scholarly journals Raising Genomic Citizens: Adolescents and the Return of Secondary Genomic Findings

2016 ◽  
Vol 44 (2) ◽  
pp. 292-308 ◽  
Author(s):  
Maya Sabatello ◽  
Paul S. Appelbaum
Keyword(s):  
Exome Sequencing ◽  
Policy Development ◽  
Incidental Findings ◽  
Pediatric Research ◽  
Genomic Research ◽  
Whole Genome ◽  
Research With Children ◽  
Intense Debate

Whole genome and exome sequencing (WGS/WES) techniques raise hope for a new scale of diagnosis, prevention, and prediction of genetic conditions, and improved care for children. For these hopes to materialize, extensive genomic research with children will be needed. However, the use of WGS/WES in pediatric research settings raises considerable challenges for families, researchers, and policy development. In particular, the possibility that these techniques will generate genetic findings unrelated to the primary goal of sequencing has stirred intense debate about whether, which, how, and when these secondary or incidental findings (SFs) should be returned to parents and minors. The debate is even more pronounced when the subjects are adolescents, for whom decisions about return of SFs may have particular implications. In this paper, we consider the rise of “genomic citizenship” and the main challenges that arise for these stakeholders: adolescents' involvement in decisions relating to return of genomic SFs, the types of SFs that should be offered, privacy protections, and communication between researchers and adolescents about SFs. We argue that adolescents' involvement in genomic SF-related decisions acknowledges their status as valuable stakeholders without detracting from broader familial interests, and promotes more informed genomic citizens.

scholarly journals Frequency and management of medically actionable incidental findings from genome and exome sequencing data; A systematic review

2021 ◽  
Author(s):  
Amal Elfatih ◽  
Idris Mohammed ◽  
Doua Abdelrahman ◽  
Borbala Mifsud
Keyword(s):  
Exome Sequencing ◽  
Incidental Findings ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Sequencing Data ◽  
Sequencing Technologies ◽  
Pathogenic Variants ◽  
Sequencing Studies ◽  
Different Populations ◽  
Genetics And Genomics

The application of whole genome/exome sequencing technologies in clinical genetics and research has resulted in the discovery of incidental findings unrelated to the primary purpose of genetic testing. The American College of Medical Genetics and Genomics published guidelines for reporting pathogenic and likely pathogenic variants that are deemed to be medically actionable, which allowed us to learn about the epidemiology of incidental findings in different populations. However, consensus guidelines for variant reporting and classification are still lacking. We conducted a systematic literature review of incidental findings in whole genome/exome sequencing studies to obtain a comprehensive understanding of variable reporting and classification methods for variants that are deemed to be medically actionable across different populations. The review highlights the elements that demand further consideration or adjustment.

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.

Ethical challenges of whole genome sequencing in translational research and answers by the EURAT-project

2015 ◽  
Vol 38 (4) ◽  
Author(s):  
Eva C. Winkler ◽  
Christoph Schickhardt
Keyword(s):  
Translational Research ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Incidental Findings ◽  
Whole Genome ◽  
Ethical Challenges ◽  
Research Subjects ◽  
Translation Research ◽  
Legal Questions ◽  
Legal Challenges

Abstract:The use of whole genome sequencing in translational research not only holds promise for finding new targeted therapies but also raises several ethical and legal questions. The four main ethical and legal challenges are as follows: (1) the handling of additional or incidental findings stemming from whole genome sequencing in research contexts; (2) the compatibility and balancing of data protection and research that is based on broad data sharing; (3) the responsibility of researchers, particularly of non-physician researchers, working in the field of genome sequencing; and (4) the process of informing and asking patients or research subjects for informed consent to the sequencing of their genome. In this paper, first, these four challenges are illustrated and, second, concrete solutions are proposed, as elaborated by the interdisciplinary Heidelberg EURAT project group, as guidelines for the use of genome sequencing in translation research and therapy in Heidelberg.

scholarly journals Ethical Considerations for the Return of Incidental Findings in Ophthalmic Genomic Research

2016 ◽  
Vol 5 (1) ◽  
pp. 3 ◽  
Author(s):  
Emmanuelle Souzeau ◽  
Kathryn P. Burdon ◽  
David A. Mackey ◽  
Alex W. Hewitt ◽  
Ravi Savarirayan ◽  
...  
Keyword(s):  
Incidental Findings ◽  
Genomic Research ◽  
Ethical Considerations

scholarly journals Challenges of using next generation sequencing in newborn screening

2015 ◽  
Vol 97 ◽  
Author(s):  
EYAL REINSTEIN
Keyword(s):  
Newborn Screening ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Ethical Issues ◽  
Whole Genome ◽  
Short Article ◽  
Public Health Programs ◽  
Whole Exome ◽  
Metabolic Conditions ◽  
Widespread Dissemination

SummaryWhole-genome and whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. The term newborn screening refers to public health programs designed to screen newborns for various treatable metabolic conditions, by measuring levels of circulating blood metabolites. The availability and significant decrease in sequencing costs has raised the question of whether metabolic newborn screening should be replaced by whole-genome or whole-exome sequencing. While newborn genome sequencing can potentially increase the number of disorders identified by newborn screening, the generalization of its practice raises a number of important ethical issues. This short article argues that there are medical, psychological, ethical and economic reasons why widespread dissemination of newborn screening is still premature.

scholarly journals The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health

2021 ◽  
Vol 9 ◽  
Author(s):  
Audrey C. Woerner ◽  
Renata C. Gallagher ◽  
Jerry Vockley ◽  
Aashish N. Adhikari
Keyword(s):  
Newborn Screening ◽  
Exome Sequencing ◽  
Genetic Disorders ◽  
Population Based ◽  
Lessons Learned ◽  
Screening Tests ◽  
Whole Genome ◽  
Whole Exome ◽  
Challenges And Opportunities ◽  
History Of

Newborn screening (NBS) is a population-based program with a goal of reducing the burden of disease for conditions with significant clinical impact on neonates. Screening tests were originally developed and implemented one at a time, but newer methods have allowed the use of multiplex technologies to expand additions more rapidly to standard panels. Recent improvements in next-generation sequencing are also evolving rapidly from first focusing on individual genes, then panels, and finally all genes as encompassed by whole exome and genome sequencing. The intersection of these two technologies brings the revolutionary possibility of identifying all genetic disorders in newborns, allowing implementation of therapies at the optimum time regardless of symptoms. This article reviews the history of newborn screening and early studies examining the use of whole genome and exome sequencing as a screening tool. Lessons learned from these studies are discussed, along with technical, ethical, and societal challenges to broad implementation.

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