A haplotype-linked four base pair deletion upstream of the A gamma globin gene coincides with decreased gene expression.
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.
INSERM Unité 129, ICGM, CHU Cochin, Paris, France.
C
C
Beldjord
R
R
Ducrocq
S
S
Nadifi
C
C
Lapoumeroulie
J
J
Elion
D
D
Labie
D001483:Base Sequence; D002872:Chromosome Deletion; D015870:Gene Expression / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length
D005914:Globins