Loss of balancing selection in the βS globin locus

Abstract

BackgroundProbably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations.MethodsWe investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in future generations.ResultsGenotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa.ConclusionsSuch loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy.

Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

“…The HCHS/SOL cohort represents a diverse subsample of Hispanics/Latinos across the U.S., with varying admixture proportions of three continental ancestry groups: Amerindians, Africans, and Europeans. The beta-globin hemoglobin S and hemoglobin C variants, alpha-globin 3.8kb deletion, and G6PD A- variant have previously been shown to contribute to RBC phenotypic variance among U.S. African Americans[ 41 , 42 ]. Here, we establish that these same common African ancestral hemoglobin and G6PD gene variants are associated with quantitative RBC phenotypes among U.S. Hispanics/Latinos.…”

Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring

“…When populations were combined and input into STRUCTURE, the programme assigned the two populations into two separate clusters; one (Hausa) being more defined than the other. This is perhaps due to the fact that the Hausa, with their extended families, widely practiced polygamy and higher percentage of within-village marriages seems to be more endogamous than Massalit [ 11 ]. Structure also partitioned each Hausa and Massalit into two substructures, although this was not justified in terms of Fst or in the programme output values, which indicate that the candidate genes used in the analysis, with their adaptive non-neutral nature and limited numbers of SNPs are probably not the best population differentiation markers.…”

“…Such differences of malaria status is speculated to be due to differences in the immune response an outcome of the difference in the genetic structure, which is in turn could be attributed to the genetic history and ethnic variations between populations as seen in West Africa[ 1 , 21 ]. The relationship of the sickle-cell mutation in the haemoglobin gene (sickle), population structure and malaria in these villages is reported elsewhere [ 11 ]. The analysis of the interaction and combined effect of sickle with some of these polymorphisms might prove interesting for an in-depth understanding of the overall mechanism of malaria susceptibility/protection in these populations.…”

The rural urban divide, insights from immuno-genetic profiles and implications for health

“…How much natural selection is responsible for such differences in expression remains to be answered. Populations of the rural area sampled in this study were a subject of extended investigation over three decades for transmission of infectious diseases where the area is endemic for both malaria and visceral leishmaniasis (3,14,15). Conversely prolonged exposure overtime in some cases may result in genetic and epigenetic differences.…”