Ультрадисперсные порошки на основе железа как катализаторы синтеза жидких углеводородов из СО и Н[2]

International audienceTo date, uniparental disomy (UPD) with phenotypic relevance is described for different chromosomes and it is likely that additional as yet unidentified UPD phenotypes exist. Due to technical difficulties and limitations of time and resources, molecular analyses for UPD using microsatellite markers are only performed in cases with specific phenotypic features. In this study, we carried out a whole genome UPD screening based on a microarray genotyping technique. Six patients with the diagnosis of both complete or segmental UPD including Prader-Willi syndrome (PWS; matUPD15), Angelman syndrome (AS; patUPD15), Silver-Russell syndrome (SRS; matUPD7), Beckwith-Wiedemann syndrome (BWS; patUPD11p), pseudohypoparathyroidism (PHP; patUPD20q) and a rare chromosomal rearrangement (patUPD2p, matUPD2q), were genotyped using the GeneChip Human Mapping 10K Array. Our results demonstrate the presence of UPD in the patients with high efficiency and reveal clues about the mechanisms of UPD formation. We thus conclude that array based SNP genotyping is a fast, cost-effective, and reliable approach for whole genome UPD screening

Whole genome expression analyses of single- and double-knock-out mice implicate partially overlapping functions of alpha- and gamma-synuclein

α-Synuclein has been implicated in the pathogenesis of Parkinson’s disease. The function of α-synuclein has not been deciphered yet; however, it might play a role in vesicle function, transport, or as a chaperone. α-Synuclein belongs to a family of three proteins, which includes β- and γ-synuclein. γ-Synuclein shares 60% similarity with α-synuclein. Similar to α-synuclein, a physiological function for γ-synuclein has not been defined yet, but it has been implicated in tumorgenesis and neurodegeneration. Interestingly, neither α- (SNCA−/−), γ- (SNCG−/−), nor α/γ- (SNCA_G−/−) deficient mice are present with any obvious phenotype. Using microarray analysis, we thus investigated whether deficiency of α- and γ-synuclein leads to similar compensatory mechanisms at the RNA level and whether similar transcriptional signatures are altered in the brain. Sixty-five genes were differentially expressed in all mice. SNCA−/− mice and SNCG−/− mice shared 84 differentially expressed genes, SNCA−/− and SNCA_G−/− expressed 79 genes, and SNCG−/− and SNCA_G−/− expressed 148 genes. For many of the physiological pathways such as dopamine receptor signaling (down-regulated), cellular development, nervous system function, and cell death (up-regulated), we found groups of genes that were similarly altered in SNCA−/− and SNCG−/− mice. In one of the pathways altered in both models, we found Mapk1 as the core transcript. Other gene groups, however, such as TGF-β signaling and apoptosis pathways genes were significantly up-regulated in the SNCA−/− mice but down-regulated in SNCG−/− mice. β-synuclein expression was not significantly altered in any of the models

UPDtool: a tool for detection of iso- and heterodisomy in parent-child trios using SNP microarrays

Abstract Summary: UPDtool is a computational tool for detection and classification of uniparental disomy (UPD) in trio SNP-microarray experiments. UPDs are rare events of chromosomal malsegregation and describe the condition of two homologous chromosomes or homologous chromosomal segments that were inherited from one parent. The occurrence of UPD can be of major clinical relevance. Though high-throughput molecular screening techniques are widely used, detection of UPDs and especially the subclassification remains complex. We developed UPDtool to detect and classify UPDs from SNP microarray data of parent–child trios. The algorithm was tested using five positive controls including both iso- and heterodisomic segmental UPDs and 30 trios from the HapMap project as negative controls. With UPDtool, we were able to correctly identify all occurrences of non-mosaic UPD within our positive controls, whereas no occurrence of UPD was found within our negative controls. In addition, the chromosomal breakage points could be determined more precisely than by microsatellite analysis. Our results were compared with both the gold standard, microsatellite analysis and SNPtrio, another program available for UPD detection. UPDtool is platform independent, light weight and flexible. Because of its simple input format, UPDtool may also be used with other high-throughput technologies (e.g. next-generation sequencing). Availability and implementation: UPDtool executables, documentation and examples can be downloaded from http://www.uni-tuebingen.de/uni/thk/de/f-genomik-software.html. Contact:  [email protected] Supplementary information:  Supplementary data are available at Bioinformatics online.</jats:p

Single Molecule Molecular Inversion Probes for High Throughput Germline Screenings in Dystonia

Background: This study's aim was to investigate a large cohort of dystonia patients for pathogenic and rare variants in the ATM gene, making use of a new, cost-efficient enrichment technology for NGS-based screening. Methods: Single molecule Molecular Inversion Probes (smMIPs) were used for targeted enrichment and sequencing of all protein coding exons and exon-intron boundaries of the ATM gene in 373 dystonia patients and six positive controls with known ATM variants. Additionally, a rare-variant association study was performed. Results: One patient (0.3%) was compound heterozygous and 21 others were carriers of variants of unknown significance (VUS) in the ATM gene. Although mutations in sporadic dystonia patients are not common, exclusion of pathogenic variants is crucial to recognize a potential tumor predisposition syndrome. SmMIPs produced similar results as routinely used NGS-based approaches. Conclusion: Our results underline the importance of implementing ATM in the routine genetic testing of dystonia patients and confirm the reliability of smMIPs and their usability for germline screenings in rare neurodegenerative conditions