Types Of Genetic Information Research Articles

Influence of Genetic Information on Neonatologists' Decisions: A Psychological Experiment.

Genetic testing is expanding among ill neonates, yet the influence of genetic results on medical decision-making is not clear. With this study, we sought to determine how different types of genetic information with uncertain implications for prognosis influence clinicians' decisions to recommend intensive versus palliative care. We conducted a national study of neonatologists using a split sample experimental design. The questionnaire contained 4 clinical vignettes. Participants were randomly assigned to see one of 2 versions that varied only regarding whether they included the following genetic findings: (1) a variant of uncertain significance; (2) a genetic diagnosis that affects neurodevelopment but not acute survival; (3) a genetic versus nongenetic etiology of equally severe pathology; (4) a pending genetic testing result. Physicians answered questions about recommendations they would make for the patient described in each vignette. Vignette versions that included a variant of uncertain significance, a diagnosis foreshadowing neurodevelopmental impairment, or a genetic etiology of disease were all associated with an increased likelihood of recommending palliative rather than intensive care. A pending genetic test result did not have a significant effect on care recommendations. Findings from this study of hypothetical cases suggest neonatologists apply uncertain genetic findings or those that herald neurodevelopmental disability in problematic ways. As genetic testing expands, understanding how it is used in decision-making and educating clinicians regarding appropriate use are paramount.

Evaluating parents\u2019 decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study: a randomized controlled trial protocol

BackgroundUsing next-generation sequencing (NGS) in newborn screening (NBS) could expand the number of genetic conditions detected pre-symptomatically, simultaneously challenging current precedents, raising ethical concerns, and extending the role of parental decision-making in NBS. The NC NEXUS (Newborn Exome Sequencing for Universal Screening) study seeks to assess the technical possibilities and limitations of NGS-NBS, devise and evaluate a framework to convey various types of genetic information, and develop best practices for incorporating NGS-NBS into clinical care. The study is enrolling both a healthy cohort and a cohort diagnosed with known disorders identified through recent routine NBS. It uses a novel age-based metric to categorize a priori the large amount of data generated by NGS-NBS and interactive online decision aids to guide parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS, and, for parents randomized to have the option of requesting them, additional findings (diagnosed and healthy cohorts). Secondary outcomes assess parents’ reactions to the study and to decision-making.Methods/designParticipants are parents and children in a well-child cohort recruited from a prenatal clinic and a diagnosed cohort recruited from pediatric clinics that treat children with disorders diagnosed through traditional NBS (goal of 200 children in each cohort). In phase 1, all parent participants use an online decision aid to decide whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In phase 2, parents who consent to NGS-NBS are randomized to a decision arm or control arm (2:1 allocation) and learn their child’s NGS-NBS results, which include conditions from standard (non-NGS) NBS plus other highly actionable childhood-onset conditions. Parents in the decision arm use a second decision aid to make decisions about additional results from their child’s sequencing. In phase 3, decision arm participants learn additional results they have requested. Online questionnaires are administered at up to five time points.DiscussionNC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research.Trial registrationclinicaltrials.gov, NCT02826694. Registered on 11 July, 2016.

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers.

Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into recipient cells. In this review, we focus on the dysregulated H. pylori- and EBV-associated miRNAs while trying to unveil possible causal mechanisms. Moreover, we discuss the role of exosomes as vehicles for miRNA delivery in H. pylori- and EBV-related carcinogenesis.

Attitudes of non‐African American focus group participants toward return of results from exome and whole genome sequencing

Exome sequencing and whole genome sequencing (ES/WGS) present individuals with the opportunity to benefit from a broad scope of genetic results of clinical and personal utility. Yet, it is unclear which genetic results people want to receive (i.e., what type of genetic information they want to learn about themselves) or conversely not receive, and how they want to receive or manage results over time. Very little is known about whether and how attitudes toward receiving individual results from ES/WGS vary among racial/ethnic populations. We conducted 13 focus groups with a racially and ethnically diverse parent population (n = 76) to investigate attitudes toward return of individual results from WGS. We report on our findings for non-African American (non-AA) participants. Non-AA participants were primarily interested in genetic results on which they could act or "do something about." They defined "actionability" broadly to include individual medical treatment and disease prevention. The ability to plan for the future was both a motivation for and an expected benefit of receiving results. Their concerns focused on the meaning of results, specifically the potential inaccuracy and uncertainty of results. Non-AA participants expected healthcare providers to be involved in results management by helping them interpret results in the context of their own health and by providing counseling support. We compare and contrast these themes with those we previously reported from our analysis of African American (AA) perspectives to highlight the importance of varying preferences for results, characterize the central role of temporal orientation in framing expectations about the possibility of receiving ES/WGS results, and identify potential avenues by which genomic healthcare disparities may be inadvertently perpetuated.

