A Short Review of Human γ-Globin Gene Anomalies

Abstract

This paper summarizes various anomalies involving the duplicated y-globin genes which are normally arranged as -^Gγ-^Aγ-. Variations include^Gγ→^Aγand ^Aγ→^Gγ replacements; newborn heterozygotes for these anomalies have low ^Gγ (^Aγ^Aγ/^¤γ^Aγ) or high ^Gγ values (^Gγ^Gγ/^Gγ^Aγ). Additional abnormalities include the deletion of one γ-globin gene (-^Aγ-; γ-thalassemia), γ-globin gene triplications (^Gγ-^AGγ-^Aγ-; ^Gγ-^Gγ-^Aγ) and γ-globin gene quadruplications (^Gγ-^Gγ-^Gγ-^Aγ-); several of these conditions are found in different populations but at low frequencies. In adults, the ^Gγto ^Aγ ratio in the Hb F and often also the Hb F level, are directly related to specific structural characteristics of the chromosome; specific mutations in the promoter sequences 5’ to ^Gγor to ^Aγ, for instance, may result in increased ^Gγ or ^Aγ chain production with an increase in Hb F levels (nondeletional ^Gγ- or ^Aγ-HPFH) or with only modest changes in the total Hb F (normal adults; Swiss-HPFH). Similar variations have been observed in SS patients

Contribution of gene conversion in the evolution of the human ?-like globin gene family

“…In the human β-like globin gene locus, unequal crossover takes place frequently, with hemoglobin (Hb) Lepore (Ottolenghi et al 1979) and Hb Kenya (Huisman et al 1972) as the most characteristic examples. The increase or decrease of gene copies in the α-like or the β-like globin gene clusters are further examples of homologous unequal crossover, which leads to phenotypes of various severity (Harano et al 1985;Yang et al 1986;Huisman 1987).…”

A Family with γ-Thalassemia and High Hb A2Levels

“…Isolated deletions of g-globin genes, are classified as g-thalassemias (19). Most cases of deletions and rearrangements of g-globin genes, such as duplication of one gene with the absence of the other one, have been identified in newborns of different ethnic origin (18,20,21) presenting with an alteration of the normal G gand A g-globin ratio.…”

α:Non–α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

“…Samples were prepared in acetic acid and 2-mercaptoethanol and electrophoresed for 4.5 h at 150 V [23] . After electrophoresis, the gels were stained in coomassie blue for 24 h and then destained for few days. All instruments were calibrated by standard methods.…”

“…The determination of the location and the mechanism of action of this medication and similar drugs will determine the study direction of more efficient drugs or a multi-drug combination. There are only a few studies on the effect of this medication on α:non-α and Gγ:Aγ ratio [24] . Thus, analyzing these indices in TI patients seemed necessary in order to better elucidate the mechanism of action of HU on β globin gene cluster expression.…”