Haplotype analyses of haemoglobin C and haemoglobin S and the dynamics of the evolutionary response to malaria in Kassena-Nankana District of Ghana.

Anita Ghansah,Paul Milligan,Lucas Amenga-Etego,William O Rogers,Kirk A Rockett,Dominic P Kwiatkowski,Taane G Clark,Michael D Wilson,Thomas Anyorigiya,Abraham R Oduro,Abraham Hodgson,Kwadwo A Koram

doi:10.1371/journal.pone.0034565

Abstract

BackgroundHaemoglobin S (HbS) and C (HbC) are variants of the HBB gene which both protect against malaria. It is not clear, however, how these two alleles have evolved in the West African countries where they co-exist at high frequencies. Here we use haplotypic signatures of selection to investigate the evolutionary history of the malaria-protective alleles HbS and HbC in the Kassena-Nankana District (KND) of Ghana.Methodology/Principal FindingsThe haplotypic structure of HbS and HbC alleles was investigated, by genotyping 56 SNPs around the HBB locus. We found that, in the KND population, both alleles reside on extended haplotypes (approximately 1.5 Mb for HbS and 650 Kb for HbC) that are significantly less diverse than those of the ancestral HbA allele. The extended haplotypes span a recombination hotspot that is known to exist in this region of the genomeSignificanceOur findings show strong support for recent positive selection of both the HbS and HbC alleles and provide insights into how these two alleles have both evolved in the population of northern Ghana.

Highlights

Haemoglobin S or ‘‘sickle Haemoglobin’’ (HbS) – rs334 and Haemoglobin C (HbC) – rs33930165 are glutamic acidRvaline and glutamic acidRlysine substitutions, respectively, at codon six of the HBB gene encoding the b-globin component of haemoglobin
The population controls consisted of 2 major ethnic groups (Kassem 63.0%, Nankan 33.4%, other 3.6%), in which we observed no differences in allele frequency for both HbS and HbC (Table 1)
HbC is reported to be an allele under malaria-driven selection in parts of West Africa where it exists at high frequency [4,5]. like other recently selected alleles such as those found in the glucose-6-phosphate dehydrogenase or lactase dehydrogenase the HbS allele would be expected to maintain its ancestral haplotypic relations over a relatively long genetic distance [24,25,26,27]

Summary

Introduction

Haemoglobin S or ‘‘sickle Haemoglobin’’ (HbS) – rs334 and Haemoglobin C (HbC) – rs33930165 are glutamic acidRvaline and glutamic acidRlysine substitutions, respectively, at codon six of the HBB gene encoding the b-globin component of haemoglobin. HbS and HbC result from substitutions at the second and first position of HBB codon six, respectively. Haemoglobin S (HbS) and C (HbC) are variants of the HBB gene which both protect against malaria. It is not clear, how these two alleles have evolved in the West African countries where they co-exist at high frequencies. We use haplotypic signatures of selection to investigate the evolutionary history of the malaria-protective alleles HbS and HbC in the Kassena-Nankana District (KND) of Ghana

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Discussion

Conclusion