{"id":{"repo_id":"oxford-brookes","oai_identifier":"tle:542e2554-f642-4dc8-8f84-10ca0cf60459:d6bd9758-527a-46cd-bfe2-c433766e8fca:1"},"canonical_url":"https://search.dev.ndltd.org/etd/oxford-brookes/tle:542e2554-f642-4dc8-8f84-10ca0cf60459:d6bd9758-527a-46cd-bfe2-c433766e8fca:1","repository":{"repo_id":"oxford-brookes","name":"Oxford Brookes University","base_url":"https://radar.brookes.ac.uk/radar/oai"},"display":{"title":"The molecular basis of thalassaemia in Sri Lanka","abstract":"Blood samples from over 1600 schoolchildren revealed a prevalence of both trait and HbE trait, averaging 2.3% and 0.8% respectively. With the present popUlation estimate at 18.6 million, it is predicted that approximately 2650 patients with l3-thalassaemia major and 956 with HbE/I3-thalassaemia should consume >5% of the current health budget for treatment of these patients. Patients with the phenotype of severe thalassaemia, from seven centres, were analysed to understand the molecular basis of the disease. Twenty-four l3-globin gene mutations were identified with three mutations accounting for 84.4% of the 1234 alleles: IVSI-5 (G--7C) 56.1 %; IVSI-l (G--7A) 15.2% and HbE 13.1 %. Sixteen mutations have previously been described on the Indian subcontinent and demonstrate close regional links between the popUlations, especially North East India, and were supported by haplotype association. The IVSI-l (G--7A) mutation occurs commonly in countries around the Mediterranean but very rarely on the Indian subcontinent. In Sri Lanka it is associated with a different 3' haplotype, suggesting a multicentric origin. Three new mutations were found; a frameshift codon 6-10 IVSI-129 (A--7C) in the consensus splice site and a second frame shift, CD55 (-A). Four a-gene arrangements were demonstrated. An allele frequency of the a+-thalassaemia gene deletions were 6.5% and 1.1% for the _a3.7 deletion and the _a4.2 deletion, respectively. Cord blood analysis of Hb Bart's levels confirmed an estimated level of 7.1 % for a single a-gene nonexpression. Extra a-genes are common and the first instance of homozygosity for the aaaa arrangement was observed. No aOthalassaemia was revealed and only a single polymorphism was associated with a possible extremely mild a-thalassaemia allele. The phenotype associated with the various l3-globin genotypes was found to be extremely variable. Within the many factors that modify this phenotype the Xmn-I polymorphism was significantly associated with the level of haemoglobin expressed. A +1+ genotype appeared to be a good indicator of a milder outcome. The incidence of a-gene deletions was low in patients with HhElI3-thalassaemia and thus proposed this as a strong modifier for a mild phenotype. Other factors were associated with specific complications.","abstract_html":"Blood samples from over 1600 schoolchildren revealed a prevalence of both trait and HbE trait, averaging 2.3% and 0.8% respectively. With the present popUlation estimate at 18.6 million, it is predicted that approximately 2650 patients with l3-thalassaemia major and 956 with HbE/I3-thalassaemia should consume >5% of the current health budget for treatment of these patients. Patients with the phenotype of severe thalassaemia, from seven centres, were analysed to understand the molecular basis of the disease. Twenty-four l3-globin gene mutations were identified with three mutations accounting for 84.4% of the 1234 alleles: IVSI-5 (G--7C) 56.1 %; IVSI-l (G--7A) 15.2% and HbE 13.1 %. Sixteen mutations have previously been described on the Indian subcontinent and demonstrate close regional links between the popUlations, especially North East India, and were supported by haplotype association. The IVSI-l (G--7A) mutation occurs commonly in countries around the Mediterranean but very rarely on the Indian subcontinent. In Sri Lanka it is associated with a different 3' haplotype, suggesting a multicentric origin. Three new mutations were found; a frameshift codon 6-10 IVSI-129 (A--7C) in the consensus splice site and a second frame shift, CD55 (-A). Four a-gene arrangements were demonstrated. An allele frequency of the a+-thalassaemia gene deletions were 6.5% and 1.1% for the _a3.7 deletion and the _a4.2 deletion, respectively. Cord blood analysis of Hb Bart's levels confirmed an estimated level of 7.1 % for a single a-gene nonexpression. Extra a-genes are common and the first instance of homozygosity for the aaaa arrangement was observed. No aOthalassaemia was revealed and only a single polymorphism was associated with a possible extremely mild a-thalassaemia allele. The phenotype associated with the various l3-globin genotypes was found to be extremely variable. Within the many factors that modify this phenotype the Xmn-I polymorphism was significantly associated with the level of haemoglobin expressed. A +1+ genotype appeared to be a good indicator of a milder outcome. The incidence of a-gene deletions was low in patients with HhElI3-thalassaemia and thus proposed this as a strong modifier for a mild phenotype. Other factors were associated with specific complications.","abstract_has_math":false,"creators":["Fisher, Christopher A."],"institution":"Oxford Brookes University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2002,"date_issued":"2002","date_published":"2002","updated_at":"2026-07-24T03:43:53Z","subjects":[],"languages":["en"],"rights":["All rights reserved"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.24384/1t0e-9c57","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Fisher, Christopher A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2002"]},{"key":"dc:publisher","label":"Institution","values":["Oxford Brookes University"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["All rights reserved"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.24384/1t0e-9c57","https://radar.brookes.ac.uk/radar/file/542e2554-f642-4dc8-8f84-10ca0cf60459/1/fisher2002molecular.