In vivo deletion of a GWAS-identified Myb distal enhancer acts on Myb expression, globin switching, and clinical erythroid parameters in β-thalassemia.

ABSTRACT: Genome-wide association studies (GWAS) have identified numerous genetic variants linked to human diseases, mostly located in non-coding regions of the genome, particularly in putative enhancers. However, functional assessment of the non-coding GWAS variants has progressed at slow pace, since the functions of the vast majority of genomic enhancers have not been defined, impeding interpretation of disease-susceptibility variants. The HBS1L-MYB intergenic region harbors multiple SNPs associated with clinical erythroid parameters, including fetal hemoglobin levels, a feature impacting disease severity of beta-hemoglobinopathies such as sickle cell anemia and beta-thalassemia. HBS1L-MYB variants cluster in the vicinity of several MYB enhancers, altering MYB expression and globin switching. We a

SUBMITTER: Deleuze V 

PROVIDER: S-EPMC11910609 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature