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  • 1
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    Kottyan, L. C., Zoller, E. E., Bene, J., Lu, X., Kelly, J. A., Rupert, A. M., Lessard, C. J., Vaughn, S. E., Marion, M., Weirauch, M. T., Namjou, B., Adler, A., Rasmussen, A., Glenn, S., Montgomery, C. G., Hirschfield, G. M., Xie, G., Coltescu, C., Amos, C., Li, H., Ice, J. A., Nath, S. K., Mariette, X., Bowman, S., for UK Primary Sjogren's Syndrome Registry, Rischmueller, M., Lester, S., Brun, J. G., Goransson, L. G., Harboe, E., Omdal, R., Cunninghame-Graham, D. S., Vyse, T., Miceli-Richard, C., Brennan, M. T., Lessard, J. A., Wahren-Herlenius, M., Kvarnstrom, M., Illei, G. G., Witte, T., Jonsson, R., Eriksson, P., Nordmark, G., Ng, W.-F., for UK Primary Sjogren's Syndrome Registry, Anaya, J.-M., Rhodus, N. L., Segal, B. M., Merrill, J. T., James, J. A., Guthridge, J. M., Hal Scofield, R., Alarcon-Riquelme, M., Bae, S.-C., Boackle, S. A., Criswell, L. A., Gilkeson, G., Kamen, D. L., Jacob, C. O., Kimberly, R., Brown, E., Edberg, J., Alarcon, G. S., Reveille, J. D., Vila, L. M., Petri, M., Ramsey-Goldman, R., Freedman, B. I., Niewold, T., Stevens, A. M., Tsao, B. P., Ying, J., Mayes, M. D., Gorlova, O. Y., Wakeland, W., Radstake, T., Martin, E., Martin, J., Siminovitch, K., Moser Sivils, K. L., Gaffney, P. M., Langefeld, C. D., Harley, J. B., Kaufman, K. M.
    Oxford University Press
    Publication Date: 2014-12-24
    Description: Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5 – TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5 – TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb ( P -value meta = 6 x 10 –49 ; OR = 1.38–1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 ( P -values EU = 10 –27 –10 –32 , OR = 1.7–1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5–TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5 – TNPO3 .
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2011-07-22
    Description: Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value 〈 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154982/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154982/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinch, Anjali G -- Tandon, Arti -- Patterson, Nick -- Song, Yunli -- Rohland, Nadin -- Palmer, Cameron D -- Chen, Gary K -- Wang, Kai -- Buxbaum, Sarah G -- Akylbekova, Ermeg L -- Aldrich, Melinda C -- Ambrosone, Christine B -- Amos, Christopher -- Bandera, Elisa V -- Berndt, Sonja I -- Bernstein, Leslie -- Blot, William J -- Bock, Cathryn H -- Boerwinkle, Eric -- Cai, Qiuyin -- Caporaso, Neil -- Casey, Graham -- Cupples, L Adrienne -- Deming, Sandra L -- Diver, W Ryan -- Divers, Jasmin -- Fornage, Myriam -- Gillanders, Elizabeth M -- Glessner, Joseph -- Harris, Curtis C -- Hu, Jennifer J -- Ingles, Sue A -- Isaacs, William -- John, Esther M -- Kao, W H Linda -- Keating, Brendan -- Kittles, Rick A -- Kolonel, Laurence N -- Larkin, Emma -- Le Marchand, Loic -- McNeill, Lorna H -- Millikan, Robert C -- Murphy, Adam -- Musani, Solomon -- Neslund-Dudas, Christine -- Nyante, Sarah -- Papanicolaou, George J -- Press, Michael F -- Psaty, Bruce M -- Reiner, Alex P -- Rich, Stephen S -- Rodriguez-Gil, Jorge L -- Rotter, Jerome I -- Rybicki, Benjamin A -- Schwartz, Ann G -- Signorello, Lisa B -- Spitz, Margaret -- Strom, Sara S -- Thun, Michael J -- Tucker, Margaret A -- Wang, Zhaoming -- Wiencke, John K -- Witte, John S -- Wrensch, Margaret -- Wu, Xifeng -- Yamamura, Yuko -- Zanetti, Krista A -- Zheng, Wei -- Ziegler, Regina G -- Zhu, Xiaofeng -- Redline, Susan -- Hirschhorn, Joel N -- Henderson, Brian E -- Taylor, Herman A Jr -- Price, Alkes L -- Hakonarson, Hakon -- Chanock, Stephen J -- Haiman, Christopher A -- Wilson, James G -- Reich, David -- Myers, Simon R -- 090532/Wellcome Trust/United