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- Title
Molecular analysis of α-thalassemia in Nepal: correlation with malaria endemicity.
- Authors
Sakai, Y.; Kobayashi, S.; Shibata, H.; Furuumi, H.; Endo, T.; Fucharoen, S.; Hamano, S.; Acharya, G. P.; Kawasaki, T.; Fukumaki, Y.
- Abstract
Abstract Thalassemia is a prevalent hereditary disorder characterized by impaired synthesis of globin chains. It has been suggested that the high frequency of thalassemia might reflect heterozygote advantage due to reduced susceptibility to malaria. In Nepal, malaria has often occurred in places below the altitude of 1200m. We carried out a microepidemiological study on thalassemia in two neighboring populations in Nepal, the Danuwar and the Tamang. Settlements of the Danuwar are located below the limit of the malarial zone (1200m in altitude), whereas those of the Tamang are found in malaria-free uplands. Three heterozygotes for hemoglobin (HbE) were observed in the Danuwars. We detected one type (-alpha[sup 3.71]) of alpha[sup +]-thalassemia that involves a deletion of 3.7kb, leading to a loss of one of two alpha-globin genes, in the Danuwars, at a high gene frequency of 63%, while the gene frequency in the Tamangs was only 5%. Analysis of the alpha-globin gene cluster revealed that four different haplotypes were associated with the type of alpha[sup +]-thalassemia in the Danuwars. Nucleotide sequences of the D-loop region in the mitochondrial DNA of the two populations indicated a similar nucleotide diversity in each population. The fixation index, Fsi, representing the degree of genetic differentiation estimated from mitochondrial DNA diversities (F[sub ST], 0.05), was smaller than that obtained from the gene frequencies of alpha[sup +]-thalassemia (F[sub ST], 0.55). If we assume neutral molecular evolution in the D-loop region of mitochondrial DNA, these results suggest that the high frequency of alpha[sup +]-thalassemia may be due to biological adaptation to the malarial environment rather than to events such as a bottleneck.
- Subjects
NEPAL; GLOBIN genes; THALASSEMIA; MALARIA; MEDICAL genetics; GENETICS
- Publication
Journal of Human Genetics, 2000, Vol 45, Issue 3, p127
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1007/s100380050198