Using next-generation sequencing to isolate mutant genes from forward genetic screens

2014 ◽  
Vol 15 (10) ◽  
pp. 662-676 ◽  
Author(s):  
Korbinian Schneeberger
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Genetic Screens ◽  
Forward Genetic Screens ◽  
Mutant Genes ◽  
Generation Sequencing

Abstract 050: Mutational Spectrum in a Cohort of Chinese Sporadic Dilated Cardiomyopathy by Next-generation Sequencing

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Lei Xu ◽  
Aijun Sun ◽  
Yunzeng Zou ◽  
Kai Hu ◽  
Zheng Fan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Dilated Cardiomyopathy ◽  
Genetic Basis ◽  
Next Generation ◽  
Genetic Studies ◽  
1000 Genomes ◽  
Mutational Screening ◽  
The Mean ◽  
Mutant Genes ◽  
Generation Sequencing

Rationale: Dilated cardiomyopathy (DCM) is a leading cause of heart failure and have a genetic basis in 20-30% of cases. Genetic studies in familial DCM have found mutations identified in more than 30 genes. However, the genetics of sporadic DCM is still unknown. Objective: To provide new insights into the pathophysiology of sporadic DCM, a mutational screening on 30 DCM-causing genes in a cohort was performed. Methods and Results: Patients diagnosed with idiopathic DCM were recruited into the study and underwent clinical evaluation. Genomic DNA was isolated from the peripheral blood and then 30 genes ( ACTC, DES, SGCD, MYH7, TNNT2, TPM1, TTN, VCL, MYBPC3, CSRP3, ACTN2, PLN, LDB3, MYH6, ABCC9, TNNC1, TCAP, TNNI3, EYA4, TMPO, PSEN1/2, CRYAB, PDLIM3, MYPN, LAMA4, ILK, ANKRD1, RBM20, LMNA , and SCN5A ) of every sample were detected by next-generation sequencing. All called variants were compared against National Center for Biotechnology Information SNP Database build 137 and the March 2012 release of the 1000 Genomes project. All variants identified in the cohort were compared in ethnic-matched controls consisting of 197 adult Chinese from the 1000 Genomes. The pathogenicity of the variants absent from controls were evaluated by SIFT software. Sixty-six adult Chinese unrelated DCM patients were tested for up to 30 genes causing familial DCM. The mean age was 49.14±15.97 years. Every patient was detected nonsynonymous variants, and the total 87 variants were composed of 39 novel and 48 known. Among the whole 87 variants, 34 satisfied the criteria (1) absent from ethnic-matched controls and (2) altering evolutionary conservation of amino acid verified by SIFT analysis, which were considered pathogenic mutations, identified in 30 patients accounting for 45.45% of the cohort. The 2 most frequent genes involved in mutation positive patients were SCN5A (12.12%) and MYH7 (10.61%). Conclusions: Mutant genes found in familial DCM were also common in sporadic DCM, and the discovery of novel mutations spanned the spectrum of DCM genetics, implicating that genetic etiologies play an important role in pathogenesis of sporadic DCM.

Labordiagnostik bei gastrointestinalen Tumoren

2020 ◽  
Vol 11 (05) ◽  
pp. 232-238
Author(s):  
Marcus Kleber
Keyword(s):  
Next Generation Sequencing ◽  
Kolorektales Karzinom ◽  
Next Generation ◽  
Generation Sequencing

ZUSAMMENFASSUNGDas kolorektale Karzinom (KRK) ist einer der häufigsten malignen Tumoren in Deutschland. Einer frühzeitigen Diagnostik kommt große Bedeutung zu. Goldstandard ist hier die Koloskopie. Die aktuelle S3-Leitlinie Kolorektales Karzinom empfiehlt zum KRK-Screening den fäkalen okkulten Bluttest. Für das Monitoring von Patienten vor und nach Tumorresektion werden die Messung des Carcinoembryonalen Antigens (CEA) und der Mikrosatellitenstabilität empfohlen. Für die Auswahl der korrekten Chemotherapie scheint derzeit eine Überprüfung des Mutationsstatus, mindestens des KRAS-Gens und des BRAF-Gens, sinnvoll zu sein. Eine Reihe an neuartigen Tumormarkern befindet sich momentan in der Entwicklung, hat jedoch noch nicht die Reife für eine mögliche Anwendung in der Routinediagnostik erreicht. Den schnellsten Weg in die breite Anwendung können Next-Generation-Sequencing-basierte genetische Tests finden.

Next-Generation Sequencing of Sporadic Schwannomas Reveals Critical Importance of NF2 Alteration

2016 ◽  
Vol 77 (S 01) ◽  
Author(s):  
Pankaj Agarwalla ◽  
Wenya Bi ◽  
William Gibson ◽  
Shakti Ramkissoon ◽  
Steven Schumacher ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Critical Importance ◽  
Generation Sequencing
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