Resistance to malaria in humans: the impact of strong, recent selection.
Resistance to malaria in humans: the impact of strong, recent selection.
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DOI：
10.1186/1475-2875-11-349
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发表时间：
2012-10-22
期刊：
影响因子：
3
通讯作者：
Hedrick PW
中科院分区：
文献类型：
--
作者：
Hedrick PW
疟疾是全球主要的死亡原因之一，近数千年来一直被认为是人类最有效的选择类型。因此，参与疟疾抗性的基因是最近强有力的选择的极好例子。1949年，霍尔丹最初提出，传染病可能是人类群体中一种强大的选择性力量。疟疾抗药性具有很强的选择性作用的证据包括，由这些抗疟变种的多效性效应引起的一些有害遗传病的高发频率，其中许多是“功能丧失”突变体。这种选择是最近的证据来自于对其中一些抗疟疾等位基因的年龄进行基因测年，得出的年龄比现在不到5000年，通常比其他人类基因变异要晚得多。提出了一种从当代病例对照数据中估计选择系数的方法。在这里描述的情况下，选择远远大于1%，显著高于通常观察到的其他人类遗传变异。根据这些选择系数，可以预测β-珠蛋白基因座上的等位基因S和C的联合变化，以及α-地中海贫血症单倍型和S的变异，这些变异是不连锁的，但表现出上位性。群体遗传学可以用来确定过去的选择数量和模式，并预测未来发现的其他抗疟疾变异的选择。
Malaria is one of the leading causes of death worldwide and has been suggested as the most potent type of selection in humans in recent millennia. As a result, genes involved in malaria resistance are excellent examples of recent, strong selection. In 1949, Haldane initially suggested that infectious disease could be a strong selective force in human populations. Evidence for the strong selective effect of malaria resistance includes the high frequency of a number of detrimental genetic diseases caused by the pleiotropic effects of these malaria resistance variants, many of which are “loss of function” mutants. Evidence that this selection is recent comes from the genetic dating of the age of a number of these malaria resistant alleles to less than 5,000 years before the present, generally much more recent than other human genetic variants. An approach to estimate selection coefficients from contemporary case–control data is presented. In the situations described here, selection is much greater than 1%, significantly higher than generally observed for other human genetic variation. With these selection coefficients, predictions are generated about the joint change of alleles S and C at the β-globin locus, and for α-thalassaemia haplotypes and S, variants that are unlinked but exhibit epistasis. Population genetics can be used to determine the amount and pattern of selection in the past and predict selection in the future for other malaria resistance variants as they are discovered.
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影响因子：
16.6
作者：
Howes, Rosalind E.;Patil, Anand P.;Piel, Frederic B.;Nyangiri, Oscar A.;Kabaria, Caroline W.;Gething, Peter W.;Zimmerman, Peter A.;Barnadas, Celine;Beall, Cynthia M.;Gebremedhin, Amha;Menard, Didier;Williams, Thomas N.;Weatherall, David J.;Hay, Simon I.
通讯作者：
Hay, Simon I.
影响因子：
9.8
作者：
Hamblin, MT;Di Rienzo, A
通讯作者：
Di Rienzo, A
影响因子：
9.8
作者：
Currat, M;Trabuchet, G;Excoffier, L
通讯作者：
Excoffier, L
影响因子：
3
作者：
Driss A;Hibbert JM;Wilson NO;Iqbal SA;Adamkiewicz TV;Stiles JK
通讯作者：
Stiles JK
影响因子：
2.1
作者：
Hedrick, P
通讯作者：
Hedrick, P