The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kilobases

Abstract

The most common forms of hereditary persistence of fetal hemoglobin (HPFH) involve large deletions that remove the adult delta and beta genes but leave the paired fetal genes (G gamma and A gamma) intact. The size of these deletions has previously eluded exact definition. Using pulsed-field gel electrophoresis and the enzyme SfiI, which cuts only rarely in genomic DNA, we have constructed a large-scale restriction map of the beta-globin cluster in normal and HPFH DNA. The deletions in HPFH-1, which occurs in American blacks, and in HPFH-2, which occurs in Ghanaian blacks, are found to be approximately 105 kilobases (kb) in length, though the endpoints are staggered by approximately 5 kb. The fact that two previously reported gamma delta beta-thalassemia deletions to the 5′ side of the beta-globin cluster are also about 100 kb suggests a common mechanism, possibly involving the loss of a complete chromatin loop.

Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin

“…Seven cases of HPFH type 1 and 23 cases of HPFH type 2 were studied, 12 were males. Although HPFH type 1 has been reported to be the most common deletional HPFH occurring in American blacks, our sample of patients contained more HPFH type 2 than type 1, which may be due to referral bias (Collins et al, 1987). There were 72 HbF values from the newborn period to age 20 years with an average of 40AE6% (median 35AE4%, range 27AE1-90AE8%).…”

Physical mapping of the cystic fibrosis region by pulsed-field gel electrophoresis

“…A final caveat is that the sizes of the fragments reported in Tables 1 and 2 must be considered to have a potential error of at least 10%. Sizing of PFGE bands is quite sensitive to the amount of DNA per lane (Collins et al, 1987b); while we attempted to keep the DNA per lane under 3 pg, some variation in the size of a fragment from gel to gel was often seen. In our experience, one must be particularly careful in sizing DNA fragments larger than 800 kb on FIGE gels; as also noted by others (Ellis et aZ., 1987), above this range the relationship of fragment size to mobility breaks down.…”

“…When combined with restriction enzymes which cut only rarely in the genome and Southern blotting techniques to identify single-copy fragments in complete and partial digests, this approach provides a means of constructing a map of a region of several megabases (Smith et al, 1986(Smith et al, , 1987bSmith and Cantor, 1987). This has been recently accomplished in man, for example, for the Duchenne muscular dystrophy region (van Ommen et aZ., 1986;Burmeister and Lehrach, 1986;Kenwrick et al, 1987), the major histocompatibility complex (Lawrance et aZ., 1987), the human /3-globin region (Collins et al, 1987b), and regions of chromosome 4p near the Huntington disease locus (Poustka et al, 1987). We have now applied this approach to the CF region, using met, CF63, and 53.11 as molecular probes.…”

Nuclear scaffold attachment sites in the human globin gene complexes.

“…We find no clear associations between SARs and the breakpoints of the many deletions of the,-globin gene complex. This includes the group of equal-sized but staggered large deletions for which a model involving excision of a chromosomal loop across its base has been proposed (Vanin et al, 1983;Taramelli et al, 1986;Collins et al, 1987). This is no surprise as the staggered nature of the deletions mitigates against the involvement of fixed attachment sites.…”