Alpha alpha alpha alpha anti-3.7 type II: a new alpha-globin gene rearrangement suggesting that the alpha-globin gene duplication could be caused by intrachromosomal recombination

We report here a new human alpha-globin gene rearrangement carrying the two normal, alpha 2 and alpha 1, and two hybrid, alpha 1/alpha 2, globin genes in the order 5'-alpha 2-alpha 1/alpha 2-alpha 1/alpha 2-alpha 1-3'. Both the hybrid genes, subtyped with ApaI and RsaI restriction enzymes, were found to be of the uncommon anti 3.7 type II. The hybrid genes were expressed at the biosynthetic level and their interaction with the beta-thalassaemia IVS 1 nt 1 G---A mutation caused thalassaemia intermedia. We also report a case of an alpha alpha alpha-globin gene rearrangement in the twin of one of the alpha alpha alpha alpha-globin gene carriers; the duplicated gene was of the anti 4.2 type and was associated with the absence of RsaI polymorphism. The singular finding of an alpha alpha alpha alpha-anti 3.7 cluster with two identical rare hybrid genes suggests that the reciprocal unequal recombination causing the alpha-globin gene rearrangements could be of the intrachromosomal rather than the interchromosomal type.