Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association

2021 ◽  
Author(s):  
Jessica Ritter ◽  
Kristina Lisec ◽  
Martina Heinrich ◽  
Dietrich von Schweinitz ◽  
Roland Kappler ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genetic Background ◽  
Vascular Diseases ◽  
Genetic Mutation ◽  
Analysis Tool ◽  
Cardiovascular Development ◽  
Vacterl Association ◽  
Sequencing Data ◽  
Vascular Disorders ◽  
Organ Systems

Abstract Introduction The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association. Materials and Methods We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool “Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.” The study was approved by the institutional ethics committee (approval no. 026–13). Written informed consent was obtained from all patients or their parents. Results We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes. Conclusion Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.

scholarly journals The Identification of the SARS-CoV-2 Whole Genome: Nine Cases Among Patients in Banten Province, Indonesia

2021 ◽  
Author(s):  
Chris Adhiyanto ◽  
Laifa A. Hendarmin ◽  
Erike A. Suwarsono ◽  
Zeti Harriyati ◽  
Suryani ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Genetic Variants ◽  
Viral Genome ◽  
Genetic Background ◽  
Respiratory Illness ◽  
Whole Genome ◽  
Sequencing Data ◽  
Rt Pcr ◽  
Genome Sequences ◽  
Severe Patient

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the current pandemic. Viral genome sequencing has been widely applied during outbreaks to study the relatedness of this virus to other viruses, its transmission mode, pace, evolution and geographical spread, and also its adaptation to human hosts. To date, more than 90,000 SARS-CoV-2 genome sequences have been uploaded to the GISAID database. The availability of sequencing data along with clinical and geographical data may be useful for epidemiological investigations. In this study, we aimed to analyse the genetic background of SARS-CoV-2 from patients in Indonesia by whole genome sequencing. We examined nine samples from COVID-19 patients with RT-PCR cycle threshold (Ct) of less than 25 using ARTIC Network protocols for Oxford Nanopore’s Gridi On sequencer. The analytical methods were based on the ARTIC multiplex PCR sequencing protocol for COVID-19. In this study, we found that several genetic variants within the nine COVID-19 patient samples. We identified a mutation at position 614 P323L mutation in the ORF1ab gene often found in our severe patient samples. The number of SNPs and their location within the SARS-CoV-2 genome seems to vary. This diversity might be responsible for the virulence of the virus and its clinical manifestation.

scholarly journals 423. SARS-CoV-2 NGS Assay Powered by Biotia COVID-DX Software

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S278-S279
Author(s):  
Dorottya Nagy-Szakal ◽  
Mara Couto-Rodriguez ◽  
Joseph Barrows ◽  
Heather L Wells ◽  
Marilyne Debieu ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Viral Genome ◽  
Board Member ◽  
Limit Of Detection ◽  
Clinical Samples ◽  
Analysis Tool ◽  
Viral Titer ◽  
Target Enrichment ◽  
Library Preparation ◽  
Software Analysis

