RESUMO
INTRODUCTION: Hereditary spastic paraplegia is the overall term for clinically and genetically diverse disorders characterized with progressive and variable severe lower extremity spasticity. The most common causes of autosomal dominantly inherited hereditary spastic paraplegias are different mutations of the spastin gene with variable incidence in different ethnic groups, ranging between 15-40%. Mutations in the spastin gene lead to loss of spastins function, causing progressive neuronal failure, which results in axon degeneration finally. AIM: The molecular testing of spastin gene is available in the institution of the authors since January, 2014. The experience gained with the examination of the first eleven patients is described in this article. METHOD: After polymerase chain reaction, Sanger sequencing was performed to examine the 17 exons of the spastin gene. Multiplex ligation-dependent probe amplification was performed to detect greater rearrangements in the spastin gene. Eight of the patients were examined in the genetic counseling clinic of the authors and after detailed phenotype assessment spastin gene testing was obtained. The other three patients were referred to the laboratory from different outpatient clinics. RESULTS: Out of the 11 examined patients, four different pathogenic mutations were found in 5 patients. CONCLUSIONS: The first Hungarian data, gained with the examination of spastin gene are presented in this article. The five patients, in whom mutations were detected, represent 45.5% of all tested patients with hereditary spastic paraplegia, which is similar to those published in the international literature. Molecular testing and subsequent detailed genotype-phenotype correlations of the Hungarian patients may serve valuable new information about the disease, which later on may influence our therapeutic possibilities and decisions.
Assuntos
Polimorfismo de Nucleotídeo Único , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/fisiopatologia , Caminhada , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Locomoção , Masculino , Pessoa de Meia-IdadeRESUMO
Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play an important role in the development of several autoimmune diseases. We examined five susceptible (rs10889677, rs1004819, rs2201841, rs11805303, rs11209032), one protective (rs7517847) and two neutral variants (rs7530511, rs1884444) of the IL23R gene in pooled DNA of healthy Roma (Gipsy) and Hungarian population samples. Our aim was to determine the genetic variability of the major haplotype tagging polymorphisms, and the haplotype profile of IL23R between the two groups. We analyzed 273 healthy Roma and 253 Hungarian DNA samples using PCR/RFLP assay. Comparing the five susceptible conferring alleles, there were significant increase (p<0.05), while in the protective alleles, there were decrease in the allele frequencies in Roma population (p<0.05). One of the neutral alleles showed increase, the another one did not differ between the two groups. The haplotype analysis of the SNPs revealed fundamentally different association types of SNPs in the two groups; moreover, the frequencies of the various haplotypes also exhibited strong differences, as of ht4 and ht5 haplotypes were significantly higher, whereas the frequencies of ht2 and ht3 haplotypes were significantly lower in the Roma population than in Hungarians (p<0.05). The data presented here show profound differences in the IL23R genetic profiles in the Roma population, that likely has also clinical implications in respect their possible role in the development of certain immunological diseases.
Assuntos
Etnicidade/genética , Ligação Genética , Predisposição Genética para Doença , Haplótipos/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Interleucina/genética , Feminino , Frequência do Gene/genética , Humanos , Hungria , Desequilíbrio de Ligação/genética , MasculinoRESUMO
In the present study we explored glutathione S-transferase (GST) polymorphisms in selected patients who experienced accelerated myocardial injury following open heart surgery and compared these to a control group of patients without postoperative complications. 758 Patients were enrolled from which 132 patients were selected to genotype analysis according to exclusion criteria. Patients were divided into the following groups: Group I: control patients (n = 78) without and Group II.: study patients (n = 54) with evidence of perioperative myocardial infarction. Genotyping for GSTP1 A (Ile105Ile/Ala113Ala), B (Ile105Val/Ala113Ala) and C (Ile105Val/Ala113Val) alleles was performed by using real-time-PCR. The heterozygous AC allele was nearly three times elevated (18.5 vs. 7.7 %) in the patients who suffered postoperative myocardial infarction compared to controls. Contrary, we found allele frequency of 14.1 % for homozygous BB allele in the control group whereas no such allele combination was present in the study group. These preliminary results may suggest the protective role for the B and C alleles during myocardial oxidative stress whereas the A allele may represent predisposing risk for cellular injury in patients undergoing cardiac surgery.
