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.

Genetic mapping in mammals: chromosome map of domestic cat

Abstract: A genetic map of 31 biochemical loci located on 17 feline syntenic (linkage) groups has been derived by somatic cell genetic analysis of cat-rodent hybrids. Most of these syntenic groups have been assigned to one of the 19 feline chromosomes. Comparative linkage analysis of the feline biochemical loci and homologous human loci revealed considerable conservation of linkage associations between the primates and the Felidae (order Carnivora). Many of these same linkage groups have not been conserved in the murine genome. The genetic and evolutionary implications of comparative mapping analysis among mammalian species are discussed.

Patterns of molecular genetic variation among African elephant populations.

Abstract: The highly threatened African elephants have recently been subdivided into two species, Loxodonta africana (savannah or bush elephant) and L. cyclotis (forest elephant) based on morphological and molecular studies. A molecular genetic assessment of 16 microsatellite loci across 20 populations (189 individuals) affirms species level genetic differentiation and provides robust genotypic assessment of species affiliation. Savannah elephant populations show modest levels of phylogeographic subdivision based on composite microsatellite genotype, an indication of recent population isolation and restricted gene flow between locales. The savannah elephants show significantly lower genetic diversity than forest elephants, probably reflecting a founder effect in the recent history of the savannah species.

Traumatic posterior hip subluxation in American football.

Abstract: Background: Traumatic posterior hip subluxation is a potentially devastating injury that is often misdiagnosed as a simple hip sprain or strain. The purpose of the present study was to outline the injury mechanism, pathoanatomy, clinical and radiographic findings, and treatment of traumatic hip subluxation in an athletic population. Methods: Over a nine-year period, eight participants in American football who had sustained a traumatic posterior hip subluxation were evaluated and treated. The injury mechanism, clinical findings, and radiographic findings were reviewed. The mean duration of follow-up was thirty-four months. Results: The most common mechanism of injury was a fall on a flexed, adducted hip. Physical examination revealed painful limitation of hip motion. Initial radiographs demonstrated a characteristic posterior acetabular lip fracture. Initial magnetic resonance images revealed disruption of the iliofemoral ligament, hemarthrosis, and a viable femoral head. Two players were treated acutely with hip aspiration, and all eight players were treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Six players recovered and returned to the previous level of competition. Two players had development of severe osteonecrosis and ultimately required total hip arthroplasty. Conclusion: The pathognomonic radiographic and magnetic resonance imaging triad of posterior acetabular lip fracture, iliofemoral ligament disruption, and hemarthrosis defines traumatic posterior hip subluxation. Patients in whom large hemarthroses are diagnosed on magnetic resonance images should undergo acute aspiration, and all players should be treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Patients who have no sign of osteonecrosis on magnetic resonance imaging at six weeks can safely return to sports activity. Patients in whom osteonecrosis is diagnosed at six weeks are at risk for collapse and joint degeneration, and they should be advised against returning to sports. Level of Evidence: Prognostic study, Level IV (case series). See Instructions to Authors for a complete description of levels of evidence.

Genome-wide signatures of complex introgression and adaptive evolution in the big cats

Abstract: The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages.

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.