Abstract Background COVID-19 had spread quickly, causing an international public health emergency with an alarming global shortage of COVID-19 diagnostic tests. We developed and clinically validated a next-generation sequencing (NGS)-based target enrichment assay with the COVID-DX Software tailored for the detection, characterization, and surveillance of the SARS-CoV-2 viral genome. Methods The SARS-CoV-2 NGS assay consists of components including library preparation, target enrichment, sequencing, and a COVID-DX Software analysis tool. The NGS library preparation starts with extracted RNA from nasopharyngeal (NP) swabs followed by cDNA synthesis and conversion to Illumina TruSeq-compatible libraries using the Twist Library Preparation Kit via Enzymatic Fragmentation and Unique Dual Indices (UDI). The library is then enriched for SARS-CoV-2 sequences using a panel of dsDNA biotin-labeled probes, specifically designed to target the SARS-CoV-2 genome, then sequenced on an Illumina NextSeq 550 platform. The COVID-DX Software analyzes sequence results and provides a clinically oriented report, including the presence/absence of SARS-CoV-2 for diagnostic use. An additional research use only report describes the assay performance, estimated viral titer, coverage across the viral genome, genetic variants, and phylogenetic analysis. Results The SARS-CoV-2 NGS Assay was validated on 30 positive and 30 negative clinical samples. To measure the sensitivity and specificity of the assay, the positive and negative percent agreement (PPA, NPA) was defined in comparison to an orthogonal EUA RT-PCR assay (PPA [95% CI]: 96.77% [90.56%-100%] and NPA [95% CI]: 100% [100%-100%]). Data reported using our assay defined the limit of detection to be 40 copies/ml using heat-inactivated SARS-CoV-2 viral genome in clinical matrices. In-silico analysis provided >99.9% coverage across the SARS-CoV-2 viral genome and no cross-reactivity with evolutionarily similar respiratory pathogens. Conclusion The SARS-CoV-2 NGS Assay powered by the COVID-DX Software can be used to detect the SARS-CoV-2 virus and provide additional insight into viral titer and genetic variants to track transmission, stratify risk, predict outcome and therapeutic response, and control the spread of infectious disease. Disclosures Dorottya Nagy-Szakal, MD PhD, Biotia (Employee) Mara Couto-Rodriguez, MS, Biotia (Employee) Joseph Barrows, MS, Biotia, Inc. (Employee, Shareholder) Heather L. Wells, MPH, Biotia (Consultant) Marilyne Debieu, PhD, Biotia (Employee) Courteny Hager, BS, Biotia (Employee) Kristin Butcher, MS, Twist Bioscience (Employee) Siyuan Chen, PhD, Twist Bioscience (Employee) Christopher Mason, PhD, Biotia (Board Member, Employee, Shareholder) Niamh B. O’Hara, PhD, Biotia (Board Member, Employee, Shareholder)Twist (Other Financial or Material Support, I am CEO of Biotia and Biotia has business partnership with Twist)

scholarly journals Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yurong Cheng ◽  
◽  
Pascal Schlosser ◽  
Johannes Hertel ◽  
Peggy Sekula ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Inborn Errors Of Metabolism ◽  
Cell Types ◽  
Population Variation ◽  
Whole Body ◽  
Sequencing Data ◽  
Inborn Errors ◽  
Data Links ◽  
Liver And Kidney ◽  
Constraint Based Modeling

AbstractMetabolite levels in urine may provide insights into genetic mechanisms shaping their related pathways. We therefore investigate the cumulative contribution of rare, exonic genetic variants on urine levels of 1487 metabolites and 53,714 metabolite ratios among 4864 GCKD study participants. Here we report the detection of 128 significant associations involving 30 unique genes, 16 of which are known to underlie inborn errors of metabolism. The 30 genes are strongly enriched for shared expression in liver and kidney (odds ratio = 65, p-FDR = 3e−7), with hepatocytes and proximal tubule cells as driving cell types. Use of UK Biobank whole-exome sequencing data links genes to diseases connected to the identified metabolites. In silico constraint-based modeling of gene knockouts in a virtual whole-body, organ-resolved metabolic human correctly predicts the observed direction of metabolite changes, highlighting the potential of linking population genetics to modeling. Our study implicates candidate variants and genes for inborn errors of metabolism.

scholarly journals VCF.Filter: interactive prioritization of disease-linked genetic variants from sequencing data

2017 ◽  
Vol 45 (W1) ◽  
pp. W567-W572 ◽  
Author(s):  
Heiko Müller ◽  
Raul Jimenez-Heredia ◽  
Ana Krolo ◽  
Tatjana Hirschmugl ◽  
Jasmin Dmytrus ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Sequencing Data

E-health and interventional radiology in gynecology

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ibrahim Alghanimi
Keyword(s):  
Interventional Radiology ◽  
Vascular Diseases ◽  
Obstetrics And Gynecology ◽  
Content Type ◽  
Organ Systems ◽  
Preservation Of Fertility ◽  
Fluid Collections ◽  
New Procedures ◽  
Pelvic Congestion

