The 12.6 kilobase DNA deletion in Dutch beta zero-thalassaemia

Abstract

The Dutch beta zero-thalassaemia has few clinical symptoms in homozygotes, elevated fetal haemoglobin (4-11%) in heterozygotes, and has a DNA deletion previously estimated as 10 kb which removes the beta-globin gene (Gilman et al, 1984). A DNA fragment containing the breakpoints of the Dutch beta zero-thalassaemia deletion has now been cloned. Sequencing across the deletion junction region showed the 3' endpoint to be about 3 kb further 3' than originally thought, so that the deletion covers 12.6 kb. The 3' endpoint lies in a region of Kpn I (L1) repeated sequences, which is also the case for several other deletions. A six bp region of homology (AAATTT) between the 5' and 3' normal sequences at the breakpoint may have contributed to the non-homologous recombination event that led to the Dutch beta zero-thalassaemia deletion. The 12.6 kb Dutch beta zero-thalassaemia deletion is now seen to be a member of a 12-13 kb size category of deletions which also includes two delta beta-thalassaemias.