Ask about this productRelated genes to: PCDHA5 Blocking Peptide
- Gene:
- PCDHA5 NIH gene
- Name:
- protocadherin alpha 5
- Previous symbol:
- CNRS6
- Synonyms:
- CNR6, CRNR6, CNRN6, PCDH-ALPHA5
- Chromosome:
- 5q31.3
- Locus Type:
- complex locus constituent
- Date approved:
- 2000-06-28
- Date modifiied:
- 2016-10-24
Related products to: PCDHA5 Blocking Peptide
Related articles to: PCDHA5 Blocking Peptide
- Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, and , were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia. - Source: PubMed
Publication date: 2021/11/15
Handunnetthi LahiruSaatci DefneHamley Joseph CKnight Julian C - The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated. To determine the functional impact of gene mutations, we performed combined whole-exome sequencing (WES) of longitudinal patient samples with CRISPR-Cas9 drug resistance screens for lenalidomide, bortezomib, dexamethasone, and melphalan. WES of longitudinal samples from 16 MM patients identified a large number of mutations in each patient that were newly acquired or evolved from a small subclone (median 9, range 1-55), including recurrent mutations in TP53, DNAH5, and WSCD2. Focused CRISPR-Cas9 resistance screens against 170 relapse-specific mutations functionally linked 15 of them to drug resistance. These included cereblon E3 ligase complex members for lenalidomide, structural genes PCDHA5 and ANKMY2 for dexamethasone, RB1 and CDK2NC for bortezomib, and TP53 for melphalan. In contrast, inactivation of genes involved in the DNA damage repair pathway, including ATM, FANCA, RAD54B, and BRCC3, enhanced susceptibility to cytotoxic chemotherapy. Resistance patterns were highly drug specific with low overlap and highly correlated with the treatment-dependent clonal evolution in patients. The functional association of specific genetic alterations with drug sensitivity will help to personalize treatment of MM in the future. - Source: PubMed
Bohl Stephan RSchmalbrock Laura KBauhuf ImkeMeyer TatjanaDolnik AnnaSzyska MartinBlätte Tamara JKnödler SarahRöhner LindaMiller DeniseKull MiriamLanger ChristianDöhner HartmutLetai AnthonyDamm FrederikHeckl DirkBullinger LarsKrönke Jan - The early diagnosis of lung squamous cell carcinoma (LUSC) is difficult, causing an unsatisfactory prognosis. Therefore, the 5-year survival rate of LUSC is poor. This study aimed at screening the potential diagnostic and prognostic markers for LUSC. The data of LUSC gene expression profiles and DNA methylation were obtained from The Cancer Genome Atlas (TCGA) database; the differentially expressed genes (DEGs) and the differentially methylated genes (DMGs) were screened out by an independent -test and Benjamini/Hochberg methods. Further, the classifiers of the gene expression and DNA methylation markers in LUSC were constructed. After that, diagnostic and prognostic markers in LUSC were analyzed by the protein-protein interaction (PPI) network. The DEGs and the DMGs from TCGA database of LUSC were screened out. After strict filtration, we identified three potential DMGs (POU domain, class 4, transcription factor 2 [], , single-minded homolog 1 []) for early diagnosis and seven potential DEGs (G-protein coupled receptor 78 [], , myosin binding protein H [], , , , ) for prognosis of LUSC. The tumor-normal tissue classification model and prognosis model were validated in two independent datasets. In addition, the PPI network was constructed, including three DMGs and the five DEGs (, , , , ) of the seven DEGs. The potential DMGs (, , ) and DEGs (, , , , ) for the diagnosis and prognosis of LUSC identified in this article are expected to be further applied in clinical practice of the treatment of LUSC. - Source: PubMed
Publication date: 2019/11/11
Wang WeiqingWang ShaohuaChu XiaoLiu HuiXiang Ming