Characterization of the linkage disequilibrium structure and identification of tagging-SNPs in five DNA repair genes

BACKGROUND: Characterization of the linkage disequilibrium (LD) structure of candidate genes is the basis for an effective association study of complex diseases such as cancer. In this study, we report the LD and haplotype architecture and tagging-single nucleotide polymorphisms (tSNPs) for five DNA repair genes: ATM, MRE11A, XRCC4, NBS1 and RAD50. METHODS: The genes ATM, MRE11A, and XRCC4 were characterized using a panel of 94 unrelated female subjects (47 breast cancer cases, 47 controls) obtained from high-risk breast cancer families. A similar LD structure and tSNP analysis was performed for NBS1 and RAD50, using publicly available genotyping data. We studied a total of 61 SNPs at an average marker density of 10 kb. Using a matrix decomposition algorithm, based on principal component analysis, we captured >90% of the intragenetic variation for each gene. RESULTS: Our results revealed that three of the five genes did not conform to a haplotype block structure (MRE11A, RAD50 and XRCC4). Instead, the data fit a more flexible LD group paradigm, where SNPs in high LD are not required to be contiguous. Traditional haplotype blocks assume recombination is the only dynamic at work. For ATM, MRE11A and XRCC4 we repeated the analysis in cases and controls separately to determine whether LD structure was consistent across breast cancer cases and controls. No substantial difference in LD structures was found. CONCLUSION: This study suggests that appropriate SNP selection for an association study involving candidate genes should allow for both mutation and recombination, which shape the population-level genomic structure. Furthermore, LD structure characterization in either breast cancer cases or controls appears to be sufficient for future cancer studies utilizing these genes

Peculiarities of Sponsorship in Professional Road Cycling

© Springer International Publishing Switzerland 2016. All rights reserved. Sport sponsorship is any commercial agreement by which a sponsor contractually provides financing or other support in order to establish an association between the sponsor's image, brands or products and a sport sponsorship property in return for rights to promote this association and/or for granting certain agreed direct or indirect benefits. Since professional road cycling was one of the first sports to be practised commercially, sponsorship of cycling teams already started in the first editions of endurance races such as Bordeaux-Paris at the end of the nineteenth century and it has grown ever since. Today's cycling teams are in fact financed almost exclusively through sponsorship. This chapter explains the business-to-business (B2B) characteristics of team cycling sponsorship and shows how the cycling sponsorship market can be very dynamic. The duration and termination of sponsorship of cycling teams as well as a company's motives to invest in cycling sponsorship are discussed, and the importance of the integration of sponsorship into marketing communication is illustrated. We also analyse the return and effectiveness of cycling team sponsorship and conclude with some thoughts on the specific choice of the sponsorship of cycling races instead of cycling teams.status: publishe