The emergence and maintenance of sickle cell hotspots in the Mediterranean.

Authors: Penman BS,Gupta S,Buckee CO,
Address: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. bridget.penman@zoo.ox.ac.uk
Journal: Infect Genet Evol.

Publication: 2012 Oct;12(7):1543-50. doi: 10.1016/j.meegid.2012.06.001. Epub 2012 Jun 13.
Free Text: The emergence and maintenance of sickle cell hotspots in the Mediterranean.

abstract

Genetic disorders of haemoglobin (haemoglobinopathies), including the thalassaemias and sickle cell anaemia, abound in historically malarious regions, due to the protection they provide against death from severe malaria. Despite the overall spatial correlation between malaria and these disorders, inter-population differences exist in the precise combinations of haemoglobinopathies observed. Greece and Italy present a particularly interesting case study: their high frequencies of beta thalassaemia speak to a history of intense malaria selection, yet they possess very little of the strongly malaria protective mutation responsible for sickle cell anaemia, despite historical migrational links with Africa where high frequencies of sickle cell occur. Twentieth century surveys of beta thalassaemia and sickle cell in Greece, Sicily and Sardinia have revealed striking sickle cell 'hotspots' - places where the frequency of sickle cell approaches that seen in Africa while neighbouring populations remain relatively sickle cell free. It remains unclear how these hotspots have been maintained over time without sickle cell spreading throughout the region. Here we use a metapopulation model to show that (i) epistasis between the alpha and beta forms of thalassaemia can restrict the spread of sickle cell through a network of linked subpopulations and (ii) the emergence of sickle cell hotspots requires relatively low levels of gene flow, but the aforementioned epistasis increases the chances of hotspots forming.

Related Articles
Negative epistasis between α+ thalassaemia and sickle cell trait can explain interpopulation variation in South Asia.
Evolution. 2011
Negative epistasis between α+ thalassaemia and sickle cell trait can explain interpopulation variation in South Asia.
Penman BS, Habib S, Kanchan K, Gupta S. Evolution. 2011 Dec; 65(12):3625-32. Epub 2011 Aug 11.
[Thalassemia and sickle-cell disease in Norway].
Tidsskr Nor Laegeforen. 2001
[Thalassemia and sickle-cell disease in Norway].
Graesdal JS, Gundersen K, Holm B, Waage A. Tidsskr Nor Laegeforen. 2001 Feb 28; 121(6):678-80.
Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean.
Proc Natl Acad Sci U S A. 2009
Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean.
Penman BS, Pybus OG, Weatherall DJ, Gupta S. Proc Natl Acad Sci U S A. 2009 Dec 15; 106(50):21242-6. Epub 2009 Dec 1.
Review Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants.
Hum Genet. 1993
Review Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants.
Flint J, Harding RM, Clegg JB, Boyce AJ. Hum Genet. 1993 Mar; 91(2):91-117.
Review Molecular epidemiology of the thalassaemias (including haemoglobin E).
Baillieres Clin Haematol. 1992
Review Molecular epidemiology of the thalassaemias (including haemoglobin E).
Hill AV. Baillieres Clin Haematol. 1992 Jan; 5(1):209-38.

To top • Home

TraveldoctorOnline 2001 • Disclaimer • webmaster

The contents within traveldoctoronline are presented only for informational purposes and cannot substitute for professional health care or any other medical treatment.All users of this website with health problems should be oblige always to consult their medical doctor before starting any treatment.