ATA box transcription mutation in beta-thalassemia.
AUTOR(ES)
Orkin, S H
RESUMO
DNA sequence analysis of a cloned beta-globin gene from a Chinese patient with beta-thalassemia revealed a single nucleotide substitution (A leads to G) within the ATA box homology and 28 base pairs upstream from the cap site. The patient was homozygous for this particular allele based on restriction mapping at nine different polymorphic sites in the beta-globin gene cluster. Upon transient expression in HeLa cells this gene directed the production of 3-5-fold less beta-globin mRNA than the normal beta-gene. In RNA isolated from the patient's erythroid cells beta-RNA was 10-fold less abundant relative to alpha-RNA than normal, indicating close approximation of the heterologous cell expression results and the in vivo state. These findings support the validity of such transient expression assays for analysis of phenotypes associated with naturally occurring mutant genes and establish the functional significance of nucleotide substitutions at position -28 for human beta-globin gene transcription.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=326082Documentos Relacionados
- Resistance to infection in murine beta-thalassemia.
- RNA processing errors in patients with beta-thalassemia.
- Heterogeneity of DNA deletion in gamma delta beta-thalassemia.
- Molecular basis for dominantly inherited inclusion body beta-thalassemia.
- Human globin gene analysis for a patient with beta-o/delta beta-thalassemia.