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Recent advances in globin research using genome‐wide association studies and gene editing
Author(s) -
Orkin Stuart H.
Publication year - 2016
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13001
Subject(s) - genome wide association study , fetal hemoglobin , genome editing , biology , computational biology , genetic association , genetics , identification (biology) , disease , enhancer , genome , gene , medicine , gene expression , single nucleotide polymorphism , genotype , fetus , pregnancy , botany , pathology
A long‐sought goal in the hemoglobin field has been an improved understanding of the mechanisms that regulate the switch from fetal (HbF) to adult (HbA) hemoglobin during development. With such knowledge, the hope is that strategies for directed reactivation of HbF in adults could be devised as an approach to therapy for the β‐hemoglobinopathies thalassemia and sickle cell disease. Recent genome‐wide association studies (GWAS) led to identification of three loci ( BCL11A, HBS1L‐MYB , and the β‐globin cluster itself) in which natural genetic variation is correlated with different HbF levels in populations. Here, the central role of BCL11A in control of HbF is reviewed from the perspective of how findings may be translated to gene therapy in the not‐too‐distant future. This summary traces the evolution of recent studies from the initial recognition of BCL11A through GWAS to identification of critical sequences in an enhancer required for its erythroid‐specific expression, thereby highlighting an Achilles heel for genome editing.