Asunto(s)
Elementos de Facilitación Genéticos , Hemoglobina H/genética , Globinas alfa/genética , Talasemia alfa/genética , Adulto , Alelos , Cromatina/genética , Cromatina/ultraestructura , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 16/ultraestructura , Eritroblastos/patología , Eritropoyesis , Femenino , Eliminación de Gen , Regulación de la Expresión Génica , Genotipo , Hemoglobina E/genética , Hemoglobina H/análisis , Humanos , Masculino , Linaje , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Eliminación de Secuencia , Suriname/etnología , Globinas alfa/biosíntesis , Talasemia alfa/sangre , Globinas beta/genéticaRESUMEN
Hb E-Saskatoon [ß22(B4)GluâLys, HBB: c.67G > A] is a rare, nonpathological ß-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 ß-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 ß-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 ß-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 ß-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described.
Asunto(s)
Frecuencia de los Genes , Hemoglobina E/genética , Epidemiología Molecular/métodos , Brasil , Variación Genética , Haplotipos , Hemoglobinopatías/genética , Hemoglobinas Anormales/genéticaAsunto(s)
Hemoglobina E/genética , Hemoglobina Falciforme/genética , Globinas beta/genética , Adulto , Enfermedades Asintomáticas , Secuencia de Bases , Brasil , Preescolar , Femenino , Pruebas Genéticas , Hemoglobina E/análisis , Hemoglobina Falciforme/análisis , Heterocigoto , Humanos , Lactante , Recién Nacido , Masculino , Datos de Secuencia Molecular , Tamizaje NeonatalRESUMEN
BACKGROUND: Hemoglobinopathies are among the most studied and frequent pathologies. These genetic disorders are considered a very important health care threat in many tropical countries. Ecuador is a tropical Latin-American country with an important presence of afro-descendants (7.2%). Afro-descendants are among the ethnic groups with higher frequency of hemoglobinopathies reported. Ambuqui is a region within the Imbabura province with an important presence of afro-descendants (>50%). The present study analyzed the frequency of the most common hemoglobin variants in an asymptomatic afro-descendent population using capillary electrophoresis. FINDINGS: From 114 individuals, 25 (22%) reported a hemoglobin variant. All individuals that presented hemoglobin variants were heterozygotes (asymptomatic). Hemoglobin S (sickle cell trait) was the most frequent variant found (14%), followed by hemoglobin E (4.4%), Fetal (2.6%) and C (1%). CONCLUSION: Prevalence of hemoglobin S was consistent with populations from other countries, but it was lower than other Ecuadorian afro-descendent populations. Frequency of hemoglobin C was lower than other afro-descendent populations. This data suggests the possibility of gene flow from Native American individuals to the Ambuqui population there by lowering the frequency of their hemoglobin variants compared with other afro-descendant populations. Evaluating the frequency of hemoglobinopathies in Ecuadorian populations is essential. Despite the high frequency of these disorders, very few health care facilities implement hemoglobinopathies tests as a routine practice.
Asunto(s)
Población Negra/genética , Hemoglobinopatías/etnología , Hemoglobinopatías/genética , Hemoglobinas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ecuador , Electroforesis Capilar , Femenino , Hemoglobina Fetal/genética , Predisposición Genética a la Enfermedad , Genética de Población , Hemoglobina C/genética , Hemoglobina E/genética , Hemoglobina Falciforme/genética , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Rasgo Drepanocítico/genética , Adulto JovenRESUMEN
Hemoglobin profile studies have been carried out in four samples from different districts of Porto Velho (Rondônia State) in the western Amazonian region of Brazil: Candelária, Bate Estaca, Hemeron (at the State Blood Bank), and São Carlos. Samples from 337 unrelated individuals were collected during medical and paramedical team visits by professionals from the Instituto de Pesquisa em Patologia Tropical and the Centro de Pesquisa em Patologias Tropicais (both research institutes in tropical diseases). The aim of this study is to assess the frequency of alleles in the hemoglobin system, mainly alleles HB*A, *S, and *E. The overall phenotype frequencies were HB A,S = 0.025, HB A,E = 0.006, and HB A,A = 0.969. Samples from the blood bank subjects and samples from the homogeneous areas of São Carlos and Candelária plus Bate Estaca have a chi-square of heterogeneity of 6.383 (p = 0.041) and 8.406 (p = 0.015), respectively. The allele frequencies (HB*A = 0.984, HB*S = 0.012, and HB*E = 0.003) do not significantly differ from frequencies found in other Brazilian regions.
Asunto(s)
Frecuencia de los Genes , Genética de Población/estadística & datos numéricos , Hemoglobina A/genética , Hemoglobina E/genética , Hemoglobina Falciforme/genética , Polimorfismo Genético/genética , Animales , Población Negra/genética , Brasil , Emigración e Inmigración , Flujo Génico/genética , Flujo Genético , Humanos , Indígenas Sudamericanos/genética , Funciones de Verosimilitud , Malaria/sangre , Malaria/genética , Malaria/prevención & control , Fenotipo , Plasmodium/genética , Población Blanca/genéticaAsunto(s)
Hemoglobina E/genética , Talasemia beta/diagnóstico , Homocigoto , Humanos , Talasemia beta/genéticaRESUMEN
Hemoglobin E (HbE), alpha-thalassemia, and beta-thalassemia are common among Southeast Asians and often occur in compound heterozygous states that complicate neonatal screening. We describe a kindred with alpha-thalassemia-1, HbE, and beta zero-thalassemia. The proband had HbE/beta zero-thalassemia, with severe anemia and failure to thrive. His father also had HbE/beta zero-thalassemia but had coinherited alpha-thalassemia-1 and was free of symptoms.
