RESUMO
Several single-nucleotide polymorphism (SNP) genome-wide association studies (GWASs) have been completed in multiple sclerosis (MS). Follow-up studies of the variants with the most promising rankings, especially when supplemented by informed candidate gene selection, have proven to be extremely successful. In this study we report the results of a multi-stage replication analysis of the putatively associated SNPs identified in the Wellcome Trust Case Control Consortium non-synonymous SNP (nsSNP) screen. In total, the replication sample consisted of 3444 patients and 2595 controls. A combined analysis of the nsSNP screen and replication data provides evidence implicating a novel additional locus, rs3748816 in membrane metalloendopeptidase-like 1 (MMEL1; odds ratio=1.16, P=3.54 × 10â»6) in MS susceptibility.
Assuntos
ATP Citrato (pro-S)-Liase/genética , Calicreínas/genética , Esclerose Múltipla/genética , Neprilisina/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Proteínas de Ciclo Celular , Mapeamento Cromossômico , Proteínas do Citoesqueleto , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de LigaçãoAssuntos
Biotecnologia/normas , Ética Médica , Legislação Médica , Transplante Heterólogo/normas , Animais , Biotecnologia/legislação & jurisprudência , Confidencialidade/legislação & jurisprudência , Experimentação Humana , Direitos Humanos/legislação & jurisprudência , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Internacionalidade , Pesquisa/normas , Medição de Risco , Gestão de Riscos , Responsabilidade Social , SuínosRESUMO
PIP: According to Brian Ward, vaccines are probably the most efficacious and cost-effective medical interventions ever invented. He notes that surveillance of vaccine-related adverse events is important, and resources should be made available for monitoring vaccine safety at a time of increasing vaccine activity. However, in an environment of limited resources, there is a dispute over the level of resources devoted to vaccine surveillance versus vaccine deployment. In an examination of the balance of risk versus benefit, several arguments are given. Nevertheless, no tangible evidence supports the claim that the increased use of new vaccines will be more trouble than it is worth. Ward offers a more worthy argument against the use of vaccines aimed at maintaining productivity rather than securing personal health and well-being. Overall, the author upholds the importance of good vaccine surveillance but opposes the notion of shifting resources from vaccine development to vaccine surveillance.^ieng
Assuntos
Vigilância da População , Vacinas/efeitos adversos , HumanosRESUMO
The biomedical research community of the new millennium has at its disposal the resources and knowledge to bring about major changes in human health. Technological advances on a scale never before seen mean that we can consider a level of medical investigation and intervention unimaginable only 20 years ago. But with this power comes a tremendous responsibility to think carefully about how those resources should best be used. For reasons of economy, biomedical research is likely to remain focussed on the needs of rich countries. This need not, however, mean that poorer countries cannot in the future receive a greater benefit from the current community of biomedical researchers. And given the nature of disease and its disrespect for national boundaries, a more global approach to biomedical research should be attractive to rich and poor countries alike. Achieving this change, no matter how modest in scale, will require a concerted effort at all levels within the biomedical research community. Indeed, the community is at a stage when it must pay closer attention to the sensitivities and concerns of its patient population. Only then will the tremendous potential of biomedical research be embraced and supported by our societies.
Assuntos
Apoio à Pesquisa como Assunto/tendências , Pesquisa/tendências , Animais , Terapia Genética , Genoma , Humanos , Células-Tronco , Transplante HeterólogoAssuntos
DNA/análise , Antígenos HLA-DR/genética , Teste de Histocompatibilidade/métodos , Transplante de Rim/imunologia , Ácidos Nucleicos Heteroduplexes/análise , Doadores de Tecidos , Alelos , Cadáver , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DR/análise , Humanos , Polimorfismo de Fragmento de Restrição , Estudos RetrospectivosAssuntos
Genótipo , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Antígenos HLA-DR/genética , Teste de Histocompatibilidade , Fenótipo , Doadores de Tecidos , Imunologia de Transplantes/genética , Alelos , Cadáver , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Sondas de Oligonucleotídeos , Polimorfismo de Fragmento de Restrição , Imunologia de Transplantes/imunologiaRESUMO
The polymerase chain reaction (PCR) has made the technique of sequence-specific oligonucleotide (SSO) typing fast, accurate and very sensitive. These combined techniques are an ideal tool for analysing the complex patterns of polymorphism seen throughout the HLA complex. The success of the technique relies heavily on accurate and specific amplification of the DNA under study. This paper considers the principles behind the PCR amplification technique and discusses the factors which lead to optimal amplification. Primer design is discussed and a variety of sources of target DNA considered. Precautions designed to prevent contamination are discussed. Reaction components are considered both in isolation and as part of the complete reaction. Finally, a complete PCR protocol is suggested. The paper is illustrated with examples of HLA class II amplification.
Assuntos
Antígenos HLA-D/genética , Teste de Histocompatibilidade/métodos , Reação em Cadeia da Polimerase/métodos , DNA/genética , DNA Polimerase Dirigida por DNA , Contaminação de Medicamentos , Antígenos HLA-D/classificação , HumanosRESUMO
A particular haplotype defined by probes XV2c, KM19, and CS.7 at the D7S23 locus was found on 90% of chromosomes which carry cystic fibrosis (CF), but on only 11% of normal chromosomes in a UK sample of CF carriers. We show how such data can be used to calculate carrier risks for people with and without a family history of CF, and give examples of clinical applications. For parents or sibs of dead CF patients, phase and genotypes can often be assigned with only 1 to 2% error. However, this method is not suitable for prenatal testing where there is no history of CF; for couples with no family history, no fetus can be shown to be at more than 2% risk of being affected.
