Stephen J. O'Brien

Bio: Stephen J. O'Brien is an academic researcher from Saint Petersburg State University of Information Technologies, Mechanics and Optics. The author has contributed to research in topics: Population & Gene. The author has an hindex of 153, co-authored 1062 publications receiving 93025 citations. Previous affiliations of Stephen J. O'Brien include University College Cork & QIMR Berghofer Medical Research Institute.

Peroneal tendon subluxation in a case of anomalous peroneus brevis muscle

Abstract: We report a case of peroneal tendon subluxation as a result of an anomalous extension of the peroneus brevis muscle into the fibular groove, causing an encroachment phenomenon, stretching-out of the superior peroneal retinaculum, longitudinal splitting of the peroneus brevis tendon, subluxation of the peroneal tendons, and peroneal tenosynovitis. We describe a simple surgical technique for tendon stabilization, after decompression of the fibular groove.

Conservation Genetics of the Koala (Phascolarctos cinereus) : Low Mitochondrial DNA Variation Amongst Southern Australian Populations

Abstract: Summary Koala (Phascolarctos cinereus) populations in southern Australia have a history of bottlenecks ‐ earlier this century the species became extinct in South Australia, and almost so in Victoria. Subsequently large numbers of animals from island populations (founded from very few animals) have been translocated back to mainland sites and to other islands in the region. As part of a larger study of the genetic structure of koala populations in southern Australia, we have undertaken a survey of mitochondrial DNA restriction fragment length polymorphism (mtDNARFLP) variability. Genomic DNA from 91 koalas from five populations was examined using 23 restriction enzymes, and mtDNA fragments were detected using a domestic cat full-length mtDNA clone. Only one of the enzymes, TaqI, revealed polymorphism ‐ a relatively low amount of variation compared with other mammals, although low mtDNA-RFLP variation has also been reported in Queensland koalas. French Island and populations established predominantly from French Island immigrant koalas, either directly or via other island populations, were indistinguishable by haplotype frequencies. The mtDNA data are thus consistent with the interpretation that the koala translocation programme has homogenized gene frequencies amongst those populations involved. South Gippsland is not recorded as having received translocated koalas directly, and has significantly dierent mtDNA-RFLP haplotype frequencies from all other populations examined. The fact that this distinction was not previously observed in nuclear gene frequencies may reflect predominantly male-mediated dispersal in koalas.

Annotated features of domestic cat - Felis catus genome.

Abstract: Domestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors. Here we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), bisulfite sequencing of Boris, a male cat from St. Petersburg (Russia), and light 30× sequencing of Sylvester, a European wildcat progenitor of cat domestication. The annotation includes 21,865 protein-coding genes identified by a comparative approach, 217 loci of endogenous retrovirus-like elements, repetitive elements which comprise about 55.7% of the whole genome, 99,494 new SNVs, 8,355 new indels, 743,326 evolutionary constrained elements, and 3,182 microRNA homologues. The methylation sites study shows that 10.5% of cat genome cytosines are methylated. An assisted assembly of a European wildcat, Felis silvestris silvestris, was performed; variants between F. silvestris and F. catus genomes were derived and compared to F. catus. The presented genome annotation extends beyond earlier ones by closing gaps of sequence that were unavoidable with previous low-coverage shotgun genome sequencing. The assembly and its annotation offer an important resource for connecting the rich veterinary and natural history of cats to genome discovery.

The feline major histocompatibility complex is rearranged by an inversion with a breakpoint in the distal class I region.

Abstract: In order to determine the genomic organization of the major histocompatibility complex (MHC) of the domestic cat (Felis catus), DNA probes for 61 markers were designed from human MHC reference sequences and used to construct feline MHC BAC contig map spanning ARE1 in the class II region to the olfactory receptor complex in the extended class I region. Selected BAC clones were then used to identify feline-specific probes for the three regions of the mammalian MHC (class II–class III–class I) for radiation hybrid mapping and fluorescent in situ hybridization to refine the organization of the domestic cat MHC. The results not only confirmed that the p-arm of domestic cat B2 is inverted relative to human Chromosome 6, but also demonstrated that one inversion breakpoint localized to the distal segment of the MHC class I between TRIM39 and TRIM26. The inversion thus disjoined the ~2.85 Mb of MHC containing class II–class III–class I (proximal region) from the ~0.50 Mb of MHC class I/extended class I region, such that TRIM39 is adjacent to the Chromosome B2 centromere and TRIM26 is adjacent to the B2 telomere in the domestic cat.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.