HBB Expression
The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. These large family of proteins related to hemoglobin’s are encoded at five different chromosomal locations in humans. For example the α-like globin gene is expressed at chromosomal location 16p13.3. The β-like globin gene is expressed at chromosomal location 11p15.5 (UCSC Genomic Bioinformatics, 2011). Therefore the alpha (HBA) and beta (HBB) loci determines the structure of the two types of polypeptide chains in adult hemoglobin (Hardison, 2008).
In humans the expression of α-like and β-like globin genes between multigene complexes is coordinated so that equal amounts of the two types of globins are produced in all erythroid cells. And the human beta globin clusters spans about 45kb which includes five functional genes with one being a pseudo gene. The HBB gene structure is as follows: 5ʹ-epsilon, gamma G, gamma A, beta 1, pseudo gene, delta, and beta-3´ (Entrez, 2011) (Fig 1, HBB Gene Structure).
Not all genes of the HBB gene family are expressed or functional in humans at one point in development. Because of this, mutations can occur in almost every amino acid position in the HBB and HBA genes (Hardison, 2008). Both gamma globin and the single epsilon genes are expressed in early embryonic and fetal erythroid tissues. In adult life the beta and delta globin genes are expressed (Entrez, 2011). All these functional or active genes have at least three exons and two introns which are found in the erythroid globin genes.