ArticleBMC medical genetics2015
Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer.
Article in BMC medical genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Genetic Polymorphisms Associated with Fetal Hemoglobin (HbF) Levels and F-Cell Numbers: A Systematic Review of Genome-Wide Association Studies.International journal of molecular sciences · 2024Pooled it
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Systematic Review of Non-Coding Genomic Variants in Globin and Non-Globin Clusters and Their Impact on Phenotypic Severity in Thalassemia and Sickle Cell Disease.Journal of clinical medicine · 2026Review
- Comprehensive Review of Genetic and Epigenetic Regulation of Fetal Hemoglobin in β-Hemoglobinopathies: From Molecular Mechanisms to Clinical Applications.Mediterranean journal of hematology and infectious diseases · 2026Review
- The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.Human molecular genetics · 2024Article
- Significance of genetic modifiers of hemoglobinopathies leading towards precision medicine.Scientific reports · 2021Article
- A qualitative study on aspects of consent for genomic research in communities with low literacy.BMC medical ethics · 2020Article
- Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania.BMC medical genetics · 2020Article
- Genetic Modifiers of Fetal Haemoglobin in Sickle Cell Disease.Molecular diagnosis & therapy · 2019Review
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- A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia.PloS one · 2018Article
- Sickle cell disease in Africa: an overview of the integrated approach to health, research, education and advocacy in Tanzania, 2004-2016.British journal of haematology · 2017Review
- SAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients with sickle cell disease from Cameroon.BMC research notes · 2017Article
- Genetic control of erythropoiesis.Current opinion in hematology · 2017Review
- Disease burden and the role of pharmacogenomics in African populations.Global health, epidemiology and genomics · 2017Review
- Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses.American journal of hematology · 2016Review
- Pitfalls of haplotype phasing from amplicon-based long-read sequencing.Scientific reports · 2016Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCommon genetic variants residing near upstream regulatory elements for MYB, the gene encoding transcription factor cMYB, promote the persistence of fetal hemoglobin (HbF) into adulthood. While they have no consequences in healthy individuals, high HbF levels have major clinical benefits in patients with sickle cell disease (SCD) or β thalassemia. Here, we present our detailed investigation of HBS1L-MYB intergenic polymorphism block 2 (HMIP-2), the central component of the complex quantitative-trait locus upstream of MYB, in 1,022 individuals with SCD in Tanzania.
methodsWe have looked at 1022 individuals with HbSS or HbS/β(0) in Tanzania. In order to achieve a detailed analysis of HMIP-2, we performed targeted genotyping for a total of 10 SNPs and extracted additional 528 SNPs information from a genome wide scan involving the same population. Using MACH, we utilized the existing YRI data from 1000 genomes to impute 54 SNPs situated within HIMP-2.
resultsSeven HbF-increasing, low-frequency variants (β > 0.3, p < 10(-5), f ≤ 0.05) were located in two partially-independent sub-loci, HMIP-2A and HMIP-2B. The spectrum of haplotypes carrying such alleles was diverse when compared to European and West African reference populations: we detected one such haplotype at sub-locus HMIP-2A, two at HMIP-2B, and a fourth including high-HbF alleles at both sub-loci ('Eurasian' haplotype clade). In the region of HMIP-2A a putative functional variant (a 3-bp indel) has been described previously, but no such candidate causative variant exists at HMIP-2B. Extending our dataset through imputation with 1000 Genomes, whole-genome-sequence data, we have mapped peak association at HMIP-2B to an 11-kb region around rs9494145 and rs9483788, flanked by two conserved regulatory elements for MYB.
conclusionsStudies in populations from the African continent provide distinct opportunities for mapping disease-modifying genetic loci, especially for conditions that are highly prevalent there, such as SCD. Population-genetic characteristics of our cohort, such as ethnic diversity and the predominance of shorter, African-type haplotypes, can add to the power of such studies.
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