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2.
Cancers (Basel) ; 13(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34680201

RESUMO

Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes 6 and 15 (LOH-6 and LOH-15), where HLA class I genes are located. There is growing evidence indicating that LOH in HLA contributes to the immune selection of HLA loss variants and influences the resistance to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration involving HLA genes has not been systematically assessed in different types of tumors and often remains underestimated. Here, we used SNP arrays to investigate the incidence and patterns of LOH-6 and LOH-15 in a number of human cancer cell lines and tissues of different histological types. We observed that LOH in HLA is a common event in cancer samples with a prevalence of a copy neutral type of LOH (CN-LOH) that affects entire chromosome 6 or 15 and involves chromosomal duplications. LOH-6 was observed more often and was associated with homozygous HLA genotype and partial HLA loss of expression. We also discuss the immunologic and clinical implications of LOH in HLA on tumor clonal expansion and association with the cancer recurrence after treatment.

3.
Clin Kidney J ; 14(7): 1845-1847, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34221391

RESUMO

Our group identified two pathogenic variants on the PKD1 gene, c.10527_10528delGA and c.7292T>A, from unrelated families. They came from two small counties in Granada, with 61 and 26 autosomal dominant polycystic kidney disease (ADPKD) individuals affected. To determine a common ancestor, healthy and ADPKD individuals from these families were genotyped by analysing four microsatellites located on chromosome 16. Our study identified a common haplotype in all ADPKD individuals. These findings underpin our hypothesis of the founder effect and explain why there is a high frequency of ADPKD in small regions. Determining hotspots of ADPKD will help to better plan healthcare in the future.

4.
Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298868

RESUMO

Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral/imunologia , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Microambiente Tumoral/imunologia , Adulto Jovem
5.
Ann Surg Oncol ; 26(8): 2631-2639, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011905

RESUMO

BACKGROUND: Tumor human leukocyte antigen class I (HLA-I) expression plays an important role in T cell-mediated tumor rejection. Loss of HLA-I is associated with cancer progression and resistance to immunotherapy, including antibodies blocking programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling. Our objective was to analyze a correlation between HLA-I, tumor immune infiltration, and PD-L1/PD-1 axis in bladder cancer in association with the clinicopathologic features of patients. METHODS: We analyzed 85 cryopreserved bladder tumors by immunohistochemistry to investigate the expression of HLA-I, PD-L1, PD-1, CD3, CD8, and CXC chemokine receptor 4 (CXCR4). The results were correlated with tumor stage and other clinicopathologic variables of patients. RESULTS: We found a strong positive correlation between tumor HLA-I expression and infiltration with CD3+ and CD8 + T cells. PD-L1 expression was positive in 15.5% of tumors and heterogeneous in 40.5%, and was linked to a more advanced tumor stage. The majority of HLA-I-positive/heterogeneous tumors also expressed PD-L1 and PD-1, which were significantly correlated with each other and with lymphocyte infiltration. Interestingly, the analysis of the simultaneous expression of both markers revealed that 85.2% of tumors with a positive/heterogeneous HLA-I phenotype and negative for PD-L1 were mostly non-invasive, representing a 'tumor rejection' immune phenotype. CONCLUSIONS: High tumor HLA-I expression with absence of PD-L1 provides bladder cancer with an immune rejection mechanism. Evaluation of PD-L1 and HLA-I together should be considered in bladder cancer and may provide a new predictive biomarker of tumor invasiveness and of the response to 'immune checkpoint' therapy.


Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Musculares/imunologia , Recidiva Local de Neoplasia/imunologia , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Feminino , Seguimentos , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Microambiente Tumoral , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
6.
Oncotarget ; 9(3): 4120-4133, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29423109

RESUMO

Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy.

7.
Vaccines (Basel) ; 5(1)2017 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-28264447

RESUMO

Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/"soft" or irreversible/"hard" due to genetic alterations in HLA, ß2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL).

