Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

Sickle cell disease and beta-thalassemia are blood diseases caused by inherited mutations in the gene that encodes a subunit of hemoglobin, the oxygen carrier in the blood. Studies of the natural history of these diseases have identified fetal hemoglobin as a strong modifier of disease severity: sickle cell disease and beta-thalassemia patients with high fetal hemoglobin levels have less severe complications. Re-activating fetal hemoglobin production in these patients represents to date the single most promising therapeutic strategy. We and others have identified genes that regulate fetal hemoglobin production in humans. We recently showed that genetic variation at these genes explains 50% of the heritable variation in fetal hemoglobin levels. The central objective of this proposal is to generate comprehensive genetic, trasncriptomic, and epigenetic datasets that will help identifying the remaining genes that modulate fetal hemoglobin production in humans. Identification of new genes involved in fetal hemoglobin regulation might guide the development of new drugs to treat hemoglobinopathy patients.