To Study the β-Globin Haplotype Pattern of Descent of a Set of Linked Alleles Occurring on the Same Chromosome in the Northern Province of India

Objective: To study the five mutations commonly prevalent in North India, i.e., IVS-I-5 (G→C), 619 bp deletion, IVS-I-1 (G→T), codon 41/42 (-TTCT), and codon 8/9 (+G), in the beta thalassemia (β-thalassemia) major children. The specific β-thalassemia mutations of different haplotype patterns of the β-globin gene cluster will also be determined. Methods: A total of 125 children diagnosed with β-thalassemia major visiting the Department of Pediatrics of King George's Medical University were involved in the study. As per the QIAamp (Qiagen, Hilden, Germany) manufacturer guidelines, genomic DNA was isolated from whole blood. To identify the haplotype pattern within the β-globin gene cluster, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used. The respective restriction endonucleases used were Hind III/GƔ, Hinc II/Ψß, Hinf I/ß, Ava II/ß, and BamHI for the haplotype analysis in the β-globin pattern of descent of a set of linked alleles occurring on the same chromosome. Results: Among the five common mutations, 73 patients had IVS-I-5 (G→C), 28 patients had 619 bp deletion, 17 patients had IVS-I-1 (G→T), five patients had Cd 41/42 (-TTCT), and two patients had Cd 8/9 (+G) mutations. Fifteen haplotypes (haplotypes 1-15) were identified in 125 β-thalassemia major children. Among the five haplotypes observed in the IVS-I-5 (G→C) mutation, the H1 haplotype was most predominant with a frequency of 27.2%, followed by the H2, H4, H3, and H10 haplotypes in the given population. In 619 bp deletion, IVS-I-1 (G→T), codon 41/42, and codon 8/9, haplotype H9, H12, H11, and H5 were seen, respectively. Conclusion: β-thalassemia was found to be the most common in the northern province of Uttar Pradesh. The linkage of β-globin gene haplotypes with β-thalassemia mutations was explored in the northern province of Uttar Pradesh. The population of different natives is being mixed up due to migration and industrialization. These were some reasons for the occurrence of haplotypic heterogeneity. This haplotype heterogeneity was correlated with the origin of these mutations found to be unlike the origin of common ones from different provinces.