Genome-wide association studies (GWAS) in Hemoglobinopathies have identified genes, other than the globin genes, as potential modulators of the pathology of these diseases. These potential modulators are thought to act by influencing the amounts of fetal hemoglobin (HbF). One of these genes is BCL11A. Bauer et al. characterized a common SNP in the BCL11A gene which lies in a noncoding DNA sequence. Genome engineering revealed that this DNA sequence is an enhancer required in erythroid cells (but not B-lymphoid cells) for BCL11A expression, and as a consequence, for globin gene expression. This specificity suggests that genome editing may be a plausible approach to corrective cell-specific therapy for certain hemoglobinopathies.
An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Bauer et al. Science. 2013 Oct 11;342(6155):253-7. PMID: 24115442
Posted by Yannis Trakadis, MD