RESUMO
Group A human rotaviruses (HuRVA) are causative agents of acute gastroenteritis. Six viral structural proteins (VPs) and six nonstructural proteins (NSPs) are produced in RV-infected cells. NSP4 is a diarrhoea-inducing viral enterotoxin and NSP4 gene analysis revealed at least 15 (E1-E15) genotypes. This study analysed the NSP4 genetic diversity of HuRVA G2P[4] strains collected in the state of São Paulo (SP) from 1994 and 2006-2010 using reverse transcription-polymerase chain reaction, sequencing and phylogenetic analysis. Forty (97.6%) G2P[4] strains displayed genotype E2; one strain (2.4%) displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P[4]) and the NSP4 (E2) genotype of HuRVA. NSP4 phylogenetic analysis showed distinct clusters, with grouping of most strains by their genotype and collection year, and most strains from SP were clustered together with strains from other Brazilian states. A deduced amino acid sequence alignment for E2 showed many variations in the C-terminal region, including the VP4-binding domain. Considering the ability of NSP4 to generate host immunity, monitoring NSP4 variations, along with those in the VP4 or VP7 protein, is important for evaluating the circulation and pathogenesis of RV. Finally, the presence of one G2P[4]E1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.
Assuntos
Adulto , Criança , Humanos , Antígenos Virais/isolamento & purificação , Glicoproteínas/genética , RNA Viral/genética , Rotavirus/genética , Toxinas Biológicas/genética , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , Sequência de Bases , Brasil , Fezes/virologia , Variação Genética , Genótipo , Ligação Genética/genética , Técnicas Imunoenzimáticas , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Viral/isolamento & purificação , Rotavirus/classificação , Rotavirus/imunologia , Alinhamento de SequênciaRESUMO
Vitiligo is a chronic stigmatizing disease, already known for millennia, which mainly affects melanocytes from epidermis basal layer, leading to the development of hypochromic and achromic patches. Its estimated prevalence is 0.5% worldwide. The involvement of genetic factors controlling susceptibility to vitiligo has been studied over the last decades, and results of previous studies present vitiligo as a complex, multifactorial and polygenic disease. In this context, a few genes, including DDR1, XBP1 and NLRP1 have been consistently and functionally associated with the disease. Notwithstanding, environmental factors that precipitate or maintain the disease are yet to be described. The pathogenesis of vitiligo has not been totally clarified until now and many theories have been proposed. Of these, the autoimmune hypothesis is now the most cited and studied among experts. Dysfunction in metabolic pathways, which could lead to production of toxic metabolites causing damage to melanocytes, has also been investigated. Melanocytes adhesion deficit in patients with vitiligo is mainly speculated by the appearance of Köebner phenomenon, recently, new genes and proteins involved in this deficit have been found.
Assuntos
Humanos , Vitiligo/genética , Ligação Genética/genética , Doenças Autoimunes/genética , Vitiligo/imunologia , Vitiligo/metabolismo , Predisposição Genética para Doença , Estudos de Associação Genética , Melanócitos/imunologiaAssuntos
Feminino , Humanos , Masculino , Gravidez , Aconselhamento Genético/métodos , Doenças Renais Policísticas/diagnóstico , Biópsia/métodos , Ligação Genética/genética , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Técnicas de Diagnóstico Molecular/métodos , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Doenças Renais Policísticas , Doadores de Tecidos , Ultrassonografia Pré-NatalRESUMO
Families with at least 2 or more individuals having hereditary hearing loss were enrolled from different areas of Khyber Pakhtoonkhwa, mainly from district Peshawar. Detailed history was taken from each family to minimize the presence of other abnormalities and environmental causes for deafness. Families were questioned about skin pigmentation, hair pigmentation, and problems relating to balance, vision, night blindness, thyroid, kidneys, heart, and infectious diseases like meningitis, antibiotic usage, injury, and typhoid. The pedigree structures were based upon interviews with multiple family members, and pedigrees of the enrolled families were drawn using Cyrillic program (version 2.1). All families showed recessive mode of inheritance. I studied 8 families of these 10. For linkage analyses, studies for DFNB1 locus, 3 STR markers (D13S175, D13S292, and D13S787) were genotyped using polyacrylamide gel electrophoresis (PAGE) and haplotypes were constructed to determined, linkage with DFNB1 locus. From a total of 8 families, a single family-10 showed linkage to DFNB1 locus.
