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.

Chromosomal localization of satellite DNA sequences among 22 species of felids and canids (Carnivora).

Abstract: In situ hybridization was carried out using cloned satellite DNAs from the domestic cat and domestic dog as probes to metaphase chromosomes from 12 species of felids and 10 species of canids. Autoradiographic silver grains along metaphase chromosomes were counted and analyzed with regard to the mean number of grains per cell in each species, their chromosomal location, and their presence or absence on specific autosomes or sex chromosomes, where known. Among the felids and canids there was a 7.6- and 8.9-fold statistically significant difference, respectively, in the mean number of grains per cell between the species having the minimum and maximum values. Among the felids, most grains occurred on the telomeres of D- and E-group chromosomes, although departures from this general pattern also occurred. For example, the Asian golden cat and the Bornean bay cat showed substantial labeling at the centromeric region of chromosome A1, and a number of species showed some labeling at the short-arm telomeres of B-group chromosomes. Among the canids, about 90% of all grains were located at autosomal centromeres, and grains were absent from the sex chromosomes. Grains are usually distributed at chromosomal locations that stain C-band positive; however, certain C-band-positive regions without grains probably do not contain the particular satellites studied here.

Murine retroviral restriction genes Fv-4 and Akvr-1 are alleles of a single locus.

Abstract: The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, distributions, ranges of action, and phenotypes. Akvr-1 has been shown to segregate independently in backcrosses with a variety of retroviral restriction loci, including Fv-1, Fv-2, Ril-1, and Ril-2. An allelism test cross of FRG (Fv-4R) X LCRR (Akvr-1R) hybrids mated to AKR mice failed to produce any viremic offspring. These results suggested that Akvr-1R and Fv-4R are alleles of a single locus, Fv-4, on mouse chromosome 12.

Magnetic Resonance Imaging Currently Fails to Fully Evaluate the Biceps-Labrum Complex and Bicipital Tunnel.

Abstract: Purpose To determine the diagnostic accuracy of magnetic resonance imaging (MRI) for biceps-labrum complex (BLC) lesions, including the extra-articular bicipital tunnel. Methods A retrospective review of 277 shoulders with chronic refractory BLC symptoms that underwent arthroscopic subdeltoid transfer of the long head of the biceps tendon (LHBT) to the conjoint tendon was conducted. Intraoperative lesions were categorized as "inside" (labral tears and dynamic LHBT incarceration), "junctional" (LHBT partial tears, LHBT subluxation, and biceps chondromalacia), or "bicipital tunnel" (extra-articular bicipital tunnel scar/stenosis, loose bodies, LHBT instability, and LHBT partial tears) based on anatomic location. Attending radiologist–generated MRI reports were graded dichotomously as positive or negative for biceps and labral damage and then compared with intraoperative findings. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MRI with respect to intraoperative findings. Results With regard to inside lesions, MRI had an overall sensitivity, specificity, PPV, and NPV for labrum lesions of 77.3%, 68.2%, 57.3%, and 84.5% respectively. The sensitivity, specificity, PPV, and NPV of MRI for junctional lesions were 43.3%, 55.6%, 73.1%, and 26.0%, respectively. For the bicipital tunnel, MRI had a sensitivity, specificity, PPV, and NPV of 50.4%, 61.4%, 48.7%, and 63.0%, respectively. Conclusions MRI was unreliable for ruling out BLC lesions among chronically symptomatic patients, including when the bicipital tunnel was affected. Level of Evidence Level IV, diagnostic case-control study.

Phylogeography and population history of Leopardus guigna , the smallest American felid

Abstract: The guigna (Leopardus guigna) is the smallest and most-restricted New World cat species, inhabiting only around 160,000 km2 of temperate rain forests in southern South America and is currently threatened by habitat loss, fragmentation and human persecution. We investigated phylogeographic patterns of genetic diversity, demographic history and barriers to gene flow with 116 individuals sampled across the species geographic range by analyzing 1,798 base pairs of the mtDNA (496 bp HVSI region, 720 bp NADH-5 gene, 364 bp from 16S gene and 218 bp from ATP-8 gene) and 15 microsatellite loci. Mitochondrial DNA data revealed a clear phylogeographic pattern with moderate separation between northern and southern Chilean populations supporting recognized subspecific partitions based on morphology. A recent demographic expansion was inferred for the southern-most group (San Rafael Lake), presumably due to the complete coverage of this area during the last glacial period, 28000–16000 years BP. Geographical barriers such as the Andes Mountains and the Chacao Channel have partially restricted historic and more-recent gene flow and the Chiloe Island population has diverged genetically since being separated from the mainland 7000 years BP. This is the first study of the genetic structure of this threatened species throughout its whole geographic range.

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.