TY - JOUR
T1 - Detection of Transversions and Transitions in HBG2 Cis-Elements Associated with Sickle Cell Allele in Ghanaians
AU - Ababio, G. K.
AU - Ekem, I.
AU - Acquaye, J.
AU - Oppong, S. Y.
AU - Amoah, A. G.B.
AU - Brandful, J.
AU - Quaye, I. K.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023.
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - Beta globin gene
KW - Chromosome 11
KW - Cis-acting elements
KW - Short tandem repeats
KW - Sickle cell anemia
KW - Sickle cell disease
KW - Single nucleotide polymorphism
KW - Transition
KW - Transversion
UR - http://www.scopus.com/inward/record.url?scp=85163792783&partnerID=8YFLogxK
U2 - 10.1007/s10528-023-10438-1
DO - 10.1007/s10528-023-10438-1
M3 - Article
AN - SCOPUS:85163792783
SN - 0006-2928
VL - 62
SP - 666
EP - 674
JO - Biochemical Genetics
JF - Biochemical Genetics
IS - 2
ER -