NUCLEOTIDE-SEQUENCE OF THE BELGIAN G-GAMMA + (A-GAMMA-DELTA-BETA)0-THALASSEMIA DELETION BREAKPOINT SUGGESTS A COMMON MECHANISM FOR A NUMBER OF SUCH RECOMBINATION EVENTS

Various types of thalassemia or hereditary persistance of fetal hemoglobin (HPFH) are caused by deletions at the human β-globin gene cluster. Many of these molecular lesions show a clear clustering as far as size and location of their breakpoints are concerned. This might indicate common recombination mechanisms responsible for the generation of these deletions. The Belgian Gγ+(Aγδβ)0-thalassemia results from a large deletion spanning the β-globin gene cluster 3′ of the Aγ gene. The extent of this deletion, analyzed by field-inversion gel electrophoresis, is approximately 50 kb and is very similar to that of the Indian HPFH (GγAγ HPFH III) previously characterized by P. S. Henthorn et al. (1986). Proc. Natl. Acad. Sci. USA 83: 5194-5198. Isolation of the deletion junction of the Belgian Gγ+(Aγδβ)0-thalassemia by means of inverse polymerase chain reaction confirmed a very close relationship between these two independent deletions. The 3′ breakpoint of the Belgian deletion is located at the midpoint of a 160-bp palindrome, only four nucleotides 5′ from the correspondent endpoint of the Indian HPFH. © 1990.