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1.
Hemoglobin ; 43(4-5): 254-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31599656

RESUMO

To provide the molecular information on hemoglobinopathies in the Myanmar population, the study was carried out on Myanmar workers in Khon Kaen Province in northeast Thailand. A total of 300 anonymous Myanmar factory workers were randomly recruited during their annual medical checkup. Hemoglobinopathies were identified using hemoglobin (Hb) and DNA analyses. These identified heterozygous α0-thalassemia (α0-thal) [- -SEA (Southeast Asian) deletion] (n = 5, 1.7%), heterozygous α+-thal (n = 103, 34.3%), homozygous α+-thal (n = 12, 4.0%), heterozygous ß-thalassemia (ß-thal) (n = 3, 1.0%), heterozygous ß-thal with homozygous α+-thal (n = 2, 0.7%), double heterozygous ß-thal/α0-thal (n = 1, 0.3%)], heterozygous Hb E (HBB: c.79G>A) with α0-thal/α+-thal (n = 1, 0.3%), heterozygous Hb E (n = 27, 9.0%), heterozygous Hb E with α+-thal (n = 24, 8.0%), homozygous Hb E with α0-thal/α+-thal (n = 1, 0.3%), homozygous Hb E (n = 3, 1.0%) and homozygous Hb E with heterozygous α+-thal (n = 3, 1.0%). No thalassemia defect was found in the remaining 115 subjects (38.4%). Haplotypes associated with Hb E and Hb Dhonburi (or Hb Neapolis) [ß126(H4)Val→Gly, codon 126 (T>G), HBB: c.380T>G] are reported. While the proportions of α0-thal, ß-thal and Hb E are comparable to those described in neighboring countries, a markedly high prevalence of α+-thal (48.6% in total) is unexpected. The molecular information obtained should provide necessary information for diagnostic improvement and planning of a prevention and control program of severe thalassemia in the Myanmar population.


Assuntos
Hemoglobinopatias/genética , Talassemia alfa/etnologia , Hemoglobina E , Hemoglobinopatias/etnologia , Hemoglobinas/análise , Hemoglobinas Anormais , Humanos , Mianmar/etnologia , Prevalência , Análise de Sequência de DNA , Tailândia/epidemiologia
2.
Hemoglobin ; 43(4-5): 249-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581858

RESUMO

This study assessed thalassemia and hemoglobinopathies in a group of the Tay ethnic minority. Participants included 289 women of reproductive-age who enrolled in a pilot screening program for thalassemia conducted at six communities of Thai Nguyen Province, northern Vietnam. Standard procedures including complete blood count (CBC), hemoglobin (Hb) and DNA analyses were performed for all samples. The prevalence of thalassemia in 289 Tay women was 15.6% (gene frequency 0.078) for α0-thalassemia (α0-thal), 10.0% (gene frequency 0.050) for α+-thal, 7.3% (gene frequency 0.036) for ß-thalassemia (ß-thal), 2.4% (gene frequency 0.012) for Hb Constant Spring [Hb CS; α142, Term→Gln, TAA>CAA (α2), HBA2: c.427T>C] and 1.7% (gene frequency 0.009) for Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A]. Further analysis of ß-globin gene abnormalities identified four mutations including codons 41/42 (-TCTT) (HBB: c.126_129delCTTT), codon 17 (A>T) (HBB: c.52A>T), codons 71/72 (+A) (HBB: c.216_217insA), and -28 (A>G) (HBB: c.78A>G). The results hint at the remarkably high frequencies of severe forms of thalassemia that indicate a serious public health problem requiring further exploration, and most probably, also intervention within the country.


Assuntos
Hemoglobinopatias/etnologia , Grupos Minoritários , Talassemia/etnologia , Grupos Étnicos , Feminino , Frequência do Gene , Hemoglobinopatias/genética , Hemoglobinas Anormais , Humanos , Programas de Rastreamento , Mutação , Prevalência , Talassemia/genética , Vietnã/epidemiologia , Vietnã/etnologia , Talassemia alfa/etnologia , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/etnologia , Talassemia beta/genética
3.
Hemoglobin ; 43(2): 107-111, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304855

