Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation

Analysis of the molecular basis of hemoglobinopathies provides an opportuni ty to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases ref erred to the counseling unit and 889 individuals from random screening of t he population of Tripura. Characterization of mutation in 291 cases (582 al leles) was performed by the PCR-ARMS method using genomic DNA. The haplotyp e of 56 PE mutation-bearing chromosomes were identified by the RFLP-PCR met hod. Genotypes were constructed and correlated with hematological and clini cal phenotypes. IVS-1nt 5 (G-->C) mutation was observed as the most frequen t mutation, followed by codon 30 (G-->C). Production of HbE was significant ly (P < 0.001) higher in nontransfusion-dependent EP-thalassemia patients. PE mutation was observed only on four haplotypes linked to framework 2, Typ e 2 haplotype was observed mainly from chromosomes of Tripura origin, but n one from South Bengal. Homozygous E individuals with 1//1 genotype were sig nificantly (P < 0.01) more anemic compared to individuals with 2//2 genotyp e, This work creates a database of hemoglobinopathy mutations for the popul ation of Eastern India which will facilitate prenatal diagnosis and counsel ing. of 2000 Wiley-Liss, Inc.