Haplotype‐Based Regression Analysis and Inference of Case–Control Studies with Unphased Genotypes and Measurement Errors in Environmental Exposures

It is widely believed that risks of many complex diseases are determined by genetic susceptibilities, environmental exposures, and their interaction. Chatterjee and Carroll (2005, Biometrika 92, 399-418) developed an efficient retrospective maximum-likelihood method for analysis of case-control studies that exploits an assumption of gene-environment independence and leaves the distribution of the environmental covariates to be completely nonparametric. Spinka, Carroll, and Chatterjee (2005, Genetic Epidemiology 29, 108-127) extended this approach to studies where certain types of genetic information, such as haplotype phases, may be missing on some subjects. We further extend this approach to situations when some of the environmental exposures are measured with error. Using a polychotomous logistic regression model, we allow disease status to have K+ 1 levels. We propose use of a pseudolikelihood and a related EM algorithm for parameter estimation. We prove consistency and derive the resulting asymptotic covariance matrix of parameter estimates when the variance of the measurement error is known and when it is estimated using replications. Inferences with measurement error corrections are complicated by the fact that the Wald test often behaves poorly in the presence of large amounts of measurement error. The likelihood-ratio (LR) techniques are known to be a good alternative. However, the LR tests are not technically correct in this setting because the likelihood function is based on an incorrect model, i.e., a prospective model in a retrospective sampling scheme. We corrected standard asymptotic results to account for the fact that the LR test is based on a likelihood-type function. The performance of the proposed method is illustrated using simulation studies emphasizing the case when genetic information is in the form of haplotypes and missing data arises from haplotype-phase ambiguity. An application of our method is illustrated using a population-based case-control study of the association between calcium intake and the risk of colorectal adenoma.

‘Genetic exceptionalism’ and precautionary politics: regulating for uncertainty in Britain’s genetics and insurance policy process

This article critically investigates the role ‘genetic exceptionalism’ and precautionary politics played in the British policy process that resulted in a moratorium on insurers’ rights to use certain types of genetic information in underwriting decisions. The article evaluates the recommendations of key advisory committees and regulatory bodies as they tried to construct fair and pragmatic policies in a context of great social, commercial and technological uncertainty. It suggests that in trying to meet the needs of political expediency — responding to broader concern that access to life assurance might be significantly restricted in an age of increased genetic knowledge — policymakers and regulators marginalised evidence that negated fears of an emerging genetic underclass by adopting a precautionary approach to genetic risk and exclusion.

The progressing clinical utility of DNA microarrays.

The progressing clinical utility of DNA microarrays.

Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or protein: further evidence from overlapping genes

Many eukaryotic genes are split into exons and introns, the latter being removed post-transcriptionally so that only exon sequences appear in cytoplasmic RNAs. Since introns appear in both protein-encoding RNAs and non-protein-coding RNAs, they interrupt genetic information per se, not just protein-encoding information. A DNA sequence has the potential to carry more than one type of genetic information, but different types may conflict. Thus, it has been proposed that introns arose because sequences were unable to contain concomitantly complete information for the encoding both of stem-loops and of cytoplasmic products (protein and/or RNA). Stem-loop potential is held to be selectively advantageous since it promotes the recombination-dependent correction of genetic errors. Stem-loop potential, the best local measure of which is base order-dependent stem-loop potential, tends to be less in exons than in introns. This is particularly evident in genes evolving rapidly under positive Darwinian selection, where the protein-encoding function is dominant. Evidence is now presented that the rare regions where genes overlap also impose excessive encoding demands so that the concomitant coding of base order-dependent stem-loop potential is decreased. Our results are consistent with the hypothesis that sequences with high stem-loop potential arose in the early ‘RNA world’. Ancestors of modern genes would have entered this world when sequences (exons) encoding cytoplasmic products, were interspersed with sequences (introns) encoding selectively advantageous stem-loops. Purine-loading pressure would also have favoured intron formation.