621 research outputs found
Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations
Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long-term studies across Europe and consequently are considered an ecological âmodel organismâ. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long-term study populations of great titsâone in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population-specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population-specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free-living populations
Multibeam Maser Survey of methanol and excited OH in the Magellanic clouds: new detections and maser abundance estimates
âThe definitive version is available at www.blackwell-synergy.com.â Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.12888.xPeer reviewe
Characterisation of retrotransposon insertion polymorphisms in whole genome sequencing data from individuals with amyotrophic lateral sclerosis
The genetics of an individual is a crucial factor in understanding the risk of developing the neurodegenerative disease amyotrophic lateral sclerosis (ALS). There is still a large proportion of the heritability of ALS, particularly in sporadic cases, to be understood. Among others, active transposable elements drive inter-individual variability, and in humans long interspersed element 1 (LINE1, L1), Alu and SINE-VNTR-Alu (SVA) retrotransposons are a source of polymorphic insertions in the population. We undertook a pilot study to characterise the landscape of non-reference retrotransposon insertion polymorphisms (non-ref RIPs) in 15 control and 15 ALS individualsâ whole genomes from Project MinE, an international project to identify potential genetic causes of ALS. The combination of two bioinformatics tools (mobile element locator tool (MELT) and TEBreak) identified on average 1250 Alu, 232 L1 and 77 SVA non-ref RIPs per genome across the 30 analysed. Further PCR validation of individual polymorphic retrotransposon insertions showed a similar level of accuracy for MELT and TEBreak. Our preliminary study did not identify a specific RIP or a significant difference in the total number of non-ref RIPs in ALS compared to control genomes. The use of multiple bioinformatic tools improved the accuracy of non-ref RIP detection and our study highlights the potential importance of studying these elements further in ALS
On manifolds with nonhomogeneous factors
We present simple examples of finite-dimensional connected homogeneous spaces
(they are actually topological manifolds) with nonhomogeneous and nonrigid
factors. In particular, we give an elementary solution of an old problem in
general topology concerning homogeneous spaces
Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica
Type I interferon (IFN-I) and T helper 17 (TH17) drive pathology in neuromyelitis optica spectrum disorder (NMOSD) and in TH17-induced experimental autoimmune encephalomyelitis (TH17-EAE). This is paradoxical because the prevalent theory is that IFN-I inhibits TH17 function. Here we report that a cascade involving IFN-I, IL-6 and B cells promotes TH17-mediated neuro-autoimmunity. In NMOSD, elevated IFN-I signatures, IL-6 and IL-17 are associated with severe disability. Furthermore, IL-6 and IL-17 levels are lower in patients on anti-CD20 therapy. In mice, IFN-I elevates IL-6 and exacerbates TH17-EAE. Strikingly, IL-6 blockade attenuates disease only in mice treated with IFN-I. By contrast, B-cell-deficiency attenuates TH17-EAE in the presence or absence of IFN-I treatment. Finally, IFN-I stimulates B cells to produce IL-6 to drive pathogenic TH17 differentiation in vitro. Our data thus provide an explanation for the paradox surrounding IFN-I and TH17 in neuro-autoimmunity, and may have utility in predicting therapeutic response in NMOSD
CPT, T, and Lorentz Violation in Neutral-Meson Oscillations
Tests of CPT and Lorentz symmetry using neutral-meson oscillations are
studied within a formalism that allows for indirect CPT and T violation of
arbitrary size and is independent of phase conventions. The analysis is
particularly appropriate for studies of CPT and T violation in oscillations of
the heavy neutral mesons D, B_d, and B_s. The general Lorentz- and CPT-breaking
standard-model extension is used to derive an expression for the parameter for
CPT violation. It varies in a prescribed way with the magnitude and orientation
of the meson momentum and consequently also with sidereal time. Decay
probabilities are presented for both uncorrelated and correlated mesons, and
some implications for experiments are discussed.Comment: 11 pages, references added, accepted in Physical Review
Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star
A search of the time-series photometry from NASA's Kepler spacecraft reveals
a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626
with a period of 290 days. The characteristics of the host star are well
constrained by high-resolution spectroscopy combined with an asteroseismic
analysis of the Kepler photometry, leading to an estimated mass and radius of
0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for
the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the
planet. The system passes a battery of tests for false positives, including
reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A
full BLENDER analysis provides further validation of the planet interpretation
by showing that contamination of the target by an eclipsing system would rarely
mimic the observed shape of the transits. The final validation of the planet is
provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year
span. Although the velocities do not lead to a reliable orbit and mass
determination, they are able to constrain the mass to a 3{\sigma} upper limit
of 124 MEarth, safely in the regime of planetary masses, thus earning the
designation Kepler-22b. The radiative equilibrium temperature is 262K for a
planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is
a rocky planet, it is the first confirmed planet with a measured radius to
orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap
Observing Direct CP Violation in Untagged B-Meson Decays
Direct CP violation can exist in untagged B-meson decays to self-conjugate,
three-particle final states; it would be realized as a population asymmetry in
the untagged decay rate across the mirror line of the Dalitz plot of the
three-body decay. We explore the numerical size of this direct CP-violating
effect in a variety of B-meson decays to three pseudoscalar mesons; we show
that the resulting asymmetry is comparable to the partial rate asymmetry in the
analogous tagged decays, making the search for direct CP violation in the
untagged decay rate, for which greater statistics accrue, advantageous.Comment: 31 pages, REVTeX4, 1 eps figure, references added, typos corrected,
version to appear in PR
Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits
The WWgamma triple gauge boson coupling parameters are studied using p-pbar
-> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were
collected with the DO detector from an integrated luminosity of 162 pb^{-1}
delivered by the Fermilab Tevatron Collider. The cross section times branching
fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV
and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum)
pb. The one-dimensional 95% confidence level limits on anomalous couplings are
-0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
- âŠ