{"doi":"10.1073/pnas.82.7.2111","title":"Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients.","abstract":"<jats:p>We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G gamma-globin expression. In addition, haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+- ) in the gamma-globin gene region. In addition, haplotypes IX, III, and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Conversely, haplotypes I, V, and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associated with low G gamma-globin and low Hb F levels. Low G gamma-globin expression in the adult is associated with two haplotypes that are not common between thalassemia and sickle cell anemia patients. We conclude that the determinant for high G gamma-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the two diseases. The total Hb F level, unlike the high G gamma-globin expression, however, is linked to haplotypes but not to subhaplotypes, thus dissociating the two genetic effects.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1985,"id":662543,"datarank":0.8176557680348552,"base_score":5.4510384535657,"endowment":5.4510384535657,"self_citation_contribution":0.8176557680348552,"citation_network_contribution":0.0,"self_endowment_contribution":0.8176557680348552,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":232,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1729640,"name":"J Pagnier","orcid":null,"position":1,"is_corresponding":false},{"id":1729642,"name":"C Lapoumeroulie","orcid":null,"position":2,"is_corresponding":false},{"id":1729643,"name":"F Rouabhi","orcid":null,"position":3,"is_corresponding":false},{"id":1729644,"name":"O Dunda-Belkhodja","orcid":null,"position":4,"is_corresponding":false},{"id":1729645,"name":"P Chardin","orcid":null,"position":5,"is_corresponding":false},{"id":1729646,"name":"C Beldjord","orcid":null,"position":6,"is_corresponding":false},{"id":1729647,"name":"H Wajcman","orcid":null,"position":7,"is_corresponding":false},{"id":1729648,"name":"M E Fabry","orcid":null,"position":8,"is_corresponding":false},{"id":1729649,"name":"R L Nagel","orcid":null,"position":9,"is_corresponding":false},{"id":1729638,"name":"D Labie","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients.","abstract":"<jats:p>We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G gamma-globin expression. In addition, haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+- ) in the gamma-globin gene region. In addition, haplotypes IX, III, and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Conversely, haplotypes I, V, and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associated with low G gamma-globin and low Hb F levels. Low G gamma-globin expression in the adult is associated with two haplotypes that are not common between thalassemia and sickle cell anemia patients. We conclude that the determinant for high G gamma-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the two diseases. The total Hb F level, unlike the high G gamma-globin expression, however, is linked to haplotypes but not to subhaplotypes, thus dissociating the two genetic effects.</jats:p>","is_dataset_classified":null,"base_score":5.4510384535657,"endowment":5.4510384535657,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"2580306","pmcid":null,"openalex_id":"https://openalex.org/W2006641199","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL21016","title":null}],"total_grants":1,"fwci":7.0123,"citation_percentile":0.97565429,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":6},{"year":2014,"count":5},{"year":2015,"count":8},{"year":2016,"count":10},{"year":2017,"count":10},{"year":2018,"count":5},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/397502","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/397502","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.82.7.2111","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.82.7.2111","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/2580306","host_type":"repository"}],"fields_of_study":["Hemoglobinopathies and Related Disorders","Iron Metabolism and Disorders","Blood groups and transfusion","Anemia, Sickle Cell","Child, Preschool","Fetal Hemoglobin","Gene Expression Regulation","Globins","Humans","Infant","Thalassemia"],"mesh_terms":["Anemia, Sickle Cell","Child, Preschool","Fetal Hemoglobin","Gene Expression Regulation","Globins","Humans","Infant","Thalassemia"],"keywords":["Haplotype","Sickle cell anemia","Thalassemia","Globin","Biology","Hemoglobinopathy","Genetics","Heterozygote advantage","Allele","Immunology","Hemolytic anemia","Gene","Cell"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T15:43:16.610281Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}