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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.


Papers
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Journal ArticleDOI
27 Sep 1996-Science
TL;DR: The CKR5Δ32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.
Abstract: The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4 + T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele ( CKR5Δ32 ) was identified that is present at a frequency of ∼0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Δ32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

2,586 citations

Journal ArticleDOI
Erich D. Jarvis1, Siavash Mirarab2, Andre J. Aberer3, Bo Li4, Bo Li5, Bo Li6, Peter Houde7, Cai Li5, Cai Li6, Simon Y. W. Ho8, Brant C. Faircloth9, Benoit Nabholz, Jason T. Howard1, Alexander Suh10, Claudia C. Weber10, Rute R. da Fonseca11, Jianwen Li, Fang Zhang Zhang, Hui Li, Long Zhou, Nitish Narula7, Nitish Narula12, Liang Liu13, Ganesh Ganapathy1, Bastien Boussau, Shamsuzzoha Bayzid2, Volodymyr Zavidovych1, Sankar Subramanian14, Toni Gabaldón15, Salvador Capella-Gutierrez, Jaime Huerta-Cepas, Bhanu Rekepalli16, Bhanu Rekepalli17, Kasper Munch18, Mikkel H. Schierup18, Bent E. K. Lindow11, Wesley C. Warren19, David A. Ray, Richard E. Green20, Michael William Bruford21, Xiangjiang Zhan21, Xiangjiang Zhan22, Andrew Dixon, Shengbin Li4, Ning Li23, Yinhua Huang23, Elizabeth P. Derryberry24, Elizabeth P. Derryberry25, Mads F. Bertelsen26, Frederick H. Sheldon24, Robb T. Brumfield24, Claudio V. Mello27, Claudio V. Mello28, Peter V. Lovell27, Morgan Wirthlin27, Maria Paula Cruz Schneider28, Francisco Prosdocimi28, José Alfredo Samaniego11, Amhed Missael Vargas Velazquez11, Alonzo Alfaro-Núñez11, Paula F. Campos11, Bent O. Petersen29, Thomas Sicheritz-Pontén29, An Pas, Thomas L. Bailey, R. Paul Scofield30, Michael Bunce31, David M. Lambert14, Qi Zhou, Polina L. Perelman32, Amy C. Driskell33, Beth Shapiro20, Zijun Xiong, Yongli Zeng, Shiping Liu, Zhenyu Li, Binghang Liu, Kui Wu, Jin Xiao, Xiong Yinqi, Quiemei Zheng, Yong Zhang, Huanming Yang, Jian Wang, Linnéa Smeds10, Frank E. Rheindt34, Michael J. Braun35, Jon Fjeldså11, Ludovic Orlando11, F. Keith Barker6, Knud A. Jønsson6, Warren E. Johnson33, Klaus-Peter Koepfli33, Stephen J. O'Brien36, David Haussler, Oliver A. Ryder, Carsten Rahbek6, Eske Willerslev11, Gary R. Graves33, Gary R. Graves6, Travis C. Glenn13, John E. McCormack37, Dave Burt38, Hans Ellegren10, Per Alström, Scott V. Edwards39, Alexandros Stamatakis3, David P. Mindell40, Joel Cracraft6, Edward L. Braun41, Tandy Warnow2, Tandy Warnow42, Wang Jun, M. Thomas P. Gilbert31, M. Thomas P. Gilbert6, Guojie Zhang5, Guojie Zhang11 
12 Dec 2014-Science
TL;DR: A genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves recovered a highly resolved tree that confirms previously controversial sister or close relationships and identifies the first divergence in Neoaves, two groups the authors named Passerea and Columbea.
Abstract: To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.

1,624 citations

Journal ArticleDOI
01 Feb 2001-Nature
TL;DR: The potential weaknesses of limited character and taxon sampling are addressed in a comprehensive molecular phylogenetic analysis of 64 species sampled across all extant orders of placental mammals, providing new insight into the pattern of the early placental mammal radiation.
Abstract: The precise hierarchy of ancient divergence events that led to the present assemblage of modern placental mammals has been an area of controversy among morphologists, palaeontologists and molecular evolutionists. Here we address the potential weaknesses of limited character and taxon sampling in a comprehensive molecular phylogenetic analysis of 64 species sampled across all extant orders of placental mammals. We examined sequence variation in 18 homologous gene segments (including nearly 10,000 base pairs) that were selected for maximal phylogenetic informativeness in resolving the hierarchy of early mammalian divergence. Phylogenetic analyses identify four primary superordinal clades: (I) Afrotheria (elephants, manatees, hyraxes, tenrecs, aardvark and elephant shrews); (II) Xenarthra (sloths, anteaters and armadillos); (III) Glires (rodents and lagomorphs), as a sister taxon to primates, flying lemurs and tree shrews; and (IV) the remaining orders of placental mammals (cetaceans, artiodactyls, perissodactyls, carnivores, pangolins, bats and core insectivores). Our results provide new insight into the pattern of the early placental mammal radiation.

1,345 citations

Journal ArticleDOI
12 Mar 1999-Science
TL;DR: The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.
Abstract: A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.

1,274 citations

Journal ArticleDOI
14 Dec 2001-Science
TL;DR: Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana), and placental phylogeny is investigated using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set.
Abstract: Molecular phylogenetic studies have resolved placental mammals into four major groups, but have not established the full hierarchy of interordinal relationships, including the position of the root. The latter is critical for understanding the early biogeographic history of placentals. We investigated placental phylogeny using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set. Interordinal relationships are almost entirely resolved. The basal split is between Afrotheria and other placentals, at about 103 million years, and may be accounted for by the separation of South America and Africa in the Cretaceous. Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana).

1,239 citations


Cited by
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Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
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.

22,269 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。

18,940 citations

Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal ArticleDOI
Paul Burton1, David Clayton2, Lon R. Cardon, Nicholas John Craddock3  +192 moreInstitutions (4)
07 Jun 2007-Nature
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; 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 theBritish population is generally modest.
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.

9,244 citations