A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health.

A high-resolution comparative radiation hybrid map of equine chromosome 4q12-q22

In this study, we present a comprehensive 5000-rad radiation hybrid map of a 40-cM region on equine chromosome 4 (ECA4) that contains quantitative trait loci for equine osteochondrosis. We mapped 29 gene-associated sequence tagged site markers using primers designed from equine expressed sequence tags or BAC clones in the ECA4q12-q22 region. Three blocks of conserved synteny, showing two chromosomal breakpoints, were identified in the segment of ECA4q12-q22. Markers from other segments of HSA7q mapped to ECA13p and ECA4p, and a region of HSA7p was homologous to ECA13p. Therefore, we have improved the resolution of the human-equine comparative map, which allows the identification of candidate genes underlying traits of interest.

Molecular characterization of the equine collagen, type IX, alpha 2 (COL9A2) gene on horse chromosome 2p16-->p15

The mammalian collagen, type IX, alpha 2 gene (COL9A2) encodes the alpha-2 chain of type IX collagen and is located on horse chromosome 2p16-->p14 harbouring a quantitative trait locus for osteochondrosis. We isolated a bacterial artificial chromosome (BAC) clone containing the equine COL9A2 gene and determined the complete genomic sequence of this gene. Cloning and characterization of equine COL9A2 revealed that the equine gene consists of 32 exons spanning approximately 15 kb. The COL9A2 transcript encodes a single protein of 688 amino acids. Thirty two single nucleotide polymorphisms (SNPs) equally distributed in the gene were detected in a mutation scan of eight unrelated Hanoverian warmblood stallions, including one SNP that affects the amino acid sequence of COL9A2. Comparative analyses between horse, human, mouse and rat indicate that the chromosomal location of equine COL9A2 is in agreement with known chromosomal synteny relationships. The comparison of the gene structure and transcript revealed a high degree of conservation towards the other mammalian COL9A2 genes. We chose three informative SNPs for association and linkage disequilibrium tests in three to five paternal half-sib families of Hanoverian warmblood horses consisting of 44 to 75 genotyped animals. The test statistics did not reach the significance threshold of 5% and so we could not show an association of COL9A2 with equine osteochondrosis.

Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

Novel pseudo-staphylococcal cassette chromosome mec element (ψSCCmec57395) in methicillin-resistant Staphylococcus pseudintermedius CC45

Genetic characterization of methicillin-resistant Staphylococcus pseudintermedius (MRSP) from Thailand and Israel revealed the presence of a predominant atypical clonal lineage which was not typeable by SmaI-PFGE and SCCmec typing. All the atypical isolates (n = 34) belonged to CC45 (30 ST45 and 2 ST179 isolates, 1 ST57 isolate, and 1 ST85 isolate). The isolates originated from healthy and diseased dogs and cats, as well as from the environment of one clinic. Cfr9I-pulsed-field gel electrophoresis (Cfr9I-PFGE) and dru typing permitted the further distinction of CC45 isolates from the two different countries. Microarray analysis identified genes that confer resistance to β-lactams (mecA; blaZ), aminoglycosides [aac(6')-Ie-aph(2')-Ia; aph(3')-III; ant(6)-Ia], macrolides and lincosamides [erm(B)], tetracyclines [tet(M)], trimethoprim [dfr(G)], streptothricin (sat4), and chloramphenicol (catpC221). Fluoroquinolone resistance was attributed to specific amino acid substitutions, i.e., Ser84Leu in GyrA and Ser80Ile and Asp84Asn in GrlA. A novel pseudo-staphylococcal cassette chromosome (ΨSCCmec57395) element was identified in MRSP strain 57395 (sequence type ST45) by whole-genome sequencing. The 12,282-bp ΨSCCmec57395 element contained a class C1 mec gene complex but no ccr genes. In addition to the methicillin resistance gene mecA, ΨSCCmec57395 also carried determinants of resistance to heavy metals, such as arsenic, cadmium, and copper. Bsu36I restriction analysis of the ΨSCCmec57395 element amplified by long-range PCR revealed the presence of ΨSCCmec57395 in the 33 additional isolates of MRSP CC45. The ΨSCCmec57395 element represents a new class of SCCmec and has been identified in MRSP of CC45, which is a predominant clonal lineage in Israel and Thailand.

Measurement of angular correlations in Drell-Yan lepton pairs to probe Z/gamma* boson transverse momentum at sqrt(s)=7 TeV with the ATLAS detector

A measurement of angular correlations in Drell-Yan lepton pairs via the phi(eta)* observable is presented. This variable probes the same physics as the Z/gamma* boson transverse momentum with a better experimental resolution. The Z/gamma* -> e(+)e(-) and Z/gamma* -> mu(+)mu(-) decays produced in proton-proton collisions at a centre-of-mass energy of root s = 7 TeV are used. The data were collected with the ATLAS detector at the LHC and correspond to an integrated luminosity of 4.6 fb(-1). Normalised differential cross sections as a function of phi(eta)* are measured separately for electron and muon decay channels. These channels are then combined for improved accuracy. The cross section is also measured double differentially as a function of phi(eta)* for three independent bins of the Z boson rapidity. The results are compared to QCD calculations and to predictions from different Monte Carlo event generators. The data are reasonably well described, in all measured Z boson rapidity regions, by resummed QCD predictions combined with fixed-order perturbative QCD calculations or by some Monte Carlo event generators. The measurement precision is typically better by one order of magnitude than present theoretical uncertainties.

