Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence

Cruz, Pedro Rodrigues Sousa da; Ananina, Galina; Gil-da-Silva-Lopes, Vera Lúcia; Simioni, Milena; Menaa, Farid; Bezerra, Marcos André Cavalcanti; Domingos, Igor F.; Araújo, Aderson S; Pellegrino, Renata; Hákonarson, Hákon; Costa, Fernando Ferreira; Melo, Mônica Barbosa de

doi:10.1038/s41598-019-47313-2

Cited by 9 publications

(5 citation statements)

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“…However, this observation may still be generalizable to individuals with SCD‐associated PH, as it is well established that individuals with SCD come from genetically diverse backgrounds. 45 , 46 …”

Section: Discussionmentioning

confidence: 99%

“…However, this observation may still be generalizable to individuals with SCD-associated PH, as it is well established that individuals with SCD come from genetically diverse backgrounds. 45,46 In this study, we use both PBMC as well as lung tissue for evaluating eQTL analyses. It is well established that eQTL effects depend on tissue or cell types as well as environment.…”

Section: Discussionmentioning

confidence: 99%

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RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

et al. 2023

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Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)‐associated PH and pulmonary arterial hypertension (PAH). Cis ‐expression quantitative trait loci (eQTL) were queried for RASA3 using whole genome genotype arrays and gene expression profiles derived from peripheral blood mononuclear cells (PBMC) of three SCD cohorts. Genome‐wide single nucleotide polymorphisms (SNPs) near or in the RASA3 gene that may associate with lung RASA3 expression were identified, reduced to 9 tagging SNPs for RASA3 and associated with markers of PH. Associations between the top RASA3 SNP and PAH severity were corroborated using data from the PAH Biobank and analyzed based on European or African ancestry (EA, AA). We found that PBMC RASA3 expression was lower in patients with SCD‐associated PH as defined by echocardiography and right heart catheterization and was associated with higher mortality. One eQTL for RASA3 (rs9525228) was identified, with the risk allele correlating with PH risk, higher tricuspid regurgitant jet velocity and higher pulmonary vascular resistance in patients with SCD‐associated PH. rs9525228 associated with markers of precapillary PH and decreased survival in individuals of EA but not AA. In conclusion, RASA3 is a novel candidate gene in SCD‐associated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

et al. 2023

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“…Five haplotypes of the beta-globin gene, in chromosome 11, have been described and are identified based on the geographic locations where they occur more frequently. These are the Arab-Indian, Benin, Cameroon, Bantu (also called the Central African Republic (CAR) haplotype), and Senegal haplotypes (Cruz et al 2019). The quilombos Santiago do Iguapé (Northeast), Curiau, Pacoval, and Trombetas (North) were studied for these loci.…”

Section: Insights On the Within-africa Roots Of African-braziliansmentioning

confidence: 99%

Ancestry, diversity, and genetics of health-related traits in African-derived communities (quilombos) from Brazil

Joerin-Luque

Sukow

Bucco

et al. 2023

Funct Integr Genomics

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Brazilian quilombos are communities formed by enslaved Africans and their descendants all over the country during slavery and shortly after its abolition. Quilombos harbor a great fraction of the largely unknown genetic diversity of the African diaspora in Brazil. Thus, genetic studies in quilombos have the potential to provide important insights not only into the African roots of the Brazilian population but also into the genetic bases of complex traits and human adaptation to diverse environments. This review summarizes the main results of genetic studies performed on quilombos so far. Here, we analyzed the patterns of African, Amerindian, European, and subcontinental ancestry (within Africa) of quilombos from the five different geographic regions of Brazil. In addition, uniparental markers (from the mtDNA and the Y chromosome) studies are analyzed together to reveal demographic processes and sex-biased admixture that occurred during the formation of these unique populations. Lastly, the prevalence of known malaria-adaptive African mutations and other African-specific variants discovered in quilombos, as well as the genetic bases of health-related traits, are discussed here, together with their implication for the health of populations of African descent.

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“…Due to the protective effect in malaria, the sickle mutation spreads to different geographical regions, and haplotypes surrounding this mutation have subsequently diversified, leading to the phenotype patterns observable today [ 6 , 17 ]. Genetic analysis of the HBB gene cluster has revealed five distinct HbS haplotypes: Senegal (SEN), Benin (BEN), Bantu or Central African Republic (CAR), Cameroon (CAM), and Arab-Indian (AI) [ 18 , 19 ]. It has been shown that patients with AI or SEN haplotypes have the highest HbF levels associated with fewer clinical manifestations, and this is likely due to a higher prevalence of the Xmn1-HBG2 polymorphism [ 6 , 14 ].…”

Section: Introductionmentioning

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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Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence

Cited by 9 publications

References 50 publications

RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

Ancestry, diversity, and genetics of health-related traits in African-derived communities (quilombos) from Brazil

Genotypic Diversity among Angolan Children with Sickle Cell Anemia

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