scholarly journals Investigation of Fasciculation and Elongation Protein ζ-1 (FEZ1) in Peripheral Blood Reveals Differences in Gene Expression in Patients with Schizophrenia

2015 ◽  
Vol 18 (1) ◽  
pp. 31-38 ◽  
Author(s):  
T.I. Vachev ◽  
V.K. Stoyanova ◽  
H.Y. Ivanov ◽  
I.N. Minkov ◽  
N.T. Popov

Abstract Schizophrenia (SZ) is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1) may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear. The purpose of this study was to identify the characteristic gene expression patterns of FEZ1 in peripheral blood samples from schizophrenia patients. We performed quantitative reverse-transcriptase (qRT-PCR) analysis using peripheral blood from drug-free schizophrenia patients (n = 29) and age and gender-matched general population controls (n = 24). For the identification of FEZ1 gene expression patterns, we applied a comparative threshold cycle (CT) method. A statistically significant difference of FEZ1 mRNA level was revealed in schizophrenia subjects compared to healthy controls (p = 0.0034). To the best of our knowledge, this study is the first describing a down-regulation of FEZ1 gene expression in peripheral blood of patients with schizophrenia. Our results suggested a possible functional role of FEZ1 in the pathogenesis of schizophrenia and confirmed the utility of peripheral blood samples for molecular profiling of psychiatric disorders including schizophrenia. The current study describes FEZ1 gene expression changes in peripheral blood of patients with schizophrenia with significantly down-regulation of FEZ1 mRNA. Thus, our results provide support for a model of SZ pathogenesis that includes the effects of FEZ1 expression.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2897-2897
Author(s):  
Torsten Haferlach ◽  
Helmut Loeffler ◽  
Alexander Kohlmann ◽  
Martin Dugas ◽  
Wolfgang Hiddemann ◽  
...  

Abstract Balanced chromosomal rearrangements leading to fusion genes on the molecular level define distinct biological subsets in AML. The four balanced rearrangements (t(15;17), t(8;21), inv(16), and 11q23/MLL) show a close correlation to cytomorphology and gene expression patterns. We here focused on seven AML with t(8;16)(p11;p13). This translocation is rare (7/3515 cases in own cohort). It is more frequently found in therapy-related AML than in de novo AML (3/258 t-AML, and 4/3287 de novo, p=0.0003). Cytomorphologically, AML with t(8;16) is characterized by striking features: In all 7 cases the positivity for myeloperoxidase on bone marrow smears was >70% and intriguingly, in parallel >80% of blast cells stained strongly positive for non-specific esterase (NSE) in all cases. Thus, these cases can not be classified according to FAB categories. These data suggest that AML-t(8;16) arise from a very early stem cell with both myeloid and monoblastic potential. Furthermore, we detected erythrophagocytosis in 6/7 cases that was described as specific feature in AML with t(8;16). Four pts. had chromosomal aberrations in addition to t(8;16), 3 of these were t-AML all showing aberrations of 7q. Survival was poor with 0, 1, 1, 2, 20 and 18+ (after alloBMT) mo., one lost to follow-up, respectively. We then analyzed gene expression patterns in 4 cases (Affymetrix U133A+B). First we compared t(8;16) AML with 46 AML FAB M1, 41 M4, 9 M5a, and 16 M5b, all with normal karyotype. Hierachical clustering and principal component analyses (PCA) revealed that t(8;16) AML were intercalating with FAB M4 and M5b and did not cluster near to M1. Thus, monocytic characteristics influence the gene expression pattern stronger than myeloid. Next we compared the t(8;16) AML with the 4 other balanced subtypes according to the WHO classification (t(15;17): 43; t(8;21): 40; inv(16): 49; 11q23/MLL-rearrangements: 50). Using support vector machines the overall accuracy for correct subgroup assignment was 97.3% (10-fold CV), and 96.8% (2/3 training and 1/3 test set, 100 runs). In PCA and hierarchical cluster analysis the t(8;16) were grouped in the vicinity of the 11q23 cases. However, in a pairwise comparison these two subgroups could be discriminated with an accuracy of 94.4% (10-fold CV). Genes with a specific expression in AML-t(8;16) were further investigated in pathway analyses (Ingenuity). 15 of the top 100 genes associated with AML-t(8;16) were involved in the CMYC-pathway with up regulation of BCOR, COXB5, CDK10, FLI1, HNRPA2B1, NSEP1, PDIP38, RAD50, SUPT5H, TLR2 and USP33, and down regulation of ERG, GATA2, NCOR2 and RPS20. CEBP beta, known to play a role in myelomonocytic differentiation, was also up-regulated in t(8;16)-AML. Ten additional genes out of the 100 top differentially expressed genes were also involved in this pathway with up-regulation of DDB2, HIST1H3D, NSAP1, PTPNS1, RAN, USP4, TRIM8, ZNF278 and down regulation of KIT and MBD2. In conclusion, AML with t(8;16) is a specific subtype of AML with unique characteristics in morphology and gene expression patterns. It is more frequently found in t-AML, outcome is inferior in comparison to other AML with balanced translocations. Due to its unique features, it is a candidate for inclusion into the WHO classification as a specific entity.


