Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 800-807
PLENARY PAPER
-Thalassemia resulting from a negative chromosomal position
effect
Virginia M. Barbour,
Cristina Tufarelli,
Jacqueline A. Sharpe,
Zoe E. Smith,
Helena Ayyub,
Cynthia A. Heinlein,
Jacqueline Sloane-Stanley,
Karel Indrak,
William G. Wood, and
Douglas R. Higgs
From the MRC Molecular Haematology Unit, Institute of Molecular
Medicine, John Radcliffe Hospital, Headington, Oxford, England, and
the Department of Clinical Haematology, Faculty Hospital,
IP Pavlova, Olomouc, the Czech Republic.
To date, all of the chromosomal deletions that cause 
-thalassemia
remove the structural 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 cluster, next to
a structurally normal -globin gene, and silences its expression.
During development, the CpG island associated with the -globin
promoter in the rearranged chromosome becomes densely methylated and
insensitive to endonucleases, demonstrating that the normal chromatin
structure around the -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.
