Identification of Sequence Variants and Analysis of the Role of the Catechol-O-Methyl-Transferase Gene in Schizophrenia Susceptibility

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.

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Role of an Atypical Cadherin Gene, Cdh23 in Prepulse Inhibition, and Implication of CDH23 in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbab007 ◽

2021 ◽

Author(s):

Shabeesh Balan ◽

Tetsuo Ohnishi ◽

Akiko Watanabe ◽

Hisako Ohba ◽

Yoshimi Iwayama ◽

...

Keyword(s):

Prepulse Inhibition ◽

Genetic Background ◽

Posterior Probability ◽

Human Study ◽

Inbred Strains ◽

Chromosome 10 ◽

Significant Enrichment ◽

The Brain ◽

Schizophrenia Susceptibility

Abstract We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the previously reported QTLs with increased marker density. The highest logarithm of odds score (26.66) peaked at a synonymous coding and splice-site variant, c.753G>A (rs257098870), in the Cdh23 gene on chromosome 10; the c.753G (C3H) allele showed a PPI-lowering effect. Bayesian multiple QTL mapping also supported the same variant with a posterior probability of 1. Thus, we engineered the c.753G (C3H) allele into the B6 genetic background, which led to dampened PPI. We also revealed an e-QTL (expression QTL) effect imparted by the c.753G>A variant for the Cdh23 expression in the brain. In a human study, a homologous variant (c.753G>A; rs769896655) in CDH23 showed a nominally significant enrichment in individuals with schizophrenia. We also identified multiple potentially deleterious CDH23 variants in individuals with schizophrenia. Collectively, the present study reveals a PPI-regulating Cdh23 variant and a possible contribution of CDH23 to schizophrenia susceptibility.

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The role of splicing factors in retinitis pigmentosa: links to cilia

Biochemical Society Transactions ◽

10.1042/bst20200798 ◽

2021 ◽

Author(s):

Dale W. Maxwell ◽

Raymond T. O'Keefe ◽

Sudipto Roy ◽

Kathryn E. Hentges

Keyword(s):

Retinitis Pigmentosa ◽

Primary Cilium ◽

Photoreceptor Cells ◽

Genetic Mutations ◽

Splicing Factors ◽

Sequence Variants ◽

Biological Functions ◽

Progressive Degeneration

Cilia are critical to numerous biological functions, both in development and everyday homeostatic processes. Diseases arising from genetic mutations that cause cilia dysfunction are termed ciliopathies. Several ubiquitously expressed splicing factors have been implicated in the condition Retinitis Pigmentosa (RP), a group of diseases characterised by the progressive degeneration of the retina. In many types of RP the disease affects the modified primary cilium of the photoreceptor cells and thus, these types of RP are considered ciliopathies. Here, we discuss sequence variants found within a number of these splicing factors, the resulting phenotypes, and the mechanisms underpinning disease pathology. Additionally, we discuss recent evidence investigating why RP patients with mutations in globally expressed splicing factors present with retina-specific phenotypes.

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