1,514 research outputs found
Genetic control of N-glycosylation of human blood plasma proteins
Glycosylation is an important protein modification, which influences the physical and chemical properties as well as biological function of these proteins. Large-scale population studies have shown that the levels of various plasma protein N-glycans are associated with many multifactorial human diseases. Observed associations between protein glycosylation levels and human diseases have led to the conclusion that N-glycans can be considered a potential source of biomarkers and therapeutic targets. Although biochemical pathways of glycosylation are well studied, the understanding of the mechanisms underlying general and tissue-specific regulation of these biochemical reactions in vivo is limited. This complicates both the interpretation of the observed associations between protein glycosylation levels and human diseases, and the development of glycan-based biomarkers and therapeutics. By the beginning of the 2010s, high-throughput methods of N-glycome profiling had become available, allowing research into the genetic control of N-glycosylation using quantitative genetics methods, including genome-wide association studies (GWAS). Application of these methods has made it possible to find previously unknown regulators of N-glycosylation and expanded the understanding of the role of N-glycans in the control of multifactorial diseases and human complex traits. The present review considers the current knowledge of the genetic control of variability in the levels of N-glycosylation of plasma proteins in human populations. It briefly describes the most popular physical-chemical methods of N-glycome profiling and the databases that contain genes involved in the biosynthesis of N-glycans. It also reviews the results of studies of environmental and genetic factors contributing to the variability of N-glycans as well as the mapping results of the genomic loci of N-glycans by GWAS. The results of functional in vitro and in silico studies are described. The review summarizes the current progress in human glycogenomics and suggests possible directions for further research
ProbABEL package for genome-wide association analysis of imputed data
Background: Over the last few years, genome-wide association (GWA) studies became a tool of choice for the identification of loci associated with complex traits. Currently, imputed single nucleotide polymorphisms (SNP) data are frequently used in GWA analyzes. Correct analysis of imputed data calls for the implementation of specific methods which take genotype imputation uncertainty into account.Results: We developed the ProbABEL software package for the analysis of genome-wide imputed SNP data and quantitative, binary, and time-till-event outcomes under linear, logistic, and Cox proportional hazards models, respectively. For quantitative traits, the package also implements a fast two-step mixed model-based score test for association in samples with differential relationships, facilitating analysis in family-based studies, studies performed in human genetically isolated populations and outbred animal populations.Conclusions: ProbABEL package provides fast efficient way to analyze imputed data in genome-wide context and will facilitate future identification of complex trait loci
Spectral Correlation in Incommensurate Multi-Walled Carbon Nanotubes
We investigate the energy spectra of clean incommensurate double-walled
carbon nanotubes, and find that the overall spectral properties are described
by the so-called critical statistics of Anderson metal-insulator transition. In
the energy spectra, there exist three different regimes characterized by
Wigner-Dyson, Poisson, and semi-Poisson distributions. This feature implies
that the electron transport in incommensurate multi-walled nanotubes can be
either diffusive, ballistic, or intermediate between them, depending on the
position of the Fermi energy.Comment: final version to appear in Phys. Rev. Let
Study of the Baryon-Antibaryon Low-Mass Enhancements in Charmless Three-body Baryonic B Decays
The angular distributions of the baryon-antibaryon low-mass enhancements seen
in the charmless three-body baryonic B decays B+ -> p pbar K+, B0 -> p pbar Ks,
and B0 -> p Lambdabar pi- are reported. A quark fragmentation interpretation is
supported, while the gluonic resonance picture is disfavored. Searches for the
Theta+ and Theta++ pentaquarks in the relevant decay modes and possible
glueball states G with 2.2 GeV/c2 < M-ppbar < 2.4 GeV/c2 in the ppbar systems
give null results. We set upper limits on the products of branching fractions,
B(B0 -> Theta+ p)\times B(Theta+ -> p Ks) Theta++
pbar) \times B(Theta++ -> p K+) G K+) \times
B(G -> p pbar) < 4.1 \times 10^{-7} at the 90% confidence level. The analysis
is based on a 140 fb^{-1} data sample recorded on the Upsilon(4S) resonance
with the Belle detector at the KEKB asymmetric-energy e+e- collider.Comment: 14 pages, 13 figure files, update of hep-ex/0409010 for journal
submisssio
Search for CP violation in tau -> K^0_S pi nu_tau decays at Belle
We report on a search for CP violation in tau -> K^0_S pi nu_tau decays using
a data sample of 699 fb^{-1} collected in the Belle experiment at the KEKB
electron-positron asymmetric-energy collider. The CP asymmetry is measured in
four bins of the invariant mass of the K^0_S pi system and found to be
compatible with zero with a precision of O(10^{-3}) in each mass bin. Limits
for the CP violation parameter Im(eta_S) are given at a 90 % confidence level.