RESUMO

α-Thalassemia (α-thal) is one of the most common genetic disorders worldwide. The aim of this study was to investigate for the first time the α-thal mutation spectrum in the Lak population living in Lorestan Province, Iran. One hundred and seventy-six α-thal carriers participated in the study. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing were used for the detection of different mutations on the α-globin (HBA1 and HBA2) genes. A total of 11 different mutations was identified. The -α3.7 (rightward; NG_000006.1: g.34164_37967del3804) deletion was observed most frequently (56.35%), followed by α-5 ntα (HBA2: c.95+2_95+6delTGAGG), αpolyA2α (HBA2: c.*92A>G) and - -MED I (NG_000006.1: g.24664_41064del16401), with frequencies of 15.47, 9.39, and 6.08%, respectively. These four mutations accounted for more than 87.0% of the total mutated alleles. Moreover, 19 different genotypes were identified. The types and distribution pattern of the mutations identified in this study, in comparison with other studies conducted in Iran, was most similar to the Kurdish population of Kermanshah Province, Iran. Due to the lack of information on α-thal in Lorestan Province, it was not possible to compare the mutation spectrum in the Lur and Lak populations. In conclusion, our results may help in setting up a strategy for an α-thal screening program and genetic counseling in the Lak people.


Assuntos
Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Genótipo , Heterozigoto , Humanos , Irã (Geográfico)/epidemiologia , Irã (Geográfico)/etnologia , Análise de Sequência de DNA/métodos , Talassemia alfa/etnologia
4.
J Epidemiol Glob Health ; 8(3-4): 189-195, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30864762

RESUMO

This prospective study assessed the prevalence and genetic analysis of α- and ß-thalassemia and sickle cell anemia (SCA) in Southwest Iran. Hematological indices were measured in 17,581 couples living in Khuzestan Province, Southwest Iran. Individuals with mean corpuscular volume <80, mean corpuscular hemoglobin <27, hemoglobin A2 ≥3/5 were considered as ß-thalassemia traits. Prevalence of minor ß-thalassemia, α-thalassemia, SCA, iron deficiency anemia, and silent thalassemia were respectively identified in 995 (5.6%), 1169 (6.65%), 1240 (7.05%), 911 (5.18%), and 1134 (6.45%) individuals using a multiplex amplification refractory mutation system, and direct DNA sequencing of globin genes. Three codons IVS-II-1 (G → A; 26%; n = 13), IVS-I-1 (G → T; 16%; n = 8), and IVS-I-110 (G → A; 14%; n = 7) were the most frequent mutants and IVS-II-1 was the most common ß-thalassemia mutation. Also, based on a gap-polymerase chain reaction assay, genotype frequencies of α-globin mutations were -α3.7 kb (50%; n = 25), Med/ααthal (12%; n = 6), and -α4.2/αα (10%; n = 5), which were the most frequent deletion mutants (72% in total). The most common deletion (50%) was -α3.7 kb. Our data suggest that the population of Southwest Iran is at high risk of α- and ß-thalassemia caused by these deletion mutants and SCA. Our findings will be useful for developing an efficient control program and genetic counseling.


Assuntos
Anemia Falciforme , Testes Genéticos , Prevalência , alfa-Globinas/genética , Talassemia alfa , Adulto , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Índices de Eritrócitos , Feminino , Testes Genéticos/métodos , Testes Genéticos/estatística & dados numéricos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Estudos Prospectivos , Deleção de Sequência , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/etnologia , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/etnologia , Talassemia beta/genética
5.
Taiwan J Obstet Gynecol ; 56(4): 487-494, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28805606

