Next Generation Sequencing Based Clinical Molecular Diagnosis of Human Genetic Disorders

2017 ◽  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Genetic Disorders ◽  
Next Generation ◽  
Human Genetic Disorders ◽  
Generation Sequencing

scholarly journals Challenges in the diagnosis and discovery of rare genetic disorders using contemporary sequencing technologies

2020 ◽  
Vol 19 (4) ◽  
pp. 243-258 ◽  
Author(s):  
Eleanor G Seaby ◽  
Sarah Ennis
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Genetic Disorders ◽  
Next Generation Sequencing Data ◽  
Disease Genes ◽  
Incomplete Penetrance ◽  
Next Generation ◽  
Sequencing Data ◽  
New Gene ◽  
Generation Sequencing

Abstract Next generation sequencing (NGS) has revolutionised rare disease diagnostics. Concomitant with advancing technologies has been a rise in the number of new gene disorders discovered and diagnoses made for patients and their families. However, despite the trend towards whole exome and whole genome sequencing, diagnostic rates remain suboptimal. On average, only ~30% of patients receive a molecular diagnosis. National sequencing projects launched in the last 5 years are integrating clinical diagnostic testing with research avenues to widen the spectrum of known genetic disorders. Consequently, efforts to diagnose genetic disorders in a clinical setting are now often shared with efforts to prioritise candidate variants for the detection of new disease genes. Herein we discuss some of the biggest obstacles precluding molecular diagnosis and discovery of new gene disorders. We consider bioinformatic and analytical challenges faced when interpreting next generation sequencing data and showcase some of the newest tools available to mitigate these issues. We consider how incomplete penetrance, non-coding variation and structural variants are likely to impact diagnostic rates, and we further discuss methods for uplifting novel gene discovery by adopting a gene-to-patient-based approach.

scholarly journals Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Majida Charif ◽  
Céline Bris ◽  
David Goudenège ◽  
Valérie Desquiret-Dumas ◽  
Estelle Colin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinal Ganglion Cells ◽  
Molecular Diagnosis ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Genetic Disorders ◽  
Retinal Ganglion ◽  
Next Generation ◽  
Pathogenic Variants ◽  
Generation Sequencing

Advances in next-generation sequencing (NGS) facilitate the diagnosis of genetic disorders. To evaluate its use for the molecular diagnosis of inherited optic neuropathy (ION), a blinding disease caused by the degeneration of retinal ganglion cells, we performed genetic analysis using targeted NGS of 22 already known and candidate genes in a cohort of 1,102 affected individuals. The panel design, library preparation, and sequencing reactions were performed using the Ion AmpliSeq technology. Pathogenic variants were detected in 16 genes in 245 patients (22%), including 186 (17%) and 59 (5%) dominant and recessive cases, respectively. Results confirmed that OPA1 variants are responsible for the majority of dominant IONs, whereas ACO2 and WFS1 variants are also frequently involved in both dominant and recessive forms of ION. All pathogenic variants were found in genes encoding proteins involved in the mitochondrial function, highlighting the importance of mitochondria in the survival of retinal ganglion cells.

scholarly journals A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement

2015 ◽  
Vol 53 (2) ◽  
pp. 98-110 ◽  
Author(s):  
Megana K Prasad ◽  
Véronique Geoffroy ◽  
Serge Vicaire ◽  
Bernard Jost ◽  
Michael Dumas ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Genetic Disorders ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals Next-Generation Sequencing of Lung Cancer EGFR Exons 18-21 Allows Effective Molecular Diagnosis of Small Routine Samples (Cytology and Biopsy)

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83607 ◽  
Author(s):  
Dario de Biase ◽  
Michela Visani ◽  
Umberto Malapelle ◽  
Francesca Simonato ◽  
Valentina Cesari ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Next Generation ◽  
Generation Sequencing
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