The γ-Chain in a Ghanaian Adult, Homozygous for Hereditary Persistence of Fetal Haemoglobin

Abstract

Fetal haemoglobin consists of α- and γ-chains. There are two types of human γ-chains:one, (Gγ) in which residue 136 is one of glycine, and another (Aγ), in which that position is occupied by a residue of alanine. Some time ago a homozygote for the high persistent fetal haemoglobin gene was found in Ghana whose sole red cell pigment was fetal haemoglobin. The nature of the fetal haemoglobin in this individual has now been determined. It is entirely of the Gγ-type.

Further Investigations of the <i>γ</i>-Chain in a Ghanaian Adult, Homozygous for Hereditary Persistence of Fetal Haemoglobin

“…The other approach involves chain sepa ration of Hb F and tryptic hydrolysis of the y-chains. Peptide chromato grams are prepared and the yTp XIV peptide is isolated and analysed [1,16]. The yTp XIV has to be separated from yTp II by paper electropho resis in a pH 3.5 buffer (pyridine-acetic acid-water 5:50:945 by volume), a process which results in loss of material up to 50%.…”

“…Blood samples were obtained from infants heterozygous for Hb F Texas I [6], Hb F Port Royal [71, Hb F Poole [8] and adult homozygous for HPFH [1], homoz ygous Hb S with raised Hb F, and a patient with raised Hb F due to leukaemia. The Hb F fractions were either separated from haemolysates by DEAE Sephadex chro matography [9] prior to removing the haem [10] or the total haemolysate was used for the determination o f glycine/alanine ratio at position /136.…”

“…Each sample was di vided into two portions; in the first, chain separation was carried out [11], and the /-chain digested with trypsin and fingerprints prepared [12]. The yTp XIV (133-144) peptide was separated from yTp II (9-17) by paper electrophoresis at pH 3.5 as previously described [1], Globin from the other portion (10 mg) was treated with cyanogen bromide [13] in 70% formic acid and lyophilised. It was then re-dissolved in pH 6.4 buffer (pyridine-acetic acid-water 100:4:900 by volume) and ap plied on Whatman N o.…”

“…Patients of African and Indian origin homozygous for HPFH have been found to synthesize mainly the Gy-chain type [3,4]; whereas those of Caucasian origin have been shown to synthesize mainly the Ay type [5]. In our previous publication [1], a patient from Ghana, homozygous for HPFH was reported to synthesize c,y-chains only, on the basis of the amino acid analysis of /Tp XIV (residues 133-144), of the Hb F on this subject. On reading our article, Prof. W. A. Sch r o e d e r of the California Institute of Technology, Pasadena, wrote: '... when we have had analyses with Gly = 0.91 and Ala = 2.17 such as you show for yTp XIV, it has been shown by PTH degradation of y CB-3 that the de parture of these values from 1.00 and 2.00 was indeed real, both PTH (3-phenyl-2-thiohydantoin)-glycine and PTH-alanine were detectable in posidon 136.'…”

Biosynthetic Studies and <i>γ</i>-Chain Composition in the Greek Type of Hereditary Persistence of Fetal Hemoglobin and in Its Association with <i>β</i>-Thalässemia

“…Two main forms of HPFH have been described: the Negro and the Greek type. In the Negro type the heterozy gote shows Hb F ranging between 15 and 30%>, while the homozygote presents 100°/o Hb F [7,14,23,27]. In the Greek type only the heterozygote has been so far observed: in this form the Hb F is about 15°/o of the total hemoglobin [8], In both these conditions the Hb F is homogeneously distributed among the erythrocytes: this property was formerly considered to discriminate between HPFH and //-thalassemia; on the other hand, some types of HPFH with low percentages of Hb F and heterogeneous distribution of this he moglobin among the erythrocytes have been described [2,12,19,20,28], Since Schroeder et al [24] have dem onstrated that the /-chains are codified by two different structural genes, carrying gly cine or alanine respectively at position 136 (°/ and A/), the composition of fetal hemo globin in HPFH has been carefully studied.…”