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Original Research
The β-goblin gene architecture in individuals with and without sickle cell disease in Nigeria: Implications for β-thalassaemia trait diagnosis
Submitted: 25 August 2025 | Published: 28 January 2026
About the author(s)
Oluwatoyin A. Babalola, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria; and, Department of Molecular Biology and Biotechnology, College of Natural and Applied Sciences, Chrisland University, Abeokuta, NigeriaBiobele J. Brown, Department of Paediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria
Foluke Fasola, Department of Haematology, College of Medicine, University of Ibadan, Ibadan, Nigeria
Jing Zhang, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Illinois, Chicago, United States
Yonglan Zheng, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Illinois, Chicago, United States
Abayomi B. Odetunde, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
Adeyinka G. Falusi, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
Olufunmilayo Olopade, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Illinois, Chicago, United States
Abstract
Background: β-thalassaemia is considered rare in Africa; however, recent screening-based studies suggest a β-thalassaemia trait prevalence of 6% – 10% among individuals with sickle cell disease (SCD) and up to 25% in those without SCD. Co-inheritance with SCD may modify disease severity, highlighting the need for molecular confirmation.
Objective: To ascertain the prevalence and genetic basis of β-thalassaemia trait in Nigerians with and without SCD.
Methods: We recruited 260 participants (130 per group; aged 3 years – 69 years, median [interquartile range] = 16 [9–29]). Haemoglobin fractions were analysed using high-performance liquid chromatography, and full blood counts were obtained. A 1.6 kb region of the β-globin gene was amplified and sequenced by Sanger sequencing. Variants were annotated and haplotypes constructed. An additional 26 samples from a separate SCD cohort were also genotyped.
Results: Molecular analysis revealed a β-thalassaemia trait prevalence of < 1% in both groups, contrasting with recent screening-based reports. In addition to sickle cell, haemoglobin C, and β-thalassaemia mutations, eight other variants were identified, three of which were unique to SCD patients and in linkage disequilibrium. Sickle cell and haemoglobin C mutations occurred on the major ancestral haplotype, whereas the only β-thalassaemia mutation detected (rs33915217C>A) was associated with a minor ancestral haplotype atypical of Africa. Two rare variants (rs537944366T>C and rs33915217C>A) are reported for the first time in the Yoruba population.
Conclusion: These findings indicate a low prevalence of β-thalassaemia trait in Nigeria and underscore the need to re-evaluate diagnostic approaches in African populations for optimal clinical management of SCD and other anaemias.
What this study adds: This study provides the first molecular confirmation of the low prevalence of β-thalassaemia trait in the Yoruba population. It identifies two rare variants, including a β-thalassaemia mutation on a minor, atypical haplotype, and highlights the limitations of high-performance liquid chromatography, underscoring the importance of genetic testing for accurate diagnosis.
Keywords
Sustainable Development Goal
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