The 12.6 kilobase DNA deletion in Dutch β°‐thalassaemia

Abstract

SummaryThe Dutch β°‐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 β‐globin gene (Gilman et al, 1984). A DNA fragment containing the breakpoints of the Dutch β°‐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 (LI) 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 β°‐thalassaemia deletion. The 12.6 kb Dutch β°‐thalassaemia deletion is now seen to be a member of a 12–13 kb size category of deletions which also includes two δβ‐thalassaemias.