scholarly journals Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

2017 ◽  
Vol 20 (4) ◽  
pp. 435-443 ◽  
Author(s):  
Anath C Lionel ◽  
Gregory Costain ◽  
Nasim Monfared ◽  
Susan Walker ◽  
Miriam S Reuter ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Test ◽  
Diagnostic Yield ◽  
Gene Sequencing ◽  
Whole Genome ◽  
Targeted Gene Sequencing

scholarly journals Low-level rifampin resistance and rpoB mutations in Mycobacterium tuberculosis: An analysis of whole-genome sequencing and drug susceptibility test data in New York

2020 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Donna Kohlerschmidt ◽  
Pascal Lapierre ◽  
Herns A. Modestil ◽  
...  
Keyword(s):  
New York ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Critical Concentration ◽  
Gene Sequencing ◽  
Drug Susceptibility ◽  
Whole Genome ◽  
Drug Resistant ◽  
Low Level ◽  
Indicator Tube

Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.

scholarly journals An Atypical Outbreak of Food-Borne Botulism Due to Clostridium botulinum Types B and E from Ham

2014 ◽  
Vol 53 (2) ◽  
pp. 722-726 ◽  
Author(s):  
Christelle Mazuet ◽  
Jean Sautereau ◽  
Christine Legeay ◽  
Christiane Bouchier ◽  
Philippe Bouvet ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clostridium Botulinum ◽  
Gene Sequencing ◽  
Whole Genome ◽  
Content Type ◽  
Food Borne ◽  
Botulinum Neurotoxins

An outbreak of human botulism was due to consumption of ham containing botulinum neurotoxins B and E. AClostridium botulinumtype E strain isolated from ham was assigned to a new subtype (E12) based onbont/Egene sequencing and belongs to a new multilocus sequence subtype, as analyzed by whole-genome sequencing.

Increased Diagnostic Yield of Spastic Paraplegia with or Without Cerebellar Ataxia Through Whole-Genome Sequencing

2019 ◽  
Vol 18 (4) ◽  
pp. 781-790 ◽  
Author(s):  
Aryun Kim ◽  
Kishore R. Kumar ◽  
Ryan L. Davis ◽  
Amali C. Mallawaarachchi ◽  
Velimir Gayevskiy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Cerebellar Ataxia ◽  
Genome Sequencing ◽  
Diagnostic Yield ◽  
Whole Genome ◽  
Spastic Paraplegia

The Efficacy of Whole Genome Sequencing and RNA-Seq in the Diagnosis of Whole Exome Sequencing Negative Patients with Complex Neurological Phenotypes

2021 ◽  
Author(s):  
Bianca Blake ◽  
Lauren I. Brady ◽  
Nicholas A. Rouse ◽  
Peter Nagy ◽  
Mark A. Tarnopolsky
Keyword(s):  
Whole Genome Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genome Sequencing ◽  
Diagnostic Yield ◽  
Whole Genome ◽  
Rna Seq ◽  
Complete Coverage ◽  
Whole Exome ◽  
Chromosome Microarray

AbstractWhole-genome sequencing (WGS) is being increasingly utilized for the diagnosis of neurological disease by sequencing both the exome and the remaining 98 to 99% of the genetic code. In addition to more complete coverage, WGS can detect structural variants (SVs) and intronic variants (SNVs) that cannot be identified by whole exome sequencing (WES) or chromosome microarray (CMA). Other multi-omics tools, such as RNA sequencing (RNA-Seq), can be used in conjunction with WGS to functionally validate certain variants by detecting changes in gene expression and splicing. The objective of this retrospective study was to measure the diagnostic yield of duo/trio-based WGS and RNA-Seq in a cohort of 22 patients (20 families) with pediatric onset neurological phenotypes and negative or inconclusive WES results in lieu of reanalysis. WGS with RNA-Seq resulted in a definite diagnosis of an additional 25% of cases. Sixty percent of these solved cases arose from the identification of variants that were missed by WES. Variants that could not be unequivocally proven to be causative of the patients' condition were identified in an additional 5% of cases.

scholarly journals Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease

Ophthalmology ◽  
2016 ◽  
Vol 123 (5) ◽  
pp. 1143-1150 ◽  
Author(s):  
Jamie M. Ellingford ◽  
Stephanie Barton ◽  
Sanjeev Bhaskar ◽  
Simon G. Williams ◽  
Panagiotis I. Sergouniotis ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Diagnostic Yield ◽  
Diagnostic Testing ◽  
Retinal Disease ◽  
Molecular Diagnostic ◽  
Whole Genome ◽  
Inherited Retinal Disease

First tier rapid whole genome sequencing increases diagnostic yield and changes management in children admitted in intensive care

2021 ◽  
Vol 132 ◽  
pp. S102
Author(s):  
Guylaine D’Amours ◽  
Julie Gauthier ◽  
Fadi Hamdan ◽  
Audrey Meleu ◽  
Catalina Maftei ◽  
...  
Keyword(s):  
Intensive Care ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Diagnostic Yield ◽  
Whole Genome

scholarly journals Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy

2020 ◽  
Vol 13 (5) ◽  
pp. 504-514
Author(s):  
Zuhair N. Al-Hassnan ◽  
Abdulrahman Almesned ◽  
Sahar Tulbah ◽  
Ali Alakhfash ◽  
Faten Alhadeq ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genome Sequencing ◽  
Founder Mutation ◽  
Genetic Test ◽  
Whole Genome ◽  
Childhood Onset ◽  
Whole Exome ◽  
The Impact

Background: Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale. Methods: To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted. Cases with childhood-onset cardiomyopathy were consecutively recruited. Based on the likelihood of founder mutation and on the clinical diagnosis, genetic test was categorized to either (1) targeted genetic test with targeted mutation test, single-gene test, or multigene panel for Noonan syndrome, or (2) untargeted genetic test with whole-exome sequencing or whole-genome sequencing. Several bioinformatics tools were used to filter the variants. Results: Two-hundred five unrelated probands with various forms of cardiomyopathy were evaluated. The median age of presentation was 10 months. In 30.2% (n=62), targeted genetic test had a yield of 82.7% compared with 33.6% for whole-exome sequencing/whole-genome sequencing (n=143) giving an overall yield of 53.7%. Strikingly, 96.4% of the variants were homozygous, 9% of which were found in 4 dominant genes. Homozygous variants were also detected in 7 novel candidates ( ACACB, AASDH, CASZ1, FLII, RHBDF1, RPL3L, ULK1 ). Conclusions: Our work demonstrates the impact of consanguinity on the genetics of childhood-onset cardiomyopathy, the value of adopting a categorized population-sensitive genetic approach, and the opportunity of uncovering novel genes. Our data suggest that if a founder mutation is not suspected, adopting whole-exome sequencing/whole-genome sequencing as a first-line test should be considered.

scholarly journals Accurate Whole Genome Sequencing as the Ultimate Genetic Test

2015 ◽  
Vol 61 (1) ◽  
pp. 305-306 ◽  
Author(s):  
Radoje Drmanac ◽  
Brock A Peters ◽  
George M Church ◽  
Clifford A Reid ◽  
Xun Xu
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Test ◽  
Whole Genome
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