Project description:We report two genetic mutations of GRM1, which are Grm1-S458A and Grm1b-R889W, identified from two natural short sleep families. The introduction of these mutations into mouse models also causes the mice to sleepless. Thus, these findings suggest GRM1 is another short sleep gene and highlight the essential roles of mGluRs in regulating human sleep.
Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data is available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1 and JAK3 were detected in 73%, 14%, 6%, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact.
Project description:AFF4 is a component of super elongation complex (SEC), which plays an important role in mobilizing paused RNA polymerase II at gene promoter regions. Using exome sequenging, we have identified a novel genetic disorder caused by missense mutations in AFF4. We propose CHOPS syndrome as a name for this new diagnosis. To evaluate the effect of identified missense mutations of AFF4, utilizing patient derived skin fibroblast cell lines, the gene expression analysis was perfomred. To characterize the transcriptome pattern observed in CHOPS syndrome, the skin fibroblast samples from two CHOPS syndrome probands and three healthy control subjects were used. Samples used for expression array include two CHOPs syndrome samples (CDL160: 6 year-old Caucasian female with 254S mut and CDL444: 12 year-old Caucasian male with 254A mut) and three age gender matched controls (GM01652: 11 year-old Caucasian female, GM02036 11 year-old Caucasian female and GM08398: 8 year-old Caucasian male).
Project description:We have modeled the Fnip2 rs2291007 genetic variant in the mouse genome. In this study we aimed to investigate the effect of this genetic variant in the transcriptome of two metabolically relevant tissues: liver and white adipose tissue (WAT)
Project description:This is a prospective, single-center, clinical study.This study is to evaluate the feasibility of genetic susceptibility screening based on the detection of tumor tissue mutations by a NGS panel.
Project description:Genetic disruption of Gsr in mouse elicits only subtle changes in the liver transcriptome. Transcriptome analysis of Gsr-null livers was performed to further our understanding of pathways that may compensate for loss of Gsr, one of the two NADPH-dependent cytosolic disulfide reductases.
Project description:This SuperSeries is composed of the following subset Series: GSE35551: Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression (1) GSE35552: Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression (2) GSE35553: Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression (3) Refer to individual Series
Project description:This model describes the multistep process that transform a normal cell and its descendants into a malignant tumour by considering three populations: normal, premalignant and cancer cells. Created by COPASI 4.24(Build 197)
Abstract:
Tumorigenesis has been described as a multistep process, where each step is associated with a genetic alteration, in the direction to progressively transform a normal cell and its descendants into a malignant tumour. Into this work, we propose a mathematical model for cancer onset and development, considering three populations: normal, premalignant and cancer cells. The model takes into account three hallmarks of cancer: self-sufficiency on growth signals, insensibility to anti-growth signals and evading apoptosis. By using a nonlinear expression to describe the mutation from premalignant to cancer cells, the model includes genetic instability as an enabling characteristic of tumour progression. Mathematical analysis was performed in detail. Results indicate that apoptosis and tissue repair system are the first barriers against tumour progression. One of these mechanisms must be corrupted for cancer to develop from a single mutant cell. The results also show that the presence of aggressive cancer cells opens way to survival of less adapted premalignant cells. Numerical simulations were performed with parameter values based on experimental data of breast cancer, and the necessary time taken for cancer to reach a detectable size from a single mutant cell was estimated with respect to some parameters. We find that the rates of apoptosis and mutations have a large influence on the pace of tumour progression and on the time it takes to become clinically detectable.