Haplotype Analysis Of Beta-Thalassaemia Major And Carriers With Filipino Beta Degrees-Deletion In Sabah, Malaysia

Objective: The Filipino beta degrees-deletion has been reported as a unique mutation in East Malaysia with a severe phenotype due to the complete absence of beta-globin chain synthesis. In this study, the haplotype patterns of the beta-globin gene cluster were used to relate the human genetic variation to this specific beta-thalassaemia mutation.Methods: The 376 study subjects included 219 beta-thalassaemia major (beta-TM) patients with homozygous Filipino beta degrees-deletion and 157 carriers with heterozygous Filipino beta degrees-deletion from 10 government hospitals in different regions of Sabah. Genomic DNA was isolated from whole blood using silica membrane based DNA purification protocol. Polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) was conducted on five markers within the beta-globin gene cluster to construct the haplotype patterns.Results: Four haplotypes (Haplotype I-IV) were identified with Haplotype I as the predominant haplotype with the highest frequency of 0.98, followed by Haplotype II, III and Haplotype IV with 0.02. Haplotype I was strongly linked with the Filipino beta degrees-deletion among the indigenous population.Conclusion: Haplotype I as the predominant haplotype suggests the patients with the Filipino beta degrees-deletion in Sabah have a similar origin.