Sequence analysis of the gamma-globin gene locus from a patient with the
deletion form of hereditary persistence of fetal hemoglobin
CA Stolle, LA Penny, S Ivory, BG Forget and EJ Benz
Department of Internal Medicine, Yale University School of Medicine, New
Haven, CT 06510.
The gamma-globin genes from a patient homozygous for a deletion form of
hereditary persistence of fetal hemoglobin (HPFH-1) have been cloned and
sequenced. The DNA sequence of the patient's gamma-globin genes corresponds
to a previously identified sequence framework (chromosome A) with the
exception of 10 base changes. Seven of these base changes can be attributed
to normal allelic variation generated by small gene conversion events. The
remaining three base changes are present in a 0.76 kb HindIII fragment
containing a putative enhancer located 3' to the A gamma-globin gene. The
same three base changes have also been described in the Seattle variant of
nondeletion HPFH. We have analyzed 16 alleles from non-HPFH individuals and
five alleles from individuals with nondeletion or deletion HPFH for the
presence of these base changes by polymerase chain reaction amplification
of cloned or chromosomal DNA and hybridization to allele-specific
oligonucleotide probes. Although these base changes were found in an
individual with HPFH-2, they were not found in the DNA from two patients
with nondeletion HPFH. More importantly, all three base changes were
detected in DNA from five non-HPFH individuals and appear to be common in
blacks. We conclude that these base changes do not correlate with an HPFH
phenotype and that the significant mutation in HPFH-1 is the deletion of
over 100 kb of genomic DNA.
Volume 75,
Issue 2,
pp. 499-504,
01/15/1990
Copyright © 1990 by The American Society of Hematology
