Unusual β-Globin Haplotype Distribution in Newborns from Bengo, Angola

Borges, Eliana Lourenço; Tchonhi, Chissengo; Couto, C.; Gomes, Verónica; Amorim, António; Prata, Maria João; Brito, Miguel

doi:10.1080/03630269.2019.1647230

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…However, they also identified five children with the AI haplotype. Another study reported an even more heterogeneous frequency of haplotype carriers with 82.2% CAR, 11.2% BEN and 6.6% SEN in Angola [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Genotypic Diversity among Angolan Children with Sickle Cell Anemia

Delgadinho

Ginete

Santos³

et al. 2021

IJERPH

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Background. Sickle cell anemia (SCA) is an inherited blood disorder that affects over 300,000 newborns worldwide every year, being particularly prevalent in Sub-Saharan Africa. Despite being a monogenic disease, SCA shows a remarkably high clinical heterogeneity. Several studies have already demonstrated the existence of some polymorphisms that can provide major clinical benefits, producing a mild phenotype. Moreover, the existence of distinct haplotypes can also influence the phenotype patterns of certain populations, leading to different clinical manifestations. Our aim was to assess the association between polymorphisms in genes previously related to SCA disease severity in an Angolan pediatric population. Methods. This study analyzed clinical and biological data collected from 192 Angolan children. Using NGS data, we classified the HBB haplotypes based on four previously described SNPs (rs3834466, rs28440105, rs10128556, and rs968857) and the genotype for the SNPs in HBG2 (rs7482144), BCL11A (rs4671393, rs11886868, rs1427407, rs7557939), HBS1L-MYB (rs66650371) and BGLT3 (rs7924684) genes. Results. The CAR haplotype was undoubtedly the most common HBB haplotype in our population. The HbF values and the ratio of gamma chains were statistically significant for almost all of the variants studied. We reported for the first time an association between rs7924684 in the BGLT3 gene and gamma chains ratio. Conclusions. The current findings emphasize the importance personalized medicine would have if applied to SCA patient care, since some of the variants studied might predict the phenotype and the overall response to treatment.

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Section: Discussionmentioning

confidence: 99%

Genotypic Diversity among Angolan Children with Sickle Cell Anemia

Delgadinho

Ginete

Santos³

et al. 2021

IJERPH

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“…Second, the prevalence of the Bantu haplotype in Eastern Africa and into Madagascar and the archipelago of Mayotte reflects ancient and recent migrant paths of the Bantu expansion, and more recent migrations. Third, the occurrence of ~7% of the SEN haplotype in the Bengo population of Angola where it was previously absent reflects changing population and disease dynamics that should be important to public health and genetic medicine ( 26 ). Fourth, the excess of ‘atypical’ haplotypes (RFPL recombinants that differ from the five major types) in indigenous southern African populations is consistent with low malaria pressure necessary to maintain the conservation of the HBB haplotypes in these populations ( 16 ).…”

Section: Common Variants In Haemoglobin Genesmentioning

confidence: 99%

Evolutionary history of sickle-cell mutation: implications for global genetic medicine

Esoh

Wonkam

2021

Human Molecular Genetics

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Resistance afforded by the sickle-cell trait against severe malaria has led to high frequencies of the sickle-cell mutation [HBB; c.20 T > A, p.Glu6Val; OMIM: 141900 (HBB-βS)] in most parts of Africa. High-coverage sequencing and genotype data have now confirmed the single African origin of the sickle-cell gene variant [HBB; c.20 T > A, p.Glu6Val; OMIM: 141900 (HBB-βS)]. Nevertheless, the classical HBB-like genes cluster haplotypes remain a rich source of HBB-βS evolutionary information. The overlapping distribution of HBB-βS and other disease-associated variants means that their evolutionary genetics must be investigated concurrently. In this review: 1) we explore the evolutionary history of HBB-βS and its implications in understanding human migration within and out of Africa: e.g. HBB haplotypes and recent migration paths of the Bantu expansion, occurrence of ~ 7% of the Senegal haplotype in Angola reflecting changes in population/SCD dynamics, and existence of all five classical HBB haplotype in Cameroon and Egypt suggesting a much longer presence of HBB-βS in these regions; 2) we discuss the time estimates of the emergence of HBB-βS in Africa; and finally, 3) we discuss implications for genetic medicine in understanding complex epistatic interactions between HBB-βS and other gene variants selected under environmental pressure in Africa e.g. variants in HBB, HBA, G6PD, APOL, APOE, OSBPL10, RXRA.

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