC8 showing susceptibility to schizophrenia.

RESULTS:

To accomplish the goals set out by the experimenter this study had to be done in two parts. The first part constitutes the investigation into the effect...