8.
Int J Cancer ; 140(4): 888-899, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27785783

RESUMO

We wanted to analyze whether tumor HLA class I (HLA-I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA-I expression (49.1%) or showed a selective HLA-A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA-I expression but with a percentage of HLA-I negative cells between 10 and 25%. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of ß2-microglobulin (ß2-m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated "immune-permissive tumor microenvironment (TME)," was characterized by positive tumor HLA-I expression, intratumoral infiltration with cytotoxic T-CD8+ cells, M1-inflammatory type macrophages, and a diffuse pattern of FAP+ cancer-associated fibroblasts. In contrast, another pattern defined as "non-immune-permissive TME" was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages. In conclusion, this study revealed marked differences between HLA class I-positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Genes MHC Classe I , Antígenos HLA/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Idoso , Idoso de 80 Anos ou mais , Apresentação de Antígeno , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Progressão da Doença , Regulação para Baixo , Endopeptidases , Feminino , Fibroblastos/patologia , Gelatinases/análise , Antígenos HLA/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Macrófagos/patologia , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Serina Endopeptidases/análise , Evasão Tumoral/genética , Evasão Tumoral/imunologia
9.
Hemoglobin ; 35(1): 80-3, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21250884

RESUMO

We studied five unrelated Mexican carriers of the Spanish (δß)(0)-thalassemia [(δß)(0)-thal] mutation to characterize the size of the deletion, the 5' and 3' breakpoints and the 5' ß-globin haplotype. Sequence analysis revealed the presence of an 89,548 bp deletion. The δ- and ß-globin genes, two olfactory receptor genes (OR51V1 and OR52A1) and two pseudogenes (OR52Z1P and OR51A1P) were deleted. The 5' breakpoint was located at the same position as previously reported, and the 3' breakpoint was situated 7.0 kb downstream of OR52A1 and 11.7 kb upstream of OR52A5. The Spanish (δß)(0)-thal allele was associated with the 5' haplotype 2 [- + + - +] in the studied patients. Because this mutation is relatively frequent in Spain, and the Mexican population contains a high level of Spanish genetic background, we propose that the mutation in both populations share a common ancestral origin.


Assuntos
Americanos Mexicanos/genética , Deleção de Sequência , Talassemia/genética , Globinas beta/genética , Globinas delta/genética , Alelos , Sequência de Bases , Pontos de Quebra do Cromossomo , Haplótipos , Heterozigoto , Humanos , México/epidemiologia , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase , Pseudogenes , Receptores Odorantes/deficiência , Receptores Odorantes/genética , Análise de Sequência de DNA , Espanha/etnologia , Talassemia/etnologia , Globinas beta/deficiência , Globinas delta/deficiência
10.
Hemoglobin ; 34(6): 509-15, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21077758

RESUMO

Between 1978 and 2009, we studied 1,863 Mexican Mestizo patients with clinical data compatible with a hemoglobinopathy. Of these patients, 382 had some hemoglobin (Hb) abnormality (20.5%), 128 had a sickle cell hemoglobinopathy, representing a general frequency of 6.9%, which is similar to the percentage observed in previous studies on Mexican Mestizos. We analyzed the 5' ß-globin haplotype (5'Hp) in 79 unrelated ß(S) chromosomes (26 ß(S)/ß(S), 14 ß(S)/ß(Thal), nine ß(S)/ß(A) and four ß(S)/ß(D)), and four haplotypes were observed: 72.2% CAR 24.1% Benin, 2.5% Senegal and 1.2% Cameroon; the last two are reported for first time in Mexico. In some Latin American populations such as Brazil, the Bantu haplotype predominates, while in others such as Jamaica, the Benin haplotype is the most frequent, showing heterogeneity of African genes as a consequence of different regions involved in the slave trade.


Assuntos
Etnicidade/genética , Hemoglobina Falciforme/genética , Mutação de Sentido Incorreto , Saúde da Família , Frequência do Gene , Heterogeneidade Genética , Genótipo , Geografia , Haplótipos , Hemoglobinopatias/genética , Humanos , México , Globinas beta/genética
11.
Genet Mol Biol ; 33(1): 9-11, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21637597

RESUMO

We analyzed the SLC4A1 gene in three Mexican patients with Hereditary Spherocytosis (HS). The promoter and all 20 exons were investigated through heteroduplex analysis and DNA sequencing. No DNA changes were detected in one of the three patients. Two well-known polymorphisms, Memphis I and the Diego-a blood group, were detected in another one. In the third, the HS phenotype could be explained by the novel 1885_1888dupCCGG mutation found in heterozygosis. This frameshift mutation is predicted to result in a truncated and unstable protein lacking normal functions.