RESUMO

OBJECTIVE: Accurate and efficient pre-implantation genetic diagnosis (PGD) based on the analysis of single or oligo-cells is needed for timely identification of embryos that are affected by deleterious genetic traits in in vitro fertilization (IVF) clinics. Polymerase chain reaction (PCR) is the backbone of modern genetic diagnoses, and a spectrum of PCR-based techniques have been used to detect various thalassemia mutations in prenatal diagnosis (PND) and PGD. Among thalassemias, SEA-type α-thalassemia is the most common variety found in Asia, and can lead to Bart's hydrops fetalis and serious maternal complications. MATERIALS AND METHODS: To formulate an efficient digital PCR for clinical diagnosis of SEA-type α-thalassemia in cultured embryos, we conducted a pilot study to detect the α-globin and SEA-type deletion alleles in blastomere biopsies with a highly sensitive microfluidics-based digital PCR method. Genomic DNA from embryo biopsy samples were extracted, and crude DNA extracts were first amplified by a conventional PCR procedure followed by a nested PCR reaction with primers and probes that are designed for digital PCR amplification. RESULTS: Analysis of microfluidics-based PCR reactions showed that robust signals for normal α-globin and SEA-type deletion alleles, together with an internal control gene, can be routinely generated using crude embryo biopsies after a 106-fold dilution of primary PCR products. CONCLUSION: The SEA-type deletion in cultured embryos can be sensitively diagnosed with the digital PCR procedure in clinics. The adoption of this robust PGD method could prevent the implantation of IVF embryos that are destined to develop Bart's hydrops fetalis in a timely manner. The results also help inform future development of a standard digital PCR procedure for cost-effective PGD of α-thalassemia in a standard IVF clinic.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Testes Genéticos/métodos , Reação em Cadeia da Polimerase/métodos , Diagnóstico Pré-Implantação/métodos , Talassemia alfa/diagnóstico , Alelos , Ásia Sudeste , Biópsia/métodos , Técnicas de Cultura Embrionária/métodos , Humanos , Projetos Piloto , Deleção de Sequência , Talassemia alfa/embriologia , Talassemia alfa/etnologia
6.
Sci Rep ; 7(1): 4690, 2017 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-28680061

RESUMO

Alpha (α)-thalassaemia is one of the most prevalent hereditary blood disorders, commonly affecting Southeast Asian people, with the highest incidence (30-40%) being seen in northern Thailand. However, this high incidence was estimated without consideration of the variations between ethnic populations and the geographical location of the populations. To address this issue, a total of 688 samples from 13 different northern Thai ethnic groups (30 villages) categorized into three linguistic groups were genotyped for deletional alpha-thalassaemia (-α3.7, -α4.2, --SEA and --THAI) and/or non-deletional alpha-thalassaemia (αCS and αPS) via multiplex gap-PCR and dot-blot hybridization, respectively. Alpha+(-α3.7, -α4.2, αCS and αPS) and alpha°-thalassaemia (--SEA and --THAI) allele frequencies (with 95% Confidence Interval) were the highest in the Sino-Tibetan group [0.13 (0.08-0.18)] and the Tai-Kadai group [0.03 (0.02-0.05)], respectively. With regards to ethnicity, the varying allele frequency of α+ and α°-thalassaemia amongst a variety of ethnic groups was observed. The highest α+-thalassaemia allele frequency was found in the Paluang [0.21 (0.10-0.37)] while α°-thalassaemia allele frequency was the highest in the Yuan [0.04 (0.01-0.10)]. These detailed results of alpha thalassaemia allele frequency and genetic diversity amongst the northern Thai ethnic groups demonstrate the need for ethnicity based thalassaemia prevention programs.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Técnicas de Genotipagem/métodos , alfa-Globinas/genética , Talassemia alfa/genética , Grupo com Ancestrais do Continente Asiático/genética , Frequência do Gene , Humanos , Reação em Cadeia da Polimerase Multiplex , Deleção de Sequência , Tailândia/etnologia , Talassemia alfa/etnologia
7.
Am J Clin Pathol ; 147(6): 589-595, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575177

RESUMO

Objectives: To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results. Methods: In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia. Results: Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS ß-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant. Conclusions: This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants.


Assuntos
Hemoglobina A Glicada/análise , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia , Identificação Biométrica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Testes Hematológicos/métodos , Humanos , Masculino , Prevalência , Talassemia alfa/sangue , Talassemia alfa/etnologia , Talassemia beta/sangue , Talassemia beta/etnologia
8.
Ann Hematol ; 96(6): 1005-1014, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28337528

RESUMO

The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely clear how genetic and environmental factors interplay to modify clinical severity in affected individuals. Previous studies suggested that altered structure or function of alpha-hemoglobin-stabilizing protein (AHSP) could modify the clinical phenotypes of thalassemias. The present study attempted to explore the potential role of AHSP in the pathophysiology of HbH disease in 95 Chinese and Thai/Sino-Thai patients with deletional and non-deletional form of this disease. We identified six polymorphic sites in AHSP which were subgrouped into major haplotype clades. No association between AHSP genotypes or haplotypes and clinical phenotypes was observed. Instead, multiple linear regression analysis indicated that expression of AHSP correlated negatively with age (P < 0.001) and hemoglobin (P = 0.007), but positively with reticulocyte count (P = 0.003) and severity score (P = 0.003). Subgroup analysis showed that AHSP expression was higher in the non-deletional form than in the deletional form (P < 0.001). Moreover, specific types of non-deletional HbH disease with production of mutant alpha-globin chains that do not bind to AHSP (Hb Constant Spring and Hb Pakse) showed the highest AHSP expression. The present findings demonstrate that AHSP expression is a biomarker of HbH disease severity and infer an important role of AHSP in modulating the pathophysiology of this disease. Pharmacological or genetic means to alter AHSP expression may be a novel approach for amelioration of disease severity in HbH disease.


