scholarly journals Detection of GBA missense mutations and other variants using the Oxford Nanopore MinION

2018 ◽  
Author(s):  
Melissa Leija-Salazar ◽  
Fritz J. Sedlazeck ◽  
Katya Mokretar ◽  
Stephen Mullin ◽  
Marco Toffoli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gaucher Disease ◽  
Missense Mutations ◽  
Compound Heterozygosity ◽  
Flow Cells ◽  
Oxford Nanopore ◽  
Base Pair Deletion ◽  
The Common ◽  
Exonic Deletion ◽  
Intronic Snps

AbstractPurposeMutations in GBA cause Gaucher disease when biallelic, and are strong risk factors for Parkinson’s disease when heterozygous. GBA analysis is complicated by the nearby pseudogene. We aimed to design and validate a method for sequencing GBA on the Oxford Nanopore MinION.MethodsWe sequenced an 8.9 kb amplicon from DNA samples of 17 individuals, including patients with Parkinson’s and Gaucher disease, on older and current (R9.4) flow cells. These included samples with known mutations, assessed in a blinded fashion on the R9.4 data. We used NanoOK for quality metrics, two different aligners (Graphmap and NGMLR), Nanopolish and Sniffles to call variants, and Whatshap for phasing.ResultsWe detected all known mutations, including the common p.N409S (N370S) and p.L483P (L444P), and three rarer ones, at the correct zygosity, as well as intronic SNPs. In a sample with the complex RecNciI allele, we detected an additional coding mutation, and a 55-base pair deletion. We confirmed compound heterozygosity where relevant. False positives were easily identified.ConclusionThe Oxford Nanopore MinION can detect missense mutations and an exonic deletion in this difficult gene, with the added advantage of phasing and intronic analysis. It can be used as an efficient diagnostic tool.

Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene

1996 ◽  
Vol 75 (04) ◽  
pp. 546-550 ◽  
Author(s):  
Marianne Schwartz ◽  
Albert Békássy ◽  
Mikael Donnér ◽  
Thomas Hertel ◽  
Stefan Hreidarson ◽  
...  
Keyword(s):  
Base Pair ◽  
Hot Spot ◽  
Missense Mutations ◽  
Nucleotide Substitutions ◽  
Exon 2 ◽  
Wiskott Aldrich Syndrome ◽  
Base Pair Deletion ◽  
Reliable Diagnosis ◽  
Wasp Gene ◽  
Detection Of Mutations

SummaryTwelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.

scholarly journals The common risk factors for progression and mortality in COVID-19 patients: a meta-analysis

2021 ◽  
Author(s):  
Li Zhang ◽  
Jie Hou ◽  
Fu-Zhe Ma ◽  
Jia Li ◽  
Shuai Xue ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Common Risk Factors ◽  
The Common

scholarly journals Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype

2009 ◽  
Vol 182 (6) ◽  
pp. 3902-3918 ◽  
Author(s):  
François-Xavier Hubert ◽  
Sarah A. Kinkel ◽  
Pauline E. Crewther ◽  
Ping Z. F. Cannon ◽  
Kylie E. Webster ◽  
...  
Keyword(s):  
Base Pair ◽  
Deletion Mutation ◽  
Base Pair Deletion ◽  
The Common

Mating type control in Saccharomyces cerevisiae: a frameshift mutation at the common DNA sequence, X, of the HML alpha locus

1984 ◽  
Vol 4 (1) ◽  
pp. 203-211
Author(s):  
K Tanaka ◽  
T Oshima ◽  
H Araki ◽  
S Harashima ◽  
Y Oshima
Keyword(s):  
Mating Type ◽  
Base Pair ◽  
Reading Frame ◽  
Base Pair Deletion ◽  
A Cell ◽  
Alpha Gene ◽  
The Common ◽  
Type Switch ◽  
Diploid Cells ◽  
Mat Locus

A mutation defective in the homothallic switching of mating type alleles, designated hml alpha-2, has previously been characterized. The mutation occurred in a cell having the HO MATa HML alpha HMRa genotype, and the mutant culture consisted of ca. 10% a mating type cells, 90% nonmater cells of haploid cell size, and 0.1% sporogenous diploid cells. Genetic analyses revealed that nonmater haploid cells have a defect in the alpha 2 cistron at the MAT locus. This defect was probably caused by transposition of a cassette originating from the hml alpha-2 allele by the process of the homothallic mating type switch. That the MAT locus of the nonmater cells is occupied by a DNA fragment indistinguishable from the Y alpha sequence in electrophoretic mobility was demonstrated by Southern hybridization of the EcoRI-HindIII fragment encoding the MAT locus with a cloned HML alpha gene as the probe. The hml alpha-2 mutation was revealed to be a one-base-pair deletion at the ninth base pair in the X region from the X and Y boundary of the HML locus. This mutation gave rise to a shift in the open reading frame of the alpha 2 cistron. A molecular mechanism for the mating type switch associated with the occurrence of sporogenous diploid cells in the mutant culture is discussed.

scholarly journals Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1751 ◽  
Author(s):  
Lucy M Collins ◽  
Janelle Drouin-Ouellet ◽  
Wei-Li Kuan ◽  
Timothy Cox ◽  
Roger A Barker
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Risk ◽  
Gaucher Disease ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Autophagic Flux ◽  
Clinical Progression ◽  
Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

scholarly journals Risk factors for Hyperhomocysteinemia for Specific MTHFR C677T Genotypes and Gender in Chinese Population.

