Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion
SH Orkin, BP Alter, C Altay, MJ Mahoney… - … England Journal of …, 1978 - Mass Medical Soc
SH Orkin, BP Alter, C Altay, MJ Mahoney, H Lazarus, JC Hobbins, DG Nathan
New England Journal of Medicine, 1978•Mass Medical SocWe applied a recently developed and more direct technic to diagnose thalassemia
syndromes associated with deletion of particular globin structural genes and to assess a
fetus at risk for one of those conditions, δβ-thalassemia. The method allows assessment of
the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA.
Cellular DNA fragments produced by cleavage using two specific restriction endonucleases
are separated on the basis of size by agarose-gel electrophoresis, and the distribution of …
syndromes associated with deletion of particular globin structural genes and to assess a
fetus at risk for one of those conditions, δβ-thalassemia. The method allows assessment of
the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA.
Cellular DNA fragments produced by cleavage using two specific restriction endonucleases
are separated on the basis of size by agarose-gel electrophoresis, and the distribution of …
Abstract
We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, δβ-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization.
We observed the total deletion of α-globin genes in homozygous α-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular β and β-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and δβ-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for δβ-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth. (N Engl J Med 299:166–172, 1978)
The New England Journal Of Medicine