A haplotype-linked four base pair deletion upstream of the Aγ globin gene coincides with decreased gene expression

✍ Scribed by Cherif Beldjord; Rolande Ducrocq; Sellama Nadifi; Claudine Lapoumeroulie; Jacques Elion; Dominique Labie

• Book ID: 104670012
• Publisher: Springer
• Year: 1992
• Tongue: English
• Weight: 496 KB
• Volume: 89
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00221951

✦ Synopsis

During normal human development, a switch is classically observed in the relative expression of the two gamma globin genes, the G gamma/A gamma ratio varying from 70/30 at birth to 40/60 by the end of the first year. An exception to this developmental pattern is linked to the presence of an XmnI restriction site at a position -158 to the Cap site of the G gamma gene. Another exception is observed in individuals homozygous for two easily detectable variations of the A gamma gene: the presence of a threonine residue at codon 75 and a HindIII site within the second intron. A 4-bp deletion has been described around position -225 in some thalassemic patients presenting with these variations. In this study, we find this deletion to be haplotype-linked in a series of 156 individuals of various ethnic origins and presenting with various normal and pathological phenotypes. In sickle cell patients heterozygous for this 4-bp deletion, the relative expression of the A gamma genes on the two chromosomes can be measured by estimating the A gamma T and A gamma I chains, the former always being synthesized at a lower rate. These results suggest a functional role for the deleted sequence.