Premium
Four base‐pair DNA deletion in human A γ globin‐gene promoter associated with low A γ expression in adults
Author(s) -
Oilman John G.,
Johnson Mary E.,
Mishima Noboru
Publication year - 1988
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1988.tb04235.x
Subject(s) - dna , microbiology and biotechnology , gene , genetics , base pair , gene expression , promoter , biology , base (topology) , mathematical analysis , mathematics
Summary Fetal haemoglobin (α 2 γ 2 ) is predominant in red cells of the fetus and newborn baby, and is largely replaced after birth by adult haemoglobin (α 2 β 2 ). The two types of γ chains ( A γ and G γ) are generally less than 1% of total β‐like chain in adults, and the G γ: A γ ratio is typically 40:60. Higher G γ values (> 50% of γ chain) are frequently associated with a T for C nucleotide substitution 158 base pairs 5’of the G γ Cap site (‐158). The first exception to this rule was a β ‐thalassaemia in a Black family that was associated with about 60% G γ in heterozygotes. A DNA fragment containing the G γ and A γ genes of the high G γ haplotype of this case has now been cloned. DNA sequencing from ‐ 383 to the Cap site showed no differences from normal for the G γ gene, except for C at ‐ 158. For the A γ gene, however, a deletion of four base pairs (AGCA) at ‐ 222 to ‐ 225 was found. It is hypothesized that this deletion causes reduced A γ globin gene expression in adults, which suggests that promoter elements important for the regulation of fetal haemoglobin expression in adults extend upstream at least to ‐225.