Loss of balancing selection in the βS globin locus

BMC Medical Genetics

Research Article

Hani B Ishag¹  Hiba S Mohammed¹  Ibrahim M Elhassan¹  Ayman A Hussain¹  Eltahir AG Khalil¹  Muntaser E Ibrahim¹  Niven A Salih¹  Ibrahim A Almugtaba²  Abeir M Elzein³  Dominic Kwiatkowski⁴ 

[1] Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Medical Campus, Qasser Street, Khartoum, Sudan;Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Medical Campus, Qasser Street, Khartoum, Sudan;School of Mathematical Sciences, University of Khartoum, Khartoum, Sudan;Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Medical Campus, Qasser Street, Khartoum, Sudan;Wellcome Trust Centre for Human Genetics, Roosevelt Drive Headington, OX3 University of Oxford, Oxford, UK;Wellcome Trust Centre for Human Genetics, Roosevelt Drive Headington, OX3 University of Oxford, Oxford, UK;

关键词: Malaria;    Thalassemia;    Visceral Leishmaniasis;    Falciparum Malaria;    Clinical Malaria;   

DOI  :  10.1186/1471-2350-11-21

 received in 2009-05-04, accepted in 2010-02-03,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Salih et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.