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Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
The success of invasive species has been explained by two contrasting but non-exclusive views: (i) intrinsic factors make some species inherently good invaders; (ii) species become invasive as a result of extrinsic ecological and genetic influences such as release from natural enemies, hybridization or other novel ecological and evolutionary interactions. These viewpoints are rarely distinguished but hinge on distinct mechanisms leading to different management scenarios. To improve tests of these hypotheses of invasion success we introduce a simple mathematical framework to quantify the invasiveness of species along two axes: (i) interspecific differences in performance among native and introduced species within a region, and (ii) intraspecific differences between populations of a species in its native and introduced ranges. Applying these equations to a sample dataset of occurrences of 1,416 plant species across Europe, Argentina, and South Africa, we found that many species are common in their native range but become rare following introduction; only a few introduced species become more common. Biogeographical factors limiting spread (e.g. biotic resistance, time of invasion) therefore appear more common than those promoting invasion (e.g. enemy release). Invasiveness, as measured by occurrence data, is better explained by inter-specific variation in invasion potential than biogeographical changes in performance. We discuss how applying these comparisons to more detailed performance data would improve hypothesis testing in invasion biology and potentially lead to more efficient management strategies.