12.
Genet. mol. biol ; 33(1): 9-11, 2010.
Artigo em Inglês | LILACS | ID: lil-566149

RESUMO

We analyzed the SLC4A1 gene in three Mexican patients with Hereditary Spherocytosis (HS). The promoter and all 20 exons were investigated through heteroduplex analysis and DNA sequencing. No DNA changes were detected in one of the three patients. Two well-known polymorphisms, Memphis I and the Diego-a blood group, were detected in another one. In the third, the HS phenotype could be explained by the novel 1885_1888dupCCGG mutation found in heterozygosis. This frameshift mutation is predicted to result in a truncated and unstable protein lacking normal functions.

13.
Hemoglobin ; 33(6): 492-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19958195

RESUMO

We studied a fast-moving, abnormal hemoglobin (Hb) identified as Fannin-Lubbock-I [beta119(GH2)Gly-->Asp] in a homozygous Mexican girl. To date, homozygosity for the Hb Fannin-Lubbock-I variant has not been reported. Her parents and five other relatives were heterozygotes. The 5' beta-globin haplotype analysis showed that the mutation was associated with haplotype 2 [- + + - +]for the epsilon, (G)gamma, (A)gamma, 5' and 3 'psibeta-globin sites, and also segregated with the TGTTC haplotype, which was constructed with five polymorphic sites of the beta-globin gene [exon 1-nucleotide (nt) 6 (C>T) and IVS-II-16 (C>G), IVS-II-46 (T>C), IVS-II-74 (G>T), and IVS-II-81 (C>T). In 1994, a variant with an additional mutation at codon 111 [beta111(G13)Val-->Leu] was described in five Spanish families. This variant was termed Hb Fannin-Lubbock-II, and the question of the existence of Hb Fannin-Lubbock-I arose. However, based on our findings, we were able to confirm the existence of Hb Fannin-Lubbock-I and propose that this mutation has a different origin from the one identified in Spanish families.


Assuntos
Hemoglobinas Anormais/genética , Homozigoto , Mutação Puntual , Globinas beta/genética , Éxons , Saúde da Família , Feminino , Haplótipos , Humanos , Lactente , México , Linhagem
14.
Hemoglobin ; 33(1): 66-71, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19205976

RESUMO

beta-Globin haplotypes have been used to investigate the origin and spread of beta-globin mutations such as Hb S [beta 6(A3)Glu-->Val, GAG>GTG], Hb E [beta 26(B8)Glu-->Lys, GAG>AAG], and beta-thalassemia (beta-thal). Molecular analyses revealed the presence of 17 beta-thal mutations in the Mexican population; the most frequent of these are the nonsense codon 39 (C>T), IVS-I-1 (G>A), IVS-I-110 (G>A), and -28 (A>C). To improve our knowledge about their origin, we analyzed the 5' haplotypes by restriction fragment length polymorphism. The codon 39 mutation (n = 17) was observed with five 5' haplotypes: 1 (59%), 2 (23%), and 4, 6, and 9 (6% each). The IVS-I-1 mutation (n = 15) was found with five 5' haplotypes: 1 (73.6%), 2, 3, 5, and 11 (6.6% each), whereas the IVS-I-110 (n = 9) and -28 mutations (n = 1) were only associated with haplotype 1. In the population studied, the codon 39 and IVS-I-1 mutations show a multicentric origin, whereas the IVS-I-110 and -28 mutations have an apparent single origin. Further investigation is required for the analysis of the polymorphisms surrounding the beta-globin gene.


Assuntos
Haplótipos , Mutação , Globinas beta/genética , Talassemia beta/genética , Análise Mutacional de DNA , Variação Genética , Genética Populacional , Humanos , México/epidemiologia
15.
Gynecol Obstet Invest ; 67(1): 14-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18716398

RESUMO

BACKGROUND/AIMS: It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia. METHODS: 46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP. RESULTS: The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p > 0.05). CONCLUSION: The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.