Assuntos
Estudos de Coortes , Conexinas/genética , Surdez/epidemiologia , Surdez/etiologia , Surdez/genética , Estudos de Associação Genética , Ligação Genética/genética , Haplótipos/genética , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Perda Auditiva/genética , Humanos , Paquistão , Linhagem , PrevalênciaRESUMO
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6 percent (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.
Assuntos
Feminino , Humanos , Masculino , Heterogeneidade Genética , Ligação Genética/genética , Síndrome de Marfan/genética , Proteínas dos Microfilamentos/genética , Fator de Crescimento Transformador beta/genética , Distribuição de Qui-Quadrado , Estudos de Coortes , Marcadores Genéticos , Escore Lod , Taxa de Mutação , Síndrome de Marfan/diagnósticoRESUMO
Asthma is the most common chronic childhood disease in developed nations and its prevalence has increased in the world over the last 25 years. It is a complex disease with both genetic and environmental risk factors. Asthma is caused by multiple interacting genes, some having a protective effect and others contributing to the disease pathogenesis, with each gene having its own tendency to be influenced by the environment. This article reviews the current state of the genetics of asthma in six categories, viz. epidemiology, management, aetiology, family and twin studies, segregation and linkage studies, and candidate genes and single nucleotide polymorphisms (SNPs).
Assuntos
Asma/epidemiologia , Asma/genética , Causalidade , Doenças em Gêmeos/genética , Interação Gene-Ambiente , Ligação Genética/genética , Predisposição Genética para Doença/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , PrevalênciaRESUMO
Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy of motor and sensory impairment with distal predominance. Atrophy and weakness of lower limbs are the first signs of the disease. It can be classified, with the aid of electromyography and nerve conduction studies, as demyelinating (CMT1) or axonal (CMT2). OBJECTIVE: Clinical and neurophysiological investigation of a large multigenerational family with CMT2 with autosomal dominant mode of transmission. METHOD: Fifty individuals were evaluated and neurophysiological studies performed in 22 patients. RESULTS: Thirty individuals had clinical signs of motor-sensory neuropathy. Babinski sign was present in 14 individuals. Neurophysiological study showed motor-sensory axonal polyneuropathy. CONCLUSION: The clinical and neurophysiological characteristics of this family does not differ from those observed with other forms of CMT, except for the high prevalence of Babinski sign.
A doença de Charcot-Marie-Tooth (CMT) é uma neuropatia hereditária de acometimento sensitivo e motor de predomínio distal. Atrofia e fraqueza em membros inferiores são os primeiros sinais da doença. Pode ser classificada, com auxílio da eletroneuromiografia, em desmielinizante (CMT1) ou axonal (CMT2). OBJETIVO: Investigação clínica e neurofisiológica de família com portadores de CMT2 de herança dominante. MÉTODO: Foi feita avaliação neurológica de 50 indivíduos e eletroneuromiografia em 22 pacientes. RESULTADOS: Trinta indivíduos tinham sinais clínicos de neuropatia sensitivo-motora. Sinal de Babinski estava presente em 14 indivíduos. A eletroneuromiografia demonstrou polineuropatia axonal sensitiva e motora. CONCLUSÃO: As características clínicas e neurofisiológicas desta família não se diferem das observadas em outras formas de CMT, exceto pela alta prevalência de sinal de Babinski.
Assuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Charcot-Marie-Tooth/fisiopatologia , Tratos Piramidais/fisiopatologia , Doença de Charcot-Marie-Tooth/genética , Eletromiografia/métodos , Ligação Genética/genética , Linhagem , FenótipoRESUMO
The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR) families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1). The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1)/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024) in vicinity of mental retardation (MR) locus (MRT1)/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.
