| 1 | Biochem. Biophys. Res. Commun. 2006 Jun 344: 1241-5 |
|---|---|
| PMID | 16650384 |
| Title | A further study of a possible locus for schizophrenia on the X chromosome. |
| Abstract | Several studies suggest that the X chromosome may contain a gene for schizophrenia. In the present study, we recruited 142 male schizophrenic patients and their biological mothers from all parts of the United Kingdom to detect a genetic association for the SYP/CACNA1F locus in the Xp11 region and the FACL4 locus in the Xq22.3-Xq23 region. The haplotype-based haplotype relative risk (HHRR) analysis showed allelic association for rs2071316 (chi2=6.85, P=0.009) and rs5905724 (chi2=5.3, P=0.021) at the CACNA1F locus, but not for rs5943414 and rs1324805 at the FACL4 locus and rs3817678 at the SYP locus. The haplotype analysis showed a weak association for the rs3817678-rs2071316-rs5905724 haplotypes (chi2=12.19, df=4, P=0.016) but did not show such an association for the rs5943414-rs1324805 haplotypes (chi2=3.96, df=2, P=0.138). Because the linkage disequilibrium signal was detected only at the CACNA1F locus, this gene should perhaps be considered as being a candidate for schizophrenia although further work is needed to draw firm conclusions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Biochem. Biophys. Res. Commun. 2006 Jun 344: 1241-5 |
| PMID | 16650384 |
| Title | A further study of a possible locus for schizophrenia on the X chromosome. |
| Abstract | Several studies suggest that the X chromosome may contain a gene for schizophrenia. In the present study, we recruited 142 male schizophrenic patients and their biological mothers from all parts of the United Kingdom to detect a genetic association for the SYP/CACNA1F locus in the Xp11 region and the FACL4 locus in the Xq22.3-Xq23 region. The haplotype-based haplotype relative risk (HHRR) analysis showed allelic association for rs2071316 (chi2=6.85, P=0.009) and rs5905724 (chi2=5.3, P=0.021) at the CACNA1F locus, but not for rs5943414 and rs1324805 at the FACL4 locus and rs3817678 at the SYP locus. The haplotype analysis showed a weak association for the rs3817678-rs2071316-rs5905724 haplotypes (chi2=12.19, df=4, P=0.016) but did not show such an association for the rs5943414-rs1324805 haplotypes (chi2=3.96, df=2, P=0.138). Because the linkage disequilibrium signal was detected only at the CACNA1F locus, this gene should perhaps be considered as being a candidate for schizophrenia although further work is needed to draw firm conclusions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Int. J. Dev. Neurosci. 2011 May 29: 225-36 |
| PMID | 20888897 |
| Title | Molecular evidence that cortical synaptic growth predominates during the first decade of life in humans. |
| Abstract | Theories concerning the pathology of human neurodevelopmental disorders that emerge in adolescence, such as schizophrenia, often hypothesize that there may be a failure of normal cortical synaptic loss or pruning. However, direct evidence that synaptic regression is a major developmental event in the adolescent human cortex is limited. Furthermore, developmental work in rodents suggested that synaptic regression in adolescence is not a major feature of cortical development. Thus, we set out to determine when and to what extent molecular markers of synaptic terminals [synaptophysin (SYP), SNAP-25, syntaxin1A (STX1A), and vesicle-associated membrane protein 1 (VAMP1)] are reduced during postnatal human life spanning from 1 month to 45 years (n = 69) using several different quantitative methods, microarray, qPCR and immunoblotting. We found little evidence for a consistent decrease in synaptic-related molecular markers at any time point, but instead found clear patterns of gradual increases in expression of some presynaptic markers with postnatal age (including SNAP-25, VAMP1 and complexin 1 (CPLX1) mRNAs and 6/6 presynaptic proteins evaluated). A measure of synaptic plasticity [growth-associated protein of 43 kDa (GAP-43)] was elevated in neonates, and continued robust expression throughout life. Since CPLX1 protein is enriched in inhibitory terminals we also tested if the protein product of complexin 2 (CPLX2), which is enriched in excitatory neurons, is more specifically reduced in development. In contrast to CPLX1, which showed a steady increase in both mRNA and protein levels during postnatal development (both r > 0.58, p < 0.001), CPLX2 mRNA decreased from infants to toddlers (r = -0.56, p < 0.001), while CPLX2 protein showed a steady increase until young adulthood (r = 0.55, p < 0.001). Furthermore, we found that indices of the dendrites [microtubule associated protein 2 (MAP2)] and spines (spinophilin and postsynaptic density protein of 95 kDa (PSD95)] showed some evidence of reduction over time at the mRNA level but the opposite pattern, of a developmental increase, was found for PSD95 and spinophilin protein levels. Taken together, the postnatal changes in molecular components of synapses supports the notion that growth and strengthening of synaptic elements is a major developmental event occurring in the frontal cortex throughout childhood and that maintenance of steady state levels of synapse-associated molecules may predominate during human adolescence. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Schizophr. Res. 2012 May 137: 14-9 |
| PMID | 22348818 |
| Title | Genetic and functional analyses of the gene encoding synaptophysin in schizophrenia. |
| Abstract | Synaptophysin (SYP) has been shown to be critical for regulating neurotransmitter release and synaptic plasticity, a process thought to be disrupted in schizophrenia. In addition, abnormal SYP expression in different brain regions has been linked to this disorder in postmortem brain studies. We investigated the involvement of the SYP gene in the susceptibility to schizophrenia. We searched for genetic variants in the promoter region, all exons, and both UTR ends of the SYP gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study. We identified 2 common SNPs (c.*4+271A>G and c.*4+565T>C) in the SYP gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. In addition, we identified 6 rare variants in 7 out of 586 patients, including 1 variant (g.-511T>C) located at the promoter region, 1 synonymous (A104A) and 2 missense variants (G293A and A324T) located at the exonic regions, and 2 variants (c.*31G>A and c.*1001G>T) located at the 3'UTR. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated the influence of g.-511T>C and c.*1001G>T on the regulatory function of the SYP gene, while that the influence of c.*31G>A may be tolerated. In silico analysis demonstrated the functional relevance of other rare variants. Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of SYP in this disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |