| 1. |
- Brawand, David, et al.
(författare)
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The genomic substrate for adaptive radiation in African cichlid fish
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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| 2. |
- Crowther-Swanepoel, Dalemari, et al.
(författare)
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Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 132-136
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.39; P = 2.11 x 10(-9)), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10(-10)), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10(-7)) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10(-7)). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.
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| 3. |
- Speedy, Helen E., et al.
(författare)
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A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 x 10(-9)), 4q26 (rs6858698, P = 3.07 x 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 x 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 x 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 x 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 x 10(-10)) and 8q22.3 (rs2511714, P = 2.90 x 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.
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| 4. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 6. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 7. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 8. |
- Donoghue, Eleanor, et al.
(författare)
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Fluid-Rock Interaction in the Miocene, Post-Caldera, Tejeda Intrusive Complex, Gran Canaria (Canary Islands) : Insights from Mineralogy, and O- and H-Isotope Geochemistry
- 2010
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Ingår i: Journal of Petrology. - : Oxford University Press (OUP). - 0022-3530 .- 1460-2415. ; 51:10, s. 2149-2176
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Tidskriftsartikel (refereegranskat)abstract
- The intra-caldera volcaniclastic deposits of the Miocene Tejeda caldera on Gran Canaria host an similar to 12 km diameter intrusive complex comprising a peralkaline, trachytic to phonolitic cone sheet swarm surrounding a central core of hypabyssal syenite stocks. Both intrusive rock types display textural and mineralogical features indicative of secondary fluid-rock interaction, including (1) deuteric mineral phases (e.g. aegirine, alkali-amphibole, analcime), (2) turbid alkali feldspars, and (3) hydrothermal mineral phases (phyllosilicates, Fe-Ti oxides, Mn-oxides, and quartz). Altered cone sheets have whole-rock delta O-18 values ranging from 0 center dot 1 to 10 center dot 0 parts per thousand (n = 22), and whole-rock delta D values between -62 and -149 parts per thousand (n = 28). Three altered syenite samples have whole-rock delta O-18 values of 2 center dot 5, 1 center dot 5, and 0 center dot 9 parts per thousand, and corresponding delta D values of -91, -99, and -121 parts per thousand. The H2O concentrations of the altered cone sheets range from 0 center dot 4 to 0 center dot 8 wt % (n = 28), and the altered syenites have H2O concentrations of 0 center dot 5, 0 center dot 5, and 0 center dot 6 wt %, respectively. The majority of altered samples are depleted in O-18 relative to the typical delta O-18 range for unaltered trachytes and syenites (delta O-18 = 6-8 parts per thousand), indicative of interaction with local meteoric water (delta O-18 c. -8 parts per thousand) at temperatures epsilon 150 degrees C. Only one cone sheet sample appears petrographically unaltered and has a typical 'igneous' isotopic composition (delta O-18 = 7 center dot 1 parts per thousand, delta D = -48 parts per thousand) and a relatively high H2O concentration (2 center dot 2 wt %). A weak correlation (r = 0 center dot 55) between delta D and H2O is observed in the cone sheets, reflecting the combined effects of magmatic H2O exsolution, and subsequent deuteric and hydrothermal alteration. No systematic variation in delta O-18 or delta D was detected across the cone sheet swarm, most likely reflecting overprinting of isotopic compositions during successive intrusive events. However, the highest delta O-18 values (8 center dot 2-10 center dot 0 parts per thousand) occur in clay-bearing cone sheets from the central part of the intrusive complex, suggesting enhanced infiltration of relatively cool meteoric water in this area. Overall, at least three phases of fluid-rock interaction can be distinguished: (1) deuteric alteration (c. 300-500 degrees C) by late magmatic fluids expelled from a solidifying crystal mush; (2) hydrothermal alteration (epsilon 150-300 degrees C) by meteoric water during the final stages of crystallization and/or immediately following solidification of the intrusive complex; (3) retrograde alteration related to the influx of relatively cool (150 degrees C) meteoric waters.
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| 9. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 10. |
- Jeffery, Adam J., et al.
(författare)
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The pre-eruptive magma plumbing system of the 2007–2008 dome-forming eruption of Kelut volcano, East Java, Indonesia
- 2013
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Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 166:1, s. 275-308
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Tidskriftsartikel (refereegranskat)abstract
- Kelut volcano, East Java, is an active volcanic complex hosting a summit crater lake that has been the source of some of Indonesia’s most destructive lahars. In November 2007, an effusive eruption lasting approximately 7 months led to the formation of a 260-m-high and 400-m-wide lava dome that displaced most of the crater lake. The 2007–2008 Kelut dome comprises crystal-rich basaltic andesite with a texturally complex crystal cargo of strongly zoned and in part resorbed plagioclase (An47–94), orthopyroxene (En64–72, Fs24–32, Wo2–4), clinopyroxene (En40–48, Fs14–19, Wo34–46), Ti-magnetite (Usp16–34) and trace amounts of apatite, as well as ubiquitous glomerocrysts of varying magmatic mineral assemblages. In addition, the notable occurrence of magmatic and crustal xenoliths (meta-basalts, amphibole-bearing cumulates, and skarn-type calc-silicates and meta-volcaniclastic rocks) is a distinct feature of the dome. New petrographical, whole rock major and trace element data, mineral chemistry as well as oxygen isotope data for both whole rocks and minerals indicate a complex regime of magma-mixing, decompression-driven resorption, degassing and crystallisation and crustal assimilation within the Kelut plumbing system prior to extrusion of the dome. Detailed investigation of plagioclase textures alongside crystal size distribution analyses provide evidence for magma mixing as a major pre-eruptive process that blends multiple crystal cargoes together. Distinct magma storage zones are postulated, with a deeper zone at lower crustal levels or near the crust-mantle boundary (>15 km depth), a second zone at mid-crustal levels (~10 km depth) and several magma storage zones distributed throughout the uppermost crust (<10 km depth). Plagioclase-melt and amphibole hygrometry indicate magmatic H2O contents ranging from ~8.1 to 8.6 wt.% in the lower crustal system to ~1.5 to 3.3 wt.% in the mid to upper crust. Pyroxene and plagioclase δ18O values range from 5.4 to 6.7 ‰, and 6.5 to 7.6 ‰, respectively. A single whole rock analysis of the 2007–2008 dome lava gave a δ18O value of 7.6 ‰, whereas meta-basaltic and calc-silicate xenoliths are characterised by δ18O values of 6.2 and 10.3 ‰, respectively. Magmatic δ18O values calculated from individual pyroxene and plagioclase analyses range from 5.7 to 7.0 ‰, and 6.2 to 7.4 ‰, respectively. This range in O-isotopic compositions is explained by crystallisation of pyroxenes in the lower to mid-crust, where crustal contamination is either absent or masked by assimilation of material having similar δ18O values to the ascending melts. This population is mixed with isotopically distinct plagioclase and pyroxenes that crystallised from a more contaminated magma in the upper crustal system. Binary bulk mixing models suggest that shallow-level, recycled volcaniclastic sedimentary rocks together with calc-silicates and/or limestones are the most likely contaminants of the 2007–2008 Kelut magma, with the volcaniclastic sediments being dominant.
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