Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

Traceability of values for catalytic activity concentration of enzymes : a certified reference material for aspartate transaminase

Background: A new reference material for the liver enzyme aspartate transaminase (AST) (L-aspartate: 2-oxoglutarate-aminotransferase, EC 2.6.1.1), also called aspartate aminotransferase (ASAT), has been developed under the code ERM-AD457/IFCC. This certified reference material (CRM) for AST has been produced from a human type recombinant AST expressed in Escherichia coli and a buffer containing bovine serum albumin, and has been lyophilised. Methods: The homogeneity and the stability of the material have been tested and the catalytic activity concentration has been characterised by 12 laboratories using the reference procedure for AST at 37 degrees C from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Results: The certified catalytic activity concentration and certified uncertainty of AST in the reconstituted material are (1.74 +/- 0.05) mkat/L or (104.6 +/- 2.7) U/L (with a coverage factor k = 2; 95% confidence interval). Conclusions: Both the certified value and uncertainty are traceable to the International System of Units (SI). The material is aiming to control the IFCC reference procedure for AST at 37 degrees C, which will then be used to assign values to calibrants and control materials. The present paper highlights the scientific challenges and innovations which were encountered during the development of this new CRM

Histoire naturelle des animaux sans vert\ue8bres : pr\ue9sentant les caract\ue8res g\ue9n\ue9raux et particuliers de ces animaux, leur distribution, leurs classes, leurs familles, leurs genres, et la citation des principales esp\ue8ces qui s\u27y rapportent : pr\ue9c\ue9d\ue9e d\u27une introduction offrant la d\ue9termination des caract\ue8res essentiels de l\u27animal, sa distinction du v\ue9g\ue9tal et des autres corps naturels, enfin, l\u27exposition des principes fondamentaux de la zoologie /

t.10 (1844

Histoire naturelle des animaux sans vert\ue8bres : pr\ue9sentant les caract\ue8res g\ue9n\ue9raux et particuliers de ces animaux, leur distribution, leurs classes, leurs familles, leurs genres, et la citation des principales esp\ue8ces qui s\u27y rapportent : pr\ue9c\ue9d\ue9e d\u27une introduction offrant la d\ue9termination des caract\ue8res essentiels de l\u27animal, sa distinction du v\ue9g\ue9tal et des autres corps naturels, enfin, l\u27exposition des principes fondamentaux de la zoologie /

t.3 (1840

Traité de botanique générale /

2:Atla