Molecular analysis of α-thalassemia in Nepal: Correlation with malaria endemicity

Yasuyoshi Sakai, Shigeru Kobayashi, Hiroki Shibata, Hiroyasu Furuumi, Toshiyasu Endo, Supan Fucharoen, Shinjiro Hamano, Gopal P. Acharya, Terukazu Kawasaki, Yasuyuki Fukumaki

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

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 E (HbE) were observed in the Danuwars. We detected one type (-α3.71) of α+- thalassemia that involves a deletion of 3.7kb, leading to a loss of one of two α-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 α-globin gene cluster revealed that four different haplotypes were associated with the type of α+-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, F(ST), representing the degree of genetic differentiation estimated from mitochondrial DNA diversities (F(ST), 0.05), was smaller than that obtained from the gene frequencies of α+-thalassemia (F(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 α+-thalassemia may be due to biological adaptation to the malarial environment rather than to events such as a bottleneck.

元の言語英語
ページ(範囲)127-132
ページ数6
ジャーナルJournal of Human Genetics
45
発行部数3
DOI
出版物ステータス出版済み - 1 1 2000

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Nepal
Thalassemia
Malaria
Globins
Mitochondrial DNA
Gene Frequency
Heterozygote
Biological Adaptation
Hemoglobin E
Population
Genetic Drift
Molecular Evolution
Multigene Family
Haplotypes
Nucleotides
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

これを引用

Sakai, Y., Kobayashi, S., Shibata, H., Furuumi, H., Endo, T., Fucharoen, S., ... Fukumaki, Y. (2000). Molecular analysis of α-thalassemia in Nepal: Correlation with malaria endemicity. Journal of Human Genetics, 45(3), 127-132. https://doi.org/10.1007/s100380050198

Molecular analysis of α-thalassemia in Nepal : Correlation with malaria endemicity. / Sakai, Yasuyoshi; Kobayashi, Shigeru; Shibata, Hiroki; Furuumi, Hiroyasu; Endo, Toshiyasu; Fucharoen, Supan; Hamano, Shinjiro; Acharya, Gopal P.; Kawasaki, Terukazu; Fukumaki, Yasuyuki.

:: Journal of Human Genetics, 巻 45, 番号 3, 01.01.2000, p. 127-132.

研究成果: ジャーナルへの寄稿記事

Sakai, Y, Kobayashi, S, Shibata, H, Furuumi, H, Endo, T, Fucharoen, S, Hamano, S, Acharya, GP, Kawasaki, T & Fukumaki, Y 2000, 'Molecular analysis of α-thalassemia in Nepal: Correlation with malaria endemicity', Journal of Human Genetics, 巻. 45, 番号 3, pp. 127-132. https://doi.org/10.1007/s100380050198
Sakai, Yasuyoshi ; Kobayashi, Shigeru ; Shibata, Hiroki ; Furuumi, Hiroyasu ; Endo, Toshiyasu ; Fucharoen, Supan ; Hamano, Shinjiro ; Acharya, Gopal P. ; Kawasaki, Terukazu ; Fukumaki, Yasuyuki. / Molecular analysis of α-thalassemia in Nepal : Correlation with malaria endemicity. :: Journal of Human Genetics. 2000 ; 巻 45, 番号 3. pp. 127-132.
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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 E (HbE) were observed in the Danuwars. We detected one type (-α3.71) of α+- thalassemia that involves a deletion of 3.7kb, leading to a loss of one of two α-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 α-globin gene cluster revealed that four different haplotypes were associated with the type of α+-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, F(ST), representing the degree of genetic differentiation estimated from mitochondrial DNA diversities (F(ST), 0.05), was smaller than that obtained from the gene frequencies of α+-thalassemia (F(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 α+-thalassemia may be due to biological adaptation to the malarial environment rather than to events such as a bottleneck.",
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AU - Endo, Toshiyasu

AU - Fucharoen, Supan

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