| 1. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 2. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Pearson, Emma J., et al.
(författare)
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A lacustrine GDGT-temperature calibration from the Scandinavian Arctic to Antarctic : Renewed potential for the application of GDGT-paleothermometry in lakes
- 2011
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Ingår i: Geochimica et Cosmochimica Acta. - Oxford : Elsevier BV. - 0016-7037 .- 1872-9533. ; 75:20, s. 6225-6238
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative climate reconstructions are fundamental to understand long-term trends in natural climate variability and to test climate models used to predict future climate change. Recent advances in molecular geochemistry have led to calibrations using glycerol dialkyl glycerol tetraethers (GDGTs), a group of temperature-sensitive membrane lipids found in Archaea and bacteria. GDGTs have been used to construct temperature indices for oceans (TEX(86) index) and soils (MBT/CBT index). The aim of this study is to examine GDGT-temperature relationships and assess the potential of constructing a GDGT-based palaeo-thermometer for lakes. We examine GDGT-temperature relationships using core top sediments from 90 lakes across a north-south transect from the Scandinavian Arctic to Antarctica including sites from Finland, Sweden, Siberia, the UK, Austria, Turkey, Ethiopia, Uganda, Chile, South Georgia and the Antarctic Peninsula. We examine a suite of 15 GDGTs, including compounds used in the TEX(86) and MBT/CBT indices and reflecting the broad range of GDGT inputs to small lake systems. GDGTs are present in varying proportions in all lakes examined. The TEX(86) index is not applicable to our sites because of the large relative proportions of soil derived and methanogenic components. Similarly, the MBT/CBT index is also not applicable and predicts temperatures considerably lower than those measured. We examine relationships between individual GDGT compounds and temperature, pH, conductivity and water depth. Temperature accounts for a large and statistically independent fraction of variation in branched GDGT composition. We propose a GDGT-temperature regression model with high accuracy and precision (R(2) = 0.88; RMSE = 2.0 degrees C; RMSEP = 2.1 degrees C) for use in lakes based on a subset of branched GDGT compounds and highlight the potential of this new method for reconstructing past temperatures using lake sediments. (C) 2011 Elsevier Ltd. All rights reserved.
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