MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts’ maps could uncover functionally and clinically related genes.

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“…The gene MPZL1 (MIM#604376), contacted by both KCTD13 and SH2B1, is associated with SCZ. 92 It is a downstream target of PTPN11 . 93 …”

Section: Methodsmentioning

confidence: 99%

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

et al. 2016

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“…Tkachev et al 16 found that MPZL1/PZR was significantly upregulated in schizophrenia patients compared with healthy controls (1.29-fold, P=0.0263). Common SNPs in MPZL1/PZR gene were recently reported to be associated with schizophrenia in 523 case-parent triad family of Han Chinese (P=0.0017) 17 .…”

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confidence: 99%

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia

Shi¹,

Li²,

Xu³

et al. 2011

Nat Genet

223

158

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Schizophrenia is a severe mental disorder affecting ~1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 patients and 6,468 healthy controls (1,578 cases and 1,592 controls from the Northern Han; 1,238 cases and 2,856 controls from the Central Han; 934 cases and 2,020 controls from the Southern Han); and we followed up the top association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese. Meta-analysis identified genome-wide significant association of common SNPs with schizophrenia on chromosome 8p12 (rs16887244, P=1.27×10−10) and 1q24.2 (rs10489202, P=9.50×10−9). Our findings provide new insights into the pathogenesis of schizophrenia.

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“…We previously reported that DNA methylation status in the CpG island of the SRY (sex determining region Y)‐box 10 ( SOX10 ) gene correlated with a downregulated expression of SOX10 and other oligodendrocyte‐related genes 8 . In addition, several oligodendrocyte‐related genes have been proposed to be susceptibility genes for schizophrenia, including myelin‐oligodendrocyte glycoprotein ( MOG ), 15 myelin‐associated glycoprotein ( MAG ), 16,17 proteolipid protein 1 ( PLP1 ), 18 gelsolin ( GSN ), 19 oligodendrocyte lineage transcription factor 2 ( OLIG2 ), 20 myelin protein zero‐like 1 ( MPZL1 ), 21 and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase ( CNP ) 22 . Although none of them have yet been replicated across different populations, 23,24 identifying the primary cause of the change would provide important insights into the pathophysiology of schizophrenia.…”

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confidence: 99%

Effect of a functional single nucleotide polymorphism in the 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase gene on the expression of oligodendrocyte‐related genes in schizophrenia

Iwamoto¹,

Ueda²,

Bundo³

et al. 2008

Psychiatry Clin Neurosci

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Aims: Although the expression of oligodendrocyte-related genes in post-mortem brains of patients with schizophrenia is consistently reported to be downregulated, the cause of the change remains unclear. The A-allele of rs2070106 within the 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP), an oligodendrocyte-related gene, was reported to show reduced expression compared with the G-allele, and proposed to be associated with schizophrenia. Methods:The effect of the rs2070106 genotype on the expression of CNP and other oligodendrocyterelated genes was examined using data previously obtained from DNA microarray studies of postmortem brains.Results: It was found that the effect of rs2070106 genotype on the CNP expression was transcript specific, and that the genotype was not associated with the expression of other oligodendrocyte-related genes. Conclusions:The rs207016 genotype is not likely to contribute to the reported coordinated downregulation of oligodendrococyte-related genes in schizophrenia.

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MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese

Cited by 9 publications

References 24 publications

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia

Effect of a functional single nucleotide polymorphism in the 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase gene on the expression of oligodendrocyte‐related genes in schizophrenia

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