The 12.6 kilobase DNA deletion in Dutch β°-thalassaemia

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Abstract
The Dutch .beta.0-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.0-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 kg. 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.0-thalassaemia deletion. The 12.6 kg Dutch .beta.0-thalassaemia deletion is now seen to be a member of 12-13 kg size category of deletions which also includes two .delta..beta.-thalassaemias.