Characterisation of chromatin states in erythroid cells from a patient with a unique severe HbH genotype (ATAC-Seq)

Analyses of mutations within the a-globin cluster which downregulate a-globin expression and cause a-thalassaemia provide the basis for genetic counselling and pre-natal diagnosis of this common form of anemia. Understanding the mechanisms by which such mutations cause a-thalassemia has established many of the principles by which mammalian genes are regulated and how this goes awry in human genetic disease. ATAC-Seq and NG Capture-C data from an individual (NSE) with a unique a-globin genotype involving a deletion of the main alpha-globin enhancer on one allele and the --/SEA mutation on the other help to address how the human a-globin cluster is normally regulated. Overall design: To identify new regulatory elements as marked by chromatin accessibility, which might explain the mild phenotype, ATAC-seq was carried out at day 13 of erythroid differentiation from CD34+ cells isolated from the patient's peripheral blood. Sequencing was carried out on two culture samples grown in parallel from the patient in identical culture conditions, with 3 technical replicates within each overall duplicate.