title: Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals.
abstract: BACKGROUND
  Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population.
  
  
  METHODS
  A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests.
  
  
  RESULTS
  Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia.
  
  
  CONCLUSIONS
  The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Elza Miyuki
authors.initials: EM
authors.lastname: Kimura
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Denise Madureira
authors.initials: DM
authors.lastname: Oliveira
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Susan Elisabeth
authors.initials: SE
authors.lastname: Jorge
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Daniela Maria
authors.initials: DM
authors.lastname: Ribeiro
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Tânia Regina
authors.initials: TR
authors.lastname: Zaccariotto
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Magnun Nueldo Nunes
authors.initials: MN
authors.lastname: Santos
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Almeida
authors.affiliation: National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil; Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Dulcinéia Martins
authors.initials: DM
authors.lastname: Albuquerque
authors.affiliation: National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil; Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; National Institute of Blood Science and Technology, National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology (MCT), Brazil. Electronic address: sonati@fcm.unicamp.br.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Sonati
keywords: Alpha-globin genes; Alpha-globin variants; Alpha-thalassemia; Hemoglobinopathies; Multiethnic populations
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