Assuntos
Glutationa Transferase/genética , Infarto do Miocárdio/genética , Polimorfismo Genético/genética , Alelos , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Fatores de RiscoRESUMO
INTRODUCTION: In the past decade the study of genomic disorders has received more interest. Array comparative genome hybridization is a widely spread diagnostic method in the research of genomic disorders. This method was implemented in the laboratory of the authors in 2012. AIM: This molecular cytogenetic method was first used to examine patients with complex developmental disorders in whom no genetic background was identified by traditional methods. METHOD: The authors complemented traditional diagnostic methods with array comparative genome hybridization, which has not been used in routine diagnostics in Hungary so far. RESULTS: Using this novel method the authors were able to identify genomic alterations in 7 out of 18 patients with complex developmental disorders. They found de novo alterations in 6 out of 7 patients, which were most likely causative in the development of the phenotype, while in one case they detected a familial genomic alteration. This method helped the authors to determine the breakpoint of genomic variation in their patients and delineate the affected genes contributing to the phenotype. CONCLUSIONS: These results call attention to the usefulness of next generation diagnostic methods available in the laboratory of the authors.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 9/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Deleção de Genes , Perfilação da Expressão Gênica , Doenças Raras/genética , Anormalidades Múltiplas/diagnóstico , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Hungria , Hibridização in Situ Fluorescente , Doenças Raras/diagnósticoRESUMO
One of the most common psychiatric disorders during childhood is attention deficit hyperactivity disorder, which affects 5-6% of children worldwide. Symptoms include attention deficit, hyperactivity, forgetfulness and weak impulse control. The exact mechanism behind the development of the disease is unknown. However, current data suggest that a strong genetic background is responsible, which explains the frequent occurrence within a family. Literature data show that copy number variations are very common in patients with attention deficit hyperactivity disorder. The authors present a patient with attention deficit hyperactivity disorder who proved to have two approximately 400 kb heterozygous microduplications at 6p25.2 and 15q13.3 chromosomal regions detected by comparative genomic hybridization methods. Both duplications affect genes (6p25.2: SLC22A23; 15q13.3: CHRNA7) which may play a role in the development of attention deficit hyperactivity disorder. This case serves as an example of the wide spectrum of indication of the array comparative genome hybridization method.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Hibridização Genômica Comparativa , Duplicação Gênica , Heterozigoto , Receptor Nicotínico de Acetilcolina alfa7/genética , Criança , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 6/genética , Variações do Número de Cópias de DNA , HumanosRESUMO
In this study the emergence of rotavirus A genotype G12 in children <5 years of age is reported from Cameroon during 2010/2011. A total of 135 human stool samples were P and G genotyped by reverse transcriptase PCR. Six different rotavirus VP7 genotypes were detected, including G1, G2, G3, G8, G9, and G12 in combinations with P[4], P[6] and P[8] VP4 genotypes. Genotype G12 predominated in combination with P[8] (54.1%) and P[6] (10.4%) genotypes followed by G1P[6] (8.2%), G3P[6] (6.7%), G2P[4] (5.9%), G8P[6] (3.7%), G2P[6] (0.7%), G3P[8] (0.7%), and G9P[8] (0.7%). Genotype P[6] strains in combination with various G-types represented a substantial proportion (N=44, 32.6%) of the genotyped strains. Partially typed strains included G12P[NT] (2.2%); G3P[NT] (0.7%); G(NT)P[6] (1.5%); and G(NT)P[8] (0.7%). Mixed infections were found in five specimens (3.7%) in several combinations including G1+ G12P[6], G2+ G3P[6] + P[8], G3+ G8P[6], G3 + G12P[6] + P[8], and G12P[6] +P[8]. The approximately 10% relative frequency of G12P[6] strains detected in this study suggests that this strain is emerging in Cameroon and should be monitored carefully as rotavirus vaccine is implemented in this country, as it shares neither G- nor P-type specificity with strains in the RotaTeq® and Rotarix® vaccines. These findings are consistent with other recent reports of the global spread and increasing epidemiologic importance of G12 and P[6] strains.