2020 ◽  
Author(s):  
Hang Xiang ◽  
Tianyuan Xiang ◽  
Muyang Yan ◽  
Sheng Yu ◽  
Matthew John Horwedel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Linear Regression Analysis ◽  
Mthfr C677t ◽  
Multiple Linear Regression Analysis ◽  
Plasma Homocysteine ◽  
Independent Variables ◽  
Specific Risk ◽  
Physical Examinations ◽  
The Common ◽  
And Gender

Abstract Background­-- Our previous studies have identified that both gender and genotype of MTHFR C677T were independent variables for plasma homocysteine (Hcy) levels. Based on these results, we want to further explore their systemic information, in order to find specific risk factors for each genetic group, which might be used as predictors or targeting markers for lowering Hcy levels. Patients and Methods­--This cross section study was performed through November 2017 to July 2019. A total of 4534 adults aged 20-75y were selected for this study, and all of them underwent a physical examinations and MTHFR C677T genotyping. Results--The average of Hcy level was higher in TT genotype than CC and CT genotypes (P=0.000). Multiple linear regression analysis found that except the common protective factors (folate and Vit B12) and risk factor (Cr), each group has it specific risk factors for HHcy---female-CT (age, SBP and Hb), female-TT (SBP and AST); male-CC (age, AST and Hb), male-CT (age and AST) and male-TT (SBP, AST and Hb).Conclusion--The plasma Hcy level was influenced by different risk factors for specific gender and genotype. These risk factors might be useful for prediction or prevention of HHcy in the future.

scholarly journals Clinical and Demographic Predictors of Mortality due to COVID-19 Pandemic: A Retrospective Study

2021 ◽  
Vol 11 (5) ◽  
pp. 74-81
Author(s):  
Ayushi Rajkumar Jain ◽  
Doss Prakash ◽  
Sheetal Swamy
Keyword(s):  
Risk Factors ◽  
Mortality Rate ◽  
Early Stage ◽  
Major Complication ◽  
Respiratory Arrest ◽  
Chi Square ◽  
High Risk Factors ◽  
Demographic Predictors ◽  
Chi Square Test ◽  
The Common

The alarming statistics of COVID-19 surges up in 2021 throwing an enormous burden on the healthcare system across the world. According to WHO reports on 14th April 2021, globally 136,996,364 confirmed COVID-19 cases are reported across the continents, including 2,951,832 deaths. The state of Maharashtra reported the maximum number of cases of India including high mortality rate. This study was conducted to identify and describe the relation of different predictors (Age, gender, duration of hospital stay, presence of co morbidities) of mortality among the COVID-19 deceased patients by retrospectively analyzing the medical case records of 121 patients from a dedicated COVID hospital at Aurangabad from July 2020 to December 2020. Chi-square test was performed to assess the association between causes of death with different cluster of variables and their significance. This study helps us to identify risk factors that show association between various predictors and mortality rate in COVID-19 patients. Out of 121 deaths, 96 (79%) were male, 61 (49.6%) were in age group between 60-79 years, ARDS was one of the major complication in the deceased patients accounting 29.8% and cardio respiratory arrest was the common cause of death among the deceased patients with 85%. It was also observed that mortality rate was very higher in the initial five days of hospitalization with critical care support. Our result findings provide clinical inferences for physicians to identify high-risk factors with COVID-19 at a very early stage. Key words: COVID-19, Mortality rate, Demographic predictors, Co-morbidities, Cardio respiratory arrest.

scholarly journals Microbial diversity characterization of seawater in a pilot study using Oxford Nanopore Technologies long-read sequencing

2020 ◽  
Author(s):  
Michael Liem ◽  
Tonny Regensburg-Tuïnk ◽  
Christiaan Henkel ◽  
Hans Jansen ◽  
Herman Spaink
Keyword(s):  
Microbial Diversity ◽  
Environmental Samples ◽  
Sea Water ◽  
Flow Cells ◽  
Oxford Nanopore ◽  
Challenging Tasks ◽  
Long Read ◽  
Close Relatives ◽  
Oxford Nanopore Technologies

Abstract Objective: Currently the majority of non-culturable microbes in sea water are yet to be discovered, Nanopore offers a solution to overcome the challenging tasks to identify the genomes and complex composition of oceanic microbiomes. In this study we evaluate the utility of Oxford Nanopore Technologies (ONT) sequencing to characterize microbial diversity in seawater from multiple locations. We compared the microbial species diversity of retrieved environmental samples from two different locations and time points.Results: With only three ONT flow cells we were able to identify thousands of organisms, including bacteriophages, from which a large part at species level. It was possible to assemble genomes from environmental samples with Flye. In several cases this resulted in >1 Mbp contigs and in the particular case of a Thioglobus singularis species it even produced a near complete genome. k-mer analysis reveals that a large part of the data represents species of which close relatives have not yet been deposited to the database. These results show that our approach is suitable for scalable genomic investigations such as monitoring oceanic biodiversity and provides a new platform for education in biodiversity.

scholarly journals Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China

2021 ◽  
Author(s):  
Judith Ju Ming Wong ◽  
Qalab Abbas ◽  
Soo Lin Chuah ◽  
Ririe Fachrina Malisie ◽  
Kah Min Pon ◽  
...  
Keyword(s):  
Risk Factors ◽  
South Asia ◽  
Cultural Practices ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
World Health ◽  
Logistic Regression Models ◽  
Clinical Presentations ◽  
The Common ◽  
Health Organization

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.

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