Absence of mtDNA mutations in leukocytes of CADASIL patients

<p>Abstract</p> <p>Background</p> <p>Ultrastructural and biochemical abnormalities of mitochondria have been reported in skeletal muscle biopsies of CADASIL patients with mutations in the <it>NOTCH3 </it>nuclear gene. Additionally, it was proposed that <it>NOTCH3 </it>gene mutations may predispose the mitochondrial DNA (mtDNA) to mutations.</p> <p>Methods</p> <p>We sequenced the entire mitochondrial genome in five Arab patients affected by CADASIL.</p> <p>Results</p> <p>The mean number of mtDNA sequence variants (synonymous and nonsynonymous) in CADASIL patients was not statistically significantly different from that in controls (<it>p </it>= 0.378). After excluding haplogroup specific single nucleotide polymorphisms (SNPs) and proved silent polymorphisms, no known or novel pathologic mtDNA mutation(s) could be detected in any patient. Additionally, there was no difference in the prevalence of different mitochondrial haplogroups between patients and controls.</p> <p>Conclusion</p> <p>Our study group is too small for any valid conclusion to be made. However, if our observation is confirmed in larger study group, then mtDNA mutations or mitochondrial haplogroups may not be important in the pathogenesis of CADASIL.</p

Overview on the Blockchain-Based Supply Chain Systematics and Their Scalability Tools

Modern IT technologies shaped the shift in economic models with many advantages on cost, optimization, and time to market. This economic shift has increased the need for transparency and traceability in supply chain platforms to achieve trust among partners. Distributed ledger technology (DLT) is proposed to enable supply chains systems with trust requirements. In this paper, we investigate the existing DLT-based supply chain projects to show their technical part and limitations and extract the tools and techniques used to avoid the DLT scalability issue. We then set the requirements for a typical DLT-based supply chain in this context. The analyses are based on the scalability metrics such as computing, data storage, and transaction fees that fit the typical supply chain system. This paper highlights the effects of Blockchain techniques on scalability and their incorporation in supply chains systems. It also presents other existing solutions that can be applied to the supply chain. The investigation shows the necessity of having such tools in supply chains and developing them to achieve an efficient and scalable system. The paper calls for further scalability enhancements throughout introducing new tools and/or reutilize the current ones. Doi: 10.28991/esj-2021-SP1-04 Full Text: PD

A de novo marker chromosome derived from 9p in a patient with 9p partial duplication syndrome and autism features: genotype-phenotype correlation

<p>Abstract</p> <p>Background</p> <p>Previous studies focusing on candidate genes and chromosomal regions identified several copy number variations (CNVs) associated with increased risk of autism or autism spectrum disorders (ASD).</p> <p>Case Presentation</p> <p>We describe a 17-year-old girl with autism, severe mental retardation, epilepsy, and partial 9p duplication syndrome features in whom GTG-banded chromosome analysis revealed a female karyotype with a marker chromosome in 69% of analyzed metaphases. Array CGH analysis showed that the marker chromosome originated from 9p24.3 to 9p13.1 with a gain of 38.9 Mb. This mosaic 9p duplication was detected only in the proband and not in the parents, her four unaffected siblings, or 258 ethnic controls. Apart from the marker chromosome, no other copy number variations (CNVs) were detected in the patient or her family. Detailed analysis of the duplicated region revealed: i) an area extending from 9p22.3 to 9p22.2 that was previously identified as a critical region for the 9p duplication syndrome; ii) a region extending from 9p22.1 to 9p13.1 that was previously reported to be duplicated in a normal individual; and iii) a potential ASD locus extending from 9p24.3 to 9p23. The ASD candidate locus contained 34 genes that may contribute to the autistic features in this patient.</p> <p>Conclusion</p> <p>We identified a potential ASD locus (9p24.3 to 9p23) that may encompass gene(s) contributing to autism or ASD.</p

Down-regulation of OPA1 in patients with primary open angle glaucoma

PURPOSE: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. METHODS: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the β-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. CONCLUSIONS: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG

High-resolution analysis of DNA copy number alterations in patients with primary open-angle glaucoma

PURPOSE: To determine whether patients with isolated primary open-angle glaucoma (POAG) have evidence of chromosomal copy number alterations. METHODS: Twenty-seven Caucasian and African-American POAG patients and 12 ethnically matched controls were carefully screened for possible glaucoma and tested for chromosomal copy number alterations using high resolution array comparative genomic hybridization. RESULTS: No POAG patient had evidence of chromosomal copy number alterations when compared to normal ethnically matched controls. Additionally, there was no evidence of somatic mosaicism in any tested POAG patient. CONCLUSIONS: Chromosomal deletions and/or duplications were not detected in POAG patients as compared to controls. Other chromosomal imbalances such as translocations, inversions, and some ploidies cannot be detected by current array comparative genomic hybridization technology, and other nuclear genetic, mitochondrial abnormalities, or epigenetic factors cannot be excluded as a possible contributing factor to POAG pathogenesis

Single-cell whole-genome amplification technique impacts the accuracy of SNP microarray-based genotyping and copy number analyses

Methods of comprehensive microarray-based aneuploidy screening in single cells are rapidly emerging. Whole-genome amplification (WGA) remains a critical component for these methods to be successful. A number of commercially available WGA kits have been independently utilized in previous single-cell microarray studies. However, direct comparison of their performance on single cells has not been conducted. The present study demonstrates that among previously published methods, a single-cell GenomePlex WGA protocol provides the best combination of speed and accuracy for single nucleotide polymorphism microarray-based copy number (CN) analysis when compared with a REPLI-g- or GenomiPhi-based protocol. Alternatively, for applications that do not have constraints on turnaround time and that are directed at accurate genotyping rather than CN assignments, a REPLI-g-based protocol may provide the best solution

The systems-activity concept of innovation – the imperative for sustainable social programming of a solidarity society

Historically, scientific and technological progress has determined the emergence and continuous development of forms of its social organization, objectively forming the images of solidarity society corresponding to these forms. It is argued that the main social phenomenon accompanying scientific and technological progress is innovation, and it is hypothesized that this concept can be based on the ontological concept of innovation. On the basis of well-known methods of ontological research, the method of dialectic-systemic construction of innovation as a system of unitary social activity which generates new opportunities of social development leading to growth of social quality of the solidarity society is proposed. The system-activity concept of innovation is substantiated and its invariant conceptual structure, which is defined as the unity of two innovative structures: the phenomenon of innovation and the manifestation of innovation, which determine the organization and management of innovation, is constructed. The proposed concept of innovation can only be the imperative of sustainable social programming of a solidarity society, which provides a method of dialectical-systemological construction of innovation that allows detailing the original invariant conceptual structure for each specific image of a solidarity society due to a particular stage of scientific and technological progress