Purpose This paper aims to summarize the radiological interventions that can be used by obstetricians and gynecologists. Design/methodology/approach E-health systems apply in all hospital sectors in the world; interventional radiology (IR) now includes transcatheter and percutaneous techniques that can be applied to various organ systems, including the female reproductive system and pelvis. Interventional radiologists can now offer many services to obstetricians and gynecologists. With the advent of new procedures and refinement of existing techniques, there are now a number of procedures that can be used to treat both vascular and non-vascular diseases. This review summarizes the radiological interventions that can be used by obstetricians and gynecologists. Findings This review is intended to help gynecologists and obstetricians understand the role of IR in their specialty. Many valuable vascular and nonvascular interventional services can be provided by radiologists for both obstetric and gynecological indications. Many of these IR procedures are minimally invasive with less risk to the patients. Originality/value IR is now being used to treat some conditions encountered in obstetrics and gynecology, in particular, uterine leiomyomas, placenta accreta, postpartum hemorrhage and pelvic congestion syndrome. Moreover, with the help of IR, radiologists can also manage several nonvascular pathologies, including drainage of pelvic abscesses, fallopian tube recanalization, image-guided biopsy and fluid collections involving ovarian lesions. The major challenges faced when performing obstetric IR procedures are reduction of radiation exposure for the patient and fetus and preservation of fertility. This review highlights the role of IR in the treatment of various vascular and nonvascular pathologies encountered in obstetrics and gynecology.

scholarly journals Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
William S DeWitt ◽  
Anajane Smith ◽  
Gary Schoch ◽  
John A Hansen ◽  
Frederick A Matsen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Genetic Background ◽  
Cell Receptor ◽  
Sequencing Data ◽  
Human T Cell ◽  
Disease Associations ◽  
Repertoire Sequencing ◽  
Mhc Polymorphism ◽  
Occurrence Patterns

The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.

GEMPROT: visualization of the impact on the protein of the genetic variants found on each haplotype

2018 ◽  
Vol 35 (14) ◽  
pp. 2492-2494
Author(s):  
Tania Cuppens ◽  
Thomas E Ludwig ◽  
Pascal Trouvé ◽  
Emmanuelle Genin
Keyword(s):  
Genetic Variants ◽  
Protein Sequence ◽  
Sequence Data ◽  
Protein Sequences ◽  
Supplementary Information ◽  
Analysis Tool ◽  
Functional Protein ◽  
Key Players ◽  
On Line ◽  
The Impact

Abstract Summary When analyzing sequence data, genetic variants are considered one by one, taking no account of whether or not they are found in the same individual. However, variant combinations might be key players in some diseases as variants that are neutral on their own can become deleterious when associated together. GEMPROT is a new analysis tool that allows, from a phased vcf file, to visualize the consequences of the genetic variants on the protein. At the level of an individual, the program shows the variants on each of the two protein sequences and the Pfam functional protein domains. When data on several individuals are available, GEMPROT lists the haplotypes found in the sample and can compare the haplotype distributions between different sub-groups of individuals. By offering a global visualization of the gene with the genetic variants present, GEMPROT makes it possible to better understand the impact of combinations of genetic variants on the protein sequence. Availability and implementation GEMPROT is freely available at https://github.com/TaniaCuppens/GEMPROT. An on-line version is also available at http://med-laennec.univ-brest.fr/GEMPROT/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Modeling Type 1 Diabetes Using Pluripotent Stem Cell Technology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kriti Joshi ◽  
Fergus Cameron ◽  
Swasti Tiwari ◽  
Stuart I. Mannering ◽  
Andrew G. Elefanty ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stem Cell ◽  
Genetic Variants ◽  
Genetic Background ◽  
Pluripotent Stem Cell ◽  
Cell Types ◽  
Polygenic Inheritance

Induced pluripotent stem cell (iPSC) technology is increasingly being used to create in vitro models of monogenic human disorders. This is possible because, by and large, the phenotypic consequences of such genetic variants are often confined to a specific and known cell type, and the genetic variants themselves can be clearly identified and controlled for using a standardized genetic background. In contrast, complex conditions such as autoimmune Type 1 diabetes (T1D) have a polygenic inheritance and are subject to diverse environmental influences. Moreover, the potential cell types thought to contribute to disease progression are many and varied. Furthermore, as HLA matching is critical for cell-cell interactions in disease pathogenesis, any model that seeks to test the involvement of particular cell types must take this restriction into account. As such, creation of an in vitro model of T1D will require a system that is cognizant of genetic background and enables the interaction of cells representing multiple lineages to be examined in the context of the relevant environmental disease triggers. In addition, as many of the lineages critical to the development of T1D cannot be easily generated from iPSCs, such models will likely require combinations of cell types derived from in vitro and in vivo sources. In this review we imagine what an ideal in vitro model of T1D might look like and discuss how the required elements could be feasibly assembled using existing technologies. We also examine recent advances towards this goal and discuss potential uses of this technology in contributing to our understanding of the mechanisms underlying this autoimmune condition.

