The 32·6 kb Indian δβ-thalassaemia deletion ends in a 3·4 kb L1 element downstream of the β-globin gene


Dr John G. Gilman, Division of Hematology, Department of Medicine, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467, U.S.A.


Summary. The Indian δβ-thalassaemia, with elevated fetal γ globin gene expression, was previously found to have a large deletion beginning 1 kb 3’of the Aγ globin gene at GenBank HUMHBB coordinate 42151, and extending into a new L1 sequence. We have now determined the 3’breakpoint of this deletion, and in doing so we have extended the known β-globin gene cluster DNA sequence from its end at 73326 to projected GenBank coordinate 79016. These data show that the deletion is 32–6 kb long, terminating 11 kb 3’of the β-globin gene. This 3’breakpoint is at 74772, within a 3.4 kb partial L1 repeat at 74263–77665; the Black (Aγδβ)°-thalassaemia also terminates in this L1, at 76508. In addition, two Alu sequences were found, at 73692–73816 and 78171–78441. Among the protein-binding DNA sequence motifs 3’to the Indian δβ-thalassaemia breakpoint, at 76581/76607 there is a TGATAA/ACACCC pair that binds the erythroid-specific GATA-1 and ubiquitous CACCC-box binding proteins. We hypothesize that elevated fetal haemoglobin may be due to an enhancer or enhancers 3’to the deletion breakpoints and may involve the TGATAA/ ACACCC pair.