Assuntos
Proteínas Sanguíneas/genética , Haplótipos , Chaperonas Moleculares/genética , Polimorfismo Genético , Talassemia alfa/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Expressão Gênica , Genótipo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tailândia , Adulto Jovem , Talassemia alfa/etnologia , Talassemia alfa/patologia
9.
Eur J Haematol ; 98(6): 553-562, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28160324

RESUMO

OBJECTIVE: α-Thalassemia, one of the most common genetic diseases, is caused by deletions or point mutations affecting one to four α-globin genes. Molecular diagnosis is important to prevent the most severe forms of the disease. However, the diagnosis of α-thalassemia is complex due to a high variability of the genetic defects involved, with over 250 described mutations. We summarize herein the findings of genetic analyses of DNA samples referred to our laboratory for the molecular diagnosis of α-thalassemia, along with a detailed clinical description. METHODS: We utilized a diagnostic algorithm including Gap-PCR, to detect known deletions, followed by sequencing of the α-globin gene, to identify known and novel point mutations, and multiplex ligation-dependent probe amplification (MLPA) for the diagnosis of rare or novel deletions. RESULTS: α-Thalassemia was diagnosed in 662 of 975 samples referred to our laboratory. Most commonly found were deletions (75.3%, including two novel deletions previously described by us); point mutations comprised 25.4% of the cases, including five novel mutations. Our population included mostly Jews (of Ashkenazi and Sephardic origin) and Muslim Arabs, who presented with a higher rate of point mutations and hemoglobin H disease. Overall, we detected 53 different genotype combinations causing a spectrum of clinical phenotypes, from asymptomatic to severe anemia. CONCLUSION: Our work constitutes the largest group of patients with α-thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations.


Assuntos
Anemia/diagnóstico , Hemoglobina H/genética , Mutação Puntual , Deleção de Sequência , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etnologia , Anemia/genética , Anemia/patologia , Árabes , Sequência de Bases , Criança , Pré-Escolar , Feminino , Expressão Gênica , Genótipo , Humanos , Lactente , Israel , Judeus , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Reação em Cadeia da Polimerase Multiplex/métodos , Fenótipo , Análise de Sequência de DNA , Índice de Gravidade de Doença , alfa-Globinas/química , Talassemia alfa/etnologia , Talassemia alfa/genética , Talassemia alfa/patologia
10.
Gene ; 619: 71-75, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26877226

RESUMO

Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies. The objective of this study was to update and reveal the prevalence of thalassemia and mutation spectrum in the Baise region of southern China. We screened 47,500 individuals from Baise region by hematological and genetic analysis. Totally, 11,432 (24.07%) subjects were diagnosed as being carriers and patients of thalassemia, including 7290 (15.35%) subjects with α-thalassemia, 3152 (6.64%) subjects with ß-thalassemia and 990 (2.08%) subjects with both α-thalassemia and ß-thalassemia. Ten α-thalassemia mutations and 31 genotypes were identified in the α-thalassemia carriers and patients. Meanwhile, 13 ß-thalassemia mutations and 26 genotypes were characterized in the ß-thalassemia carriers and patients. Furthermore, the true prevalence of nondeletional mutations and Thailand type (-THAI) deletion mutation were first reported in this study. In addition, three cases of αα/ααα3.7, five cases of HKαα/αα and two rare ß-globin mutations, -86 (G>C) and CD 121 (G>T) were first identified in the Chinese Zhuang ethnic populations. Our data indicated that there was great heterogeneity and extensive spectrum of thalassemias in the Baise populations. The findings will be useful for genetic counseling and prevention of severe thalassemia in this region.


