THE DELETION IN BOTH COMMON TYPES OF HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN IS APPROXIMATELY 105 KILOBASES

  • 1 December 1987
    • journal article
    • research article
    • Vol. 70  (6) , 1797-1803
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 Sfil, 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.