title: High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin?
abstract: Hb E-Saskatoon [β22(B4)Glu→Lys, HBB: c.67G > A] is a rare, nonpathological β-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using β-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the β-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified β-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the β-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described.
authors.affiliation: a Universidade Federal de Ciencias da Saude , Porto Alegre , Brazil.|b Departamento de Genética , Instituto de Biociências, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Sandrine C
authors.initials: SC
authors.lastname: Wagner
authors.affiliation: b Departamento de Genética , Instituto de Biociências, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Lindenau
authors.affiliation: c Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil and.
authors.forename: Simone M de
authors.initials: SM
authors.lastname: Castro
authors.affiliation: c Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil and.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Santin
authors.affiliation: c Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil and.
authors.forename: Carina F
authors.initials: CF
authors.lastname: Zaleski
authors.affiliation: c Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil and.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Azevedo
authors.affiliation: d Laboratório de Genética Humana e Médica , Universidade Federal do Pará , Belém , Brazil.
authors.forename: Ândrea K C
authors.initials: ÂK
authors.lastname: Ribeiro Dos Santos
authors.affiliation: d Laboratório de Genética Humana e Médica , Universidade Federal do Pará , Belém , Brazil.
authors.forename: Sidney E B
authors.initials: SE
authors.lastname: Dos Santos
authors.affiliation: b Departamento de Genética , Instituto de Biociências, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D001938:Brazil; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006446:Hemoglobin E / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D017720:Molecular Epidemiology / Q000379:methods*
chemical_list: D006455:Hemoglobins, Abnormal; D006446:Hemoglobin E; C052830:hemoglobin E Saskatoon
keywords: Brazilian population; Hb E-Saskatoon; Keywords Ancestry; β-globin haplotype