The emergence and maintenance of sickle cell hotspots in the Mediterranean

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