Loss of balancing selection in the betaS globin locus.
BACKGROUND
Probably 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.


METHODS
We 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.


RESULTS
Genotype 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.


CONCLUSIONS
Such 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.
Department of Molecular Biology, Institute of Endemic Diseases, Medical Campus, Qasser Street, University of Khartoum, Khartoum, Sudan.
Niven A
NA
Salih
Ayman A
AA
Hussain
Ibrahim A
IA
Almugtaba
Abeir M
AM
Elzein
Ibrahim M
IM
Elhassan
Eltahir A G
EA
Khalil
Hani B
HB
Ishag
Hiba S
HS
Mohammed
Dominic
D
Kwiatkowski
Muntaser E
ME
Ibrahim
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007407:Interviews as Topic; D008288:Malaria / Q000453:epidemiology* / Q000235:genetics*; D010961:Plasmodium / Q000472:pathogenicity; D011110:Polymorphism, Genetic / Q000235:genetics*; D012641:Selection, Genetic; D012805:Sickle Cell Trait / Q000235:genetics*; D055815:Young Adult
D006451:Hemoglobin, Sickle