Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium.

Purpose: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders.

Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial.

Background: Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey.

Methods: The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES.

Actionability of commercial laboratory sequencing panels for newborn screening and the importance of transparency for parental decision-making.

Background: Newborn screening aims to identify individual patients who could benefit from early management, treatment, and/or surveillance practices. As sequencing technologies have progressed and we move into the era of precision medicine, genomic sequencing has been introduced to this area with the hopes of detecting variants related to a vastly expanded number of conditions. Though implementation of genomic sequencing for newborn screening in public health and clinical settings is limited, commercial laboratories have begun to offer genomic screening panels for neonates.

Engaging community stakeholders in research on best practices for clinical genomic sequencing.

Maximizing the utility and equity of genomic sequencing integration in clinical care requires engaging patients, their families, and communities. The NCGENES 2 study explores the impact of engagement between clinicians and caregivers of children with undiagnosed conditions in the context of a diagnostic genomic sequencing study. A Community Consult Team (CCT) of diverse parents and advocates for children with genetic and/or neurodevelopmental conditions was formed.

Parents' perceptions of personal utility of exome sequencing results.

Purpose: Clinical genome or exome sequencing (GS/ES) provides a diagnosis for many individuals with suspected genetic disorders, but also yields negative or uncertain results for the majority. This study examines how parents of a child with an undiagnosed condition attribute personal utility to all types of ES results.

Methods: Return of 31 exome sequencing results was observed during clinic sessions, followed by semistructured interviews with parents one month later.

An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening.

Objective: To assess the performance of a standardized, age-based metric for scoring clinical actionability to evaluate conditions for inclusion in newborn screening and compare it with the results from other contemporary methods.

Study Design: The North Carolina Newborn Exome Sequencing for Universal Screening study developed an age-based, semiquantitative metric to assess the clinical actionability of gene-disease pairs and classify them with respect to age of onset or timing of interventions. This categorization was compared with the gold standard Recommended Uniform Screening Panel and other methods to evaluate gene-disease pairs for newborn genomic sequencing.

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination.

Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process.