Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean

被引：43

作者：

Penman, Bridget S. ^{[2
]}

Pybus, Oliver G. ^{[2
]}

Weatherall, David J. ^{[1
]}

Gupta, Sunetra ^{[2
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[2] Univ Oxford, Dept Zool, Oxford OX1 3PS, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 50期

基金：

英国惠康基金;

关键词：

epistasis; host genetics; malaria; thalassemia; human evolution; PLASMODIUM-FALCIPARUM; BETA-THALASSEMIA; ALPHA-THALASSEMIA; RED-CELL; MALARIA; POPULATION;

D O I：

10.1073/pnas.0910840106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of alpha-and beta-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when alpha-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions.

引用

页码：21242 / 21246

页数：5

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