Insight into regulation of switch from fetal to adult hemoglobin

Investigators designed a study to enhance understanding of the cis-regulatory sequences of the β-globin locus required for silencing or activation of fetal hemoglobin. These cis-regulatory sequences, which direct patterns of gene expression essential for development and physiology, have been implicated in the regulation of the β-globin locus, in which common genetic polymorphisms have been identified. An understanding of how the switch from fetal hemoglobin to adult hemoglobin is regulated is important to the development of therapeutic approaches to fetal hemoglobin induction in the β-hemoglobinopathies.

Researchers identified 3 families (2 from Sri Lanka and 1 American child of Kurdish origin) with elevated fetal hemoglobin levels. Genetic studies, using polymerase chain reaction assays and DNA sequencing, revealed unusual deletions in the β-globin locus: a new thalassemia deletion and a rare hereditary persistence of fetal hemoglobin deletion. Comparison of the 2 deletions resulted in identification of a small intergenic region required for fetal hemoglobin gene silencing. By comparing these deletions and other previously mapped deletions, investigators elucidated an intergenic region that is necessary for fetal globin silencing (Sankaran VG, et al. N Engl J Med. 2011;365[9]:807-814).

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