scholarly journals Next-generation sequencing for identifying new genes in rare genetic diseases: many challenges and a pinch of luck

2013 ◽  
Vol 14 (7) ◽  
pp. 309 ◽  
Author(s):  
Amélie Bonnefond ◽  
Philippe Froguel
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Diseases ◽  
Next Generation ◽  
New Genes ◽  
Rare Genetic Diseases ◽  
Generation Sequencing

Influence of Next-Generation Sequencing on Advancements in the Diagnosis of Major Psychiatric Diseases - A Review

2020 ◽  
Author(s):  
Maheen Nisar
Keyword(s):  
Next Generation Sequencing ◽  
Mental Disorders ◽  
Attention Deficit Disorder ◽  
Autism Spectrum ◽  
Next Generation ◽  
Single Nucleotide Variants ◽  
New Genes ◽  
Depth Analysis ◽  
Pubmed Search ◽  
Generation Sequencing

Rapid progress is being made in the development of next-generation sequencing (NGS) technologies, allowing repeated findings of new genes and a more in-depth analysis of genetic polymorphisms behind the pathogenesis of a disease. In a field such as psychiatry, characteristic of vague and highly variable somatic manifestations, these technologies have brought great advances towards diagnosing various psychiatric and mental disorders, identifying high-risk individuals and towards more effective corresponding treatment. Psychiatry has the difficult task of diagnosing and treating mental disorders without being able to invariably and definitively establish the properties of its illness. This calls for diagnostic technologies that go beyond the traditional ways of gene manipulation to more advanced methods mainly focusing on new gene polymorphism discoveries, one of them being NGS. This enables the identification of hundreds of common and rare genetic variations contributing to behavioral and psychological conditions. Clinical NGS has been useful to detect copy number and single nucleotide variants and to identify structural rearrangements that have been challenging for standard bioinformatics algorithms. The main objective of this article is to review the recent applications of NGS in the diagnosis of major psychiatric disorders, and hence gauge the extent of its impact in the field. A comprehensive PubMed search was conducted and papers published from 2013-2018 were included, using the keywords, “schizophrenia” or “bipolar disorder” or “depressive disorder” or “attention deficit disorder” or “autism spectrum disorder” and “next-generation sequencing”

scholarly journals CBX2-dependent transcriptional landscape: implications for human sex development and its defects

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Patrick Sproll ◽  
Wassim Eid ◽  
Anna Biason-Lauber
Keyword(s):  
Next Generation Sequencing ◽  
Rna Sequencing ◽  
Current Knowledge ◽  
Next Generation ◽  
Steroidogenic Factor 1 ◽  
Sex Development ◽  
New Genes ◽  
Differences Of Sex Development ◽  
Generation Sequencing ◽  
Transcriptional Landscape

Abstract Sex development, a complex and indispensable process in all vertebrates, has still not been completely elucidated, although new genes involved in sex development are constantly being discovered and characterized. Chromobox Homolog 2 (CBX2) is one of these new additions and has been identified through a 46,XY girl with double heterozygous variants on CBX2.1, causing Differences of Sex Development (DSD). The mutated CBX2.1 failed to adequately regulate downstream targets important for sex development in humans, specifically steroidogenic factor 1 (NR5A1/SF1). To better place CBX2.1 in the human sex developmental cascade, we performed siRNA and CBX2.1 overexpression experiments and created a complete CRISPR/Cas9-CBX2 knockout in Sertoli-like cells. Furthermore, we deployed Next Generation Sequencing techniques, RNA-Sequencing and DamID-Sequencing, to identify new potential CBX2.1 downstream genes. The combination of these two next generation techniques enabled us to identify genes that are both bound and regulated by CBX2.1. This allowed us not only to expand our current knowledge about the influence of CBX2.1 in human sex development, but also to advance our insight in the mechanisms governing one of the most important decisions during embryonal development, the commitment to either female or male gonads.

Detection of mosaic mutations by next generation sequencing in genetic diseases with any mode of inheritance

Mitochondrion ◽  
2015 ◽  
Vol 24 ◽  
pp. S18
Author(s):  
Lan Qin ◽  
Xia Tian ◽  
Hui Yu ◽  
Cavatina Truong ◽  
Nancy Braverman ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Diseases ◽  
Next Generation ◽  
Generation Sequencing ◽  
Mode Of Inheritance

Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes

2014 ◽  
Vol 67 (12) ◽  
pp. 1099-1103 ◽  
Author(s):  
Irene Madrigal ◽  
Maria Isabel Alvarez-Mora ◽  
Olof Karlberg ◽  
Laia Rodríguez-Revenga ◽  
Dei M Elurbe ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Next Generation Sequencing ◽  
Genetic Diseases ◽  
Genetic Defect ◽  
Disease Diagnosis ◽  
Underlying Disease ◽  
Next Generation ◽  
Genetic Syndromes ◽  
Biomedical Diagnosis ◽  
Generation Sequencing

AimsThe causes of intellectual disability, which affects 1%–3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases.MethodsWhole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes.ResultsWe present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose.ConclusionsThe accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.

scholarly journals Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives

2021 ◽  
Author(s):  
Emil E. Vorsteveld ◽  
Alexander Hoischen ◽  
Caspar I. van der Made
Keyword(s):  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Primary Immunodeficiencies ◽  
Next Generation ◽  
Inborn Errors ◽  
New Genes ◽  
Whole Exome ◽  
Generation Sequencing

AbstractPrimary immunodeficiencies comprise a group of inborn errors of immunity that display significant clinical and genetic heterogeneity. Next-generation sequencing techniques and predominantly whole exome sequencing have revolutionized the understanding of the genetic and molecular basis of genetic diseases, thereby also leading to a sharp increase in the discovery of new genes associated with primary immunodeficiencies. In this review, we discuss the current diagnostic yield of this generic diagnostic approach by evaluating the studies that have employed next-generation sequencing techniques in cohorts of patients with primary immunodeficiencies. The average diagnostic yield for primary immunodeficiencies is determined to be 29% (range 10–79%) and 38% specifically for whole-exome sequencing (range 15–70%). The significant variation between studies is mainly the result of differences in clinical characteristics of the studied cohorts but is also influenced by varying sequencing approaches and (in silico) gene panel selection. We further discuss other factors contributing to the relatively low yield, including the inherent limitations of whole-exome sequencing, challenges in the interpretation of novel candidate genetic variants, and promises of exploring the non-coding part of the genome. We propose strategies to improve the diagnostic yield leading the way towards expanded personalized treatment in PIDs.

Sign in / Sign up

Export Citation Format

Share Document