| 1. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 2. |
- Rudbeck Jepsen, Martin, et al.
(author)
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Transitions in European land-management regimes between 1800 and 2010
- 2015
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In: Land use policy. - : Elsevier BV. - 0264-8377 .- 1873-5754. ; 49:SI, s. 53-64
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Journal article (peer-reviewed)abstract
- Land use is a cornerstone of human civilization, but also intrinsically linked to many global sustainability challenges—from climate change to food security to the ongoing biodiversity crisis. Understanding the underlying technological, institutional and economic drivers of land-use change, and how they play out in different environmental, socio-economic and cultural contexts, is therefore important for identifying effective policies to successfully address these challenges. In this regard, much can be learned from studying long-term land-use change. We examined the evolution of European land management over the past 200 years with the aim of identifying (1) key episodes of changes in land management, and (2) their underlying technological, institutional and economic drivers. To do so, we generated narratives elaborating on the drivers of land use-change at the country level for 28 countries in Europe. We qualitatively grouped drivers into land-management regimes, and compared changes in management regimes across Europe. Our results allowed discerning seven land-management regimes, and highlighted marked heterogeneity regarding the types of management regimes occurring in a particular country, the timing and prevalence of regimes, and the conditions that result in observed bifurcations. However, we also found strong similarities across countries in the timing of certain land-management regime shifts, often in relation to institutional reforms (e.g., changes in EU agrarian policies or the emergence and collapse of the Soviet land management paradigm) or to technological innovations (e.g., drainage pipes, tillage and harvesting machinery, motorization, and synthetic fertilizers). Land reforms frequently triggered changes in land management, and the location and timing of reforms had substantial impacts on land-use outcomes. Finally, forest protection policies and voluntary cooperatives were important drivers of land-management changes. Overall, our results demonstrate that land-system changes should not be conceived as unidirectional developments following predefined trajectories, but rather as path-dependent processes that may be affected by various drivers, including sudden events.
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| 3. |
- Szatmari, Peter, et al.
(author)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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