Kingdom -- CA060691/CA/NCI NIH HHS/ -- CA092447/CA/NCI NIH HHS/ -- CA100374/CA/NCI NIH HHS/ -- CA100598/CA/NCI NIH HHS/ -- CA1116460/CA/NCI NIH HHS/ -- CA1116460S1/CA/NCI NIH HHS/ -- CA121197/CA/NCI NIH HHS/ -- CA121197S2/CA/NCI NIH HHS/ -- CA127219/CA/NCI NIH HHS/ -- CA1326792/CA/NCI NIH HHS/ -- CA140388/CA/NCI NIH HHS/ -- CA141716/CA/NCI NIH HHS/ -- CA148085/CA/NCI NIH HHS/ -- CA148127/CA/NCI NIH HHS/ -- CA22453/CA/NCI NIH HHS/ -- CA54281/CA/NCI NIH HHS/ -- CA55769/CA/NCI NIH HHS/ -- CA58223/CA/NCI NIH HHS/ -- CA63464/CA/NCI NIH HHS/ -- CA68485/CA/NCI NIH HHS/ -- CA68578/CA/NCI NIH HHS/ -- CA77305/CA/NCI NIH HHS/ -- CA87895/CA/NCI NIH HHS/ -- CA88164/CA/NCI NIH HHS/ -- ES007784/ES/NIEHS NIH HHS/ -- ES011126/ES/NIEHS NIH HHS/ -- ES06717/ES/NIEHS NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- GM08016/GM/NIGMS NIH HHS/ -- GM091332/GM/NIGMS NIH HHS/ -- HD33175/HD/NICHD NIH HHS/ -- HG004726/HG/NHGRI NIH HHS/ -- HHSN268200960009C/PHS HHS/ -- HL084107/HL/NHLBI NIH HHS/ -- N01-HC-65226/HC/NHLBI NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- R01 CA052689/CA/NCI NIH HHS/ -- R01 CA092447/CA/NCI NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- R01 HL084107-04/HL/NHLBI NIH HHS/ -- R01-CA73629/CA/NCI NIH HHS/ -- U01 HG004168/HG/NHGRI NIH HHS/ -- U01 HG004168-03/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Jul 20;476(7359):170-5. doi: 10.1038/nature10336.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21775986" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/ethnology ; African Americans/*genetics ; Alleles ; Amino Acid Motifs ; Base Sequence ; Chromosome Mapping ; Crossing Over, Genetic/*genetics ; Europe/ethnology ; European Continental Ancestry Group/genetics ; Evolution, Molecular ; Female ; Gene Frequency ; Genetics, Population ; Genome, Human/*genetics ; Genomics ; Haplotypes/genetics ; Histone-Lysine N-Methyltransferase/chemistry/genetics/metabolism ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Probability
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2019
    Description: Einkorn, emmer, and rivet are three species of wheat that have largely been neglected in modern agriculture. There is a revived interest in these species as potentially successful alternatives to mainstream wheat in organic and low-input cropping systems and as sources of highly nutritious food. However, the availability of literature studies concerning rotational positions and soil tillage management is still scarce. The aim of this study was to explore the field (cover, disease resistance, yield) and quality performance (protein, fats, fiber, polyphenols, flavonoids, and antioxidant activity) of these species when organically grown in the United Kingdom. As part of the H2020 DIVERSIFOOD project, different cultivars of each species, including landraces, populations, old varieties, and where available, commercial varieties, were included in the experiment. Rotational position and tillage systems significantly affected the main agronomic performance of the minor cereals investigated, suggesting that low fertility and shallow-non-inversion tillage might be suitable options to manage tall species. Emmer showed the highest incidence of foliar diseases, whereas einkorn and rivet wheat appeared quasi-immune to the main fungal diseases (stripe rust, septoria). In addition, nutritional and nutraceutical investigation showed that the rotational position and soil management also affect metabolic pathways differently by species and within species, by genotype. Our results suggest a good potential to introduce these species in sustainable cropping systems. Furthermore, the interesting species and cultivar-by-management interactions observed can pave the way for future, better focused, research on these underutilized and underexplored species.