Assuntos
Frequência do Gene , Hemoglobinas Anormais/genética , Talassemia alfa/genética , Talassemia beta/genética , China , Humanos , Mutação , Prevalência , Talassemia alfa/epidemiologia , Talassemia alfa/etnologia , Talassemia beta/epidemiologia , Talassemia beta/etnologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-27847257

RESUMO

Thalassaemia is the most common monogenic disorder worldwide. It is common in areas with prevalent malaria as thalassaemic red cells provide immunity against the parasite. The incidence of thalassaemia carriers is high in regions such as Mediterranean, Middle East, Indian subcontinent, Southeast Asia and South China. In the past few decades, migrants from the thalassaemia prevalent countries to non-prevalent countries, mainly North America and Central and North Europe, are rapidly increasing in number. The non-prevalent countries may not have established pre-natal screening system for thalassaemia. The genetic subtypes among the different ethnic groups vary; this may pose challenges in prenatal diagnosis. Genetic counselling on the postnatal course of thalassaemia may be affected by the genotype-phenotype correlation and coinheritance of other genetic diseases. New treatment methods improve the survival of patient with thalassaemia major, but some late complications that occur with longer survival have been recently discovered.


Assuntos
Emigração e Imigração , Refugiados , Migrantes , Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia , Árabes , Ásia Sudeste/epidemiologia , Ásia Sudeste/etnologia , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , China/etnologia , Europa (Continente)/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Aconselhamento Genético , Humanos , Incidência , Índia/epidemiologia , Índia/etnologia , Região do Mediterrâneo/epidemiologia , Região do Mediterrâneo/etnologia , Oriente Médio/epidemiologia , Oriente Médio/etnologia , Mutação , América do Norte/epidemiologia , Gravidez , Diagnóstico Pré-Natal , Talassemia alfa/etnologia , Talassemia beta/etnologia
12.
Genet Mol Res ; 15(2)2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27173219

RESUMO

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.


Assuntos
Hemoglobina A/genética , Hemoglobinas Anormais/genética , Talassemia alfa/genética , Humanos , Malásia , Mutação Puntual , Polimorfismo de Fragmento de Restrição , Talassemia alfa/etnologia
13.
Hemoglobin ; 40(4): 285-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27189862

RESUMO

This study was carried out to ascertain the allelic frequency of α(+)-thalassemia (α(+)-thal) in Scheduled caste and scheduled tribe populations of the Damoh district of Madhya Pradesh, India. Random blood samples of Scheduled tribe (267) and Scheduled caste (168), considering the family as a sampling unit, were analyzed for the presence of the -α(3.7) (rightward) (NG_000006.1: g.34164_37967del3804) and -α(4.2) (leftward) (AF221717) deletions. α(+)-Thal was significantly higher in the Scheduled tribals (77.9%) as compared to the scheduled caste population (9.0%). About 58.0% scheduled tribals carried at least one chromosome with the -α(3.7) deletion and 20.0% scheduled tribals carried the -α(4.2) deletion. Frequency for the -α(3.7) allele was 0.487 in the scheduled tribal populations in comparison to 0.021 in scheduled castes. Allelic frequency for -α(4.2) was 0.103 and 0.024, respectively, in the above communities. No Hardy-Weinberg equilibrium for α-thal gene (p < 0.05) was detected in the tribal population, indicating the presence of selection pressures in favor of α-thal mutation and adaptation.


Assuntos
Grupos Populacionais/genética , Talassemia alfa/epidemiologia , Alelos , Frequência do Gene , Humanos , Índia/epidemiologia , Índia/etnologia , Seleção Genética , Talassemia alfa/etnologia , Talassemia alfa/genética
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(1): 150-6, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26913412

RESUMO

OBJECTIVE: To investigate the common mutation spectrum of α- and ß-thalassemia in Yunnan childbearing-aged population. METHODS: The common mutation types of α- or ß-globin genes were detected by multiple Gap-PCR and the PCR-reversed dot blotting, and the unknown mutation types were determined by DNA sequencing in DNA samples of hypochromic microcytic anemia patients and carriers who were confirmed to be positive by serologic screaning, then the mutation types of globin in Yunnan population were analyzed statistically. RESULTS: A total of 40 kinds of mutation types were detected in 685 detected persons, among them the 3 commonest mutation types of α-globin genes were --(SEA)/αα (49.09%), -α(3.7)/αα (36.67%) and α(CS)α/αα (8.79%), the 3 commonest genetypes of ß-globin gene were CD26(GAG>AAG)/N (43.78%), CD41-42(-CTTT)/N (20.1%) and CD17(AAG>TAG)/N (18.9%). There were 348 Han and 212 Dai ethnic persons in 685 cases, but their mutation of globin genes were different between these 2 ethnic groups. The results also showed that the gene mutation types were mostly concentrated in Dai ethnic individuals, since 28 of 38 detected α-ß-thalassemia cases were Dai ethnic individuals. CONCLUSION: The mutation spectrums of α- and ß-globin genes in Yunnan childbearing-aged population are diverse and different from that in other areas of China.


