RESUMO
Mutations on the delta-sarcoglycan gene have been associated with the development of both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. Recently, the polymorphism c.-94C>G was associated with HCM in Japanese patients. The aim of our study was to evaluate the frequency of c.-94C>G polymorphism in Mexican-Amerindian and Mexican-Mestizo populations. We analyzed the frequency of this polymorphism in 165 Mexican-Amerindian individuals (23 Triquis, 25 Zapotecos, 24 Mayas, 41 Nahuas, and 52 Mixtecos) and 100 unrelated Mexican-Mestizos. Allele frequencies were similar in all Amerindian groups (0.33 Triquis, 0.54 Zapotecos, 0.54 Mayas, 0.46 Nahuas, and 0.49 Mixtecos). When compared with Mexican-Mestizos, only Triquis were different (p = 0.00742). However, when comparing the total sample of the Amerindian population with the Mestizos, the difference was not significant (p = 0.12225). Allele frequencies of Mexican populations were higher than in Asians and less than African and European populations (p < 0.05). These data show that the distribution of the C allele is higher in Mexican populations studied and consequently it is necessary to define if this may be associated with genetic susceptibility for HCM in the Mexican patients.
Assuntos
Indígenas Norte-Americanos/genética , Polimorfismo de Nucleotídeo Único , Sarcoglicanas/genética , Adulto , Idoso , Alelos , Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica Familiar/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , México , Pessoa de Meia-Idade , MutaçãoRESUMO
To investigate the origin of von Willebrand disease in Mexican Mestizo population, we analyzed exons 18, 19, 20, 28, 45, and 52 of the VWF gene from 34 Mexican Mestizo index cases, 28 of them affected but not related, using DNA amplification by polymerase chain reaction and direct sequencing. We found three novel mutations: E1447Q in one patient with type 1; P2781S in one patient with type 2M; and P812L in another type 1/2N patient. These mutations were not found in 100 normal alleles. Moreover, we found other mutations previously reported in the literature; one of them (G1609R) was the most frequent (6/28) in patients with VWD type 2A. This is the first molecular study in a Mexican group that has a particular mixture of Indigenous, Caucasian, and African genes.
Assuntos
Alelos , Éxons , Mutação de Sentido Incorreto , Doenças de von Willebrand/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México , Fator de von Willebrand/genéticaRESUMO
Von Willebrand Factor (VWF) is a large multimeric glycoprotein expressed in the megakaryocytes and endothelial cells of all vertebrates. It participates fundamentally in the primary and secondary hemostasis because it induces the adhesion of platelets to vascular subendothelium and promotes aggregation of platelets when blood vessels and capillaries are damaged. In addition, VWF links to factor VIII which avoids its proteolysis. The deficiency or the inadequate synthesis of the VWF causes von Willebrand disease (VWD), which is the most common hereditary bleeding disorder in humans principally from mucous and cutaneous sites. VWD is difficult to detect with accuracy due to interrelation among VWF with different components of hemostasis, although it is performed by different tests of haemostatic system, and the basic mechanisms in VWD are herein emphasized. The diagnosis of VWD is difficult due to the heterogeneous manifestation of the disease, which also complicates its classification. This article focuses on the molecular aspects of the disease and discusses their possible clinical implications.
Assuntos
Doenças de von Willebrand/genética , Humanos , Biologia Molecular , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/genéticaRESUMO
BACKGROUND: Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples. METHODS: 32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays. RESULTS: We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution. CONCLUSION: Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation.
Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/biossíntese , Adulto , Idoso , Neoplasias da Mama/etnologia , Linhagem Celular Tumoral , Análise por Conglomerados , Citoplasma/metabolismo , DNA Complementar/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , México , Pessoa de Meia-Idade , Proteínas Mitocondriais , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Distribuição TecidualRESUMO
Five polymorphic restriction enzyme sites in the beta globin gene cluster (HindIII Gγ-Hind III Aγ-, Ava IIINV-2 ß-and Hpa I and Bam HI 3'ß-globin gene) were studied in individuals from 13 families: 13 homozygote patients for sickle cell anemia, two double heterozygotes (one SC and one S/ßThal ), 35 AS heterozygotes (23 parents and 12 siblings), one father (A/ßThal ), and three normal siblings. In addition, 17 normal unrelated Mexican subjects were studied. All subjects were from the state of Veracruz on the coast of the Gulf of Mexico. The Southern blot technique was used. Fifteen haplotypes were identified in the 142 chromosomes. Five were the most frequent: two haplotypes, (+-+++) (52.4%) and (--+-+) (19.0%) were associated with ßS chromosomes; two haplotypes, (--+++) (38.2%) and (---++) (19.7%), were linked with ßA chromosomes, and the fifth (--++-) was present in both types of chromosomes. Haplotype (+-+++) corresponded to the Bantu or Senegal type. With Hinc II analysis after PCR amplification in both the 5' and 3' regions of the ψß-globin gene, it was possible to distinguish between these African types, as in the former both restriction sites are absent. This analysis was done in 23 ßS and 10 ßA subjects. All ßS chromosomes disclosed the Bantu type, while ßA were similar to Caucasians. Bantu and Benin haplotypes have been found with high frequency in African populations, indicating the great influence of African genes in the population of the Mexican coasts. In addition, two previously unidentified haplotypes were found: (++--+) and (-++++). These can be explainded by crossing-over events and/or by new mutations. © 1995 Wiley-Liss, Inc.
RESUMO
El estudio de los marcadores genéticos ha tenido gran importancia en la investigación en biomedicina. En los últimos años, el empleo de las enzimas de restricción ha permitido el establecimiento de polimorfismos directamente en la molécula del DNA, lo que ha revolucionado la localización o mapeo de los genes en los cromosomas, la prevención y el diagnóstico de los padecimientos genéticos y el análisis de los orígenes de las distintas poblaciones. En este trabajo se discuten las implicaciones de estos recientes desarrollos y sus aplicaciones en el estudio de la población latinoamericana, en particular, de la población mexicana
Assuntos
Humanos , Triagem de Portadores Genéticos , Análise Mutacional de DNA/métodos , Análise Mutacional de DNA , Genética/classificação , Genética/tendências , Marcadores Genéticos/genéticaRESUMO
Con el objeto de averiguar la frecuencia de paternidad extraconyugal, dato que es de interés desde el punto de vista de la epidemiología genética y de la genética de población, se estudiaron en 217 familias nucleares, los grupos sanguíneos de los sistemas ABO, Rh, MN, Ss, Duffy, P y las variantes electroforéticas de la fosfatasa ácida eritrocítica, haptoglobinas y grupo específico Gc. La combinación de estos marcadores tiene una probabilidad de exclusión de paternidad de 0.80. En el 2.3 por ciento de las familias se encontró que el padre putativo no podría ser el padre biológico. Un objetivo secundario fue contribuir a la caracterización de la población urbana del país, para lo cual se calculó la frecuencia de los marcadores en el grupo de los progenitores. Los resultados obtenidos en este estudio se compararon con otros del Distrito Federal, encontrando diferencias estadísticamente significativas con algunos de ellos, lo que corrobora la gran heterogeneidad genética de nuesta población
Assuntos
Humanos , Ilegitimidade , Paternidade , Antígenos de Grupos Sanguíneos , México , ProbabilidadeRESUMO
Este artículo tiene como finalidad informar de la utilidad de los marcadores genéticos para corroborar la paternidad en un caso de dos niños intercambiados en una maternidad. A las dos familias nucleares se les determinaron grupos sanguíneos ABO, Rh (CcDEe), MNSs, Duffy, Kidd, Kell y P, y las variantes electroforéticas de la fosfatasa ácida eritrocítica. Este último marcador permitió establecer que, en este caso, efectivamente los niños habían sido cambiados, por lo que cada familia recuperó a su verdadero hijo
Assuntos
Humanos , Masculino , Feminino , Paternidade , Marcadores Genéticos , Eritrócitos/enzimologia , Fosfatase Ácida/sangueRESUMO
Se analizó la frecuencia de las variantes electroforéticas de la fosfatasa ácida eritrocítica en 113 individuos originarios del Distrito Federal y 70 del interior de la República. En todos ellos sus cuatro abuelos fueron mexicanos por nacimiento. No se encontraron diferencias estadísticamente significativas entre ambos grupos (p > 0.9), por lo que se combinaron en uno solo obteniendo las siguientes frecuencias génicas determinadas por cuenta genica: pa=0.1514, pb=0.8378 y pc=0.0108. El grupo estudiado en el presente trabajo difiere estadísticamente de otra muestra del Distrito Federal, así como de tres poblaciones de indígenas mexicanos, lo que corrobora la heterogeneidad de la población del Distrito Federal