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.

A Common HLA–DPA1 Variant is a Major Determinant of Hepatitis B Virus Clearance in Han Chinese

Abstract: A recent genome-wide study showed that the single nucleotide polymorphisms (SNPs) in the HLA-DP region were associated with chronic hepatitis B virus (HBV) infection in Japanese and Thai persons. We tested the effects of HLA-DP SNPs for all major HBV outcomes in Han Chinese (n = 1742): HBV resistance, clearance, chronic infection, cirrhosis, and hepatocellular carcinoma. HLA - DPA1 rs3077 T was strongly associated with decreased risk of chronic HBV infection (odds ratio, .62; P = .001), consistent with the previous report. We showed for the first time to our knowledge that it is a predictor for HBV clearance (odds ratio, 2.41; P < .001). However, rs3077 was not associated with the development of cirrhosis or hepatocellular carcinoma.

T-Lymphocyte Profiles in FIV-Infected Wild Lions and Pumas Reveal CD4 Depletion

Abstract: Feline immunodeficiency virus (FIV) is a lentivirus related to human immunodeficiency virus (HIV) that causes feline AIDS in the domestic cat (Felis catus). Serological surveys indicate that at least 25 other species of cat possess antibodies that cross-react with domestic cat FIV. Most infected nondomestic cat species are without major symptoms of disease. Long-term studies of FIV genome variation and pathogenesis reveal patterns consistent with coadaptation of virus and host in free-ranging FIV-Ple–infected African lions (Panthera leo) and FIV-Pco–infected pumas (Puma concolor) populations. This report examined correlates of immunodeficiency in wild and captive lions and pumas by quantifying CD5+, CD4+, and CD8+ T-cell subsets. Free-ranging FIV-Ple–infected lions had immunofluorescence flow cytometry (IFC) profiles marked by a dramatic decline in CD4+ subsets, a reduction of the CD4+/CD8+ ratio, reduction of CD8+ β high cells, and expansion of the CD8+ β low subset relative to uninfected lions. An overa...

Nature and origin of polymorphism in feline MHC class II DRA and DRB genes.

Abstract: Transcripts of the MHC class II DRA and DRB gene homologues of the domestic cat (Felis catus) were cloned and sequenced to compare the pattern and process of DR gene divergence. Homologous DRB exon 2 sequences from 36 feral domestic cats throughout the world plus from three species of Felidae (tiger cat, Iriomote cat, and Geoffroy's cat) were also determined. Limited variation in the domestic cat Feca-DRA gene was observed, but abundant variation in the Feca-DRB gene was seen comprising 61 distinct DRB alleles. Phylogenetic analyses resolved at least five monophyletic feline DRB allelic lineages (DRB*1 to *5), which are clearly distinct from those of human (HLA-DRB1 to 9 lineages), mouse (H-2Ebeta b, u, f), and dog DRB alleles. Approximately 80% of individual cats contained three to six distinct DRB sequences, indicating that feline MHC maintains two to three DRB loci. Five cats had three DRB sequences in a single allelic lineage, indicating the occurrence of recent gene duplication of feline DRB genes. DRB sequences isolated from three exotic cats demonstrated close association with a particular domestic cat DRB lineage, suggesting that these allelic lineages are derived from common ancestral alleles that existed prior to the divergence of these feline species about 10 to 15 million years ago. Patterns of synonymous and nonsynonymous nucleotide substitution rates that occurred in Ag recognition sites (ARS) and nonrecognition (NAR) sites demonstrated a strong role of natural selection--positive selection for Ag recognition sites and negative selection for nonrecognition sites of feline DRB sequences--in the process of evolution of DR molecules.

Distribution of Two HIV-1–Resistant Polymorphisms (SDF1-3′A and CCR2-64I) in East Asian and World Populations and Its Implication in AIDS Epidemiology

Abstract: Summary Chemokine receptor CCR2 and stromal-derived factor (SDF-1) are involved in HIV infection and AIDS symptom onset. Recent cohort studies showed that point mutations in these two genes, CCR2-64I and SDF1-3′A, can delay AIDS onset ⩾16 years after seroconversions. The protective effect of CCR2-64I is dominant, whereas that of SDF1-3′A is recessive. SDF1-3′A homozygotes also showed possible protection against HIV-1 infection. In this study, we surveyed the frequency distributions of the two alleles at both loci in world populations, with emphasis on those in east Asia. The CCR2-64I frequencies do not vary significantly in the different continents, having a range of 0.1–0.2 in most populations. A decreasing cline of the CCR2-64I frequency from north to south was observed in east Asia. In contrast, the distribution of SDF1-3′A in world populations varies substantially, and the highest frequency was observed in Oceanian populations. Moreover, an increasing cline of the SDF1-3′A frequency from north to south was observed in east Asia. The relative hazard values were computed to evaluate the risk of AIDS onset on the basis of two-locus genotypes in the east Asian and world populations.

The evolution of cats. Genomic paw prints in the DNA of the world's wild cats have clarified the cat family tree and uncovered several remarkable migrations in their past.

Abstract: Ju ly 20 07 Elegant and enigmatic, cats tantalize not only those of us who share our sofas with the smaller versions but scientists who have tried to puzzle out the origin and evolution of their larger cousins. Where did the modern cat family evolve? Why and when did they leave their homes and migrate across continents? How many species actually exist, and which ones are closely related? Experts generally agree that there are 37 species in the family Felidae, but they have offered dozens of classification schemes, ordering cat species in as few as two to as many as 23 genera. Who could argue? Under the skin, one cat species appears pretty similar to another. They look like big cats, midsize cats and small cats. Distinguishing a lion’s skull from a tiger’s can be a challenge even for an expert, and genetic investigations that we have tried over the past two decades have failed to sort the cats into definitive groupings. In recent years, however, a revolution in sequencing the genomes of various creatures, spearheaded by the Human Genome Project and by powerful technologies to probe DNA, has provided some extremely valuable new tools for inquiry. Drawing on Genomic paw prints in the DNA of the world’s wild cats have clarified the cat family tree and uncovered several remarkable migrations in their past

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.