Molecular characterization and mutational analysis of beta-globin gene among Kodagu population of Karnataka, India

Introduction and Aim: Beta-thalassemia is a hereditary blood disorder caused by genotypic alterations in the HBB gene. Over 400 mutations have been identified, which are known to be responsible for this disease. In this study, we investigated the mutations for the globin gene prevalent among adult beta-thalassemia trait positive individuals and their distribution within the Kodagu community of Karnataka, India.   Materials and Methods: This study included 100 individuals (81 Females and 19 males) in the age group of 18-28 years previously tested as carriers for beta-thalassemia trait. Blood collected from each individual was subjected to genomic DNA extraction and PCR amplification of a 610 bp fragment of the beta-globin gene. The PCR product was purified and sequenced. The gene sequences were subjected to mutation analyses and characterization using bioinformatics tools.   Results: The study identified 13 known and 27 novel mutations for this study population. Among the known mutations observed 2 were of type synonymous (HBB:c.9T>C and HBB:c.18T>G), 5 missense (HBB:c.146T>G; HBB:c.149C>T; HBB:c.151A>T; HBB:c.203T>G; HBB:c.269G >A) and 6 intronic (HBB:c.92+2T >G; HBB:c.92+5G>C; HBB:c.315+16G>C; HBB:c.315+74T>G and HBB:c.315+81C>T). HBB:c.-6G>C  at the 5'UTR region and IVS-II-16 G>C, an intronic variant, was observed to be the most common mutation showing highest frequency of 82.1%. Several novel mutation types were identified in Exon 2 (3 missense; 2 synonymous),            Intron I and Intron II.    Conclusion: This study is the first of its kind for the Kodagu population, which identified several previously known and novel mutations in the HBB gene within this population. Since, our study subjects were carriers of very mild or silent beta-thalassemia trait, the mutations observed particularly the novel mutations warrant further investigation for a better understanding and management of beta-thalassemia in this population.