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.

Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily.

Abstract: Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8, suggested gene symbol IL8) is a cytokine that chemoattracts and activates neutrophils. Using a panel of human-rodent cell hybrids that preferentially segregate human chromosomes and in situ hybridization, the MDNCF/IL-8 gene was placed on the human gene map at position 4q12-q21. This is the same location where at least three other members (platelet factor 4, melanoma growth stimulatory activity, and interferon-γ induced factor) of the platelet factor 4 gene superfamily reside. In addition, a restriction fragment length polymorphism was identified using MDNCF as a probe in screening genomic DNA digested with HindIII from unrelated individuals.

Phylogeographic Subspecies Recognition in Leopards (Panthera pardus): Molecular Genetic Variation

Abstract: The incorporation of precise definitions for taxonomic units into wildlife legislation has necessitated the reevaluation of the taxonomy of endangered and threatened species. We used the subspecies recognition criteria proposed by Avise and Ball (1990) and O’Brien and Mayr (1991) to examine the infraspecific taxonomy of the leopard, Panthera pardus, a geographically widespread species with 27 currently recognized trinomial designations. Samples from named subspecies revealed appreciable genetic diversity using three molecular methods: allozymes, mitochondrial DNA restriction sites, and feline-specific minisatellites. Continental populations and subspecies from Africa and Asia possessed the highest amount of molecular genetic variation, whereas relatively lower amounts of diversity were present in island populations. Molecular data were analyzed using three phylogenetic methods (distance-matrix, maximum parsimony, and maximum likelihood) to resolve genetic differentiation below the species level The combined results revealed phylogenetic distinction of six geographically isolated groups of leopards: (1) African, (2) central Asian, (3) Indian, (4) Sri Lankan, (5) Javan, and (6) east Asian. Based on the combined molecular analyses and supporting morphological data (Miththapala 1992), u,e recommend that subspecific leopard taxonomy be revised to comprise eight subspecies: (1) P. p. pardus, Africa; (2) P. p. saxicolor, central Asia; (3) P. p. fusca, Indian subcontinent; (4) P. p. kotiya, Sri Lanka; (5) P. p. melas, Java; (6) P. p. orientalis, Amur; (7) P. p. japonensis, northern China; and (8) P. p. delacouri, southern China. In most cases, designated subspecies conform to historic geological barriers that would have facilitated allopatric genetic divergence. La incorporacion de definiciones precisas para unidades taxonomicas en legislacion de la vida silvestre ha necesitado de la re-evaluacion de la taxonomia de especies amenazadas y en peligo de extincion. Utilizamos los criterios de reconocimiento de subespecies propuestos por Avise y Ball (1990) y O’Brien y Mayr (1991) para examinar la taxonomia intraespecifica del leopardo Panthera pardus, una especie ampliamente dispersa con 27 designaciones trinomiales reconocidas. Muestras de supuestas subespecies revelaron una diversidad genetica apreciable, usando tres metodos moleculares: Alozimas, sitios de restriccion en ADN mitocondrial y minisatelites felino-especificos: Poblaciones continentales y subespecies de Africa y Asia poseen la mas alta cantidad de variacion genetica molecular, mientras que en poblaciones insulares estuvieron presentes cantidades relativamente bajas de diversidad. Los datos moleculares fueron analizados utilizando tres metodos filogeneticos (Matriz de distancia, maxima parsimonia y maxima proximidad) para resolver diferenciaciones geneticas por debajo del nivel de especie. Los resultados combinados revelaron la distincion filo-genetica de seis grupos de leopardos geograficamente aislados: 1) Africano, 2) Centro asiatico, 3) Hindu, 4) Sri Lankano, 5) Javano y, 6) Este asiatico. Basados en el analisis molecular combinado y soportados en datos morfologicos (Miththapala, 1992), recomendamos la revision taxonomica a nivel de subespecie que comprende ocho subespecies: 1) P. p. pardus, Africa; 2) P. p. saxicolor, Asia central; 3) P. p. fusca, subcontinente Hindu; 4) P. p. kotiya, Sri Lanka; 5) P. p. melas, Java; 6) P. p. orientalis, Amur; 7) P. p. japonensis, norte Chino; 8) P. p. delacouri, sur Chino. En la mayoria de los casos las subespecies designadas estan conformadas por barreras geologicas historicas que pudieron haber facilitado divergencia genetica alopatrica.

Specifying and Sustaining Pigmentation Patterns in Domestic and Wild Cats

Abstract: Color markings among felid species display both a remarkable diversity and a common underlying periodicity. A similar range of patterns in domestic cats suggests a conserved mechanism whose appearance can be altered by selection. We identified the gene responsible for tabby pattern variation in domestic cats as Transmembrane aminopeptidase Q (Taqpep), which encodes a membrane-bound metalloprotease. Analyzing 31 other felid species, we identified Taqpep as the cause of the rare king cheetah phenotype, in which spots coalesce into blotches and stripes. Histologic, genomic expression, and transgenic mouse studies indicate that paracrine expression of Endothelin3 (Edn3) coordinates localized color differences. We propose a two-stage model in which Taqpep helps to establish a periodic pre-pattern during skin development that is later implemented by differential expression of Edn3.

The Adequacy of Morphology for Reconstructing the Early History of Placental Mammals

Abstract: Systematic Biology Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t713658732 The Adequacy of Morphology for Reconstructing the Early History of Placental Mammals Mark S. Springer a; Angela Burk-Herrick a; Robert Meredith a; Eduardo Eizirik b; Emma Teeling c; Stephen J. O'Brien d; William J. Murphy e a Department of Biology, University of California, Riverside, Riverside, CA, USA b Faculdade de Biociencias, PUCRS, Porto Allegre, RS, Brazil c School of Biological and Environmental Sciences, University College Dublin Belfield, Dublin, Ireland d Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD, USA e Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA

Patterns of Genetic Diversity in Remaining Giant Panda Populations

Abstract: The giant panda ( Ailuropoda melanoleuca ) is among the more familiar symbols of species conser- vation. The protection of giant panda populations has been aided recently by the establishment of more and better-managed reserves in existing panda habitat located in six mountain ranges in western China. These re- maining populations are becoming increasingly isolated from one another, however, leading to the concern that historic patterns of gene flow will be disrupted and that reduced population sizes will lead to diminished genetic variability. We analyzed four categories of molecular genetic markers (mtDNA restriction-fragment- length polymorphisms (RFLP), mtDNA control region sequences, nuclear multilocus DNA fingerprints, and mi- crosatellite size variation) in giant pandas from three mountain populations (Qionglai, Minshan, and Qin- ling) to assess current levels of genetic diversity and to detect evidence of historic population subdivisions. The three populations had moderate levels of genetic diversity compared with similarly studied carnivores for all four gene measures, with a slight but consistent reduction in variability apparent in the smaller Qinling population. That population also showed significant differentiation consistent with its isolation since historic times. From a strictly genetic perspective, the giant panda species and the three populations look promising insofar as they have retained a large amount of genetic diversity in each population, although evidence of re- cent population reduction—likely from habitat loss—is apparent. Ecological management to increase habi- tat, population expansion, and gene flow would seem an effective strategy to stabilize the decline of this en- dangered species.

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.