scholarly journals The effect of vascular diseases on bioimpedance measurements: mathematical modeling

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
Yomna H. Shash ◽  
Mohamed A. A. Eldosoky ◽  
Mohamed T. Elwakad
Keyword(s):  
Mathematical Models ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Impedance Analysis ◽  
Wide Field ◽  
Vascular Disorders ◽  
Non Invasive ◽  
Novel Method ◽  
Inner Vessel ◽  
Arteries And Veins

Introduction: The non-invasive nature of bioimpedance technique is the reason for the adoption of this technique in the wide field of bio-research. This technique is useful in the analysis of a variety of diseases and has many advantages. Cardiovascular diseases are the most dangerous diseases leading to death in many regions of the world. Vascular diseases are disorders that affect the arteries and veins. Most often, vascular diseases have greater impacts on the blood flow, either by narrowing or blocking the vessel lumen or by weakening the vessel wall. The most common vascular diseases are atherosclerosis, wall swelling (aneurysm), and occlusion. Atherosclerosis is a disease caused by the deposition of plaques on the inner vessel wall, while a mural aneurysm is formed as a result of wall weakness. The main objective of this study was to investigate the effects of vascular diseases on vessel impedance. Furthermore, this study aimed to develop the measurement of vessel abnormalities as a novel method based on the bioimpedance phenomenon. Methods: Mathematical models were presented to describe the impedance of vessels in different vascular cases. In addition, a 3D model of blood vessels was simulated by COMSOL MULTIPHYSICS.5, and the impedance was measured at each vascular condition. Results: The simulation results clarify that the vascular disorders (stenosis, blockage or aneurysm) have significant impact on the vessel impedance, and thus they can be detected by using the bio-impedance analysis. Moreover, using frequencies in KHz range is preferred in detecting vascular diseases since it has the ability to differentiate between the healthy and diseased blood vessel. Finally, the results can be improved by selecting an appropriate electrodes configuration for analysis. Conclusion: From this work, it can be concluded that bioimpedance analysis (BIA) has the ability to detect vascular diseases. Furthermore, the proposed mathematical models are successful at describing different cases of vascular disorders.

scholarly journals Genome Size Estimation and Full-Length Transcriptome of Sphingonotus tsinlingensis: Genetic Background of a Drought-Adapted Grasshopper

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Zhao ◽  
Hang Wang ◽  
Ping Li ◽  
Kuo Sun ◽  
De-Long Guan ◽  
...  
Keyword(s):  
Genome Size ◽  
Genetic Background ◽  
Tandem Repeats ◽  
Full Length ◽  
Arid Environments ◽  
Size Estimation ◽  
Sequencing Data ◽  
Protein Coding ◽  
Grasshopper Species ◽  
Hsp Genes

Sphingonotus Fieber, 1852 (Orthoptera: Acrididae), is a grasshopper genus comprising approximately 170 species, all of which prefer dry environments such as deserts, steppes, and stony benchlands. In this study, we aimed to examine the adaptation of grasshopper species to arid environments. The genome size of Sphingonotus tsinlingensis was estimated using flow cytometry, and the first high-quality full-length transcriptome of this species was produced. The genome size of S. tsinlingensis is approximately 12.8 Gb. Based on 146.98 Gb of PacBio sequencing data, 221.47 Mb full-length transcripts were assembled. Among these, 88,693 non-redundant isoforms were identified with an N50 value of 2,726 bp, which was markedly longer than previous grasshopper transcriptome assemblies. In total, 48,502 protein-coding sequences were identified, and 37,569 were annotated using public gene function databases. Moreover, 36,488 simple tandem repeats, 12,765 long non-coding RNAs, and 414 transcription factors were identified. According to gene functions, 61 cytochrome P450 (CYP450) and 66 heat shock protein (HSP) genes, which may be associated with drought adaptation of S. tsinlingensis, were identified. We compared the transcriptomes of S. tsinlingensis and two other grasshopper species which were less tolerant to drought, namely Mongolotettix japonicus and Gomphocerus licenti. We observed the expression of CYP450 and HSP genes in S. tsinlingensis were higher. We produced the first full-length transcriptome of a Sphingonotus species that has an ultra-large genome. The assembly characteristics were better than those of all known grasshopper transcriptomes. This full-length transcriptome may thus be used to understand the genetic background and evolution of grasshoppers.

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