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Detection of Transversions and Transitions in HBG2 Cis-Elements Associated with Sickle Cell Allele in Ghanaians

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Abstract

Short tandem repeats located 5ʹ prime to the β-globin gene, have been observed to be in linkage disequilibrium with the HbS allele, and thought to affect the severity of sickle cell disease. Here, we report on new mutants within the HBG2 region that may impact sickle cell disease. To determine the cis-acting elements microsatellites, indels and single nucleotide polymorphisms (SNPs), within the HBG2 region by sequencing, in subjects with sickle cell disease. The case–control study was located at the Center for Clinical Genetics, Sickle cell unit, Korle–Bu Teaching Hospital. A questionnaire was used for demographic data and clinical information. Hematological profile (red blood cell, white blood cell, platelet, hemoglobin and mean corpuscular volume) were assessed in 83 subjects. A set of 45 samples comprising amplified DNA on the HBG2 gene from HbSS (22), HbSC (17) and 6 controls (HbAA) were sequenced. Differences in the microsatellite region between sickle cell disease (SCD) (HbSS and HbSC) genotypes and control subjects were identified by counting and assessed by Chi-square analysis. Red blood cells, hematocrit, platelets, white blood cells and hemoglobin indices differed in genotypic groups. HbSS subjects were affirmed to have severer hemolytic anemia than HbSC subjects. Two indels (T1824 and C905) were seen in both SS and SC genotypes. Two peculiar SNPs: G:T1860 (transition) and A:G1872 transversions were found within the HBG2 gene that were significantly associated with the HbSS genotype (Fisher’s exact test, p = 0.006) and HbS allele respectively (Fisher’s exact test, p = 0.006). Cis-acting elements in HbSS and HbSC were different and may contribute to the phenotype seen in the disease state.

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Data Availability

Data are available at Synapse with an ID being syn30013389 and a running title as Cis-acting elements and SCD.

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Acknowledgements

This work was partly supported by grants from the GETFund and College of Health Sciences, University of Ghana Medical School. The authors duly acknowledge the staffs of cardiothoracic unit of the Korle-Bu Teaching Hospital, Accra, Ghana; patients and staffs of Sickle cell clinic, and also, Medical Biochemistry, Univ. of Ghana SBAHS.

Funding

Work from the authors’ laboratory was partly supported by Grants from GETFund, College of Health Sciences, University of Ghana Medical School and Funding support from IKQ.

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Author notes

  1. I. K. Quaye

    Present address: Regent University College of Science and Technology, Dansoman, Accra, Ghana

  2. J. Brandful—Deceased.

Authors and Affiliations

  1. Department of Medical Biochemistry, University of Ghana Medical School, Accra, Ghana

    G. K. Ababio & S. Y. Oppong

  2. Department of Hematology, University of Cape Coast School of Medicine, Cape Coast, Ghana

    I. Ekem

  3. Department of Hematology, University of Ghana Medical School, Accra, Ghana

    J. Acquaye

  4. Department of Medicine, University of Ghana Medical School, Accra, Ghana

    A. G. B. Amoah

  5. Department of Virology, Noguchi Memorial Institute of Medical Research, Legon, Ghana

    J. Brandful

  6. Department of Biochemistry, University of Namibia Medical School, Windhoek, Namibia

    I. K. Quaye

  7. Department of Chemical Pathology, University of Ghana Medical School, Accra, Ghana

    S. Y. Oppong

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Contributions

AGK performed bench work and wrote the manuscript. JB provided technical supervision. IQ, EI and JA supervised the work till completion. IQ revised and or reviwed the manuscript IQ and AGK prepared the Tables. All authors reviewed the manuscript.

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Correspondence to G. K. Ababio or I. K. Quaye.

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Ababio, G.K., Ekem, I., Acquaye, J. et al. Detection of Transversions and Transitions in HBG2 Cis-Elements Associated with Sickle Cell Allele in Ghanaians. Biochem Genet 62, 666–674 (2024). https://doi.org/10.1007/s10528-023-10438-1

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  • DOI: https://doi.org/10.1007/s10528-023-10438-1

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