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. 2008 Dec 22:9:115.
doi: 10.1186/1471-2350-9-115.

DNA methylation and mRNA expression of SYN III, a candidate gene for schizophrenia

Brenda C Murphy  1 , Richard L O'Reilly, Shiva M Singh
Affiliations

DNA methylation and mRNA expression of SYN III, a candidate gene for schizophrenia

Brenda C Murphy et al. BMC Med Genet. .

Abstract

Background: The synapsin III (SYN III) gene on chromosome 22q is a candidate gene for schizophrenia susceptibility due to its chromosome location, neurological function, expression patterns and functional polymorphisms.

Methods: This research has established the mRNA expression of SYN III in 22 adult human brain regions as well as the methylation specificity in the closest CpG island of this gene. The methylation specificity studied in 31 brain regions (from a single individual) was also assessed in 51 human blood samples (representing 20 people affected with schizophrenia and 31 normal controls) including a pair of monozygotic twin discordant for schizophrenia and 2 non-human primates.

Results: The results show that the cytosine methylation in this genomic region is 1) restricted to cytosines in CpG dinucleotides 2) similar in brain regions and blood and 3) appears conserved in primate evolution. Two cytosines (cytosine 8 and 20) localized as the CpG dinucleotide are partially methylated in all brain regions studied. The methylation of these sites in schizophrenia and control blood samples was variable. While cytosine 8 was partially methylated in all samples, the distribution of partial to complete methylation at the cytosine 20 was 22:9 in controls as compared to 18:2 in schizophrenia (p = 0.82). Also, there is no difference in methylation between the affected and unaffected member of a monozygotic twin pair.

Conclusion: The variation in SYN III methylation studied is 1) not related to schizophrenia in the population sample or a monozygotic twin pair discordant for schizophrenia and 2) not related to the mRNA level of SYN IIIa in different human brain regions.

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Figures

Figure 1
Figure 1
Genomic organization of SYN III gene and its distal CpG island on chromosome 22q12 (A) and the nucleotide sequence (antisense strand of NCBI Accession Number Z83846, nucleotides 87366 to 87522) used for methylation analysis (B). Underlined sequences represent the location of sodium bisulfite PCR primers, cytosines are numbered 1–26 with three 5'CpGs 3' (#3, 8 and 20) shown in bold.
Figure 2
Figure 2
RT-PCR results for SYN III and two internal controls (GAPD and Actin) in 22 human brain-specific regions and blood.
Figure 3
Figure 3
Sequence flurograms (using reverse primer) show partial methylation of cytosine 8 and 20 in human brain specific regions. A. (cerebellar vermis) shows prominent methylation of cytosine 8 and 20 (both sites showing C and a trace of T), B. (caudate; head) shows partial methylation (N call by sequencer) of cytosines 8 and 20.
Figure 4
Figure 4
Sequence flurograms (Panel A using forward primer; C and D using reverse primer). Panel A show partial methylation (G and trace of A) of cytosine 8 and 20. Panel B show partial methylation (N call by sequencer) of cytosine 8 and partial methylation (G and trace of A) of cytosine 20. Panel C show partial methylation (N call by sequencer) at both cytosine 8 and 20. Panel A, B and C are the results of individuals labeled SZ2, C3 and C11 respectively.
Figure 5
Figure 5
Methylation property of cytosine 8 and 20 in two non-human primates; cynomologous monkey (A) and baboon (B).
See this image and copyright information in PMC

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References

    1. Evergren E, Benfenati F, Shupliakov O. The synapsin cycle: A view from the synaptic endocytic zone. J Neurosci Res. 2007;85:2648–2656. doi: 10.1002/jnr.21176. - DOI - PubMed
    1. Kao H, Porton B, Czernik AJ, Feng J, Yiu G, Haring M, Benfenati F, Greengard P. A third member of the synapsin gene family. Proc Natl Acad Sci USA. 1998;95:4667–4672. doi: 10.1073/pnas.95.8.4667. - DOI - PMC - PubMed
    1. Porton B, Kao H, Greengard P. Characterization of transcripts from the synapsin III gene locus. J of Neurochem. 1999;73:2266–2271. doi: 10.1046/j.1471-4159.1999.0732266.x. - DOI - PubMed
    1. Ferreira A, Rapoport M. The synapsins: beyond the regulation of neurotransmitter release. Cell Mol Life Sci. 2002;59:589–595. doi: 10.1007/s00018-002-8451-5. - DOI - PMC - PubMed
    1. Stober G, Meyer J, Nanda I, Wienker TF, Saar K, Knapp M, Jatzke S, Schmid M, Lesch KP, Beckmann H. Linkage and family-based association study of schizophrenia and the synapsin III locus that maps to chromosome 22q13. Am J Med Genet. 2000;96:392–397. doi: 10.1002/1096-8628(20000612)96:3<392::AID-AJMG29>3.0.CO;2-R. - DOI - PubMed

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