Asunto(s)
Hemoglobina E/genética , Talasemia alfa/genética , Talasemia beta/genética , Adulto , Asia Sudoriental/etnología , Preescolar , Femenino , Asesoramiento Genético , Genotipo , Heterocigoto , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal , Talasemia alfa/complicaciones , Talasemia alfa/etnología , Talasemia beta/complicaciones , Talasemia beta/etnologíaRESUMEN
OBJECTIVES: To facilitate the differential diagnosis of hemoglobin FE in newborn infants (homozygous hemoglobin E vs hemoglobin E-beta O-thalassemia). METHODS: The beta-globin gene in DNA from infants found to have hemoglobin FE in the California newborn screening program was amplified by the polymerase chain reaction, and the product was digested with Mnl I, which fails to cut the product when the hemoglobin E mutation is present. When both amplified alleles fail to be cut, homozygous EE is diagnosed. If only one allele is cut, a beta-globin allele without the E mutation is present (non-E), which is most likely a gene with a beta O-thalassemia mutation. RESULTS: Samples from 18 infants revealed an EE genotype, and from two samples a non-E/E genotype was determined. Clinical examination of these two patients confirmed a diagnosis of hemoglobin E-beta O-thalassemia. An independent clinical diagnosis agreed with DNA analysis for all 17 of the 20 infants for whom follow-up and family studies were available. The DNA results were obtained within a week, but the clinical diagnoses often could not be resolved unequivocally for months. CONCLUSIONS: The direct analysis of patient DNA samples for the hemoglobin E mutation allowed rapid and accurate diagnosis in this sample of infants with hemoglobin FE on the newborn screen. This rapid discriminatory test should reduce cost and simplify the diagnostic approach for these patients, which currently consists of expensive and lengthy follow-up until clinical data and family studies result in a diagnosis.
Asunto(s)
Asiático/genética , Hemoglobina E/genética , Tamizaje Neonatal , Talasemia/genética , Electroforesis de las Proteínas Sanguíneas , California/epidemiología , Análisis Mutacional de ADN , Diagnóstico Diferencial , Hemoglobina Fetal/análisis , Tamización de Portadores Genéticos , Homocigoto , Humanos , Recién Nacido , Reacción en Cadena de la Polimerasa , Talasemia/diagnóstico , Talasemia/epidemiologíaAsunto(s)
Hemoglobina E/genética , Adulto , Niño , Preescolar , Familia , Femenino , Homocigoto , Humanos , India/etnología , Recién Nacido , Masculino , Trinidad y TobagoRESUMEN
We report the first case of homozygous E in the West Indies, and describe the family, whose ancestors came to Trinidad from India approximately 100 years ago (AU)
Asunto(s)
Humanos , Recién Nacido , Femenino , Adulto , Hemoglobina E/genética , Trinidad y Tobago , India/etnología , Familia , HomocigotoAsunto(s)
Hemoglobinas Anormales/genética , Heterocigoto , Adolescente , Adulto , África Occidental/etnología , Asia Sudoriental/etnología , Electroforesis de las Proteínas Sanguíneas , Colombia/etnología , Femenino , Hemoglobina A/genética , Hemoglobina C/genética , Hemoglobina E/genética , Hemoglobina J/genética , Hemoglobinas Anormales/análisis , Humanos , Lactante , Masculino , MoscúRESUMEN
In an electrophoretic study of 15,661 Jamaican cord bloods, 8 rare beta-chain variants were found in 18 subjects in addition to the common beta-chain variants, Hb S and Hb C. The heterozygote frequencies for Hb S and Hb C were 10.1% and 3.7% respectively. The most frequent of the rare beta-chain variants were Hb Korle Bu (beta 73 Asp leads to Asn) (7 cases) and Hb O su-Christiansborg (beta 52 Asp leads to Asn) (3 cases). One new beta-chain variant, Hb Caribbean (beta 91 Leu leads to Arg) was found.
Asunto(s)
Sangre Fetal , Variación Genética , Hemoglobinas Anormales/genética , Cromatografía por Intercambio Iónico , Electroforesis en Gel de Almidón , Femenino , Hemoglobina E/genética , Hemoglobina Falciforme/genética , Humanos , Recién Nacido , Jamaica , MasculinoRESUMEN
In an electrophoretic study of 15,661 Jamaican cord bloods, 8 rare beta-chain variants were found in 18 subjects in addition to the common beta-chain variants, Hb S and Hb C. The heterozygote frequencies for Hb S and Hb C were 10.1 percent and 3.7 percent respectively. The most frequent of the rare beta-chain variants were Hb Korle Bu (beta 73 Asp leads to Asn) (7 cases) and Hb O su-Christiansborg (beta 52 Asp leads to Asn) (3 cases). One new beta-chain variant, Hb Caribbean (beta 91 Leu leads to Arg) was found. (AU)