scholarly journals Meeting summary: ethical aspects of whole exome and whole genome sequencing studies (WES/WGS) in rare diseases, Tel Aviv, Israel, January 2013

2013 ◽  
Vol 95 (2-3) ◽  
pp. 53-56 ◽  
Author(s):  
LUBA FARBEROV ◽  
AVITAL GILAM ◽  
OFER ISAKOV ◽  
NOAM SHOMRON
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genetic Basis ◽  
Diagnostic Tools ◽  
Whole Genome ◽  
Ethical Aspects ◽  
Genomic Technologies ◽  
Whole Exome ◽  
Sequencing Studies

SummaryA recent E-Rare workshop reviewed the ethical aspects of whole exome and whole genome-sequencing studies (WES and WGS, respectively) in rare diseases. Leveraging new genomic technologies, which output vast amounts of known and novel genetic variants, researchers are learning more about the genetic basis and mechanisms involved in rare diseases. In some cases, these findings are translated into diagnostic tools for the benefit of rare disease patients. Among the disclosed data, which can assist in treatment management, incidental findings await, bringing with them ethical concerns for the clinicians, researchers and patients.

Genetics of neuropsychiatric disease

2020 ◽  
pp. 127-140
Author(s):  
Stefania Bruno ◽  
Nayana Lahiri
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Disorders ◽  
Single Gene ◽  
Diagnostic Techniques ◽  
Genetic Influences ◽  
Whole Genome ◽  
Neuropsychiatric Disease ◽  
Genomic Technologies ◽  
Whole Exome

To better understand the intricacies of genetic influences on neuropsychiatric disease, it is important first to have a grounding in the models of human inheritance and current diagnostic techniques. This chapter covers the fundamentals of genetic disorders, giving insights into chromosomal, single-gene, and mitochondrial disorders. Moreover, it explores the changing applications of genomic technologies, such as whole exome and whole genome sequencing, through the lens of their implications for neuropsychiatry. Clinical examples are provided to give an idea of the genetic underpinnings of Alzheimer’s disease, Parkinson’s disease, and other familiar disorders.

scholarly journals Genetic Basis of Pancreas Cancer Development and Progression: Insights from Whole-Exome and Whole-Genome Sequencing

2012 ◽  
Vol 18 (16) ◽  
pp. 4257-4265 ◽  
Author(s):  
Christine A. Iacobuzio-Donahue ◽  
Victor E. Velculescu ◽  
Christopher L. Wolfgang ◽  
Ralph H. Hruban
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Basis ◽  
Pancreas Cancer ◽  
Cancer Development ◽  
Whole Genome ◽  
Whole Exome

scholarly journals Estimating sequencing error rates using families

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kelley Paskov ◽  
Jae-Yoon Jung ◽  
Brianna Chrisman ◽  
Nate T. Stockham ◽  
Peter Washington ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Exome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Error Rates ◽  
Sequencing Error ◽  
Whole Genome ◽  
Sequencing Data ◽  
Sequencing Platform ◽  
Whole Exome

Abstract Background As next-generation sequencing technologies make their way into the clinic, knowledge of their error rates is essential if they are to be used to guide patient care. However, sequencing platforms and variant-calling pipelines are continuously evolving, making it difficult to accurately quantify error rates for the particular combination of assay and software parameters used on each sample. Family data provide a unique opportunity for estimating sequencing error rates since it allows us to observe a fraction of sequencing errors as Mendelian errors in the family, which we can then use to produce genome-wide error estimates for each sample. Results We introduce a method that uses Mendelian errors in sequencing data to make highly granular per-sample estimates of precision and recall for any set of variant calls, regardless of sequencing platform or calling methodology. We validate the accuracy of our estimates using monozygotic twins, and we use a set of monozygotic quadruplets to show that our predictions closely match the consensus method. We demonstrate our method’s versatility by estimating sequencing error rates for whole genome sequencing, whole exome sequencing, and microarray datasets, and we highlight its sensitivity by quantifying performance increases between different versions of the GATK variant-calling pipeline. We then use our method to demonstrate that: 1) Sequencing error rates between samples in the same dataset can vary by over an order of magnitude. 2) Variant calling performance decreases substantially in low-complexity regions of the genome. 3) Variant calling performance in whole exome sequencing data decreases with distance from the nearest target region. 4) Variant calls from lymphoblastoid cell lines can be as accurate as those from whole blood. 5) Whole-genome sequencing can attain microarray-level precision and recall at disease-associated SNV sites. Conclusion Genotype datasets from families are powerful resources that can be used to make fine-grained estimates of sequencing error for any sequencing platform and variant-calling methodology.

scholarly journals Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

2021 ◽  
Author(s):  
Michael Abbott ◽  
Lynda McKenzie ◽  
Blanca Viridiana Guizar Moran ◽  
Sebastian Heidenreich ◽  
Rodolfo Hernández ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Genetic Testing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genomic Medicine ◽  
Future Research ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Peace Of Mind

AbstractNovel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost–benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.

scholarly journals Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yury A. Barbitoff ◽  
Dmitrii E. Polev ◽  
Andrey S. Glotov ◽  
Elena A. Serebryakova ◽  
Irina V. Shcherbakova ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequence Coverage ◽  
Coding Sequence ◽  
Whole Exome

scholarly journals Readability of informed consent forms for whole-exome and whole-genome sequencing

2017 ◽  
Vol 9 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Emilia Niemiec ◽  
Danya F. Vears ◽  
Pascal Borry ◽  
Heidi Carmen Howard
Keyword(s):  
Informed Consent ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Consent Forms ◽  
Whole Exome

scholarly journals Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Lingxia Zhang ◽  
Ke Huang ◽  
Shugang Wang ◽  
Haidong Fu ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Muscle Weakness ◽  
Growth Retardation ◽  
Gitelman Syndrome ◽  
Compound Heterozygous ◽  
Whole Genome ◽  
Whole Exome ◽  
Laboratory Test Results

Gitelman syndrome (GS, OMIM 263800) is a genetic congenital tubulopathy associated with salt loss, which is characterized by hypokalemic metabolic toxicity, hypocalciuria, and hypomagnesemia. GS, which is typically detected in adolescence or adulthood, has long been considered a benign tubular lesion; however, the disease is associated with a significant decrease in the quality of life. In this study, we assessed the genotype–phenotype correlations based on the medical histories, clinical symptoms, laboratory test results, and whole-exome sequencing profiles from pediatric patients with GS. Between January 2014 and December 2020, all 31 consecutively enrolled patients complained of fatigue, salt craving, and muscle weakness. Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in SLC12A3 were detected in 4, 24, and 3 patients, respectively. GS patients often present with muscle weakness and fatigue caused by hypokalemia and hypomagnesemia. Therefore, early diagnosis of GS is important in young children to reduce the possibility of growth retardation, tetany, and seizures. Next-generation sequencing such as whole-exome or whole-genome sequencing provides a practical tool for the early diagnosis and improvement of GS prognosis. Further whole-genome sequencing is expected to reveal more variants in SLC123A among GS patients with single heterozygous mutations.

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