ALBERT

Description: Much is known about the evolution of plant immunity components directed against specific pathogen strains: They show pervasive functional variation and have the potential to coevolve with pathogen populations. However, plants are effectively protected against most microbes by generalist immunity components that detect conserved pathogen-associated molecular patterns (PAMPs) and control the onset of PAMP-triggered immunity. In Arabidopsis thaliana , the receptor kinase flagellin sensing 2 (FLS2) confers recognition of bacterial flagellin (flg22) and activates a manifold defense response. To decipher the evolution of this system, we performed functional assays across a large set of A. thaliana genotypes and Brassicaceae relatives. We reveal extensive variation in flg22 perception, most of which results from changes in protein abundance. The observed variation correlates with both the severity of elicited defense responses and bacterial proliferation. We analyzed nucleotide variation segregating at FLS2 in A. thaliana and detected a pattern of variation suggestive of the rapid fixation of a novel adaptive allele. However, our study also shows that evolution at the receptor locus alone does not explain the evolution of flagellin perception; instead, components common to pathways downstream of PAMP perception likely contribute to the observed quantitative variation. Within and among close relatives, PAMP perception evolves quantitatively, which contrasts with the changes in recognition typically associated with the evolution of R genes.

Description: Motivation : High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. Results : We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent–daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays. Availability : The R package absfilter for library clonality simulations and detection of amplification-biased sites is available from http://updepla1srv1.epfl.ch/waszaks/absfilter Contact : sebastian.waszak@epfl.ch or bart.deplancke@epfl.ch Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5–30.1 Mb) in 393 unrelated patients with typical ( n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 x 10 –6 , odds ratio = 26.2, 95% confidence interval: 7.9–68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy ( n = 330) and genetic generalized epilepsies ( n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 x 10 –4 ). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.

Description: Analysis of the human and mouse genomes identified an abundance of conserved non-genic sequences (CNGs). The significance and evolutionary depth of their conservation remain unanswered. We have quantified levels and patterns of conservation of 191 CNGs of human chromosome 21 in 14 mammalian species. We found that CNGs are significantly more conserved than protein-coding genes and noncoding RNAS (ncRNAs) within the mammalian class from primates to monotremes to marsupials. The pattern of substitutions in CNGs differed from that seen in protein-coding and ncRNA genes and resembled that of protein-binding regions. About 0.3% to 1% of the human genome corresponds to a previously unknown class of extremely constrained CNGs shared among mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dermitzakis, Emmanouil T -- Reymond, Alexandre -- Scamuffa, Nathalie -- Ucla, Catherine -- Kirkness, Ewen -- Rossier, Colette -- Antonarakis, Stylianos E -- New York, N.Y. -- Science. 2003 Nov 7;302(5647):1033-5. Epub 2003 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Medical Genetics and National Center of Competence in Research (NCCR) Frontiers in Genetics, University of Geneva Medical School and University Hospitals, 1211 Geneva, Switzerland. Emmanouil.Dermitzakis@medecine.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526086" target="_blank"〉PubMed〈/a〉

Description: The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christie, J M -- Reymond, P -- Powell, G K -- Bernasconi, P -- Raibekas, A A -- Liscum, E -- Briggs, W R -- New York, N.Y. -- Science. 1998 Nov 27;282(5394):1698-701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution of Washington, 260 Panama Street, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9831559" target="_blank"〉PubMed〈/a〉

Description: DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kilpinen, Helena -- Waszak, Sebastian M -- Gschwind, Andreas R -- Raghav, Sunil K -- Witwicki, Robert M -- Orioli, Andrea -- Migliavacca, Eugenia -- Wiederkehr, Michael -- Gutierrez-Arcelus, Maria -- Panousis, Nikolaos I -- Yurovsky, Alisa -- Lappalainen, Tuuli -- Romano-Palumbo, Luciana -- Planchon, Alexandra -- Bielser, Deborah -- Bryois, Julien -- Padioleau, Ismael -- Udin, Gilles -- Thurnheer, Sarah -- Hacker, David -- Core, Leighton J -- Lis, John T -- Hernandez, Nouria -- Reymond, Alexandre -- Deplancke, Bart -- Dermitzakis, Emmanouil T -- GM25232/GM/NIGMS NIH HHS/ -- HG004845/HG/NHGRI NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):744-7. doi: 10.1126/science.1242463. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136355" target="_blank"〉PubMed〈/a〉

