RESUMEN
The current shift moves the governance of animal welfare away from the government towards the private market and the consumers. We have studied the intentions, content, and on-farm inspection results from different sets of animal welfare legislation and private standards with an aim to highlight the most important opportunities and risks identified in relation to the trend of increasingly relying on private standards for safeguarding or improving farm animal welfare. Our results show that different focuses, intentions, animal welfare requirements, inspection methods (i.e., methods for measuring and evaluating the compliance with a regulation), and inspection results, together with the use of vague wordings and a drive towards more flexible regulations does certainly not facilitate the interpretation and implementation of animal welfare regulations, especially not in relation to each other. Since farmers today often have to comply with several animal welfare regulations, including private standards, it is important to stress that a given regulation should never be seen as a single, stand-alone phenomenon, and the policymakers must hence consider the bigger picture, and apply the standards in relation to other existing regulations. This is especially relevant in relation to the legislation, a level that a private standard can never ignore.
RESUMEN
Recently, several non-HLA loci have been shown to be convincingly associated with Multiple Sclerosis (MS) susceptibility, assumingly indicating important pathways in the pathogenesis. A genotype influence on disease outcome measures by these genes would support a role of these pathways in ongoing tissue damage. Here, however, we report a consistent dissociation between causation and progression for five non-HLA genotypes (IL7R, IL2RA, CLEC16A, CD226 and SH2B3) in 1776 Scandinavian MS patients.
Asunto(s)
Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Predisposición Genética a la Enfermedad/genética , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/inmunología , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad/etnología , Antígenos HLA/inmunología , Humanos , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Péptidos y Proteínas de Señalización Intracelular , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Masculino , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/inmunología , Esclerosis Múltiple/patología , Noruega/epidemiología , Proteínas/genética , Proteínas/inmunología , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/inmunología , Suecia/epidemiologíaRESUMEN
Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment. For multiple sclerosis such a unique setting is reported in Southern Ostrobothnia in Finland, where the prevalence and familial occurrence of multiple sclerosis (MS) are exceptionally high. Here, we have studied one of the best replicated MS loci, 5p, and monitored for haplotypes shared among 72 regional MS cases, the majority of which are genealogically distantly related. The haplotype analysis over the 45 Mb region, covering the linkage peak identified in Finnish MS families, revealed only modest association at IL7R (P = 0.04), recently implicated in MS, whereas most significant association was found with one haplotype covering the C7-FLJ40243 locus (P = 0.0001), 5.1 Mb centromeric of IL7R. The finding was validated in an independent sample from the isolate and resulted in an odds ratio of 2.73 (P = 0.000003) in the combined data set. The identified relatively rare risk haplotype contains C7 (complement component 7), an important player of the innate immune system. Suggestive association with alleles of the region was seen also in more heterogeneous populations. Interestingly, also the complement activity correlated with the identified risk haplotype. These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles.
Asunto(s)
Cromosomas Humanos Par 5/genética , Complemento C7/genética , Esclerosis Múltiple/genética , Estudios de Casos y Controles , Finlandia , Estudio de Asociación del Genoma Completo , Haplotipos , HumanosRESUMEN
Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS.
Asunto(s)
Esclerosis Múltiple/genética , Miosinas/genética , Polimorfismo Genético/genética , Estudios de Casos y Controles , Familia , Genotipo , Humanos , Población Blanca/genéticaRESUMEN
Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher VAV1 messenger RNA expression. VAV1 expression was increased in individuals with multiple sclerosis and correlated with tumor necrosis factor and interferon-gamma expression in peripheral blood and cerebrospinal fluid cells. We conclude that VAV1 plays a central role in controlling central nervous system immune-mediated disease and proinflammatory cytokine production critical for disease pathogenesis.
Asunto(s)
Encefalomielitis Autoinmune Experimental/fisiopatología , Esclerosis Múltiple/fisiopatología , Proteínas Proto-Oncogénicas c-vav/fisiología , Animales , Linfocitos T CD4-Positivos/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Interferón gamma/genética , Esclerosis Múltiple/inmunología , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-vav/genética , Sitios de Carácter Cuantitativo , Ratas , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
IL7 is a nonredundant cytokine, essential for T cell survival and development in humans. We genotyped nine tagging single nucleotide polymorphisms (SNP), representing all parts of the IL7 gene, in 1,210 Swedish multiple sclerosis (MS) patients and 1,234 healthy controls. None of the SNPs showed a significantly different distribution in MS, and haplotype analysis also failed to reveal differences between patients and controls. We conclude that the IL7 gene is very unlikely to influence the genetic susceptibility to MS in this population.
Asunto(s)
Interleucina-7/genética , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non-HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor alpha chain (IL7Ralpha), indeed contribute to the non-HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7Ralpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.
Asunto(s)
Predisposición Genética a la Enfermedad , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-7/genética , Adulto , Estudios de Casos y Controles , Dinamarca , Femenino , Finlandia , Expresión Génica , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Interleucina-7/genética , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Desequilibrio de Ligamiento , Modelos Logísticos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Noruega , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , SueciaRESUMEN
We have investigated the genetic involvement of the CD4 and the LAG3 genes, two appealing candidates for MS due to their suggested role in MS pathology. We genotyped a Swedish case-control material consisting of 920 MS patients and 778 controls in an initial study of CD4, three SNPs showed a significant association with MS. An independent material consisting of 1720 Nordic MS patients and 1416 controls were used for confirmation of associated markers in CD4 and to do a confirmative study of the LAG3 gene from previous findings. The result, including a total of 2640 MS patients and 2194 controls shows no significant association with CD4 and LAG3 and MS. We conclude that these genes are of minor importance in regard of genetic predisposition to the MS.