Evidence for localization of genes for human α-globin on the long arm of chromosome 4

Abstract

THERE is disagreement about the site of the human haemoglobin structural genes, mapping of which has been attempted by in situ hybridisation^1–4 and family studies^5,6. After in situ hybridisation of human metaphase chromosomes with radioactive globin mRNA Price et al.¹ suggested that the haemoglobin structural genes are located on the long arm of chromosome 2 and on the long arm of a B-group chromosome, the latter carrying the genes for β, γ and δ chains. Their approach was criticised because of the low specific activity of the ³H-mRNA assay used^7,8, but Atwood et al.² and Price and Hirschhorn^3,4 confirmed the original assignments using human complementary DNA (cDNA). Finally it was decided that the B-group chromosome that carries haemoglobin loci is chromosome 4^3,4. Family studies gave results consistent with loose linkage between the locus of the MN blood group and β-thalassaemia. The MN blood group has been mapped tentatively on the long arm of chromosome 2 or on the distal end of the long arm of chromosome 4 (refs 9, 10). But the localisation of the MN system on 2q is inconsistent with data from family studies^11–13, and the distal segment of 4q has been considered more probable¹¹. For similar reasons the β-globin locus has been mapped tentatively on chromosome 4 (ref. 5). We report here a study of globin synthesis which confirms that chromosome 4 is the site of the structural gene for α-globin.