Clinical Validity and Utility of Long-Read Sequencing in Sickle Cell Disease: Lessons for Population Screening and Policy

Kungu Erisa

Faculty of Pharmacy Kampala International University Uganda

Email: erisa.kungu@studwc.kiu.ac.ug

ABSTRACT

Sickle cell disease (SCD) is a prevalent monogenic disorder with significant morbidity and mortality worldwide, particularly in low- and middle-income countries. Early diagnosis through population screening is critical to reduce adverse health outcomes and enable timely interventions. Long-read sequencing (LRS) technologies, including Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), offer substantial advantages over short-read approaches, providing comprehensive detection of HbS variants, structural variations, haplotype phasing, and mosaicism within globin gene clusters. This review evaluates the clinical validity and utility of LRS for SCD, emphasizing its potential for newborn and carrier screening programs, particularly in resource-limited settings. It discusses technical requirements, workforce training, data governance, ethical considerations, and health economic implications. Lessons from bench-to-population perspectives underscore the importance of tiered implementation strategies, infrastructure investment, and stakeholder engagement. Findings highlight that integrating LRS into population screening programs can enhance diagnostic accuracy, inform clinical decision-making, and support equitable access to genomic-informed care. Future research should focus on longitudinal monitoring, pilot implementation studies, and cost-effectiveness analyses to guide policy development and sustainable adoption of LRS for SCD screening globally.

Keywords: Sickle Cell Disease (SCD), Long-Read Sequencing (LRS), Population Screening, Clinical Validity and Utility, and Genomic Policy and Implementation

CITE AS: Kungu Erisa (2026). Clinical Validity and Utility of Long-Read Sequencing in Sickle Cell Disease: Lessons for Population Screening and Policy. RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 6(1):13-20. https://doi.org/10.59298/RIJBAS/2026/611320