Assuntos
Família , Ligação Genética/genética , Predisposição Genética para Doença , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Técnicas de Diagnóstico Molecular/métodos , Paquistão/epidemiologia , Serina Endopeptidases/genéticaRESUMO
BACKGROUND: Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary myocardial disorder morphologically characterized by subtle to severe replacement of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to be highly prevalent in European population with recent reports implicating it to be a major cause of sudden death in young individuals even from American and Asian population. AIM: To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three families affected with ARVC from India. MATERIALS AND METHODS: Three families comprising of 42 affected/unaffected members were included in the study. Three microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed using LINKAGE program version 5.2 RESULTS AND DISCUSSION: LOD scores from linkage analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV have shown positive value hinting the involvement of this locus in the etiology of ARVC, while linkage analysis in the SB family ruled out involvement of DSP, TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci. Therefore, linkage analysis carried out in the present study indicates that ARVC-6 (cumulative LOD score is equal to plus 1.203376 at θ is equal to 0.05) could be the locus harboring the mutated gene in two out of three families.
Assuntos
Adulto , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/etiologia , Displasia Arritmogênica Ventricular Direita/genética , Criança , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Família , Feminino , Ligação Genética/genética , Humanos , Índia/epidemiologia , Escore Lod , Masculino , Repetições de Microssatélites , Mutagênese Insercional/genética , Reação em Cadeia da Polimerase/métodosRESUMO
OBJECTIVE@#To validate the genetic characteristics and distribution of DXS7424-DXS101 on X chromosome in Han population.@*METHODS@#DXS7424 and DXS101 loci were genotyped by PCR, PAGE and silvers stain methods. Their genetic parameters were analyzed by Arlequin software.@*RESULTS@#There were 37 haplotypes detected in 151 Han unrelated males. The frequencies ranged from 0.0066 to 0.1391, with a GD value of 0.9453 and a DP value of 0.9389. Haplotypes 16-23 were the most common haplotypes in Han population.@*CONCLUSION@#Analysis of combined DXS7424 and DXS101 haplotypes appears to be a powerful means in population genetics and forensic practice for determination of identity and paternity.
Assuntos
Humanos , Masculino , Alelos , China/etnologia , Cromossomos Humanos X/genética , Frequência do Gene , Ligação Genética/genética , Genética Populacional , Haplótipos , Reação em Cadeia da Polimerase , Polimorfismo Genético , Sequências de Repetição em TandemAssuntos
Atrofia , Cegueira/congênito , Encéfalo/patologia , Consanguinidade , Surdez/congênito , Humanos , Lactente , Ligação Genética/genética , Magnésio/sangue , Masculino , Deficiência Intelectual/genética , Microftalmia/genética , Descolamento Retiniano/congênito , Corpo Vítreo/anormalidades , Cromossomo X/genéticaRESUMO
En este trabajo se ilustra la utilidad del análisis de simulación por computadora, para la selección de familias útiles en el mapeo de genes por medio de la técnica de enlace génico. Analizamos ocho familias con trastorno obsesivo compulsivo, quienes clínicamente tienen un patrón de herencia autosómico dominante. En estas familias simulamos la cosegregación de un marcador polimórfico, con un 50 por ciento de heterozigosidad, que se hereda en estrecho enlace génico con la enfermedad. Adicionalmente, analizamos estos datos considerando varios valores de la penetrancia, así como tres diferentes porcentajes de genotipos conocidos en los sujetos estudiados (100 por ciento, 75 por ciento y 50 por ciento). Los índices lod obtenidos, demostraron que estas familias tienen el poder estadístico adecuado para llevar a cabo estudios de enlace génico, aun en condiciones no ideales, tales como una penetrancia del 80 por ciento, y desconocimiento el 50 por ciento de los genotipos
