Selection and Mutation for alpha Thalassemia in Nonmalarial and Malarial Environments

作者：Hedrick Philip W^*

来源：Annals of Human Genetics, 2011, 75: 468-474.

DOI：10.1111/j.1469-1809.2011.00653.x

• Case-control method
• deletion
• heterozygote advantage
• Kenya
• malaria
• odds ratio
• Papua New Guinea

alpha thalassemia is the result of the loss of one or both copies of the two human alpha globin genes. alpha thalassemia appears to be the most common monogenic disease in the world and is in high frequency where malaria is, or has been, endemic. In nonmalarial environments, alpha thalassemia is rare and its frequency can be explained by a balance of deletional mutation and purifying selection. In malarial environments, the loss of one or two copies of the four alpha globin genes in normal diploid genotypes confers resistance (lower mortality) to malaria. Fitness estimates from data from Kenyan and Papua New Guinea populations are used to predict the increase in the -alpha haplotype (with one deleted gene). The frequency of double deletions (- haplotypes) is higher in some Asian populations than that of single deletions. In this case, heterozygotes with normal alpha alpha haplotypes are expected to have the highest fitness. Overall, this population genetic examination provides an evolutionary framework for understanding the worldwide frequency of alpha thalassemia and the deletions that cause it in both nonmalarial and malarial environments.

• 出版日期2011-7