The Inactive fi Globin Gene on a ‘ y 9 Thalassemia Chromosome Has a Normal

We have previously described an English family with ‘y#{244} thalassemia in which a large deletion stops 25 kilobases (kb) upstream from the fl-globin gene locus. and yet the fi-globin gene is inactive in vivo. Affected family members had a fi-thalassemia minor phenotype with a normal hemoglobin A2 level. Gene mapping showed that these subjects were heterozygous for a chromosome bearing a large deletion that began in the #{176}y-globin gene. extended through the &globin gene. and continued upstream for at least 75 kb. The A,. , and fi-globin gene loci on this chromosome were intact. To examine the possibility that an additional defect was present in the $-globin gene, we cloned, sequenced, and examined the expression of the fl-globin gene from the affected chromosome. No mutation