| 1. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 2. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 3. |
- den Tex, Robert-Jan, 1969-
(författare)
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Patterns and Processes of Evolution in Sundaland
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biodiversity in the tropics is disproportionately high compared to other habitats, and also under disproportionate threat from human impact. It is necessary to understand how this diversity evolved and how it is partitioned across space in order to preserve it. In this thesis I construct phylogenies of tropical forest dependent vertebrates from Southeast Asia and the islands of the Sunda shelf, a region referred to as Sundaland. I focus on the tree squirrels (genus Sundasciurus) and Asian barbets (Aves: Family Megalaimidae), two taxa with similar ecological characteristics. I use these phylogenies to test hypotheses that have been put forward to explain high levels of tropical diversity including the Pleistocene pump and museum hypotheses. I also use phylogenies to elucidate phylogeographic patterns within the region. I find no evidence for an increase in speciation in the Pleistocene, but I do find within species structure that dates to this period. Common phylogeographic patterns were identified between many forest dependent vertebrates that suggest that populations on the island of Sumatra are generally more closely related to Malay Peninsula populations than to populations on Borneo. From a methodological viewpoint we propose careful usage of universal primers in ancient DNA studies because of our finding of increased risk of amplifying pseudogenes of the mtDNA.
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| 4. |
- Leonard, Jennifer A.
(författare)
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Ancient DNA applications for wildlife conservation
- 2008
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 17:19, s. 4186-4196
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Forskningsöversikt (refereegranskat)abstract
- Ancient DNA analyses of historical, archaeological and paleontological remains can contribute important information for the conservation of populations and species that cannot be obtained any other way. In addition to ancient DNA analyses involving a single or few individuals, population level studies are now possible. Biases inherent in estimating population parameters and history from modern genetic diversity are exaggerated when populations are small or have been heavily impacted by recent events, as is common for many endangered species. Going directly back in time to study past populations removes many of the assumptions that undermine conclusions based only on recent populations. Accurate characterization of historic population size, levels of gene flow and relationships with other populations are fundamental to developing appropriate conservation and management plans. The incorporation of ancient DNA into conservation genetics holds a lot of potential, if it is employed responsibly.
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| 5. |
- Leonard, Jennifer A., et al.
(författare)
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Phylogeography of vertebrates on the Sunda Shelf : a multi-species comparison
- 2015
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 42:5, s. 871-879
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Tidskriftsartikel (refereegranskat)abstract
- Aim Pleistocene environmental fluctuations had well-characterized impacts on the patterns of within-species divergences and diversity in temperate habitats. Here we examine the impact the Pleistocene had on widely distributed forest vertebrates in a tropical system where the distribution of the habitat was affected by those fluctuations. LocationSundaland, tropical Southeast Asia. Methods We conducted a comparative phylogeographical analysis of 28 non-migratory, forest-dependent vertebrates, for which we constructed rooted, intraspecifc phylogenies based on mitochondrial DNA sequences of individuals from at least the three major landmasses in the area (Borneo, Sumatra and the Malay Peninsula) and compared them to hypothetical phylogenies based on independent geological data and climate models regarding connections and relationships between the major landmasses of Sundaland. Java was included where possible. We dated the phylogenies to determine whether patterns of differentiation were concordant across species. Results In most species, populations on the Malay Peninsula and Sumatra were most closely related, and sister to those from Borneo. The dates of these divergences, however, varied extensively between species. Borneo harbours multiple deeply divergent lineages of many species compared to the diversity within those species. Javan populations of several birds were most divergent relative to those from the rest of the Sunda Shelf. Main conclusions These results suggest a dynamic history, including recurrent population extinctions and replacements and a strong priority effect for local populations. The close relationship between populations in Sumatra and the Malay Peninsula supports the existence of forest on the exposed shelf during the Pleistocene at many different times, and suggests that proximity was more important than the presence of palaeorivers for dispersal of forest taxa between landmasses.
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| 6. |
- Anderson, Tovi M., et al.
(författare)
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Molecular and Evolutionary History of Melanism in North American Gray Wolves
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 323:5919, s. 1339-1343
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Tidskriftsartikel (refereegranskat)abstract
- Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives.
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| 7. |
- Barsh, Gregory S., et al.
(författare)
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How the Gray Wolf Got Its Color - Response
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5936, s. 34-34
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Bergström, Anders, et al.
(författare)
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Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 9. |
- den Tex, Robert-Jan, et al.
(författare)
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Nuclear copies of mitochondrial genes : another problem for ancient DNA
- 2010
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Ingår i: Genetica. - : Springer Science and Business Media LLC. - 0016-6707 .- 1573-6857. ; 138:9-10, s. 979-984
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Tidskriftsartikel (refereegranskat)abstract
- The application of ancient DNA techniques is subject to many problems caused primarily by low quality and by low quantity of DNA. For these reasons most studies employing ancient DNA rely on the characterization of mitochondrial DNA, which is present in many more copies per cell than nuclear DNA and hence more copies are likely to survive. We used universal and taxon specific mitochondrial primers to amplify DNA from museum specimens, and found many instances where the amplification of nuclear copies of the mitochondrial gene (numts) instead of the targeted mitochondrial fragment had occurred. Furthermore, the likelihood of amplifying numts increased dramatically when universal primers were utilized. Here we suggest that ancient DNA practitioners must consider the possibility that numts can be amplified at higher rates than previously thought. This is another complication for ancient DNA studies, but it also suggests that more extensive inclusion of nuclear markers in ancient DNA studies should be feasible.
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| 10. |
- den Tex, Robert-Jan, et al.
(författare)
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Speciation dynamics in the SE Asian tropics : Putting a time perspective on the phylogeny and biogeography of Sundaland tree squirrels, Sundasciurus
- 2010
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 55:2, s. 711-720
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Tidskriftsartikel (refereegranskat)abstract
- Tropical rainforests are well known for their extraordinarily high levels of biodiversity. The origin of this species richness is still debated. For instance, the museum hypothesis states that over evolutionary time more and more species will accumulate with relatively few extinctions. In contrast, the Pleistocene diversification model argues that during the last 2 million years, climatic factors (glaciations) caused environmental changes that drove isolation and vicariant speciation events. In this study, we construct a molecular phylogeny of the Sundaland (Malay Peninsula, Sumata, Borneo, Palawan) and Greater Mindanao (Mindanao, Samar, Leyte) tree squirrels (genus Sundasciurus). Our results show that most speciation events in this forest dependent taxon occurred before the Pleistocene and that even the timing of intra-specific splits among populations from different landmasses are relatively old. Additionally, we found unexpectedly high divergence within and between highland populations of S. tenuis on Sumatra and the Malay Peninsula, highlighting the importance of Pliocene events in both speciation and within species divergences in this region. (C) 2010 Elsevier Inc. All rights reserved.
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