Evidence for localisation of genes for human alpha-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 hybridisation1–4 and family studies5,6. 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 used7,8, but Atwood et al.2 and Price and Hirschhorn3,4 confirmed the original assignments using human complementary DNA (cDNA). Finally it was decided that the B-group chromosome that carries haemoglobin loci is chromosome 43,4. 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 studies11–13, 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.