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Polymorphisms of human γ-globin genes in Mediterranean populations

Nature volume 282, pages 316–318 (1979)Cite this article

Abstract

During normal human fetal development, two γ-globin genes are expressed to give γ-globin chains, one of which contains an alanine residue and the other a glycine residue at amino acid position 136 (Aγ and Gγ, respectively)1. Recently, a human γglobin chain mutant has been described in HbFSardinia in which threonine replaces isoleucine at position 75 (ref. 2). This haemoglobin is frequently found in varying levels in Italian patients with β-thalassaemia (29 out of 32 patients), and in normal fetal cord blood in some populations (9 out of 19)3. In England the proportion of infants expressing this variant (usually at low levels but occasionally up to 40% of the total fetal globin) is approximately one in five. The number of γ-globin gene loci has long been controversial. The two chains Aγ and Gγ are non-allelic and therefore the minimum possible number of genes is two. The change in Aγ/Gγ chain ratio from 0.3 to 1.5 as fetal development proceeds led Huisman and Schroeder to propose four γ-globin genes per haploid genome4,5. Direct molecular hybridisation of γ-globin DNA sequences gave data supporting the two-gene hypothesis6–8. Because of its widespread occurrence, it has been suggested that the γ-chain in HbFsardinia is coded by a third structural gene, Tγ, non-allelic with Aγ and Gγ (ref. 3). We show here by direct restriction analysis of the γ-globin genes that people expressing HbFSardinia have two γ-globin genes per haploid set, and therefore that the γ-chain in HbFsardinia is coded for by an allele of either the Aγ or Gγ-globin gene.

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Authors and Affiliations

  1. Department of Biochemistry, St Mary's Hospital Medical School, University of London, London, W2, UK

    Peter F. R. Little, Robert Williamson & Gillian Annison

  2. Laboratory of Biochemistry, University of Amsterdam, PO Box 60,000, 1005 GA, Amsterdam, The Netherlands

    Richard A. Flavell & Ernie De Boer

  3. Sylvanus Laboratoria, Instituut voor Anthropogenetica der Rijksuniversiteit, Wassenaarse-weg 72, Leiden, The Netherlands

    L. F. Bernini

  4. Istituto di Patologia Generale, Università degli Studi, 20133, Milan, Italy

    Sergio Ottolenghi

  5. Istituto di Medicina Interna, Università di Torino, Turin, Italy

    Guiseppe Saglio & Umberto Mazza

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  1. Peter F. R. Little
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Little, P., Williamson, R., Annison, G. et al. Polymorphisms of human γ-globin genes in Mediterranean populations. Nature 282, 316–318 (1979). https://doi.org/10.1038/282316a0

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