Human alpha-globin gene expression is silenced by terminal truncation of chromosome 16p beginning immediately 3' of the zeta-globin gene.
The high level expression of the human alpha-globin genes in erythroid tissue appears to require a set of DNaseI hypersensitive sites located upstream of the human alpha-globin gene cluster. These sequences, termed the locus control region (LCR), include two erythroid specific and a number of less restricted DNaseI hypersensitive sites. In this report we describe an individual with alpha-thalassemia associated with a truncation of the short arm of chromosome 16 that removes the LCR region and inactivates the adjacent intact alpha-globin genes. This genetic study supports the critical role of the LCR in the transcriptional activation of the human alpha-globin gene cluster and substantiates the importance of LCR deletions in the etiology of alpha-thalassemia.
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia 19104.
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Romao
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Cash
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Weiss
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Liebhaber
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Pirastu
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Galanello
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Loi
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Paglietti
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Ioannou
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Cao
D015139:Blotting, Southern; D002675:Child, Preschool; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013789:Thalassemia / Q000235:genetics*
D005914:Globins