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PMID: 6714226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 3 ·No. 3 ·1984-03-00 ·Pages 593-6

Kazazian HH, Orkin SH, Antonarakis SE, Sexton JP, Boehm CD, Goff SC, Waber PG

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.

MeSH Terms
Gene Frequency Genetic Linkage Globins/genetics Humans India/ethnology Mutation Thalassemia/genetics
Chemicals
Globins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kazazian H H
Orkin S H
Antonarakis S E
Sexton J P
Boehm C D
Goff S C
Waber P G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1984-03-00
Pages
593-6
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557393
Subset
IM
Databases
GENBANK
J00093, J00094, J00096, J00158, J00159, J00160, J00161, J00162, J00163, J00164, J00165, J00166, J00167, J00168, J00169, J00170, J00171, J00172, J00173, J00174, J00175, J00177, J00178, J00179, K01239, K01890, K02544, M18047, M19067, X00423
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