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.

Genome Annotation Resource Fields—GARFIELD: A Genome Browser for Felis catus

Abstract: Annotation features from the 1.9-fold whole-genome shotgun (WGS) sequences of domestic cat have been organized into an interactive web application, Genome Annotation Resource Fields (GARFIELD) (http://lgd.abcc.ncifcrf.gov) at the Laboratory of Genomic Diversity and Advanced Biomedical Computing Center (ABCC) at The National Cancer Institute (NCI). The GARFIELD browser allows the user to view annotations on a per chromosome basis with unplaced contigs provided on placeholder chromosomes. Various tracks on the browser allow display of annotations. A Genes track on the browser includes 20 285 regions that align to genes annotated in other mammalian genomes: Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris. Also available are tracks that display the contigs that make up the chromosomes and representations of their GC content and repetitive elements as detected using the RepeatMasker (http://www.repeatmasker.org). Data from the browser can be downloaded in FASTA and GFF format, and users can upload their own data to the display. The Felis catus sequences and their chromosome assignments and additional annotations incorporate data analyzed and produced by a multicenter collaboration between NCI, ABCC, Agencourt Biosciences Corporation, Broad Institute of Harvard and Massachusetts Institute of Technology, National Human Genome Research Institute, National Center for Biotechnology and Information, and Texas A&M.

Developmental changes in pituitary–gonadal function in free-ranging lions (Panthera leo leo) of the Serengeti Plains and Ngorongoro Crater

Abstract: activity. In contrast, there were no age-related differences in ejaculate characteristics of Ngorongoro Crater lions. Seminal quality in the Crater population was poor in adult and young adult animals and was unrelated to alterations in pituitary or testicular function. In summary, only seminal quality in adult male lions was affected by location, whereas age significantly affected both basal and GnRH-stimulated testosterone secretion and seminal quality (Serengeti Plains only) in sexually mature males. The striking seminal/ endocrine differences among pride (breeding) males of different ages raises questions about the impact of age on individual reproductive performance in this species.

DNA recombination and natural selection pressure sustain genetic sequence diversity of the feline MHC class I genes.

Abstract: Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. These include: (a) a gradual accumulation of spontaneous mutational substitution over evolutionary time; (b) selection against mutational divergence in regions of the class I molecule involved in T cell receptor interaction and also in certain regions that interact with common features of antigens; (c) positive selection pressure in favor of persistence of polymorphism and heterozygosity at 57 nucleotide residues that comprise the antigen recognition site; and (d) periodic intragenic (interallelic) and intergenic recombination within the class I genes. We describe a highly conserved 23-bp nucleotide sequence within the coding region of the first alpha-helix that separates two relatively polymorphic segments located in the alpha 1 domain that may act as a template or "hot spot" for homologous recombination between class I alleles.

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.