Description: The polypyrimidine tract binding protein (PTB) is a 58-kilodalton RNA binding protein involved in multiple aspects of messenger RNA metabolism, including the repression of alternative exons. We have determined the solution structures of the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3 and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA looping when bound to two separated pyrimidine tracts within the same RNA. This leads to structural models for how PTB functions as an alternative-splicing repressor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oberstrass, Florian C -- Auweter, Sigrid D -- Erat, Michele -- Hargous, Yann -- Henning, Anke -- Wenter, Philipp -- Reymond, Luc -- Amir-Ahmady, Batoul -- Pitsch, Stefan -- Black, Douglas L -- Allain, Frederic H-T -- New York, N.Y. -- Science. 2005 Sep 23;309(5743):2054-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology, Zurich, ETH-Honggerberg, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16179478" target="_blank"〉PubMed〈/a〉

Description: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200/" 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/PMC2943200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bovine Genome Sequencing and Analysis Consortium -- Elsik, Christine G -- Tellam, Ross L -- Worley, Kim C -- Gibbs, Richard A -- Muzny, Donna M -- Weinstock, George M -- Adelson, David L -- Eichler, Evan E -- Elnitski, Laura -- Guigo, Roderic -- Hamernik, Debora L -- Kappes, Steve M -- Lewin, Harris A -- Lynn, David J -- Nicholas, Frank W -- Reymond, Alexandre -- Rijnkels, Monique -- Skow, Loren C -- Zdobnov, Evgeny M -- Schook, Lawrence -- Womack, James -- Alioto, Tyler -- Antonarakis, Stylianos E -- Astashyn, Alex -- Chapple, Charles E -- Chen, Hsiu-Chuan -- Chrast, Jacqueline -- Camara, Francisco -- Ermolaeva, Olga -- Henrichsen, Charlotte N -- Hlavina, Wratko -- Kapustin, Yuri -- Kiryutin, Boris -- Kitts, Paul -- Kokocinski, Felix -- Landrum, Melissa -- Maglott, Donna -- Pruitt, Kim -- Sapojnikov, Victor -- Searle, Stephen M -- Solovyev, Victor -- Souvorov, Alexandre -- Ucla, Catherine -- Wyss, Carine -- Anzola, Juan M -- Gerlach, Daniel -- Elhaik, Eran -- Graur, Dan -- Reese, Justin T -- Edgar, Robert C -- McEwan, John C -- Payne, Gemma M -- Raison, Joy M -- Junier, Thomas -- Kriventseva, Evgenia V -- Eyras, Eduardo -- Plass, Mireya -- Donthu, Ravikiran -- Larkin, Denis M -- Reecy, James -- Yang, Mary Q -- Chen, Lin -- Cheng, Ze -- Chitko-McKown, Carol G -- Liu, George E -- Matukumalli, Lakshmi K -- Song, Jiuzhou -- Zhu, Bin -- Bradley, Daniel G -- Brinkman, Fiona S L -- Lau, Lilian P L -- Whiteside, Matthew D -- Walker, Angela -- Wheeler, Thomas T -- Casey, Theresa -- German, J Bruce -- Lemay, Danielle G -- Maqbool, Nauman J -- Molenaar, Adrian J -- Seo, Seongwon -- Stothard, Paul -- Baldwin, Cynthia L -- Baxter, Rebecca -- Brinkmeyer-Langford, Candice L -- Brown, Wendy C -- Childers, Christopher P -- Connelley, Timothy -- Ellis, Shirley A -- Fritz, Krista -- Glass, Elizabeth J -- Herzig, Carolyn T A -- Iivanainen, Antti -- Lahmers, Kevin K -- Bennett, Anna K -- Dickens, C Michael -- Gilbert, James G R -- Hagen, Darren E -- Salih, Hanni -- Aerts, Jan -- Caetano, Alexandre R -- Dalrymple, Brian -- Garcia, Jose Fernando -- Gill, Clare A -- Hiendleder, Stefan G -- Memili, Erdogan -- Spurlock, Diane -- Williams, John L -- Alexander, Lee -- Brownstein, Michael J -- Guan, Leluo -- Holt, Robert A -- Jones, Steven J M -- Marra, Marco A -- Moore, Richard -- Moore, Stephen S -- Roberts, Andy -- Taniguchi, Masaaki -- Waterman, Richard C -- Chacko, Joseph -- Chandrabose, Mimi M -- Cree, Andy -- Dao, Marvin Diep -- Dinh, Huyen H -- Gabisi, Ramatu Ayiesha -- Hines, Sandra -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Kovar, Christie L -- Lewis, Lora R -- Liu, Yih-Shin -- Lopez, John -- Morgan, Margaret B -- Nguyen, Ngoc Bich -- Okwuonu, Geoffrey O -- Ruiz, San Juana -- Santibanez, Jireh -- Wright, Rita A -- Buhay, Christian -- Ding, Yan -- Dugan-Rocha, Shannon -- Herdandez, Judith -- Holder, Michael -- Sabo, Aniko -- Egan, Amy -- Goodell, Jason -- Wilczek-Boney, Katarzyna -- Fowler, Gerald R -- Hitchens, Matthew Edward -- Lozado, Ryan J -- Moen, Charles -- Steffen, David -- Warren, James T -- Zhang, Jingkun -- Chiu, Readman -- Schein, Jacqueline E -- Durbin, K James -- Havlak, Paul -- Jiang, Huaiyang -- Liu, Yue -- Qin, Xiang -- Ren, Yanru -- Shen, Yufeng -- Song, Henry -- Bell, Stephanie Nicole -- Davis, Clay -- Johnson, Angela Jolivet -- Lee, Sandra -- Nazareth, Lynne V -- Patel, Bella Mayurkumar -- Pu, Ling-Ling -- Vattathil, Selina -- Williams, Rex Lee Jr -- Curry, Stacey -- Hamilton, Cerissa -- Sodergren, Erica -- Wheeler, David A -- Barris, Wes -- Bennett, Gary L -- Eggen, Andre -- Green, Ronnie D -- Harhay, Gregory P -- Hobbs, Matthew -- Jann, Oliver -- Keele, John W -- Kent, Matthew P -- Lien, Sigbjorn -- McKay, Stephanie D -- McWilliam, Sean -- Ratnakumar, Abhirami -- Schnabel, Robert D -- Smith, Timothy -- Snelling, Warren M -- Sonstegard, Tad S -- Stone, Roger T -- Sugimoto, Yoshikazu -- Takasuga, Akiko -- Taylor, Jeremy F -- Van Tassell, Curtis P -- Macneil, Michael D -- Abatepaulo, Antonio R R -- Abbey, Colette A -- Ahola, Virpi -- Almeida, Iassudara G -- Amadio, Ariel F -- Anatriello, Elen -- Bahadue, Suria M -- Biase, Fernando H -- Boldt, Clayton R -- Carroll, Jeffery A -- Carvalho, Wanessa A -- Cervelatti, Eliane P -- Chacko, Elsa -- Chapin, Jennifer E -- Cheng, Ye -- Choi, Jungwoo -- Colley, Adam J -- de Campos, Tatiana A -- De Donato, Marcos -- Santos, Isabel K F de Miranda -- de Oliveira, Carlo J F -- Deobald, Heather -- Devinoy, Eve -- Donohue, Kaitlin E -- Dovc, Peter -- Eberlein, Annett -- Fitzsimmons, Carolyn J -- Franzin, Alessandra M -- Garcia, Gustavo R -- Genini, Sem -- Gladney, Cody J -- Grant, Jason R -- Greaser, Marion L -- Green, Jonathan A -- Hadsell, Darryl L -- Hakimov, Hatam A -- Halgren, Rob -- Harrow, Jennifer L -- Hart, Elizabeth A -- Hastings, Nicola -- Hernandez, Marta -- Hu, Zhi-Liang -- Ingham, Aaron -- Iso-Touru, Terhi -- Jamis, Catherine -- Jensen, Kirsty -- Kapetis, Dimos -- Kerr, Tovah -- Khalil, Sari S -- Khatib, Hasan -- Kolbehdari, Davood -- Kumar, Charu G -- Kumar, Dinesh -- Leach, Richard -- Lee, Justin C-M -- Li, Changxi -- Logan, Krystin M -- Malinverni, Roberto -- Marques, Elisa -- Martin, William F -- Martins, Natalia F -- Maruyama, Sandra R -- Mazza, Raffaele -- McLean, Kim L -- Medrano, Juan F -- Moreno, Barbara T -- More, Daniela D -- Muntean, Carl T -- Nandakumar, Hari P -- Nogueira, Marcelo F G -- Olsaker, Ingrid -- Pant, Sameer D -- Panzitta, Francesca -- Pastor, Rosemeire C P -- Poli, Mario A -- Poslusny, Nathan -- Rachagani, Satyanarayana -- Ranganathan, Shoba -- Razpet, Andrej -- Riggs, Penny K -- Rincon, Gonzalo -- Rodriguez-Osorio, Nelida -- Rodriguez-Zas, Sandra L -- Romero, Natasha E -- Rosenwald, Anne -- Sando, Lillian -- Schmutz, Sheila M -- Shen, Libing -- Sherman, Laura -- Southey, Bruce R -- Lutzow, Ylva Strandberg -- Sweedler, Jonathan V -- Tammen, Imke -- Telugu, Bhanu Prakash V L -- Urbanski, Jennifer M -- Utsunomiya, Yuri T -- Verschoor, Chris P -- Waardenberg, Ashley J -- Wang, Zhiquan -- Ward, Robert -- Weikard, Rosemarie -- Welsh, Thomas H Jr -- White, Stephen N -- Wilming, Laurens G -- Wunderlich, Kris R -- Yang, Jianqi -- Zhao, Feng-Qi -- 062023/Wellcome Trust/United Kingdom -- 077198/Wellcome Trust/United Kingdom -- BBS/B/13438/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/13446/Biotechnology and Biological Sciences Research Council/United Kingdom -- P30 DA018310/DA/NIDA NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-04/HG/NHGRI NIH HHS/ -- U54 HG003273-04S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05/HG/NHGRI NIH HHS/ -- U54 HG003273-05S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05S2/HG/NHGRI NIH HHS/ -- U54 HG003273-06/HG/NHGRI NIH HHS/ -- U54 HG003273-06S1/HG/NHGRI NIH HHS/ -- U54 HG003273-06S2/HG/NHGRI NIH HHS/ -- U54 HG003273-07/HG/NHGRI NIH HHS/ -- U54 HG003273-08/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):522-8. doi: 10.1126/science.1169588.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390049" target="_blank"〉PubMed〈/a〉

