Association Between Polymorphisms in the Promoter Region of the Sialyltransferase 8B (SIAT8B) Gene and Schizophrenia

Arai, Makoto; Yamada, Kazuo; Toyota, Tomoko; Obata, Nanako; Haga, Shukoh; Yoshida, Yuuki; Nakamura, Kazuhiko; Minabe, Yoshio; Ujike, Hiroshi; Sora, Ichiro; Ikeda, Kazuhiko; Mori, Norio; Yoshikawa, Takeo; Itokawa, Masanari

doi:10.1016/j.biopsych.2005.08.016

Cited by 114 publications

(84 citation statements)

References 36 publications

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“…Interestingly, this gene has been identified by a positional-independent approach, considering its functional involvement in the neuronal development via modification of the neural cell adhesion molecule 1 (NCAM1) molecule. 16 Among the genes reported above, a number of studies have reported positive association with SZ and BPD only for DISC1 20,21 and NRG1, 22,23 whereas the involvement of the other genes in both disorders is still uncertain.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26

et al. 2006

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Schizophrenia (SZ) and bipolar disorder (BPD) are two severe psychiatric diseases with a strong genetic component. In agreement with the 'continuum theory', which suggests an overlap between these disorders, the existence of genes that affect simultaneously susceptibility to SZ and BPD has been hypothesized. In this study we performed a 7.5 cM genome scan in a sample of 16 families affected by SZ and BPD, all originating from the same northeast Italian population. Using both parametric and non-parametric analyses we identified linkage peaks on four regions (1p, 1q, 4p and 15q), which were then subjected to a follow-up study with an increased marker density. The strongest linkage was obtained on chromosome 15q26 with a non-parametric linkage of 3.05 for marker D15S1014 (nominal P = 0.00197). Interestingly, evidence for linkage with the same marker has been reported previously by an independent study performed on SZ and BPD families from Quebec. In this region, the putative susceptibility gene ST8SIA2 (also known as SIAT8B) was recently associated with SZ in a Japanese sample. However, our allele frequency analyses of the two single-nucleotide polymorphisms (SNPs) with putative functional outcome (rs3759916 and rs3759914) suggest that these polymorphisms are unlikely to be directly involved in SZ in our population. In conclusion, our results support the presence of a gene in 15q26 that influences the susceptibility to both SZ and BPD.

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Section: Introductionmentioning

confidence: 99%

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26

et al. 2006

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“…Variations in the Ncam1 and St8siaII gene as well as dysregulation of NCAM protein have been linked to schizophrenia (Vawter, 2000;Arai et al, 2006;Atz et al, 2007;Sullivan et al, 2007;Tao et al, 2007). On the one hand, incomplete polysialylation of NCAM during brain development has been proposed as a mechanism for a predisposition to schizophrenia because it causes defects of cortical connectivity, including internal capsule defects, resembling those seen in schizophrenic patients ).…”

Section: Discussionmentioning

confidence: 99%

Thalamocortical Pathfinding Defects Precede Degeneration of the Reticular Thalamic Nucleus in Polysialic Acid-Deficient Mice

Schiff¹,

Röckle²,

Burkhardt³

et al. 2011

J. Neurosci.

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IVϪ/Ϫ ) mice characterized by severe defects of major brain axon tracts, including internal capsule hypoplasia. Here, we demonstrate that misguidance of thalamocortical fibers and deficiencies of corticothalamic connections contribute to internal capsule defects in II Ϫ/Ϫ IV Ϫ/Ϫ mice. Thalamocortical fibers cross the primordium of the reticular thalamic nucleus (Rt) at embryonic day 14.5, before they fail to turn into the ventral telencephalon, thus deviating from their normal trajectory without passing through the internal capsule. At postnatal day 1, a reduction and massive disorganization of fibers traversing the Rt was observed, whereas terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 staining indicated abundant apoptotic cell death of Rt neurons at postnatal day 5. Furthermore, during postnatal development, the number of Rt neurons was drastically reduced in 4-week-old IIN Ϫ/Ϫ triple knock-out animals displaying no internal capsule defects. Thus, degeneration of the Rt in II Ϫ/Ϫ IV Ϫ/Ϫ mice may be a consequence of malformation of thalamocortical and corticothalamic fibers providing major excitatory input into the Rt. Indeed, apoptotic death of Rt neurons could be induced by lesioning corticothalamic fibers on whole-brain slice cultures. We therefore propose that anterograde transneuronal degeneration of the Rt in polysialylation-deficient, NCAM-positive mice is caused by defective afferent innervation attributable to thalamocortical pathfinding defects.

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“…Several genes, including SEMA4B (semaphorin precursor 4B, which inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons), SV2B (synaptic vesicle protein 2B) and ST8S1A2 (a-2,8-sialyltransferase 2, which regulates normal and pathologic processes, including development, neuronal plasticity and tumour metastasis) are potential candidate genes for screening by association analysis in BP case-control cohorts. Arai et al 49 have recently examined polymorphisms in the promoter region of the ST8S1A2 gene and shown association with schizophrenia in a Japanese cohort, although association was not seen in an Italian cohort. 50 Our finding of a BP susceptibility locus on chromosome 15q25-26 is supported by evidence of linkage with other mood and psychotic disorders.…”

Section: Discussionmentioning

confidence: 99%

A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26

et al. 2008

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Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z maxÀ1 linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P = 0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region. Keywords: bipolar affective disorder; manic depressive illness; susceptibility locus; genetic linkage; chromosome 15q Bipolar (BP) affective disorder (MIM 125480) is a severe mood disorder characterised by alternating periods of mania and depression with reversion to normal behaviour in between these episodes. Bipolar disorder is a relatively common condition with a worldwide prevalence between 0.5 and 1.5% 1 and lifetime prevalence of up to 4%. 2 The disorder has a severe impact on sufferers, being ranked the sixth most debilitating disorder in the World Health Organisation Global Burden of Disease Report, 3 and results in suicide rates 15 times higher than the general population. 4 The aetiology of bipolar disorder remains unknown, with little knowledge of the underlying biological, anatomical or biochemical effects. However, family, twin and adoption studies have provided strong evidence that genetic factors contribute to the disorder with heritability estimates in the range of 60-85%. 5,6 The high heritability, increased relative risks within families, 7 and familial clustering of the disorder provide the opportunity to use genetic approaches to identify predisposing genes. The inheritance pattern of the disorder is complex with non-Mendelian inheritance suggesting the involvement of multiple genes and environmental factors.Many genetic studies have attempted to map BP susceptibility loci and have provided evidence for linkage to a number of chromosomal regions (reviewed by Baron 8 ). One meta-analysis of wholegenome linkage scans did not identify consistent loci across linkage studie...

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Association Between Polymorphisms in the Promoter Region of the Sialyltransferase 8B (SIAT8B) Gene and Schizophrenia

Cited by 114 publications

References 36 publications

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26

Thalamocortical Pathfinding Defects Precede Degeneration of the Reticular Thalamic Nucleus in Polysialic Acid-Deficient Mice

A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26

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