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

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

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

Study of B -> \rho \pi decays at Belle

This paper describes a study of B meson decays to the pseudoscalar-vector final state \rho\pi using 31.9\times 10^6 B\bar{B} events collected with the Belle detector at KEKB. The branching fractions B(B^+ \to \rho^0\pi^+) = (8.0^{+2.3+0.7}_{-2.0-0.7}) \times 10^{-6} and B(B^0 -> \rho^{+-} \pi^{-+}) = (20.8^{+6.0+2.8}_{-6.3-3.1}) \times 10^{-6} are obtained. In addition, a 90% confidence level upper limit of B(B^0 \to \rho^0\pi^0) < 5.3 \times 10^{-6}is reported.Comment: 14 pages, 3 figures, to be submitted to Phys. Lett.

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

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

Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome–Related Traits

OBJECTIVE - Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome-related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS - We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS - Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS - The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR

Measurement of CP asymmetries in B0→K0π0B^0 \to K^0\pi^0 decays

We report measurements of CP violation parameters in $B^0 \to K^0 \pi^0$ decays based on a data sample of $657 \times 10^6 B\bar{B}$ pairs collected with the Belle detector at the KEKB $e^+ e^-$ asymmetric-energy collider. We use $B^0 \to K^0_S \pi^0$ decays for both mixing-induced and direct $CP$ violating asymmetry measurements and $B^0 \to K^0_L \pi^0$ decays for the direct CP violation measurement. The CP violation parameters obtained are $\sin 2 \phi_1^{\rm eff} = +0.67 \pm 0.31{(stat)} \pm 0.08 {(syst)}$ and $\mathcal{A}_{K^0 \pi^0} = +0.14 \pm 0.13{(stat)} \pm 0.06 {(syst)}$. The branching fraction of $B^0 \to K^0 \pi^0$ decay is measured to be $\mathcal{B}(B^0 \to K^0 \pi^0) = (8.7\pm0.5 (\rm{stat.})\pm0.6 (\rm{syst.}))\times 10^{-6}$. The observed $\mathcal{A}_{K^0 \pi^0}$ value differs by 1.9 standard deviations from the value expected from an isospin sum rule.Comment: 6 pages, 3 figure

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

Search for Lepton Flavor and Lepton Number Violating tau Decays into a Lepton and Two Charged Mesons

We search for lepton flavor and lepton number violating tau decays into a lepton (ell = electron or muon) and two charged mesons (h,h' = pi^\pm or K^\pm), tau- -> ell-h+h'- and tau- -> ell+h-h'-, using 671 fb^{-1} of data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We obtain 90% C.L. upper limits on the branching fractions in the range (4.4-8.8)x10^{-8} for tau -> ehh', and (3.3-16)x10^{-8} for tau -> muhh' processes. These results improve upon previously published upper limits by factors between 1.6 to 8.8.Comment: 15 page, 7 figures, submitted to Phys. Lett.