Genome ◽  
2015 ◽  
Vol 58 (6) ◽  
pp. 305-313 ◽  
Author(s):  
Jagesh Kumar Tiwari ◽  
Sapna Devi ◽  
S. Sundaresha ◽  
Poonam Chandel ◽  
Nilofer Ali ◽  
...  

Genes involved in photoassimilate partitioning and changes in hormonal balance are important for potato tuberization. In the present study, we investigated gene expression patterns in the tuber-bearing potato somatic hybrid (E1-3) and control non-tuberous wild species Solanum etuberosum (Etb) by microarray. Plants were grown under controlled conditions and leaves were collected at eight tuber developmental stages for microarray analysis. A t-test analysis identified a total of 468 genes (94 up-regulated and 374 down-regulated) that were statistically significant (p ≤ 0.05) and differentially expressed in E1-3 and Etb. Gene Ontology (GO) characterization of the 468 genes revealed that 145 were annotated and 323 were of unknown function. Further, these 145 genes were grouped based on GO biological processes followed by molecular function and (or) PGSC description into 15 gene sets, namely (1) transport, (2) metabolic process, (3) biological process, (4) photosynthesis, (5) oxidation-reduction, (6) transcription, (7) translation, (8) binding, (9) protein phosphorylation, (10) protein folding, (11) ubiquitin-dependent protein catabolic process, (12) RNA processing, (13) negative regulation of protein, (14) methylation, and (15) mitosis. RT-PCR analysis of 10 selected highly significant genes (p ≤ 0.01) confirmed the microarray results. Overall, we show that candidate genes induced in leaves of E1-3 were implicated in tuberization processes such as transport, carbohydrate metabolism, phytohormones, and transcription/translation/binding functions. Hence, our results provide an insight into the candidate genes induced in leaf tissues during tuberization in E1-3.


2015 ◽  
Vol 64 (11) ◽  
pp. 1437-1447 ◽  
Author(s):  
Sara J. Felts ◽  
Virginia P. Van Keulen ◽  
Adam D. Scheid ◽  
Kathleen S. Allen ◽  
Renee K. Bradshaw ◽  
...  

SLEEP ◽  
2011 ◽  
Vol 34 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Abdelnaby Khalyfa ◽  
Sina A. Gharib ◽  
Jinkwan Kim ◽  
Oscar Sans Capdevila ◽  
Leila Kheirandish-Gozal ◽  
...  

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7037 ◽  
Author(s):  
Peter R. Sinnaeve ◽  
Mark P. Donahue ◽  
Peter Grass ◽  
David Seo ◽  
Jacky Vonderscher ◽  
...  

2005 ◽  
Vol 7 (5) ◽  
Author(s):  
Praveen Sharma ◽  
Narinder S Sahni ◽  
Robert Tibshirani ◽  
Per Skaane ◽  
Petter Urdal ◽  
...  

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