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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
TL;DR: A recent remarkable transposition of 7.9 kb of a typically 17.0-kb mitochondrial genome to a specific nuclear chromosomal position in the domestic cat is reported, providing an empirical glimpse of historic genomic events that may parallel the accommodation of organelles in eucaryotes.
Abstract: The mitochondrial DNA of plant and animal cells is a transcriptionally active genome that traces its origins to a symbiotic infection of eucaryotic cells by bacterial progenitors. As prescribed by the Serial Endosymbiosis Theory, symbiotic organelles have gradually transferred their genes to the eucaryotic genome, producing a functional interaction of nuclear and mitochondrial genes in organelle function. We report here a recent remarkable transposition of 7.9 kb of a typically 17.0-kb mitochondrial genome to a specific nuclear chromosomal position in the domestic cat. The integrated segment has subsequently become amplified 38–76 times and now occurs as a tandem repeat macrosatellite with multiple-length alleles resolved by pulse-field gel electrophoresis (PFGE) segregating in cat populations. Sequence determination of the nuclear mitochondrial DNA segment, Numt, revealed a d(CA)-rich 8-bp motif [ACACACGT] repeated imperfectly five times at the deletion junction that is a likely target for recombination. The extent and pattern of sequence divergence of Numt genes from the cytoplasmic mtDNA homologues plus the occurrence of Numt in other species of the family Felidae allowed an estimate for the origins of Numt at 1.8–2.0 million years ago in an ancestor of four modern species in the genus Felis. Numt genes do not function in cats; rather, the locus combines properties of nuclear minisatellites and pseudogenes. These observations provide an empirical glimpse of historic genomic events that may parallel the accommodation of organelles in eucaryotes.

603 citations

Journal ArticleDOI
TL;DR: A prospective study was performed on 318 patients to determine the specificity, specificity, and positive and negative predictive values of the test, which differentiated labral tears and acromioclavicular joint abnormalities on physical examination using a new diagnostic test.
Abstract: Labral tears and acromioclavicular joint abnormalities were differentiated on physical examination using a new diagnostic test. The standing patient forward flexed the arm to 90 degrees with the elbow in full extension and then adducted the arm 10 degrees to 15 degrees medial to the sagittal plane of the body and internally rotated it so that the thumb pointed downward. The examiner, standing behind the patient, applied a uniform downward force to the arm. With the arm in the same position, the palm was then fully supinated and the maneuver was repeated. The test was considered positive if pain was elicited during the first maneuver, and was reduced or eliminated with the second. Pain localized to the acromioclavicular joint or "on top" was diagnostic of acromioclavicular joint abnormality, whereas pain or painful clicking described as "inside" the shoulder was considered indicative of labral abnormality. A prospective study was performed on 318 patients to determine the sensitivity, specificity, and positive and negative predictive values of the test. Fifty-three of 56 patients whose preoperative examinations indicated a labral tear had confirmed labral tears that were repaired at surgery. Fifty-five of 62 patients who had pain in the acromioclavicular joint and whose preoperative examinations indicated abnormalities in the joint had positive clinical, operative, or radiographic evidence of acromioclavicular injury. There were no false-negative results in either group.

546 citations

Journal ArticleDOI
TL;DR: A precipitous drop in costs and increase in sequencing efficiency is anticipated, with concomitant development of improved annotation technology, and it is proposed to create a collection of tissue and DNA specimens for 10,000 vertebrate species specifically designated for whole-genome sequencing in the very near future.
Abstract: American Genetic Association, Gordon and Betty Moore Foundation, NHGRI Intramural Sequencing Center, and UCSC Alumni Association to cost of the Genome 10K workshop; Howard Hughes Medical Institute to D. H.; Gordon and Betty Moore Foundation to S. C. S.; A

545 citations

Journal ArticleDOI
22 Jul 2005-Science
TL;DR: In this paper, the genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution, and it was found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.
Abstract: The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.

524 citations

Journal ArticleDOI
20 Jun 1986-Cell
TL;DR: Treating HOS cells in vitro with MNNG resulted in fusion of two chromosomally disparate loci, met and tpr, generating the active met oncogene, related to the tyrosine kinase gene family.

521 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