HBG1 and HBG2 (Hemoglobin Subunit Gamma 1 and 2) are fetal-specific globin genes encoding the γ-globin chains of fetal hemoglobin (HbF, α2γ2). Expressed predominantly during fetal development, HbF replaces embryonic hemoglobin by 8-10 weeks of gestation and is gradually supplanted by adult hemoglobin (HbA, α2β2) around birth. HBG1 and HBG2 differ by a single amino acid (glycine vs. alanine at position 136) due to gene duplication. Their expression is tightly regulated by transcription factors (e.g., BCL11A, ZBTB7A) and epigenetic modifiers, with silencing occurring postnatally in most individuals.
Antibodies targeting HBG1/2 are critical tools for studying hemoglobin switching mechanisms and disorders like β-hemoglobinopathies (e.g., sickle cell disease, β-thalassemia). Reactivating γ-globin expression to boost HbF levels is a therapeutic strategy for these conditions, as HbF inhibits pathogenic hemoglobin polymerization. HBG1/2 antibodies enable detection and quantification of γ-globin protein in research models (e.g., cell lines, transgenic mice) and clinical samples. They are widely used in techniques like Western blot, immunohistochemistry, and flow cytometry to assess HbF-inducing agents (e.g., hydroxyurea, CRISPR-editing therapies). Commercial HBG1/2 antibodies are typically raised against synthetic peptides or recombinant proteins, with validation required for species cross-reactivity and specificity due to high homology between HBG1 and HBG2. Recent studies also explore their diagnostic utility in monitoring HbF levels during gene therapy or drug trials.