The novel macrolide-Lincosamide-Streptogramin B resistance gene erm(44) is associated with a prophage in Staphylococcus xylosus.

A novel erythromycin ribosome methylase gene, erm(44), that confers resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics was identified by whole-genome sequencing of the chromosome of Staphylococcus xylosus isolated from bovine mastitis milk. The erm(44) gene is preceded by a regulatory sequence that encodes two leader peptides responsible for the inducible expression of the methylase gene, as demonstrated by cloning in Staphylococcus aureus. The erm(44) gene is located on a 53-kb putative prophage designated ΦJW4341-pro. The 56 predicted open reading frames of ΦJW4341-pro are structurally organized into the five functional modules found in members of the family Siphoviridae. ΦJW4341-pro is site-specifically integrated into the S. xylosus chromosome, where it is flanked by two perfect 19-bp direct repeats, and exhibits the ability to circularize. The presence of erm(44) in three additional S. xylosus strains suggests that this putative prophage has the potential to disseminate MLSB resistance.

A comparative radiation hybrid map of sheep chromosome 10

Comparative radiation hybrid (RH) maps of individual ovine chromosomes are essential to identify genes governing traits of economic importance in sheep, a livestock species for which whole genome sequence data are not yet available. The USUoRH5000 radiation hybrid panel was used to generate a RH map of sheep chromosome 10 (OAR10) with 59 markers that span 1,422 cR over an estimated 92 Mb of the chromosome, thus providing markers every 2 Mb (equivalent to every 24 cR). The markers were derived from 46 BAC end sequences (BESs), a single EST, and 12 microsatellites. Comparative analysis showed that OAR10 shares remarkable conservation of gene order along the entire length of cattle chromosome 12 and that OAR10 contains four major homologous synteny blocks, each related to segments of the homologous human chromosome 13. Extending the comparison to the horse, dog, mouse, and chicken genome showed that these blocks share conserved synteny across species.

Scientific Rationale of a Saturn Probe Mission

We describe the main scientific goals to be addressed by future in situ exploration of Saturn.

The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein.

The hairpin structure at the 3' end of animal histone mRNAs controls histone RNA 3' processing, nucleocytoplasmic transport, translation and stability of histone mRNA. Functionally overlapping, if not identical, proteins binding to the histone RNA hairpin have been identified in nuclear and polysomal extracts. Our own results indicated that these hairpin binding proteins (HBPs) bind their target RNA as monomers and that the resulting ribonucleoprotein complexes are extremely stable. These features prompted us to select for HBP-encoding human cDNAs by RNA-mediated three-hybrid selection in Saccharomyces cerevesiae. Whole cell extract from one selected clone contained a Gal4 fusion protein that interacted with histone hairpin RNA in a sequence- and structure-specific manner similar to a fraction enriched for bovine HBP, indicating that the cDNA encoded HBP. DNA sequence analysis revealed that the coding sequence did not contain any known RNA binding motifs. The HBP gene is composed of eight exons covering 19.5 kb on the short arm of chromosome 4. Translation of the HBP open reading frame in vitro produced a 43 kDa protein with RNA binding specificity identical to murine or bovine HBP. In addition, recombinant HBP expressed in S. cerevisiae was functional in histone pre-mRNA processing, confirming that we have indeed identified the human HBP gene.

The VLT/NaCo large program to probe the occurrence of exoplanets and brown dwarfs at wide orbits II. Survey description, results, and performances

Context. Young, nearby stars are ideal targets for direct imaging searches for giant planets and brown dwarf companions. After the first-imaged planet discoveries, vast efforts have been devoted to the statistical analysis of the occurence and orbital distributions of giant planets and brown dwarf companions at wide (>= 5-6 AU) orbits. Aims. In anticipation of the VLT/SPHERE planet-imager, guaranteed-time programs, we have conducted a preparatory survey of 86 stars between 2009 and 2013 to identify new faint comoving companions to ultimately analyze the occurence of giant planets and brown dwarf companions at wide (10-2000 AU) orbits around young, solar-type stars. Methods. We used NaCo at VLT to explore the occurrence rate of giant planets and brown dwarfs between typically 0.1 and 8 ''. Diffraction-limited observations in H-band combined with angular differential imaging enabled us to reach primary star-companion brightness ratios as small as 10(-6) at 1.5 ''. Repeated observations at several epochs enabled us to discriminate comoving companions from background objects. Results. During our survey, twelve systems were resolved as new binaries, including the discovery of a new white dwarf companion to the star HD8049. Around 34 stars, at least one companion candidate was detected in the observed field of view. More than 400 faint sources were detected; 90% of them were in four crowded fields. With the exception of HD8049 B, we did not identify any new comoving companions. The survey also led to spatially resolved images of the thin debris disk around HD61005 that have been published earlier. Finally, considering the survey detection limits, we derive a preliminary upper limit on the frequency of giant planets for the semi-major axes of [10, 2000] AU: typically less than 15% between 100 and 500 AU and less than 10% between 50 and 500 AU for exoplanets that are more massive than 5 M-Jup and 10 M-Jup respectively, if we consider a uniform input distribution and a confidence level of 95%. Conclusions. The results from this survey agree with earlier programs emphasizing that massive, gas giant companions on wide orbits around solar-type stars are rare. These results will be part of a broader analysis of a total of similar to 210 young, solar-type stars to bring further statistical constraints for theoretical models of planetary formation and evolution.