A Novel Splicing Mutation Alters DSPP Transcription and Leads to Dentinogenesis Imperfecta Type II

Dentinogenesis imperfecta (DGI) type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP) gene were revealed to be the causation of DGI type II (DGI-II). In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C) lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes

Disease-Associated Mutations That Alter the RNA Structural Ensemble

Genome-wide association studies (GWAS) often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs) from the Human Gene Mutation Database (HGMD) that map to the untranslated regions (UTRs) of a gene. Rather than using minimum free energy approaches (e.g. mFold), we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, β-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD), and Hypertension), we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5′ UTRs of FTL and RB1) SNP–induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a “RiboSNitch,” that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble

Search for heavy bottom-like quarks decaying to an electron or muon and jets in ppˉp\bar{p} collisions at s=1.96\sqrt{s}=1.96 TeV

We report the most sensitive direct search for pair production of fourth-generation bottom-like chiral quarks ($b'$) each decaying promptly to $tW$. We search for an excess of events with an electron or muon, at least five jets (one indentified as due to a $b$ or $c$ quark) and an imbalance of transverse momentum using data from $p\bar{p}$ collisions collected by the CDF II detector at Fermilab with an integrated luminosity of 4.8 fb$^{-1}$. We observe events consistent with background expectation and calculate upper limits on the $b'$ pair production cross section ($\sigma_{b\bar{b'}}\lesssim 30$ fb for $m_{b'}>$375 GeV/$c^2$) and exclude $m_{b'}<372$ \gevcc at 95% confidence level.Comment: For submission to PR

First Measurement of the Angular Coefficients of Drell-Yan e(+)e(-) Pairs in the Z Mass Region from p(p)over-bar Collisions at root s=1.96 TeV

We report on the first measurement of the angular distributions of final state electrons in p (p) over bar -> gamma*/Z -> e(+)e(-) + X events produced in the Z boson mass region at root s = 1.96 TeV. The data sample collected by the CDF II detector for this result corresponds to 2.1 fb(-1) of integrated luminosity. The angular distributions are studied as a function of the transverse momentum of the electron-positron pair and show good agreement with the Lam-Tung relation, consistent with a spin-1 description of the gluon, and demonstrate that, at high values of the transverse momentum, Z bosons are produced via quark-antiquark annihilation and quark-gluon Compton processes

Search for a Very Light CP-Odd Higgs Boson in Top Quark Decays from p(p)over-bar Collisions at root s=1.96 TeV

We present the results of a search for a very light CP-odd Higgs boson a(1)(0) originating from top quark decays t -> H(+/-)b -> W-+/-(*) a(1)(0)b, and subsequently decaying into tau(+)tau(-). Using a data sample corresponding to an integrated luminosity of 2.7 fb(-1) collected by the CDF II detector in p (p) over bar collisions at 1.96 TeV, we perform a search for events containing a lepton, three or more jets, and an additional isolated track with transverse momentum in the range 3 to 20 GeV/c. Observed events are consistent with background sources, and 95% C.L. limits are set on the branching ratio of t -> H(+/-)b for various masses of H-+/- and a(1)(0)

First Search for Multijet Resonances in root s=1.96 TeV p(p)over-bar Collisions

We present the first model independent search for three-jet hadronic resonances within multijet events in root s = 1.96 TeV p (p) over bar collisions at the Fermilab Tevatron using the CDF II detector. Pair production of supersymmetric gluinos and squarks with hadronic R-parity violating decays is employed as an example of a new physics benchmark for this signature. Selection criteria based on the kinematic properties of an ensemble of jet combinations within each event help to extract signal from copious QCD background. No significant excess outside the top quark mass window is observed in data with an integrated luminosity of 3.2 fb(-1). We place 95% confidence level limits on the production cross section sigma(p (p) over bar -> XX') X BR((g) over tilde(g) over tilde -> 3 jet + 3 jet) where X, X' = (g) over tilde, (q) over tilde, or (sic), with (q) over tilde, (sic) -> (g) over tilde + jet, as a function of gluino mass, in the range of 77 GeV/c(2) to 240 GeV/c(2)