Question

A number of different types of mutations in the HBB gene can cause human β-thalassemia, a disease characterized by various levels of anemia. Many of these mutations occur within introns or in upstream noncoding sequences. Explain why mutations in these regions often lead to severe disease, although they may not directly alter the coding regions of the gene.

Answer 1

Answer:

Mutations in introns create alternative splicing site which in turn make mRNA with reduced or no translation.

Explanation:

Introns regulate the splicing of heterogenous RNA during post transcriptional modifications as well as affect the stability of mature mRNA. The stable mRNA is more likely to be translated into proteins. So, introns also regulate the translation of mRNA.  

In human beta thalassemia, mutations in intron create alternative splicing sites which in turn affect the formation of beta globin chain of hemoglobin. Lack of beta globin chain reduces the amount of functional hemoglobin and causes anemia.