Assuntos
Humanos , Família/psicologia , Genótipo , Ligação Genética/genética , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/psicologia , Informática Médica/métodos , Informática Médica/tendências , Marcadores Genéticos/genéticaRESUMO
El síndrome del cromosoma X-frágil es la causa más frecuente de retardo mental hereditario en el varón y se asocia a un marcador citogenético ubicado en la banda Xq 27.3 (FRAXA) del cromosoma X. Durante muchos años el diagnostico estuvo basado en la identificación citogenética del marcador; sin embargo, este método no ha resultado confiable para el diagnóstico prenatal y la detección de portadores masculinos o femeninos clínicamente normales. El descubrimiento de las bases moleculares de este síndrome ha permitido desarrollar sondas que posibilitan la identificación confiable de los afectados y los portadores por análisis directo del ADN. Se describen los resultados de un estudio clínico, citogenético y molecular en la familia de una probando X frágil. En el afectado un varón de 2 años 4 meses con retraso mental y dismorfias se comprobó un sitio X frágil, pero su madre y una tía no tenían signos clínicos y sitio frágil. El análisis molecular mostró, en el paciente, una banda de 6,5 Kb, que indicaba la presencia de la mutación causal, mientras la madre exhibía dos bandas, una de 5,2 y otra de 6,0 Kb, que la identifican como heterocigota. En contraste, la tía presentó una sola banda de 5,2 Kb característica de los individuos normales
Assuntos
Humanos , Masculino , Pré-Escolar , Adulto , Citogenética/métodos , Núcleo Familiar , Síndrome do Cromossomo X Frágil/genética , Análise Mutacional de DNA , DNA/genética , Ligação Genética/genética , Deficiência Intelectual/genética , Cariotipagem , Marcadores Genéticos/genética , Técnicas de Sonda Molecular , Hibridização de Ácido Nucleico , Cromossomo X/genéticaAssuntos
Animais , Colágeno/história , Peixes , Colágeno , Qualidade dos Alimentos , Ligação Genética/genética , Redução de PesoRESUMO
Cancer may arise from the genetic transformation of a single precursor cell, which proliferates to form a clone. Chromosomal abnormalities are associated with many types of tumours. Some of the chromosomal rearrangements such as translocation, deletion and insertion involve breakage of chromosomes close to known oncogenes. The close linkage between the chromosomal changes, the gene modifications and consequently altered protein function seen in malignant cells suggest that cancer is a genetic disease. Analysis of chromosomal abnormalities and oncogene amplifications in malignant cells have been found to be related to their malignant potential and hence may be utilized in the clinical management of patients with cancer.
Assuntos
Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Citogenética , Amplificação de Genes/genética , Rearranjo Gênico/genética , Humanos , Ligação Genética/genética , Biologia Molecular , Neoplasias/genética , Oncogenes/genéticaRESUMO
Descreve-se uma família afetada por forma autossômica dominante de ataxia cerebelar de início tardio (acima dos 20 anos). Oito membros da família säo estudados e dados de outros quatro afetados pela doença foram obtidos por anamnese. A média de idade de início da doença foi 37,1 ñ 5,4 anos (27-47 anos). O quadro clínico consistia basicamente de síndrome cerebelar de caráter lentamente progressivo, sem ocorrência concomitante de sinais ou sintomas decorrentes de envolvimento de outros sistemas. Estudo tomográfico computadorizado mostra atrofia cerebelar difusa com relativa preservaçäo do tronco cerebral e das estruturas supratentoriais. Estudos neurofisiológicos (neuroconduçäo motora/sensitiva, potenciais evocados visuais e auditivos) foram normais. Vinte e seis pessoas da família foram tipados para antígenos de histocompatibilidade HLA. Escores lod foram calculados utilizando programa de computador denominado LINKMAP. Ligaçäo estreita com o sistema HLA nesta família foi excluida - 0=0,02, z=(-2,17) - e a análise global dos escores lod sugerem que o gene mutante nesta família näo se localiza no cromossomo 6