| 1. |
- Lango Allen, Hana, et al.
(author)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Journal article (peer-reviewed)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 2. |
- Mondello, Stefania, et al.
(author)
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αII-spectrin breakdown products (SBDPs) : diagnosis and outcome in severe traumatic brain injury patients
- 2010
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 27:7, s. 1203-1213
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Journal article (peer-reviewed)abstract
- In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] score 6 ng/mL) and SBDP120 levels (>17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.
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| 3. |
- Müller, Roger A., et al.
(author)
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Water renewal along the aquatic continuum offsets cumulative retention by lakes : implications for the character of organic carbon in boreal lakes
- 2013
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In: Aquatic Sciences. - : Springer Science and Business Media LLC. - 1015-1621 .- 1420-9055. ; 75:4, s. 535-545
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Journal article (peer-reviewed)abstract
- The character of organic carbon (OC) in lake waters is strongly dependent on the time water has spent in the landscape as well as in the lake itself due to continuous biogeochemical OC transformation processes. A common view is that upstream lakes might prolong the water retention in the landscape, resulting in an altered OC character downstream. We calculated the number of lakes upstream for 24,742 Swedish lakes in seven river basins spanning from 56º to 68º N. For each of these lakes, we used a lake volume to discharge comparison on a landscape scale to account for upstream water retention by lakes (Tn tot). We found a surprisingly weak relationship between the number of lakes upstream and Tn tot. Accordingly, we found that the coloured fraction of organic carbon was not related to lake landscape position but significantly related to Tn tot when we analysed lake water chemical data from 1,559 lakes in the studied river basins. Thus, we conclude that water renewal along the aquatic continuum by lateral water inputs offsets cumulative retention by lakes. Based on our findings, we suggest integrating Tn tot in studies that address lake landscape position in the boreal zone to better understand variations in the character of organic carbon across lake districts.
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| 4. |
- Werren, John H, et al.
(author)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Journal article (peer-reviewed)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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