    Electronic ISSN: 2071-1050
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by MDPI
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  • 4
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    PANGAEA
    In:  EPIC3Bremerhaven, PANGAEA
    Publication Date: 2016-11-10
    Repository Name: EPIC Alfred Wegener Institut
    Type: PANGAEA Documentation , notRev
    Format: application/pdf
    Format: image/jpeg
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Geo-marine letters 4 (1984), S. 161-169 
    ISSN: 1432-1157
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Independent evidence of changes in sea level and tidal range in the Bay of Fundy during the last 9000 years is used to evaluate the lithologies in 17 cores from the sublittoral part of Chignecto Bay. The composite tidal sequence identified is complex because of changes from microtidal through mesotidal to macrotidal conditions associated with changing water depths. Despite the complex stratigraphy, lithology correlates well with the depositional environment on a bed-by-bed basis. We postulate that such variations in tidal range are important to the interpretation of “tidalite” deposits from the geologic record.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    The @journal of eukaryotic microbiology 7 (1960), S. 0 
    ISSN: 1550-7408
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Vorticellas were maintained on Bacillus cereus in a medium composed of unbuffered Proteose-Peptone, Cero-phyl, and the filtrate from boiled wheat kernels. Vorticella-free aliquots of culture medium were analyzed at critical intervals, beginning immediately before encystment and until re-encystment. Control aliquots changed insignificantly; significant changes were detected in the experimental cultures. Osmolality increased from 14 to 18 milliosmols/1, Na+ stayed in the range 2 to 3 milliequivalents/1, K+ decreased slightly below the initial value of 5 mEq/1, Ca++ decreased from 5.7 to 4 mg.%, CI fluctuated slightly down and up from 112 mg.% during the initial 8 hr., then down to 〈 104 mg.%, phosphate decreased steeply from 14 to 〈 0.6 mg.%, pH increased from 6.7 to 8.5.The results indicate that suboptimal levels of K+ Ca++ and phosphate impose upon V. microstoma a physiological stress which leads to encystment. The role played by Na+ and CI- was not clear. Osmolality was a major factor in excystment but not in encystment.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2015-08-27
    Description: Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma ( P = 6.3 x 10 –15 ), even after exclusion of a SNP residing in a known lung cancer susceptibility region ( TERT-CLPTM1L ) P = 6.6 x 10 –6 ). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2013-03-22
    Description: Recent upward revision of the 1872 Owens Valley earthquake from M w  7.4–7.5 to 7.7–7.9 implies either additional unrecognized rupture length or anomalously strong ground motions associated with this event. We investigate the first possibility through paleoseismic trenching south of the mapped surface rupture in the Haiwee area, where historical accounts suggest significant surface deformation following the earthquake. Trenching focused on a prominent north-striking scarp, herein termed the Sage Flat fault, expressed in Pleistocene alluvial fans east of Haiwee Reservoir. Surficial mapping and ground-based Light Detection and Ranging (lidar) surveying suggest that this fault accommodates east-down normal motion, and possibly a comparable amount of dextral slip. Trenching and luminescence dating brackets the timing of the most recent surface-rupturing earthquake between ~25.7 and 30.1 ka, and provides evidence for an earlier event predating this time. In combination with scarp profiling, these dates also suggest a maximum rate of normal, dip-slip fault motion up to ~0.1 mm/yr over this period. Although we discovered no evidence for recent surface rupture on the Sage Flat fault, a series of subvertical fractures and fissures cut across young trench stratigraphy, consistent with secondary deformation associated with seismic shaking. As such, we suggest that possible ground disturbance in the Haiwee area during the 1872 event primarily reflected ground shaking or liquefaction-related deformation rather than triggered slip. In addition, we infer a structural and kinematic connection between the Owens Valley fault and oblique-dextral faults north of Lower Cactus Flat in the northwestern Coso Range, rather than a west-step into northern or western Rose Valley. Consideration of these structures in the total extent of the Owens Valley fault suggests a length of 140 km, of which at least 113 km ruptured during the 1872 event. Online Material: Procedural details and expanded results from the OSL sample analyses, as well as high-resolution paleoseismic trench logs.
    Print ISSN: 0037-1106
    Electronic ISSN: 1943-3573
    Topics: Geosciences , Physics
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  • 9
    Publication Date: 2015-12-18
    Description: Motivation: Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. Results: We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. Availability and implementation: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues . Contact: yili@umich.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 10
    Publication Date: 2013-02-22
    Description: Unlike genome-wide association studies, few comprehensive studies of copy number variation's contribution to complex human disease susceptibility have been performed. Copy number variations are abundant in humans and represent one of the least well-studied classes of genetic variants; in addition, known rheumatoid arthritis susceptibility loci explain only a portion of familial clustering. Therefore, we performed a genome-wide study of association between deletion or excess homozygosity and rheumatoid arthritis using high-density 550 K SNP genotype data from a genome-wide association study. We used a genome-wide statistical method that we recently developed to test each contiguous SNP locus between 868 cases and 1194 controls to detect excess homozygosity or deletion variants that influence susceptibility. Our method is designed to detect statistically significant evidence of deletions or homozygosity at individual SNPs for SNP-by-SNP analyses and to combine the information among neighboring SNPs for cluster analyses. In addition to successfully detecting the known deletion variants on major histocompatibility complex, we identified 4.3 and 28 kb clusters on chromosomes 10p and 13q, respectively, which were significant at a Bonferroni-type-corrected 0.05 nominal significant level. Independently, we performed analyses using PennCNV, an algorithm for identifying and cataloging copy numbers for individuals based on a hidden Markov model, and identified cases and controls that had chromosomal segments with copy number 〈2. Using Fisher's exact test for comparing the numbers of cases and controls with copy number 〈2 per SNP, we identified 26 significant SNPs (protective; more controls than cases) aggregating on chromosome 14 with P -values 〈10 –8 .
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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