| 1. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Horikoshi, Momoko, et al.
(author)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Journal article (peer-reviewed)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 3. |
- Giesecke, Thomas, et al.
(author)
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Towards mapping the late Quaternary vegetation change of Europe.
- 2014
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In: Vegetation History and Archaeobotany. - : Springer Science and Business Media LLC. - 0939-6314 .- 1617-6278. ; 23:1, s. 75-86
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Journal article (peer-reviewed)abstract
- The number of well-dated pollen diagrams in Europe has increased considerably over the last 30 years and many of them have been submitted to the European Pollen Database (EPD). This allows for the construction of increasingly precise maps of Holocene vegetation change across the continent. Chronological information in the EPD has been expressed in uncalibrated radiocarbon years, and most chronologies to date are based on this time scale. Here we present new chronologies for most of the datasets stored in the EPD based on calibrated radiocarbon years. Age information associated with pollen diagrams is often derived from the pollen stratigraphy itself or from other sedimentological information. We reviewed these chronological tie points and assigned uncertainties to them. The steps taken to generate the new chronologies are described and the rationale for a new classification system for age uncertainties is introduced. The resulting chronologies are fit for most continental-scale questions. They may not provide the best age model for particular sites, but may be viewed as general purpose chronologies. Taxonomic particularities of the data stored in the EPD are explained. An example is given of how the database can be queried to select samples with appropriate age control as well as the suitable taxonomic level to answer a specific research question.
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| 4. |
- Connor, Simon E., et al.
(author)
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The ecological impact of oceanic island colonization - a palaeoecological perspective from the Azores
- 2012
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In: Journal of Biogeography. - : Wiley. - 1365-2699 .- 0305-0270. ; 39:6, s. 1007-1023
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Journal article (peer-reviewed)abstract
- Aim In many cases, human colonization drastically modified the ecosystems of remote oceanic islands before scientists arrived to document the changes. Palaeoecological records before and after human colonization provide insights into the original ecosystems and an assessment of subsequent human impact. We used pollen analysis to compare the impact of 15th century colonization of the Azores with that of natural disturbances such as volcanic eruptions and climate changes. Location Azores archipelago, Atlantic Ocean. Methods Sediment records from three highland sites in the Azores (on the islands of Pico and Flores) were dated radiometrically and analysed palynologically. Pollen taxa were classified as native, endemic or introduced based on comparison with flora lists. Data were statistically zoned and temporal trends identified using detrended correspondence analysis. Results Human colonization of the Azores resulted in rapid, widespread, persistent vegetation changes on a scale unprecedented in the last 2700 years, detectable through the decline of dominant trees, the spread of grasses and fire-tolerant species, the introduction of exotic plants, evidence for grazing and fire, and changes to soils and moisture availability. During the same period, volcanic eruptions appear to have had more localized impacts on the vegetation, lasting 5001000 years and favouring endemic taxa. The effect of late Holocene climatic changes on the highland vegetation of the Azores seems to have been minor. Palaeoecological data indicate that at least two plant species went extinct on Pico after human colonization and that some plants regarded as introduced were almost certainly part of the original flora of the islands. Despite a consistent signal of human impact, compositional differences between Juniperus brevifolia communities on Pico and Flores remained after colonization. Main conclusions Human colonization had a greater impact on the pristine vegetation of Pico and Flores than climatic changes and volcanic activity during recent millennia. The similarity between post-colonization changes on the Azores and other oceanic islands suggests a consistent pattern and scale to historical-era human impact on otherwise pristine ecosystems. These characteristics could be used to further elaborate biogeographical theory and direct conservation efforts towards species that appear most susceptible to human activity.
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| 5. |
- Adolf, Carole, et al.
(author)
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The sedimentary and remote-sensing reflection of biomass burning in Europe
- 2018
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In: Global Ecology and Biogeography. - : WILEY. - 1466-822X .- 1466-8238. ; 27:2, s. 199-212
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Journal article (peer-reviewed)abstract
- Aim: We provide the first European-scale geospatial training set relating the charcoal signal in surface lake sediments to fire parameters (number, intensity and area) recorded by satellite moderate resolution imaging spectroradiometer (MODIS) sensors. Our calibration is intended for quantitative reconstructions of key fire-regime parameters by using sediment sequences of microscopic (MIC from pollen slides, particles 10-500 mu m) and macroscopic charcoal (MAC from sieves, particles > 100 mu m). Location: North-south and east-west transects across Europe, covering the mediterranean, temperate, alpine, boreal and steppe biomes. Time period: Lake sediments and MODIS active fire and burned area products were collected for the years 2012-2015. Methods: Cylinder sediment traps were installed in lakes to annually collect charcoal particles in sediments. We quantitatively assessed the relationships between MIC and MAC influx (particles/cm(2)/year) and the MODIS-derived products to identify source areas of charcoal and the extent to which lake-sediment charcoal is linked to fire parameters across the continent. Results: Source area of sedimentary charcoal was estimated to a 40-km radius around sites for both MIC and MAC particles. Fires occurred in grasslands and in forests, with grass morphotypes of MAC accurately reflecting the burned fuel-type. Despite the lack of local fires around the sites, MAC influx levels reached those reported for local fires. Both MIC and MAC showed strong and highly significant relationships with the MODIS-derived fire parameters, as well as with climatic variation along a latitudinal temperature gradient. Main conclusions: MIC and MAC are suited to quantitatively reconstructing fire number and fire intensity on a regional scale. However, burned area may only be estimated using MAC. Local fires may be identified by using several lines of evidence, e.g. analysis of large particles (> 600 mu m), magnetic susceptibility and sedimentological data. Our results offer new insights and applications to quantitatively reconstruct fires and to interpret available sedimentary charcoal records.
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