These limits are |Im(eta_S)|<0.026 or better, depending on the parameterization
used to describe the hadronic form factors and improve upon previous limits by
one order of magnitude
Measurement of CP asymmetries in decays
We report measurements of CP violation parameters in
decays based on a data sample of pairs collected
with the Belle detector at the KEKB asymmetric-energy collider. We
use decays for both mixing-induced and direct
violating asymmetry measurements and decays for the
direct CP violation measurement. The CP violation parameters obtained are and
. The
branching fraction of decay is measured to be
. The observed value
differs by 1.9 standard deviations from the value expected from an isospin sum
rule.Comment: 6 pages, 3 figure
Observation of B+ to Lambda Lambdabar K+
We report the first observation of the charmless hyperonic B decay, B^+ -->
Lambda Lambdabar K^+, using a 140 fb^-1 data sample recorded at the Upsilon(4S)
resonance with the Belle detector at the KEKB e^+e^- collider. The measured
branching fraction is B(B^+ --> Lambda Lambdabar K^+) = 2.91 ^{+0.90}_{-0.70}
+/- 0.38 *10^-6 . We also perform a search for the related decay mode B^+ -->
Lambda Lambdabar pi^+, but do not find a significant signal. We set a 90%
confidence-level upper limit of B(B^+ --> Lambda Lambdabar pi^+) < 2.8 * 10^-6.Comment: 9 pages, 3 figures, submitted to Phys. Rev. Let
Observation of the decay B^0->D+D*-
We report the first observation of the decay B^0->D+-D*-+ with the Belle
detector at the KEKB e^+e^- collider operated at the Upsilon(4S) resonance. The
sum of branching fractions B(B^0->D+D*-)+B(B^0->D-D*+) is measured to be
(1.17+-0.26+0.22-0.25)x10^-3 using the full reconstruction method where both
charmed mesons from B^0 decays are reconstructed. A consistent value
((1.48+-0.38+0.28-0.31)x10^-3) is obtained using a partial reconstruction
technique that only uses the slow pion from the D*- ->bar D^0pi- decay and a
fully reconstructed D+ to reconstruct the B^0.Comment: 10 pages, 3 figure
Measurements of time-dependent CP asymmetries in decays using a partial reconstruction technique
We report results on time-dependent CP asymmetries in decays based on a data sample containing 657 {\times}
pairs collected with the Belle detector at the KEKB
asymmetric-energy collider at the resonance. We use a
partial reconstruction technique, wherein signal
events are identified using information only from the fast pion from the B
decay and the slow pion from the subsequent decay of the , where the
former (latter) corresponds to final states. We obtain CP
violation parameters and .Comment: 8 pages, 5 figures, 2 tables, submitted to Physical Review D (RC
Antagonistic genetic correlations for milking traits within the genome of dairy cattle
Genome-wide association studies can be applied to identify useful SNPs associated with complex traits. Furthermore, regional genomic mapping can be used to estimate regional variance and clarify the genomic relationships within and outside regions but has not previously been applied to milk traits in cattle. We applied both single SNP analysis and regional genomic mapping to investigate SNPs or regions associated with milk yield traits in dairy cattle. The de-regressed breeding values of three traits, total yield (kg) of milk (MLK), fat (FAT), and protein (PRT) in 305 days, from 2,590 Holstein sires in Japan were analyzed. All sires were genotyped with 40,646 single-nucleotide polymorphism (SNP) markers. A genome-wide significant region (P < 0.01) common to all three traits was identified by regional genomic mapping on chromosome (BTA) 14. In contrast, single SNP analysis identified significant SNPs only for MLK and FAT (P < 0.01), but not PRT in the same region. Regional genomic mapping revealed an additional significant region (P < 0.01) for FAT on BTA5 that was not identified by single SNP analysis. The additive whole-genomic effects estimated in the regional genomic mapping analysis for the three traits were positively correlated with one another (0.830-0.924). However, the regional genomic effects obtained by using a window size of 20 SNPs for FAT on BTA14 were negatively correlated (P < 0.01) with the regional genomic effect for MLK (-0.940) and PRT (-0.878). The BTA14 regional effect for FAT also showed significant negative correlations (P < 0.01) with the whole genomic effects for MLK (-0.153), FAT (-0.172), and PRT (-0.181). These negative genomic correlations between loci are consistent with the negative linkage disequilibrium expected for traits under directional selection. Such antagonistic correlations may hamper the fixation of the FAT increasing alleles on BTA14. In summary, regional genomic mapping found more regions associated with milk production traits than did single SNP analysis. In addition, the existence of non-zero covariances between regional and whole genomic effects may influence the detection of regional effects, and antagonistic correlations could hamper the fixation of major genes under intensive selection
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