Molecular epidemiology of haemoglobin in the population of Libya and the molecular biology of normal and abnormal globin gene expression

Abstract

The aim of this study is to evaluate with modern techniques the prevalence of different types of abnormal haemoglobins and thalassaemia in the population of Tripoli, Western and Southern Regions of Libya. 985 newborn babies from Tripoli were tested. Abnormal Hb's were noted in 10 samples (= 1.0%). Some of these were Hb C, Hb S, Hb S-β+ thaI, Hb Setif The aim of this study is to evaluate with modern techniques the prevalence of different types of abnormal haemoglobins and thalassaemia in the population of Tripoli, Western and Southern Regions of Libya. 985 newborn babies from Tripoli were tested. Abnormal Hb's were noted in 10 samples (= 1.0%). Some of these were Hb C, Hb S, Hb S-β+ thaI, Hb Setif and Hb F Malta 1. Among 866 adult samples were pregnant women, 14 (= 1.6%) had an abnormal Hb, including Hb S, Hb C and others. The total of 2595 blood samples from Western and Southern Region of Libya were investigated for abnormal haemoglobins. Out of these samples were tested, Hb AS (= 1.6%), Hb AC (= 0.72%), HPFH (= 1.3%), Hb CC (= 0.08%), Hb SC (= 0.04%) and Hb AX (= 0.16%). None of the 985 newborn samples which were tested had any amount of Hb Bart's (Y4), indicating that a-thalassaemia was absent or extremely rare. Among adult samples from Tripoli, 10 had an elevated Hb A2 ( > 3.6%), giving an incidence of ~-thalassaemia of 1.2%. Eleven cases from Western and Southern Regions had elevated HbA2, giving a gene incidence of β-thalassaemia of 0.5%. Eighteen different haplotypes have been found with polymorphic sites associated with 88 β~A -globin gene bearing chromosomes. Fifteen per cent of these are found in the Mediterranean, 50% in Black Africans and 35% are rare ones. Ten different haplotypes were found, associated with 40 βs globin gene-bearing chromosomes. Four major haplotypes were found. Three were y- βS-globin gene related haplotypes (Sub Hap Mor, CAR and Cameroon) and one is y_ βA_ globin gene haplotype (Sub Hap 16) and six were minor haplotypes. The β-globin DNA mutations present in 25 subjects with β-thalassaemia major and minor, in 5 patients with Hb S β-thalassaemia were analyzed by RFLP, ASOH and DNA sequencing of amplified DNA. Five different known β-thalassaemia mutations were identified. The common three β-thalassaemia mutations found in Libya were βo CD39 (C -> T) N = 14, β+ IVS-I,6 (T -> C) N = 8 and β+ IVS-I, 110 (G -> A) N = 6 and these mutations accounted for more than 90% of all β-thalassaemia alleles studied. The two rare mutations found were ~o IVS-I,I(G ->A) N = 1 and IVS-I,-1 (CD30) (G ->A) N = 1. Also, the associated haplotypes with the most common β-thalassaemia genes had been studied. Haplotypes I and VII were associated with βo CD39, Haplotypes VI and VII with β+IVS-I, 6, Haplotype I with β+IVS- I,110 and haplotype V with β °IVS-I,1. The MCH- β ° A value was used to evaluate the index of thalassaemia severity of two β+ thalassaemia from this study and those of six others from the literature which may be useful for understanding the effect of mutations in globin genes on pathophysiology meaningful gene expression.