**Figure 2.**

1.6 Kb, consist of three exons, interrupted by two introns. The HBB gene is regulated by an adjacent 5′ promoter in which a TATA, CAAT, and duplicated CACCC boxes are located. A major regulatory region, containing a strong enhancer, 50 Kb from the beta globin gene [22]. This region, locus control region (LCR), contains four (HS-1 to HS-4) erythroid specific DNAse hypersensitive sites (HSs), which are involve in DNA-protein interaction. Each HS site is constituted by a combination of several DNA motifs interacting with transcription factors, among which the most important are GATA-1 (GATA indicates the relative recognition motif), nuclear factor erythroid 2, erythroid Krüppel-like factor [23]. The importance of LCR for the control of the beta-like globin gene expression has been discovered by studying a series of naturally occurring deletions that totally or partly remove the HS sites

*Genetics of Thalassemia DOI: http://dx.doi.org/10.5772/intechopen.106748*

and result in the inactivation of the intact downstream beta globin gene. Several transcription factors bind and regulate the function of the HBB gene, the most important of which is erythroid Krüppel-like factor 1 (KLF 1), which binds the proximal CACCC box [21, 22].

Each gene cluster consist of the structural genes that are separated on both their 3′ and 5′ ends by variable stretches of non-coding DNA containing several types of regulatory sequences [23–25].

	- BRE at −37 GGGCTGG
	- TATA box at −31 CATAAAAG
	- Inr at +1 TTACATT
	- MTE at +27 ACAACTG
	- DPE at +32 AGCAA

## **5. Beta thalassemia mutation types**

Thalassemia is characterized by decrease or absence production of α- or β-globin chains, which result in α- or β-thalassemia [25]. More than 400 different types of deletional and non deletional types of mutations in α- or β-globin genes have been reported till date with diverse clinical manifestations, ranging from asymptomatic to fatal anemia [26].

• β-Thalassemia (complete absence of hemoglobin subunit beta) alleles result from nonsense, frameshift, or splicing mutations.

