The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria

The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes

Comparative Studies of Minerals between Collected and Certified Samples of Some Important Barley Cultivars Grown in Pakistan

Essential and trace elements; Na, K, Ca, Mg, Fe, Zn, Mn, Cu, Co, Cr, Ni, Pb, Cd, Ba, and Al were determined in eight barley cultivar samples collected from wheat research station, Sindh Agriculture University, Tando Jam. The dried samples were digested in HNO3 followed by H2O2, diluted with deionized water, and element at concentrations were determined with a recording atomic absorption spectrophotometer. The results were in the mg/kg range 1127.88-2312.45 (Na), 6663.3-7482.91 (K), 8.91-122.45 (Ca), 2079.08-2522.64 (Mg), 841.01-2141.9 (Fe), 30.24-53.05 (Zn), 21.93-38.69 (Mn), 7.02-10.46 (Cu), 1.66-4.41 (Co), 0.84-1.22 (Cr), 0.7-1.23 (Ni), 0.55-1.21 (Pb), 0.23-0.49 (Cd), 3.96-9.25 (Ba), and 10.42-25.35 (Al). These results of collected samples were compared with certified samples of Federal Seed Certification and Registration Department of Pakistan

TiO2/ZnO Nanocomposite Material for Efficient Degradation of Methylene Blue

In this research work, we have produced a composite material consisting titanium dioxide (TiO2) and zinc oxide (ZnO) nanostructures via precipitation method. Scanning electron microscopy (SEM) study has shown the mixture of nanostructures consisting nanorods and nano flower. Energy dispersive spectroscopy (EDS) study has confirmed the presence of Ti, Zn and O as main elements in the composite. X-ray diffraction (XID) study has revealed that the successful presence of TiO2 and ZnO in the composite. The composite material exhibits small optical energy band gap which led to reduction of the charge recombination rate of electron-hole pairs. The band gap for the composite TiO2/ZnO samples namely 1, 2, 3 and 4 is 3.18, 3.00, 2.97 and 2.83 eV respectively. Small optical bandgap gives less relaxation time for the recombination of electron and hole pairs, thus favorable photodegradation is found. The degradation efficiency for the TiO2/ZnO samples for methylene blue in order of 55.03%, 75.7%, 85.14% and 90.08% is found for the samples 1, 2, 3 and 4 respectively. The proposed study of titanium dioxide addition into ZnO is facile and inexpensive for the development of efficient photocatalysts. This can be capitalized at large scale for the energy and environmental applications.Funding Agencies|King Saud University, Riyadh, Saudi ArabiaKing Saud University [RSP-2020/79]</p

Tin as an Effective Doping Agent into ZnO for the Improved Photodegradation of Rhodamine B

We have fabricated ZnO nano rods by hydrothermal method and successively doped them with tin (Sn) using different concentrations of 25, 50, 75 and 100 mg of tin chloride. XRD of the fabricated structures showed that ZnO possess hexagonal wurtzite phase. Scanning electron microscopy (SEM) was used to explore the morphology and it shows nanorod like morphology for all samples and no considerable change in the structural features were found. The dimension of nanorod is 200 to 300 nm. The doped materials were then investigated for their photo catalytic degradation of environmental pollutant Rhodamine B. The performance of doped ZnO is compared with the pristine ZnO. Scanning electron microscopy (SEM) was used to explore the morphology and it shows nanorod like morphology for all samples and no considerable change in the structural features were found. The dimension of nanorod is 200 to 300 nm. XRD of the fabricated structures showed that ZnO possess hexagonal wurtzite phase. Photo catalytic activity of rhodamine B was investigated under UV light and a maximum degradation efficiency of 85% was obtained. The optical property reveals the reduction in band gap of upto 17.14% for 100 mg Sn doped ZnO. The degradation is followed by the pseudo order kinetics. The produced results are unique in terms of facile synthesis of Sn doped ZnO and excellent photo degradation efficiency, therefore these materials can be used for other environmental applications

Frequency of frontotemporal dementia gene variants in C9ORF72, MAPT, and GRN in academic versus commercial laboratory cohorts.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia, and elucidating its genetic underpinnings is critical. FTLD research centers typically recruit patient cohorts that are limited by the center's specialty and the ways in which its geographic location affects the ethnic makeup of research participants. Novel sources of data are needed to get population estimates of the contribution of variants in known FTLD-associated genes.MethodsWe compared FLTD-associated genetic variants in microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome nine open reading frame 72 (C9ORF72) from an academic research cohort and a commercial clinical genetics laboratory. Pathogenicity was assessed using guidelines of the American College of Medical Genetics and Genomics and a rule-based DNA variant assessment system. We conducted chart reviews on patients with novel or rare disease-associated variants.ResultsA total of 387 cases with FTLD-associated variants from the commercial (n=2,082) and 78 cases from the academic cohort (n=2,089) were included for analysis. In the academic cohort, the most frequent pathogenic variants were C9ORF72 expansions (63%, n=49), followed by GRN (26%, n=20) and MAPT (11%, n=9). Each gene's contribution to disease was similarly ranked in the commercial laboratory but differed in magnitude: C9ORF72 (89%, n=345), GRN (6%, n=24), and MAPT (5%, n=19). Of the 37 unique GRN/MAPT variants identified, only six were found in both cohorts. Clinicopathological data from patients in the academic cohort strengthened classification of two novel GRN variant as pathogenic (p.Pro166Leufs*2, p.Gln406*) and one GRN variant of unknown significance as a possible rare risk variant (p.Cys139Arg).ConclusionDifferences in gene frequencies and identification of unique pathogenic alleles in each cohort demonstrate the importance of data sharing between academia and community laboratories. Using shared data sources with well-characterized clinical phenotypes for individual variants can enhance interpretation of variant pathogenicity and inform clinical management of at-risk patients and families

The ClinGen Epilepsy Gene Curation Expert Panel-Bridging the divide between clinical domain knowledge and formal gene curation criteria.

The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes