Identification and Clinical Implications of a Novel MYO15A Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing

2019 ◽  
Vol 24 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Narges Zarepour ◽  
Mahbobeh Koohiyan ◽  
Afsaneh Taghipour-Sheshdeh ◽  
Fatemeh Nemati-Zargaran ◽  
Nader Saki ◽  
...  
Keyword(s):  
Pedigree Analysis ◽  
Genetic Linkage Analysis ◽  
Clinical Evaluations ◽  
Sequencing Technologies ◽  
The Family ◽  
New Strategy ◽  
Genetics And Genomics ◽  
Next Generation Sequencing Ngs ◽  
Very High ◽  
Generation Sequencing

Background and Objectives: Hereditary hearing loss (HL) is known by a very high genetic heterogeneity, which makes a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Method: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 3 affected members. After excluding mutations in the GJB2 and 7 other most common autosomal recessive nonsyndromic HL genes via Sanger sequencing and genetic linkage analysis in the family, we applied the Otogenetics deafness NGS panel in the proband of this family. Results: NGS results showed a novel rare variant (c.7720C>T) in the MYO15A gene. This nonsense variant in the exon 40 of the MYO15A gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics guideline. Conclusions: New DNA sequencing technologies could lead to identification of the disease causing variants in highly heterogeneous disorders such as HL.

scholarly journals Next-Generation Sequencing in Tumor Diagnosis and Treatment

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 962
Author(s):  
Dario de Biase ◽  
Matteo Fassan ◽  
Umberto Malapelle
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Diagnosis ◽  
Diagnosis And Treatment ◽  
Next Generation ◽  
Multiple Genes ◽  
Next Generation Sequencing Ngs ◽  
Very High ◽  
Generation Sequencing ◽  
High Depth

Next-Generation Sequencing (NGS) allows for the sequencing of multiple genes at a very high depth of coverage [...]

scholarly journals PostSV: A Post–Processing Approach for Filtering Structural Variations

2020 ◽  
Vol 14 ◽  
pp. 117793221989295 ◽  
Author(s):  
Eman Alzaid ◽  
Achraf El Allali
Keyword(s):  
State Of The Art ◽  
Post Processing ◽  
Structural Variations ◽  
Sequencing Technologies ◽  
Structural Differences ◽  
Overall Performance ◽  
Next Generation Sequencing Ngs ◽  
Low Coverage ◽  
Ngs Data ◽  
Generation Sequencing

Genomic structural variations are significant causes of genome diversity and complex diseases. With advances in sequencing technologies, many algorithms have been designed to identify structural differences using next-generation sequencing (NGS) data. Due to repetitions in the human genome and the short reads produced by NGS, the discovery of structural variants (SVs) by state-of-the-art SV callers is not always accurate. To improve performance, multiple SV callers are often used to detect variants. However, most SV callers suffer from high false-positive rates, which diminishes the overall performance, especially in low-coverage genomes. In this article, we propose a post-processing classification–based algorithm that can be used to filter structural variation predictions produced by SV callers. Novel features are defined from putative SV predictions using reads at the local regions around the breakpoints. Several classifiers are employed to classify the candidate predictions and remove false positives. We test our classifier models on simulated and real genomes and show that the proposed approach improves the performance of state-of-the-art algorithms.

scholarly journals Cone Dystrophy in Patient with HomozygousRP1L1Mutation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sachiko Kikuchi ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Said El Shamieh ◽  
Keiichiro Akeo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cone Dystrophy ◽  
Homozygous Mutation ◽  
Full Field ◽  
Clinical Evaluations ◽  
Normal Visual Acuity ◽  
Severe Reduction ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Cone Density

The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygousRP1L1mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygousRP1L1mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of thePCDH15,RPGRIP1, andGPR98genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of theRP1L1homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in theRP1L1gene can cause cone dystrophy.

scholarly journals BRCA1/2 NGS Somatic Testing in Clinical Practice: A Short Report

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1917
Author(s):  
Francesco Pepe ◽  
Pasquale Pisapia ◽  
Gianluca Russo ◽  
Mariantonia Nacchio ◽  
Pierlorenzo Pallante ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Adenosine Diphosphate ◽  
Routine Practice ◽  
Short Report ◽  
Ovarian Carcinomas ◽  
Thermo Fisher Scientific ◽  
Genetics And Genomics ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Fisher Scientific

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of all ovarian carcinomas. HGSOC harboring BRCA1/2 germline or somatic mutations are sensitive to the poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Therefore, detecting these mutations is crucial to identifying patients for PARPi-targeted treatment. In the clinical setting, next generation sequencing (NGS) has proven to be a reliable diagnostic approach BRCA1/2 molecular evaluation. Here, we review the results of our BRCA1/2 NGS analysis obtained in a year and a half of diagnostic routine practice. BRCA1/2 molecular NGS records of HGSOC patients were retrieved from our institutional archive covering the period from January 2020 to September 2021. NGS analysis was performed on the Ion S5™ System (Thermo Fisher Scientific, Waltham, MA, USA) with the Oncomine™ BRCA Research Assay panel (Thermo Fisher Scientific). Variants were classified as pathogenic or likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics by using the inspection of Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) and ClinVar (NCBI) databases. Sixty-five HGSOC patient samples were successfully analyzed. Overall, 11 (16.9%) out of 65 cases harbored a pathogenic alteration in BRCA1/2, in particular, six BRCA1 and five BRCA2 pathogenic variations. This study confirms the efficiency and high sensitivity of NGS analysis in detecting BRCA1/2 germline or somatic variations in patients with HGSOC.

scholarly journals First microsatellite markers for the European Robin (Erithacus rubecula) and their application in analysis of parentage and genetic diversity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Gwiazdowska ◽  
Oliwia Karpińska ◽  
Katarzyna Kamionka-Kanclerska ◽  
Patryk Rowiński ◽  
Hanna Panagiotopoulou ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Microsatellite Markers ◽  
Passerine Bird ◽  
Breeding Biology ◽  
European Robin ◽  
Extra Pair Paternity ◽  
The Family ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Variable Analysis

AbstractThe European Robin is a small passerine bird associated with woodlands of Eurasia and North Africa. Despite being relatively widespread and common, little is known of the species’ breeding biology and genetic diversity. We used Next Generation Sequencing (NGS) to develop and characterize microsatellite markers for the European Robin, designing three multiplex panels to amplify 14 microsatellite loci. The level of polymorphism and its value for assessing parentage and genetic structure was estimated based on 119 individuals, including seven full families and 69 unrelated individuals form Poland’s Białowieża Primaeval Forest and an additional location in Portugal. All markers appeared to be highly variable. Analysis at the family level confirmed a Mendelian manner of inheritance in the investigated loci. Genetic data also revealed evidence for extra-pair paternity in one family. The set of markers that we developed are proven to be valuable for analysis of the breeding biology and population genetics of the European Robin.

A Novel Pathogenic Variant in the CABP2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family

2019 ◽  
Vol 24 (5) ◽  
pp. 258-263 ◽  
Author(s):  
Mahbobeh Koohiyan ◽  
Mohammad Reza Noori-Daloii ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Mansoor Salehi ◽  
Hamidreza Abtahi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Variant ◽  
Pedigree Analysis ◽  
Gjb2 Gene ◽  
Genetic Linkage Analysis ◽  
Complex Process ◽  
Whole Exome ◽  
The Family ◽  
Iranian Family ◽  
Molecular Interpretation

Background and Objectives: Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family. Methods: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease. Results: WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines. Conclusions: Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.

scholarly journals Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1467
Author(s):  
Gema García-García ◽  
Alba Berzal-Serrano ◽  
Piedad García-Díaz ◽  
Rebeca Villanova-Aparisi ◽  
Sara Juárez-Rodríguez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Targeted Ngs ◽  
Syndromic Hearing Loss ◽  
Genetics And Genomics ◽  
Custom Panel ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.

scholarly journals Novel NGS Pipeline for Virus Discovery from a Wide Spectrum of Hosts and Sample Types

2020 ◽  
Author(s):  
Ilya Plyusnin ◽  
Ravi Kant ◽  
Anne J. Jääskeläinen ◽  
Tarja Sironen ◽  
Liisa Holm ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Domestic Animals ◽  
Metagenomic Data ◽  
Virus Discovery ◽  
Taxonomic Profiling ◽  
Sequencing Technologies ◽  
Living Organisms ◽  
Next Generation Sequencing Ngs ◽  
Microbiome Data ◽  
Generation Sequencing

ABSTRACTThe study of the microbiome data holds great potential for elucidating the biological and metabolic functioning of living organisms and their role in the environment. Metagenomic analyses have shown that humans, along with e.g. domestic animals, wildlife and arthropods, are colonized by an immense community of viruses. The current Coronavirus pandemic (COVID-19) heightens the need to rapidly detect previously unknown viruses in an unbiased way. The increasing availability of metagenomic data in this era of next-generation sequencing (NGS), along with increasingly affordable sequencing technologies, highlight the need for reliable and comprehensive methods to manage such data. In this article, we present a novel stand-alone pipeline called LAZYPIPE for identifying both previously known and novel viruses in host-associated or environmental samples and give examples of virus discovery based on it. LAZYPIPE is a Unix-based pipeline for automated assembling and taxonomic profiling of NGS libraries implemented as a collection of C++, Perl, and R scripts.

scholarly journals X-linked Retinoschisis Associated with Retinitis Punctata Albescens Caused by a Mutation in the RS1 Gene: A Family Study

2021 ◽  
Vol 15 (1) ◽  
pp. 201-205
Author(s):  
Francisco de Borja Domínguez-Serrano ◽  
Marina Soto-Sierra ◽  
María González-del Pozo ◽  
María José Morillo-Sánchez ◽  
Manuel Ramos-Jiménez ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Index Patient ◽  
Ophthalmological Examination ◽  
Genetic Characteristics ◽  
Corrected Visual Acuity ◽  
Retinitis Punctata Albescens ◽  
The Family ◽  
Next Generation Sequencing Ngs ◽  
Unusual Phenotype ◽  
Generation Sequencing

Purpose: To describe the clinical and genetic characteristics (mutation in RS1 gene) of a Spanish family with X-linked retinoschisis (XLRS) associated with retinitis punctata albescens (RPA). Methods: The detailed ophthalmological examination included best corrected visual acuity (BCVA), colour and autofluorescence photography, fluorescein angiography, optical coherence tomography and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system. Candidate variants considered to be disease-causing in the patient were confirmed and segregated in the family by Sanger sequencing. Results: We have studied three siblings of 54, 59 and 50 years old. Two of them presented with macular foveoschisis and a whitish mottling of the pigment epithelium in the peripheral and equatorial retina, while the other had macular atrophy. Electroretinography revealed a reduced b-wave, while a-wave remained unchanged. Mutation in RS1 (c.98G>A; p.Trp33*) was identified as the cause of the disease. Conclusion: XLRS is a genetic disease that leads to irreversible visual loss. We describe an unusual phenotype manifestation of a known mutation.

scholarly journals Beginner’s guide to next-generation sequencing

2021 ◽  
Author(s):  
Louise Aigrain
Keyword(s):  
Next Generation Sequencing ◽  
Sample Preparation ◽  
Third Generation ◽  
Next Generation ◽  
Sequencing Technologies ◽  
Long Read ◽  
Pros And Cons ◽  
The Cost ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Since the publication of the first draft of the human genome 20 years ago, several novel sequencing technologies have emerged. Whilst some drive the cost of DNA sequencing down, others address the difficult parts of the genome which remained inaccessible so far. But the next-generation sequencing (NGS) landscape is a fast-changing environment and one can easily get lost between second- and third- generation sequencers, or the pros and cons of short- versus long-read technologies. In this beginner’s guide to NGS, we will review the main NGS technologies available in 2021. We will compare sample preparation protocols and sequencing methods, highlighting the requirements and advantages of each technology.

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