globingenerna

Globingenerna (globin genes) are a gene family that encodes globin proteins essential for oxygen transport in vertebrate blood. The family comprises two main groups, the alpha-like and beta-like globins, which are expressed in a developmentally regulated sequence to produce different hemoglobin tetramers: HbA (alpha2beta2) in adults, HbA2 (alpha2delta2), and HbF (alpha2gamma2) during fetal life and in smaller amounts after birth.

In humans, the globin genes are organized in two clusters. The alpha-like cluster on chromosome 16 contains the zeta (embryonic) and alpha (HBA1/HBA2) genes. The beta-like cluster on chromosome 11 contains epsilon (embryonic), gamma (HBG1/HBG2), delta (HBD), and beta (HBB) genes. Expression is regulated by regulatory elements including the locus control region (LCR) upstream of the beta-like cluster and transcription factors such as GATA1 and KLF1; BCL11A suppresses gamma-globin to enable adult HbA production.

Developmental switching: early embryonic zeta and epsilon drive initial oxygen transport, followed by fetal gamma chains; after birth, beta and delta genes predominate, with HbA becoming the main form and HbA2 present at a smaller fraction.

Evolution and diversity: globin genes are widely conserved across vertebrates, arising from gene duplications and divergent regulation, with multiple pseudogenes in the clusters. The precise gene complement varies among species.

Clinical significance: Mutations in HBA1/HBA2 cause alpha-thalassemia; mutations in HBB cause beta-thalassemia; abnormal hemoglobin variants (e.g., HbS) and hereditary persistence of fetal hemoglobin (HPFH) affect disease severity and therapy; understanding globin regulation informs treatments, including strategies to induce HbF.