Assuntos
Proteínas Substratos do Receptor de Insulina/genética , Insulina/genética , Pré-Eclâmpsia/genética , Receptor de Insulina/genética , Adulto , Alelos , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Estudos Transversais , DNA/genética , DNA/metabolismo , Feminino , Haplótipos , Humanos , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/sangue , México , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/sangue , Gravidez , Receptor de Insulina/sangue , Adulto Jovem
16.
Rev Invest Clin ; 61(5): 399-404, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20184100

RESUMO

INTRODUCTION: Hemoglobin disorders are classified into three main groups: structural variants, thalassemias (thal) and hereditary persistence of fetal hemoglobin (HPFH). OBJECTIVE. This study describes the types and frequencies of hemoglobinopathies from four states of the Pacific coast of Mexico (Jalisco, Colima, Nayarit and Michoacan). MATERIAL AND METHODS. We studied 1513 Mexican individuals by hematological and biochemical analysis following the conventional methods, DNA analysis was carried out in abnormal samples. RESULTS. The frequency of hemoglobinopathies was 1.258%. Structural variants were the most common type (0.726%), with seven carriers (0.462%) and one homozygote (0.066%) for Hb S, and three heterozygotes of the following hemoglobins: C (beta6 Glu-->Lys), Fannin-Lubbock I (beta119 Gly-->Asp) and Colima (beta49 Ser-->Cys), with a frequency of 0.066% each. We observed a frequency of 0.466% for the thalassemia group, with one homozygote for the alpha3.7 (-thal) allele (0.066%), and 6 heterozygotes for beta-thal (0.40%), with the allele IVS1:110 G-->A in three subjects, and the alleles Cd 39, IVS1:5 G-->A and -28 A-->C in the three other. HPFH was detected in one subject (0.066%). Jalisco and Colima had the highest frequencies of hemoglobinopathies, 3.015% and 1.331% respectively, and the latter showed the most diversity of hemoglobin disorders. CONCLUSIONS: The observed heterogeneity of types and frequencies of hemoglobinopathies in the regions studied illustrate the importance of further investigation of these abnormalities in Mexico.


Assuntos
Hemoglobinopatias/classificação , Hemoglobinopatias/epidemiologia , Humanos , México
18.
Hemoglobin ; 28(3): 261-5, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15481896

RESUMO

We identified and characterized a novel beta-thalassemia (beta-thal) mutation due to a deletion of cytosine at codons 77/78 (-C) [CAC(His) CA- or CTG(Leu)--> -TG] found in a heterozygous state in four members of a Mexican family. The beta haplotype analysis performed on the family revealed that the frameshift at codons 77/78 (-C) mutation in this family is associated with haplotype V [- + - - - + ] and framework 2. Ten beta-thal alleles with a cytosine deletion are described at the Globin Gene Server, two of which are very near codon 77. The molecular pathology of beta-thal in the Mexican population has been shown to be heterogeneous, because some Mediterranean, Asian, private and rare alleles have been observed, a similar fact as has been observed in populations with a low frequency of beta-thal.


Assuntos
Alelos , Códon/genética , Mutação da Fase de Leitura , Haplótipos/genética , Talassemia beta/genética , Família , Feminino , Humanos , Masculino , México , Talassemia beta/patologia
20.
Rev. invest. clín ; 50(5): 395-8, sept.-oct. 1998. tab
Artigo em Inglês | LILACS | ID: lil-234152

RESUMO

Objetivo. Identificar con técnicas de biología molecular, los de Ó-Thal en poblaciones hospitalarias seleccionadas. Métodos. Diez y ocho propositi con datos hematológicos y bioquímicos sugestivos de talasemia-Ó, seleccionados de 356 pacientes con probable hemoglobinopatía provenientes de cuatro hospitales de dos ciudades, se investigaron para seis alelos comunes de talasemia-Ó. Los estudios moleculares se realizaron por reacción en cadena de la polimerasa y digestión con enzimas de restricción específicas. Resultados. El alelo Ó se identificó en dos casos: el estudio familiar mostró el mismo alelo en la madre de ambos y se detectó además heterocigocidad para HbS en uno de ellos. El análisis con Apa I reveló en ambos pacientes la deleción clase I que es el alelo más comúnmente observado en el mundo. Este estudio mostró 2/356 (0.6 por ciento) de portadores Ó, una frecuencia baja comparada con la observada en otras poblaciones del mundo. La ausencia de los otros alelos sugiere que en México la talasemia-Ó es molecularmente tan heterogénea como la talasemia-ß


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Talassemia beta/epidemiologia , Talassemia beta/genética , Globinas/genética , México/epidemiologia
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