Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Personal identity. A theoretical and experimental analysis

Published as article in: Journal of Economic Methodology, 2010, vol. 17, issue 3, pages 261-275.

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.