RESUMEN
Atrial fibrillation (AF) is a multifactorial disease with a strong genetic background. It is assumed that common and rare genetic variants contribute to the progression and recurrence of AF. The pathophysiological impact of those variants, especially when they are synonymous or non-coding, is often elusive and translation into functional experiments is difficult. In this study, we propose a method to go straight from genetic variants to defined gene targets. We focused on 55 genes from calcium signaling and 26 genes from extra cellular matrix ECM-receptor interaction that we found to be associated with the progression and recurrence of AF. These genes were mapped on protein-protein interaction data from three different databases. Based on the concept that central regulators are highly connected with their neighbors, we identified central hub proteins according to random walk analysis derived scores representing interaction grade. Our approach resulted in the identification of EGFR, RYR2, and PRKCA (calcium signaling) and FN1 and LAMA1 (ECM-receptor interaction) which represent promising targets for further functional characterization or pharmaceutical intervention.
RESUMEN
Rattus norvegicus has been considered nonphotoperiodic, but Fischer 344 (F344) rats are inhibited in growth and reproductive development by short photoperiod (SD). We tested photoresponsiveness of the genetically divergent Brown Norway (BN) strain of rats. Peripubertal males were tested in long photoperiod or SD, with or without 30% food reduction. Young males were photoresponsive, with reductions in testis size, body mass, and food intake in SD and with enhanced responses to SD when food restricted. Photoperiods < or =11 h of light inhibited reproductive maturation and somatic growth, whereas photoperiods of 12 h or more produced little or no response. F344/BN hybrids differ from both parent strains in the timing, amplitude, and critical photoperiod of photoperiodic responses, indicating genetic differences in photoperiodism between these strains. This is consistent with the hypothesis that ancestors of laboratory rats were genetically variable for photoperiodism and that different combinations of alleles for photoperiodism have been fixed in different strains of rats.