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Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/genética , Camarões/epidemiologia , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/virologia , Fezes/virologia , Genótipo , Humanos , Lactente , Epidemiologia Molecular , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/isolamento & purificaçãoRESUMO
Avian orthoreoviruses have been associated with a variety of diseases in chickens, including tenosynovitis, runting-stunting syndrome, hepatitis, myocarditis, osteoporosis, respiratory diseases, and central nervous system disease. The primary objective of our study was the molecular characterization of an avian reovirus strain, T1781, which was isolated from a broiler chicken with a central nervous system disorder in Hungary during 2012. The complete genome sequence was determined using a traditional sequencing method after cell culture adaptation of the strain. Sequence and phylogenetic analyses showed that T1781 shared only moderate nucleic acid sequence identity in several genes to previously analyzed reovirus strains from chickens, and each gene formed separate branches in the corresponding phylogenetic trees. The maximum nucleotide sequence identities of strain T1781 genes to reference avian reovirus strains ranged from 79 % to 90 %. Collectively, our analyses indicated that T1781 is a divergent chicken reovirus strain. The genetic background of this and other avian reoviruses associated with various disease manifestations needs further investigation.
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Infecções do Sistema Nervoso Central/veterinária , Genoma Viral , Orthoreovirus Aviário/genética , Doenças das Aves Domésticas/virologia , RNA Viral/genética , Infecções por Reoviridae/veterinária , Análise de Sequência de DNA , Animais , Infecções do Sistema Nervoso Central/virologia , Galinhas , Análise por Conglomerados , Hungria , Orthoreovirus Aviário/isolamento & purificação , Filogenia , Infecções por Reoviridae/virologia , Homologia de Sequência do Ácido NucleicoRESUMO
Haplotype tagging SNPs of interleukin-23 receptor gene rs1004819, rs7517847, rs7530511, rs2201841, rs1343151 and rs10889677 were determined in 396 patients with rheumatoid arthritis, 190 patients with Crohn's disease, 206 patients with ankylosing spondylitis and 182 controls. Using regression analysis models the rs1004819, rs2201841, and rs10889677 SNPs were found to confer risk for Crohn's disease and ankylosing spondylitis, while rs1343151 had a protective effect in both of these diseases, and the rs2201841 and rs10889677 SNPs showed susceptibility nature for rheumatoid arthritis. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to the rheumatoid arthritis, first in the literature. Seven different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks: thus, for rheumatoid arthritis the rs1343151 SNP was risk factor only in a specific haplotype surrounding; this can explain the controversial results published so far about this variant. More importantly, we observed, that while a specific haplotype can confer risk for rheumatoid arthritis, the same haplotype tended to protect against the development of the other two diseases. The data presented here serve evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility to or protection against a certain disease are interpreted.
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Artrite Reumatoide/genética , Doença de Crohn/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina/genética , Espondilite Anquilosante/genética , Adulto , Idoso , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Larsen-syndrome is a rare genetic skeletal dysplasia belonging to the group of actin-binding filamin B associated diseases. The features include congenital dislocations of the large joints, scoliosis and cervical kyphosis, short, broad, spatulate distal phalanges, and distinctive craniofacies. Diagnosis is based on clinical and radiographic findings and confirmed by molecular genetic testing. The authors have performed filamin B molecular genetic analysis since 2005 and have found several cases with unusual phenotypes since. This case report presents the diagnostic difficulties of a 30-year-old woman, who was operated several times with congenital hip dislocations and foot deformities. The craniofacial features, short, broad, spatulate fingers, scoliosis and cervical kyphosis directed diagnosis towards Larsen-syndrome and molecular genetic analysis confirmed a previously-described heterozygous missense mutation (c.G679A). They conclude that genetic analysis performed in time would prevent additional superfluous long diagnostic procedures in patients with rare diseases and would ensure adequate supportive therapy and management of the symptoms.
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Anormalidades Múltiplas/genética , Anormalidades Múltiplas/cirurgia , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Proteínas Contráteis/genética , Testes Genéticos , Luxações Articulares/congênito , Proteínas dos Microfilamentos/genética , Anormalidades Musculoesqueléticas/diagnóstico , Anormalidades Musculoesqueléticas/genética , Mutação , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/fisiopatologia , Adulto , Doenças do Desenvolvimento Ósseo/fisiopatologia , Códon sem Sentido , Feminino , Filaminas , Mutação da Fase de Leitura , Luxação Congênita de Quadril/genética , Luxação Congênita de Quadril/cirurgia , Humanos , Lactente , Luxações Articulares/diagnóstico , Luxações Articulares/genética , Luxações Articulares/fisiopatologia , Cifose/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Deformidades Congênitas das Extremidades Inferiores/cirurgia , Anormalidades Musculoesqueléticas/fisiopatologia , Mutação de Sentido Incorreto , Fenótipo , Escoliose/genética , Análise de Sequência de ProteínaRESUMO
INTRODUCTION: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. AIM: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. METHOD: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. RESULTS: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) CONCLUSIONS: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients.
