alpha-thalassemia resulting from a negative chromosomal position effect.
To date, all of the chromosomal deletions that cause alpha-thalassemia remove the structural alpha genes and/or their regulatory element (HS -40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human alpha cluster, next to a structurally normal alpha-globin gene, and silences its expression. During development, the CpG island associated with the alpha-globin promoter in the rearranged chromosome becomes densely methylated and insensitive to endonucleases, demonstrating that the normal chromatin structure around the alpha-globin gene is perturbed by this mutation and that the gene is inactivated by a negative chromosomal position effect. These findings highlight the importance of the chromosomal environment in regulating globin gene expression.
Barbour
V M
VM
MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, England.
Tufarelli
C
C
Sharpe
J A
JA
Smith
Z E
ZE
Ayyub
H
H
Heinlein
C A
CA
Sloane-Stanley
J
J
Indrak
K
K
Wood
W G
WG
Higgs
D R
DR
D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D019175:DNA Methylation; D005914:Globins / Q000235:genetics; D006801:Humans; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000209:etiology / Q000235:genetics*
D005914:Globins