Assuntos
alfa-Globulinas/genética , Talassemia alfa/etnologia , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/etnologia , Talassemia beta/genética , Anemia Hipocrômica/etnologia , Anemia Hipocrômica/genética , Grupo com Ancestrais do Continente Asiático , China , Análise Mutacional de DNA , Grupos Étnicos/genética , Testes Genéticos , Heterozigoto , Humanos , Mutação , Reação em Cadeia da Polimerase
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(6): 941-944, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28598129

RESUMO

OBJECTIVES: To investigate the carrying rates and genotype distribution of thalassemia gene in Han people and Tibetans in Sichuan district. METHODS: A total of 1 147 Han adults and 613 adult Tibetans were included in this study.Hematological parameters were measured with Sysmex XE-2100 automatic blood cell analyzer.Alpha thalassemia and beta thalassemia gene analyses were further performed on samples with a mean corpuscular volume (MCV) <85 fL and a mean corpuscular hemoglobin (MCH) <27 pg.Multiplex ligation-dependent probe amplification (MLPA) and reverse dot blot assays were used for detecting deletional mutations of α globin gene and non-deletional mutations of α globin and ß globin genes,respectively. RESULTS: About 1.48% (17/1 147) Han people carried alpha thalassemia gene,with --SEA/αα as the most common genotype; 1.39% (16/1 147) carried beta thalassemia gene,with CD17 and IVS-2-654 as the most common genotype.There were 2 cases with both alpha and beta thalassemia.Low MCH (<27 pg) was found in all 33 cases with positive thalassemia genes.However,5 people with positive thalassemia genes had higher than 80 fL MCV,with the highest reaching 83.7 fL.Out of 613 Tibetans,only one was found to have positive thalassemia genes. CONCLUSIONS: Sichuan Han population carry a high level of thalassemia genes,with various genotypes and pathogenic gene mutation types.Han people with < 84 fL MCV and <27 pg MCH were recommended for thalassemia gene screening.Tibetans were not recommended for routine screening of thalassemia.


Assuntos
Genótipo , Talassemia alfa/etnologia , Talassemia alfa/genética , Adulto , China , Humanos , Tibet , alfa-Globinas/genética , Globinas beta/genética
16.
Hematology ; 21(1): 54-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26292035

RESUMO

OBJECTIVE: The aim of this study was to investigate the prevalence of hemoglobin E (Hb E) as well as the hematological and the phenotypic features of Hb E-related disorders in Yunnan Province of Southwest China. METHODS: A total of 30,908 individuals from more than 30 nationalities who were childbearing population were recruited in the present study. Hematological analysis including complete blood counts and quantification of Hb levels were performed by capillary electrophoresis. The identified carriers were further detected for molecular analysis by multiple gap-polymerase chain reactions (gap-PCR) and the PCR-reverse dot-blot. RESULTS: Hematological results showed that 345 subjects were identified to be Hb E carriers (1.1%). The high incidence of carrying Hb E occurred in Achang (25.0%), Jingpo (23.5%), Dai (16.0%), and Lisu (13.6%). After performing molecular analysis in 201 carriers, 192 cases (95.5%) were heterozygous Hb E and 29 cases (14.4%) of Hb E were con-inherited with α-thal cases. The other ß-globin chain mutation included homozygous Hb E (three cases), ß(+)-thal/Hb E (one case) and ß(0)-thal/Hb E (five cases). Individuals in Dai had the most types of Hb E-related disorders. Severe anemia was observed in cases of ß(+)-thal/Hb E and ß(0)-thal/Hb E. CONCLUSIONS: There is a high prevalence of Hb E among Yunnan populations, especially in ethnic groups. In addition, the spectrums of Hb gene mutations would provide a support for the genetic counseling of Hb E-related disorders among Yunnan populations.


Assuntos
Hemoglobina E/genética , Mutação , alfa-Globinas/genética , Talassemia alfa/epidemiologia , Globinas beta/genética , Talassemia beta/epidemiologia , Adulto , Alelos , China/epidemiologia , Grupos Étnicos , Feminino , Frequência do Gene , Aconselhamento Genético , Heterozigoto , Homozigoto , Humanos , Masculino , Prevalência , Talassemia alfa/etnologia , Talassemia alfa/genética , Talassemia alfa/patologia , Talassemia beta/etnologia , Talassemia beta/genética , Talassemia beta/patologia
17.
BMJ Open ; 5(12): e010047, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26715484

RESUMO

OBJECTIVES: This study aimed to detect α- and ß-thalassaemia mutations in the Jino ethnic minority population of Yunnan Province, Southwest China. DESIGN: A total of 1613 Jino adults were continuously recruited from February 2012 to April 2012. Fasting venous blood samples were obtained to determine haematological variables. Haemoglobin analysis was conducted using high-performance liquid chromatography. Participants with hypochromic microcytic anaemia or positive haemoglobin analysis profiles were confirmed by α- and ß-globin genetic testing, including DNA microarray analysis, direct sequencing methods and multiplex gap-PCR assays. SETTING: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital. RESULTS: We found 363 suspected cases by primary screening of haematological variables and haemoglobin analysis. After further genetic testing, four types of α- and ß-thalassaemia mutation were detected in 203 out of 363 individuals. Both α(0)- and α(+)-thalassaemia mutations, --(SEA) and -α(3.7), were identified. ß-Thalassaemia mutations included CD17 (HBB:c.52A>T) and CD26 (HbE or HBB:c.79G>A). In addition, 13 HbE carriers had coexisting α(0)- or α(+)-thalassaemia deletions. Clinical haematological variables indicated that, in this study, carriers of all thalassaemic genotypes had more severe hypochromic microcytic anaemia than non-thalassaemic individuals. CONCLUSIONS: Our results provide information on the Jino ethnic minority that may be useful for further genetic counselling, prenatal screening and clinical diagnosis of thalassaemia in this region.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Grupos Minoritários , Mutação , Talassemia alfa/genética , Talassemia beta/genética , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Marcadores Genéticos , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , alfa-Globinas/genética , Talassemia alfa/etnologia , Globinas beta/genética , Talassemia beta/etnologia
18.
Blood Cells Mol Dis ; 53(4): 261-4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24857170

RESUMO

BACKGROUND: The "gray zone" of borderline hemoglobin A2 (Hb A2) may be present in a large section of the population, especially in countries where thalassemia is common. However, very little is currently known of the molecular basis of borderline Hb A2 in Chinese individuals. METHOD: In this study, we performed a comprehensive analysis of the globin genotypes and KLF1 gene mutations associated with borderline Hb A2 in 165 Chinese subjects. RESULT: Fifteen (9.1%) were positive for a molecular defect in the α-,ß-globin genes, of whom, α-thalassemia mutations and α-globin gene triplication were found in eleven cases, accounting for about 73.3% of these globin gene defects. Twenty (12.1%) were positive for a molecular defect in the KLF1 gene. Eight different mutations were identified, six of which are here reported for the first time. The most common is the G176AfsX179 mutation, accounting for 50% of the total. CONCLUSIONS: The molecular characterization of borderline Hb A2 in Chinese individuals is significantly different than in Italian population. Our data is conductive to provision of genetic counseling for Chinese individuals with borderline Hb A2.


Assuntos
Hemoglobina A2/genética , Fatores de Transcrição Kruppel-Like/genética , alfa-Globinas/genética , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/genética , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Aconselhamento Genético , Testes Genéticos , Genótipo , Humanos , Dados de Sequência Molecular , Mutação , Talassemia alfa/etnologia , Talassemia beta/etnologia
19.
Malays J Pathol ; 36(1): 27-32, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24763232

