@article{CRSIJ26000247,
                  author = {Isyaku Alhassan, Nura Garba, Muhammad Yalwa Gwarzo, Muhammad Bashir Tijjani},
                  title = {Genomic Characterization of Rare Pathogenic Variants in Sickle Cell Disease Patients Using Oxford Nanopore Sequencing: Current Advances, Clinical Applications, and Future Perspectives},
                  journal = {Cosmo Research and Science International Journal},
                  year = {2025},
                  volume = {2},
                  number = {1},
                  pages = {178-196},
                  issn = {3108-1584},
                  url = {https://cosmorsij.com/published/CRSIJ26000247.pdf},
                  abstract = {Sickle cell disease (SCD) is one of the most prevalent monogenic hereditary disorders worldwide and remains a major public health challenge, particularly in sub-Saharan Africa, the Middle East, India, and the Mediterranean region. Although SCD results from a single nucleotide substitution (c.20A>T) in the HBB gene causing the Glu6Val alteration in β-globin, considerable variability exists in disease severity, complications, and therapeutic responses among individuals with identical genotypes. This phenotypic diversity is influenced by additional genetic and epigenetic factors, including rare pathogenic variants, structural genomic alterations, copy number variations, and modifier genes involved in fatal haemoglobin regulation, inflammation, oxidative stress, erythropoiesis, and vascular biology. Conventional sequencing approaches have improved molecular diagnosis but remain limited in resolving complex genomic regions, structural variants, repetitive sequences, and long-range haplotypes. Oxford Nano pore Sequencing (ONS), a third-generation long-read sequencing technology, provides a transformative approach by enabling real-time sequencing of native DNA molecules, generation of ultra-long reads, accurate haplotype phasing, detection of structural variants, and simultaneous identification of DNA methylation patterns. This review examines the role of ONS in characterizing rare pathogenic variants associated with SCD heterogeneity and evaluates its applications in precision medicine. It discusses advances in long-read genomic analysis, detection of disease-modifying variants, characterization of the β-globin locus, pharmacogenomics profiling, and monitoring of emerging gene-editing therapies. The review also highlights current challenges, including sequencing accuracy, bioinformatics standardization, ethical considerations, cost, and limited representation of diverse populations in genomic databases. As Nano pore technology continues to improve, it holds significant potential to enhance diagnosis, prognosis, therapeutic selection, and personalized management of sickle cell disease.},
                  keywords = {Sickle Cell Disease, Oxford Nano pore Sequencing, Long-read Sequencing, Rare Pathogenic Variants, Precision Medicine, Structural Variants, Genomic Medicine, HBB Gene, Genetic Modifiers, Fetal Haemoglobin, Copy Number Variations, Haplotype Phasing, Epigenetics, Clinical Genomics, Personalized Medicine},
                  month = {July}
        }