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Blood samples from over 1600 schoolchildren revealed a prevalence of both trait and HbE trait, averaging 2.3% and 0.8% respectively. With the present popUlation estimate at 18.6 million, it is predicted that approximately 2650 patients with l3-thalassaemia major and 956 with HbE/I3-thalassaemia should consume >5% of the current health budget for treatment of these patients. Patients with the phenotype of severe thalassaemia, from seven centres, were analysed to understand the molecular basis of the disease. Twenty-four l3-globin gene mutations were identified with three mutations accounting for 84.4% of the 1234 alleles: IVSI-5 (G--7C) 56.1 %; IVSI-l (G--7A) 15.2% and HbE 13.1 %. Sixteen mutations have previously been described on the Indian subcontinent and demonstrate close regional links between the popUlations, especially North East India, and were supported by haplotype association. The IVSI-l (G--7A) mutation occurs commonly in countries around the Mediterranean but very rarely on the Indian subcontinent. In Sri Lanka it is associated with a different 3' haplotype, suggesting a multicentric origin. Three new mutations were found; a frameshift codon 6-10 IVSI-129 (A--7C) in the consensus splice site and a second frame shift, CD55 (-A). Four a-gene arrangements were demonstrated. An allele frequency of the a+-thalassaemia gene deletions were 6.5% and 1.1% for the _a3.7 deletion and the _a4.2 deletion, respectively. Cord blood analysis of Hb Bart's levels confirmed an estimated level of 7.1 % for a single a-gene nonexpression. Extra a-genes are common and the first instance of homozygosity for the aaaa arrangement was observed. No aOthalassaemia was revealed and only a single polymorphism was associated with a possible extremely mild a-thalassaemia allele. The phenotype associated with the various l3-globin genotypes was found to be extremely variable. Within the many factors that modify this phenotype the Xmn-I polymorphism was significantly associated with the level of haemoglobin expressed. A +1+ genotype appeared to be a good indicator of a milder outcome. The incidence of a-gene deletions was low in patients with HhElI3-thalassaemia and thus proposed this as a strong modifier for a mild phenotype. Other factors were associated with specific complications."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The molecular basis of thalassaemia in Sri Lanka"]}]}],"canonical_facts":{"dc:creator":["Fisher, Christopher A."],"dc:date":["2002"],"dc:description":["Blood samples from over 1600 schoolchildren revealed a prevalence of both trait and HbE trait, averaging 2.3% and 0.8% respectively. With the present popUlation estimate at 18.6 million, it is predicted that approximately 2650 patients with l3-thalassaemia major and 956 with HbE/I3-thalassaemia should consume >5% of the current health budget for treatment of these patients. Patients with the phenotype of severe thalassaemia, from seven centres, were analysed to understand the molecular basis of the disease. Twenty-four l3-globin gene mutations were identified with three mutations accounting for 84.4% of the 1234 alleles: IVSI-5 (G--7C) 56.1 %; IVSI-l (G--7A) 15.2% and HbE 13.1 %. Sixteen mutations have previously been described on the Indian subcontinent and demonstrate close regional links between the popUlations, especially North East India, and were supported by haplotype association. The IVSI-l (G--7A) mutation occurs commonly in countries around the Mediterranean but very rarely on the Indian subcontinent. In Sri Lanka it is associated with a different 3' haplotype, suggesting a multicentric origin. Three new mutations were found; a frameshift codon 6-10 IVSI-129 (A--7C) in the consensus splice site and a second frame shift, CD55 (-A). Four a-gene arrangements were demonstrated. An allele frequency of the a+-thalassaemia gene deletions were 6.5% and 1.1% for the _a3.7 deletion and the _a4.2 deletion, respectively. Cord blood analysis of Hb Bart's levels confirmed an estimated level of 7.1 % for a single a-gene nonexpression. Extra a-genes are common and the first instance of homozygosity for the aaaa arrangement was observed. No aOthalassaemia was revealed and only a single polymorphism was associated with a possible extremely mild a-thalassaemia allele. The phenotype associated with the various l3-globin genotypes was found to be extremely variable. Within the many factors that modify this phenotype the Xmn-I polymorphism was significantly associated with the level of haemoglobin expressed. A +1+ genotype appeared to be a good indicator of a milder outcome. The incidence of a-gene deletions was low in patients with HhElI3-thalassaemia and thus proposed this as a strong modifier for a mild phenotype. Other factors were associated with specific complications."],"dc:format":["application/pdf"],"dc:identifier":["https://doi.org/10.24384/1t0e-9c57","https://radar.brookes.ac.uk/radar/file/542e2554-f642-4dc8-8f84-10ca0cf60459/1/fisher2002molecular.pdf"],"dc:language":["en"],"dc:publisher":["Oxford Brookes University"],"dc:rights":["All rights reserved"],"dc:title":["The molecular basis of thalassaemia in Sri Lanka"],"dc:type":["thesis"]},"updated_at":"2026-07-24T03:43:53Z"}