Assuntos
Antivirais/metabolismo , Citocinas/metabolismo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Interferons/uso terapêutico , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Substâncias Protetoras/metabolismo , Ribavirina/uso terapêutico , Fatores de Transcrição/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Fatores de Transcrição/biossínteseRESUMO
In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to non-equine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.
Assuntos
Sequência Conservada/genética , Gastroenterite/veterinária , Genoma Viral/genética , Doenças dos Cavalos/virologia , Infecções por Rotavirus/veterinária , Rotavirus/genética , Animais , Sequência de Bases , Gastroenterite/virologia , Genes Virais/genética , Genótipo , Cavalos/virologia , Dados de Sequência Molecular , Filogenia , Infecções por Rotavirus/virologiaRESUMO
The common functional variants of the apolipoprotein A5 (APOA5) and the glucokinase regulatory protein genes (GCKR) have been shown to associate with increased fasting triglyceride (TG) levels. Albeit the basic association has been extensively investigated in several populations of different origin, less is known about quantitative traits of them. In our study accumulation rates of four APOA5 (T-1131, IVS3 + G476A, T1259C and C56G) and two GCKR (C1337T and rs780094) functional SNPs were analyzed in patients stratified into four TG quartile groups. Randomly selected 325 metabolic syndrome patients were separated into four quartile (q) groups based on the TG levels as follows q1: TG <1.38 mmol/l; q2: 1.38-1.93 mmol/l; q3: 1.94-2.83 mmol/l; and q4: TG >2.83 mmol/l. We observed significant stepwise increase of prevalence rates of minor allele frequencies in the four plasma TG quartiles for three APOA5 SNPs: -1131C (q1: 4.94%; q2: 8.64%; q3: 11.6%; q4: 12.3%), IVS3 + 476A (q1: 4.32%; q2: 7.4%; q3: 10.36%; q4: 11.1%), and 1259C (q1: 4.94%; q2: 7.41%; q3: 10.4%; q4: 11.7%). The haplotype analysis revealed, that the frequency of APOA5*2 haplotype gradually increased in q2, q3 and q4 (q1: 9.87%; q2: 14.8%; q3: 18.3%; q4: 21%). The distribution of the homozygotes of the two analyzed GCKR variants resembled to the APOA5 pattern. Contrary to the hypothetically predictable linear association coming from the current knowledge about the APOA5 and GCKR functions, the findings presented here revealed a unique, TG raise dependent gradual accumulation of the functional variants of in MS patients. Thus, the findings of the current study serve indirect evidence for the existence of rare APOA5 and GCKR haplotypes in metabolic syndrome patients with higher TG levels, which contribute to the complex lipid metabolism alteration in this disease.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Apolipoproteínas A/genética , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apolipoproteína A-V , Apolipoproteínas A/metabolismo , Primers do DNA/genética , Frequência do Gene , Haplótipos/genética , Humanos , Síndrome Metabólica/metabolismo , Prevalência , Estatísticas não ParamétricasRESUMO
UNLABELLED: Mutations of the frataxin gene give the most common underlying genetic background of recessively inheritable type ataxias in Europe. In our department, we have been establishing the molecular genetic diagnosis of Friedreich's ataxia since 2001. We analyzed a total of 221 blood samples from the whole country. METHODS: After fragment analysis we performed direct exon sequencing. RESULTS: This study summarizes the retrospective analysis of these genetic test results. Pathological alteration was identified in altogether 26 cases. 2 expanded alleles were found in intron 1 in all 26 genetically confirmed patients; which is not more than 12% of the total analyzed samples. We did exon sequencing in the case of patients having one expanded allele and found no point mutation in any of the cases. CONCLUSIONS: In our setting, we could not verify the diagnosis by genetic analysis in a remarkable number of patients, which on one hand underlines the importance of clinical neurologic and clinical genetic analyses before performing tests, and on the other hand, it raises the need to examine the patients for other ataxia types.
