Molecular characterization of a beta zero-thalassemia resulting from a 1.4
kilobase deletion
R Anand, CD Boehm, HH Kazazian and EF Vanin
Department of Biochemistry, Ohio State University, Columbus, OH 43210.
We report the characterization of a beta zero-thalassemia in an American
Black with unusually high HbA2 and HbF levels. Genomic southern analysis
indicated that the individual was heterozygous for a deletion that began
within the second intervening sequence of the beta- globin gene and
extended approximately 1.4 kb in the 5' direction. A clone spanning the
breakpoint on the abnormal chromosome was isolated and further mapped, and
the deletion joint was sequenced. Comparison of the normal beta-globin gene
and its 5' flanking region with the deletion joint sequence indicated that
the 5' breakpoint for this deletion was 484 base pairs (bp) 5' to the
transcriptional start site for the beta-globin gene and the 3' breakpoint
was 908 bp into the beta- globin gene; the deletion removed a total of
1,393 bp. Comparison of the normal 5' and 3' breakpoint sequences indicated
that this deletion was the result of a "clean" nonhomologous breakage and
reunion event; ie, no spurious bases were added during the recombinational
event. Analysis of the breakpoints of this deletion together with the
breakpoints of two other small deletions involving the beta-globin gene
suggests that the breakpoints may occur at DNA polymerase alpha pause
sites.
Volume 72,
Issue 2,
pp. 636-641,
08/01/1988
Copyright © 1988 by The American Society of Hematology
