The thalassaemia syndromes / D.J. Weatherall.

  • Weatherall, D. J.
Date:
1972
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: The thalassaemia syndromes / D.J. Weatherall. Source: Wellcome Collection.

    35/392 (page 21)
    HAEMOGLOBIN AND ITS GENETIC CONTROL 21 separate genes. A scheme for the genetic control of haemoglobin synthesis is shown in Fig. 2.7. In this model iv-chain synthesis remains active throughout foetal and adult life. In foetal life first the e and then the y-chain loci are activated, «-chains combining with e- and y-chains to produce haemoglobins Gower 2 and F respectively. After birth the y-locus is 'switched off' and the ß- and 8-loci are fully activated and a-chains now combine with ß- and S-chains to produce haemoglobins A and Az respectively. GENES ^ 136 gly 136 ala „ v ч У Y Ût ; a; ß CHAINS HAEMOGLOBINS аг £2 .136 gly (X2 У г 136 ala аг 72 Hb Gower 2 Hb F Hb A Hb A- Fig. 2.7. The genetic control of human haemoglobin synthesis. The central position of the a-chain locus or loci in both foetal and adult haemoglobin synthesis is indicated. The uncertainty about the number of a-loci is represented by the bracketed second locus. Minor loci such as the ^-locus are not included. From this model for the genetic control of haemoglobin synthesis the haemoglobin constitution of patients with different forms of inherited haemoglobinopathy can be predicted (Fig. 2.8). Thus individuals homo¬ zygous for a j6-chain variant will have no haemoglobin A but normal foetal and A2 components. Since a single gene controls a-chain synthesis in haemoglobins F, A and A25 individuals heterozygous for a-chain haemo¬ globin variants have, in addition to both normal and abnormal major haemoglobin components, normal and abnormal haemoglobin A2 and F components as well. An individual heterozygous for both an a-chain and a ;8-chain haemoglobin variant, with the genotype a^, a^, /3^, ß^, makes four haemoglobins; and a'^ß^. There are now several reported families in which one or more individuals have four haemoglobins. These relationships have been fully reviewed elsewhere