DNA sequence analysis of the Dutch beta zero-thalassemia deletion.
The Dutch beta zero-thalassemia has relatively few clinical symptoms in the homozygote. Heterozygotes have levels of fetal hemoglobin (4-11%) comparable to delta beta-thalassemia, and much higher than in typical beta zero-thalassemia. To analyze this deletion, we have cloned the abnormal 10 kb Bgl II fragment that contains the delta-globin gene into phage lambda vector EMBL4. A Hind III-Xba I fragment that includes the endpoints of the deletion was subcloned into plasmid pUC 19 and partially sequenced by the dideoxy method. The sequence of the Dutch beta zero-thalassemia DNA is like that of normal 5' DNA to 8920 (the numbering system is from reference 2). The sequence from 8915-8920 is AAATTT, which is also the normal 3' sequence from 21537-21542. From this point on, the Dutch beta zero-thalassemia sequence is like that of the normal 3' DNA. The deletion is therefore 12.6 kilobases, rather than 10 as originally estimated. It is similar to several other beta-globin gene deletions in terminating in a region of Kpn I repeated sequences, and having several base pairs of homology between 5' and 3' sequences at the break points.
D001483:Base Sequence; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D005914:Globins / Q000235:genetics; D006801:Humans; D009426:Netherlands; D013789:Thalassemia / Q000235:genetics*
D005914:Globins; D004247:DNA