Fine mapping and functional analysis of the multiple sclerosis risk gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.

Museos, memoria y turismo

Cap. 1. Museos y patrimonio: de la distancia retórica a la interlocución democrática. Iñaki Díaz Balerdi. Cap. 2. Au coeur des conflits entre memoire, histoire et developpement economique, les nouveaux enjeux des musees de société aujourd’hui. François Hubert. Cap. 3. Elites, Instituciones Públicas, identidad cultural y turismo en los orígenes del Museo Municipal de Donostia-San Sebastián. Iñaki Arrieta Urtizberea. Cap. 4. Los orígenes de la museografía etnográfica en Cataluña: el Arxiu-Museu Folklòric de Ripoll. Oriol Beltran Costa. Cap. 5. Museo de la Pesca en Palamós: espacio para la memoria de los pescadores. Miquel Martí i Llambrich. Cap. 6. Arqueología y museos en Gipuzkoa; las experiencias del Centro de Estudios ARKEOLAN (1986-2005). Mª Mercedes Urteaga Artigas. Cap. 7. Penser un Musée des Confluences: un autre discours sur soi et les autres que soi. Thierry Valentin. Cap. 8. Turismo cultural y museos: oportunidades de desarrollo comunes. El caso de Cesis, Letonia. María Fernández Sabau. Cap. 9. La gestión y el uso turístico de los museos: la experiencia de Barcelona. Jordi Juan Tresserras y Juan Carlos Matamala. Cap. 10. Museos, turismo y desarrollo local en el norte de Portugal: el Ecomuseo del Barroso. Xerardo Pereiro. Cap. 11. Turismo y patrimonio cultural en las pequeñas y medianas ciudades: el Barri Vell de Girona y el Museu d’Art de Girona. Josep Manuel Rueda Torres.