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Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Genes Recessivos , Proteínas de Ligação ao Ferro/genética , Mutação , Éxons , Ataxia de Friedreich/sangue , Humanos , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Análise de Sequência de DNA , Repetições de Trinucleotídeos , FrataxinaRESUMO
The great reed warbler has two genetically distinguishable haplogroups: "Clade A" occurs in higher proportions in Western Europe and Kazakhstan, and colonised Europe and Asia from a refugium in South-West Europe; and "Clade B", which is more common in Eastern Europe, and colonised parts of Europe from a refugium in the Middle East. Our aims were (i) to analyse the rate of differentiation in Hungarian breeding populations in order to see whether European-scale pattern is visible or not on as a small scale as the territory of Hungary and (ii) to compare the results obtained with mtDNA sequencing and microsatellite markers. To analyse the genetic differentiation, the mtDNA control region II was sequenced in 68 adult breeding birds, and 51 were fingerprinted at 11 microsatellite loci, while both analyses were performed on 36 birds (a total of 83 birds). The microsatellite data gave a better resolution and represented the fine-scale pattern of the suspected recolonisation. The lack of genetic differentiation among the breeding populations based on mitochondrial data seems to support this finding, because the admixture of the clades in this particular geographic region obliterates differentiation. Accordingly, the Fst values from different branches are significantly based on microsatellite data only. The mtDNA methods only give reliable results when a geographic and ecological factor plays a role in the population subdivision, but in the case of an intermixing population larger-scale studies are needed.
Assuntos
DNA Mitocondrial , Aves Canoras , Animais , DNA Mitocondrial/genética , Europa (Continente) , Repetições de Microssatélites/genética , Aves Canoras/genética , Europa OrientalRESUMO
Dobrava (DOBV) hantaviruses belong to the genus Hantavirus, family Bunyaviridae, and are carried by yellow-necked and striped field mice. The goal of this study was to detect DOBV using serological and genetic methods in Apodemus rodents in Hungary and in northern Croatia. During the study period, a total of 125 Apodemus sp. (67 A. agrarius, 58 A. flavicollis) were tested for the presence of hantaviruses, and 21 rodents (17%) were positive by rRT-PCR and/or ELISA. We conclude that the prevalence of DOBV is much higher than previously anticipated. The simultaneous use of molecular and serological techniques provides a highly reliable way to detect hantavirus infections.
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Ensaio de Imunoadsorção Enzimática/métodos , Murinae/virologia , Orthohantavírus/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Croácia/epidemiologia , Feminino , Corantes Fluorescentes , Orthohantavírus/genética , Hungria/epidemiologia , Masculino , Filogenia , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/virologiaRESUMO
BACKGROUND: Recent studies revealed that glucokinase regulatory protein (GCKR) variants (rs780094 and rs1260326) are associated with serum triglycerides and plasma glucose levels. Here we analyzed primarily the association of these two variants with the lipid profile and plasma glucose levels in Hungarian subjects with type 2 diabetes mellitus and metabolic syndrome; and also correlated the genotypes with the carotid intima-media thickness records. METHODS: A total of 321 type 2 diabetic patients, 455 metabolic syndrome patients, and 172 healthy controls were genotyped by PCR-RFLP. RESULTS: Both GCKR variants were found to associate with serum triglycerides and with fasting plasma glucose. However, significant association with the development of type 2 diabetes mellitus and metabolic syndrome could not be observed. Analyzing the records of the patients, a positive association of prevalence the GCKR homozygous functional variants and carotid intima-media thickness was found in the metabolic syndrome patients. CONCLUSIONS: Our results support that rs780094 and rs1260326 functional variants of the GCKR gene are inversely associated with serum triglycerides and fasting plasma glucose levels, as it was already reported for diabetic and metabolic syndrome patients in some other populations. Besides this positive replication, as a novel feature, our preliminary findings also suggest a cardiovascular risk role of the GCKR minor allele carriage based on the carotid intima-media thickness association.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Artérias Carótidas/diagnóstico por imagem , Diabetes Mellitus Tipo 2/genética , Síndrome Metabólica/genética , Polimorfismo Genético , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Frequência do Gene , Predisposição Genética para Doença , Homozigoto , Humanos , Hungria , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Triglicerídeos/sangue , UltrassonografiaRESUMO
BACKGROUND AND AIMS: A 5-bp insertion-deletion (indel) polymorphism in the promoter of interferon regulatory factor 5 (IRF5) has been associated with inflammatory bowel diseases (IBD). This polymorphism generates an additional binding site for the transcription factor SP1 and has been shown to augment the expression of IRF5. Additionally, it affects a CpG dinucleotide-dense genomic region. These features of the indel suggested that it may influence the epigenetic regulation of IRF5. The aim of this study was to investigate the potential effect of the 5-bp indel on the methylation pattern of four CpG sites upstream of the polymorphism. Possible CpG site methylation differences in this region between healthy persons and individuals suffering from IBD were also tested. METHODS: Genotype was determined by 4% polyacrylamide gel electrophoresis in 33 peripheral blood leukocyte (PBL) DNA samples. DNA methylation correlates of the genotypes were measured by bisulfite pyrosequencing. IRF5 promoter methylation in association to disease state was assessed in 87 proband (49 healthy, 18 Crohn's disease, 20 ulcerative colitis) PBL samples. RESULTS: The polymorphism did not affect the methylation pattern of the IRF5 promoter nor could we detect significant differences in the average, low methylation of the locus between healthy persons and individuals with IBD. CONCLUSIONS: These results implicate that epigenetic dysregulation of the IRF5 promoter is unlikely to be associated with IBD.
