A portable molecular laboratory for rapid genotyping in the field: application to sickle cell disease

Abstract

BackgroundSickle cell disease (SCD) is the most common recessive genetic disorder, caused by pathogenic variants of the HBB gene. SCD is associated with a range of clinical manifestations, including vaso-occlusive crises, infections, and severe anaemia, which contribute to increased morbidity and mortality. The frequency of pathogenic alleles is high in Sub-Saharan African countries, with heterozygous carriers reaching up to 25% of the population. Several methods can be employed for molecular diagnostics, with HBB gene sequencing being the most precise. However, access to DNA analyses and sequencing in Low- and Middle-Income Countries (LMICs), where SCD prevalence is high, is limited. Understanding genetic profiles is crucial at both individual and population levels, as it can guide public health strategies and facilitate accurate genetic counselling. AimThis feasibility study aimed to demonstrate that a portable medical genetic laboratory (in suitcases) can be used to genotype individuals for the HBB A, S, and C alleles and their combinations within a few hours outside of a laboratory setting. Methods and resultsWe established a portable medical genetics laboratory capable of DNA extraction and isothermal DNA amplification using a commercially available kit for the A, S, and C alleles of the HBB gene. During one single study day, this portable lab was set up in a room where the Swiss Association of Patients with SCD was holding its annual meeting. We analysed the samples of 27 participants who were aware of their A, S, or C status. We collected buccal swabs and dried blood samples for genotyping. Genotype results for all participants were obtained within five hours after sample collection. In four cases, we observed discrepancies between the buccal swab and blood genotypes; three were resolved upon repeat testing, and one reflected donor chimerism following hematopoietic stem-cell transplantation. ConclusionsThis study demonstrates the feasibility and efficiency of using a portable medical genetics laboratory for rapid genotyping of HBB SCD alleles in community settings.This approach can improve access to molecular diagnostics in resource-limited environments. Such tools have the potential to significantly enhance local capabilities for genetic screening, counselling, and public health planning in regions heavily affected by SCD.