RESUMO

Alpha (Α) thalassaemia is the most common inherited disorder in Malaysia. The clinical severity is dependant on the number of Α genes involved. Full blood count (FBC) and haemoglobin (Hb) analysis using either gel electrophoresis, high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) are unable to detect definitively alpha thalassaemia carriers. Definitive diagnosis of Α-thalassaemias requires molecular analysis and methods of detecting both common deletional and non-deletional molecular abnormailities are easily performed in any laboratory involved in molecular diagnostics. We carried out a retrospective analysis of 1623 cases referred to our laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the diagnosis of Α-thalassaemia during the period October 2001 to December 2012. We examined the frequency of different types of alpha gene abnormalities and their haematologic features. Molecular diagnosis was made using a combination of multiplex polymerase reaction (PCR) and real time PCR to detect deletional and non-deletional alpha genes relevant to southeast Asian population. Genetic analysis confirmed the diagnosis of Α-thalassaemias in 736 cases. Majority of the cases were Chinese (53.1%) followed by Malays (44.2%), and Indians (2.7%). The most common gene abnormality was ΑΑ/--(SEA) (64.0%) followed by ΑΑ/-Α(3.7) (19.8%), -Α(3.7) /--(SEA) (6.9%), ΑΑ/ΑΑCS (3.0%), --(SEA)/--(SEA) (1.2%), -Α(3.7)/-Α(3.7) (1.1%), ΑΑ/-Α(4.2) (0.7%), -Α(4.2)/--(SEA (0.7%), -Α(3.7)/-Α(4.2) (0.5%), ΑΑ(CS)/-- SEA) (0.4%), ΑΑ(CS)/ΑΑ(Cd59) (0.4%), ΑΑ(CS)/ΑΑ(CS) (0.4%), -Α(3.7)/ΑΑ(Cd59) (0.3%), ΑΑ/ΑΑ(Cd59) (0.1%), ΑΑ(Cd59)/ ΑΑ(IVS I-1) (0.1%), -Α(3.7)/ΑΑ(CS) (0.1%) and --(SEA) /ΑΑ(Cd59) (0.1%). This data indicates that the molecular abnormalities of Α-thalassaemia in the Malaysian population is heterogenous. Although Α-gene deletion is the most common cause, non-deletional Α-gene abnormalities are not uncommon and at least 3 different mutations exist. Establishment of rapid and easy molecular techniques is important for definitive diagnosis of alpha thalassaemia, an important prerequisite for genetic counselling to prevent its deleterious complications.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Hemoglobina A/genética , Hemoglobinas Anormais/genética , Talassemia alfa/etnologia , Talassemia alfa/genética , Feminino , Deleção de Genes , Heterogeneidade Genética , Heterozigoto , Humanos , Incidência , Malásia/epidemiologia , Masculino , Talassemia alfa/diagnóstico
20.
Eur J Haematol ; 90(3): 210-3, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23289742

RESUMO

Since the 1950s, a strong correlation between high carrier rates for ß-thalassemia mutations and selective survival advantage in tropical and subtropical 'malarial belt' regions has been established. Due to the relatively more complex genetics of α-thalassemia, a similar relationship was demonstrated for α-globin gene mutations only from the 1980s, with both single- and double-α-globin gene deletions prevalent in the malarial belt. Mechanistically, the single-α-globin gene deletions arise from non-allelic recombination between the homologous α1 (HBA1) and α2 (HBA2) globin genes. Compared to the -α(3.7) and ααα(anti3.7) rightward crossover alleles, much less is known about the -α(4.2) and ααα(anti4.2) leftward crossover alleles. We performed a survey of 1,285 unselected cord blood samples from the 3 major ethnic groups in Singapore. Overall, the frequency of the -α(3.7) deletion was significantly higher than its reciprocal ααα(anti3.7) triplication, consistent with positive selection for the -α(3.7) single-gene deletion. In marked contrast, there was no significant difference in frequency between the -α(4.2) and reciprocal ααα(anti4.2) alleles, suggesting the absence of positive selection for the -α(4.2) single-gene deletion. The similar ααα(anti3.7) and ααα(anti4.2) allele frequencies also suggested that the crossover rates at X and Z homology boxes are similar. Taken together, these observations suggest a differential positive selection for the -α(3.7) and -α(4.2) alleles within the same population. Further population and biological studies may be required to explain these current observations.


Assuntos
Grupos Étnicos , Deleção de Genes , Heterozigoto , alfa-Globinas/genética , Talassemia alfa/etnologia , Talassemia alfa/genética , Alelos , Troca Genética , Sangue Fetal/metabolismo , Frequência do Gene , Genótipo , Humanos , Prevalência , Seleção Genética , Singapura/epidemiologia , Talassemia alfa/sangue
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