Molecular characterization of seven beta-thalassemia mutations in Asian Indians.

Haig Kazazian, S. H. Orkin, S. E. Antonarakis, J. P. Sexton, C. D. Boehm, S. C. Goff, P. G. Waber

Research output: Contribution to journalArticle

Abstract

To characterize systematically the mutations which produce beta-thalassemia in Asian Indians, we first determined the DNA polymorphism haplotype in the beta-globin gene cluster of 44 beta-thalassemia chromosomes in the ethnic group. Nine different haplotypes were observed. Upon molecular cloning and partial DNA sequencing of one beta-gene from each of eight haplotypes and two from the ninth, seven different mutations were found. None of these have been identified in Mediterranean patients, even among the five haplotypes which appeared identical in the two groups. Asian Indian mutations included one nonsense and three frameshift mutations, one deletion affecting an acceptor splice site, and two mutations affecting a donor splice site. The correlation of a specific mutation with a specific haplotype was high but not invariant. Two mutations were associated with more than one haplotype but, in each instance, the mutation spread to a new haplotype could be explained most simply by recombination 5' to the beta-globin gene. In addition, four mutations, one reported here and three others previously reported, have been observed on two chromosome backgrounds that are identical except for the status of a polymorphic HinfI site 5' to the beta gene. This HinfI site does not show significant linkage disequilibrium with markers both 5' and 3' to it, suggesting that it lies within a region of relative sequence randomization.

Original languageEnglish (US)
Pages (from-to)593-596
Number of pages4
JournalThe EMBO journal
Volume3
Issue number3
StatePublished - Mar 1984
Externally publishedYes

Fingerprint

beta-Thalassemia
Haplotypes
Genes
RNA Splice Sites
Mutation
beta-Globins
Chromosomes
Cloning
DNA
Polymorphism
Frameshift Mutation
Linkage Disequilibrium
Molecular Cloning
Multigene Family
Random Allocation
DNA Sequence Analysis
Ethnic Groups
Genetic Recombination

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Kazazian, H., Orkin, S. H., Antonarakis, S. E., Sexton, J. P., Boehm, C. D., Goff, S. C., & Waber, P. G. (1984). Molecular characterization of seven beta-thalassemia mutations in Asian Indians. The EMBO journal, 3(3), 593-596.

Molecular characterization of seven beta-thalassemia mutations in Asian Indians. / Kazazian, Haig; Orkin, S. H.; Antonarakis, S. E.; Sexton, J. P.; Boehm, C. D.; Goff, S. C.; Waber, P. G.

In: The EMBO journal, Vol. 3, No. 3, 03.1984, p. 593-596.

Research output: Contribution to journalArticle

Kazazian, H, Orkin, SH, Antonarakis, SE, Sexton, JP, Boehm, CD, Goff, SC & Waber, PG 1984, 'Molecular characterization of seven beta-thalassemia mutations in Asian Indians.', The EMBO journal, vol. 3, no. 3, pp. 593-596.
Kazazian H, Orkin SH, Antonarakis SE, Sexton JP, Boehm CD, Goff SC et al. Molecular characterization of seven beta-thalassemia mutations in Asian Indians. The EMBO journal. 1984 Mar;3(3):593-596.
Kazazian, Haig ; Orkin, S. H. ; Antonarakis, S. E. ; Sexton, J. P. ; Boehm, C. D. ; Goff, S. C. ; Waber, P. G. / Molecular characterization of seven beta-thalassemia mutations in Asian Indians. In: The EMBO journal. 1984 ; Vol. 3, No. 3. pp. 593-596.
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