Assuntos
Metilação de DNA/genética , Doenças Inflamatórias Intestinais/genética , Fatores Reguladores de Interferon/genética , Regiões Promotoras Genéticas/genética , Adulto , Ilhas de CpG/genética , Feminino , Humanos , Mutação INDEL/genética , MasculinoRESUMO
Epidemiological trends of the globally most common rotavirus genotype, G1P[8], were investigated in Hungary during a 16-year period by sequencing and phylogenetic analysis of the surface antigens. Antigen shift among epidemiologically major G1P[8] strains was observed in 6 seasons, as indicated by changes in the sublineages of the G1 VP7 and the P[8] VP4 genes. The temporal clustering of some rotavirus VP4 and VP7 gene sublineages and the periodic emergence and/or resurgence of previously unrecognized rotavirus sublineages in the study population suggest a dynamic nature for these common strains. Recently established international strain surveillance networks may help to identify and track the spread of epidemiologically important rotavirus strains across countries and continents.
Assuntos
Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Substituição de Aminoácidos , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Humanos , Hungria/epidemiologia , Rotavirus/classificação , Infecções por Rotavirus/virologia , Fatores de TempoRESUMO
Rotavirus strain surveillance is being conducted in many countries before and after introduction of newly licensed vaccines to assess the impact of the vaccines on rotavirus strains. Here we describe a strain surveillance study in the Budapest area of Hungary (2003-2006) based on RNA profile analysis, genotyping by multiplex PCR and nucleotide sequencing. Among 1,983 G-typed rotaviruses we identified G1 (22%), G2 (4.8%), G3 (3.5%), G4 (18.5%), G6 (1.1%), G8 (<0.1%, n = 1), G9 (42%), and G12 (3.4%) specificities. Information on P genotype incidence was determined for a subset of samples (n = 814). In addition to the globally important strains, a variety of uncommon antigen combinations were also found, for example, P[9],G3; P[14],G6; or P[14],G8. Sequence and phylogenetic analysis of the VP7, VP4, VP6, and NSP4 genes of selected strains with uncommon antigen combinations demonstrated high similarity with certain bovine, porcine, feline, equine, and lapine rotaviruses, respectively. Continued surveillance is needed to assess the role of animal rotaviruses in human diseases.
Assuntos
Variação Genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/genética , Zoonoses/virologia , Adolescente , Animais , Antígenos Virais/análise , Criança , Pré-Escolar , Fezes/virologia , Genótipo , Humanos , Hungria/epidemiologia , Lactente , Dados de Sequência Molecular , Filogenia , Rotavirus/classificação , Rotavirus/imunologia , Infecções por Rotavirus/genéticaRESUMO
Rotavirus-associated enteritis has been reported in pheasants, but there is no information on the genetic/antigenic features of pheasant rotaviruses. In this study, we sequenced the VP7-encoding genome segment of three pheasant rotavirus strains detected during 2008 in Hungary. The full-length genome segment was 1,070 bp long, while the open reading frame was predicted to encode a 330-aa-long protein. The nucleotide sequence identities among the three pheasant rotavirus strains were high (> or =94%), whereas the range of nucleotide sequence identities to other avian and mammalian rotavirus VP7 genes fell between 68 and 73% and between 60 and 66%, respectively. Our findings indicate that these Hungarian pheasant rotaviruses need to be considered representatives of a new VP7 genotype specificity, designated G23.