title: An IVS-I-117 (G-->A) acceptor splice site mutation in the alpha 1-globin gene is a nondeletional alpha-thalassaemia-2 determinant in an Indian population.
abstract: In 1991 we reported the identification of two deletional alpha-thalassaemia-2 determinants (-3.7 kb and -4.2 kb) and one nondeletional alpha-thalassaemia-2 determinant (Hb Koya Dora alpha 2 codon 142, TAA-->TCA) in a tribal population in Central India (Gupta et al, 1991). Evidence was obtained at that time for the possible presence of an additional nondeletional alpha-thalassaemia-2 because of low levels of Hb S (< 28%) in some Hb S heterozygotes with a simple alpha-thalassaemia-2 heterozygosity (-alpha/alpha alpha). This abnormality has now been identified as a G-->A mutation at IVS-I-117 of the alpha 1-globin gene (acceptor splice site) which makes this gene nonfunctional. Its frequency was established at approximately 6% which raises the total frequency of alpha-thalassaemia determinants in this population to approximately 60%. Subjects with a deletional alpha-thalassaemia-2 and the newly discovered alpha 1 acceptor splice junction mutation in trans appear to have an alpha chain deficiency similar to that of an alpha-thalassaemia-2 homozygote (-alpha/-alpha). An additional change (C-->G) at the Cap -4 site was observed in six alpha 1- and one alpha 2-globin genes; this polymorphism is not associated with a decrease in alpha chain synthesis and is not linked to the IVS-I-117 (G-->A) mutation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: M A
authors.initials: MA
authors.lastname: Cürük
authors.forename: E
authors.initials: E
authors.lastname: Baysal
authors.forename: R B
authors.initials: RB
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000737:chemistry; D005260:Female; D005914:Globins / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D007194:India / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015345:Oligonucleotide Probes; D017085:alpha-Thalassemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
chemical_list: D006451:Hemoglobin, Sickle; D015345:Oligonucleotide Probes; D005914:Globins; D004247:DNA