Description: Motivation: Only a few large systematic studies have evaluated the impact of copy number variants (CNVs) on common diseases. Several million individuals have been genotyped on single nucleotide variation arrays, which could be used for genome-wide CNVs association studies. However, CNV calls remain prone to false positives and only empirical filtering strategies exist in the literature. To overcome this issue, we defined a new quality score (QS) estimating the probability of a CNV called by PennCNV to be confirmed by other software. Results: Out-of-sample comparison showed that the correlation between the consensus CNV status and the QS is twice as high as it is for any previously proposed CNV filters. ROC curves displayed an AUC higher than 0.8 and simulations showed an increase up to 20% in statistical power when using QS in comparison to other filtering strategies. Superior performance was confirmed also for alternative consensus CNV definition and through improving known CNV-trait associations. Availability and Implementation: http://goo.gl/T6yuFM Contact: zoltan.kutalik@unil.ch or aurelien@mace@unil.ch Supplementary information: Supplementary data are available at Bioinformatics online.

Description: We derive a simple formula relating tsunami amplitude in the far field to seismic moment, distance and azimuth from propagating rupture. Our formula is obtained from a comparison of a set of 4650 Pacific-wide simulations, computed for a series of sources spread over 10 subduction zones and four order of magnitudes in seismic moments. Our simulations are run both for a real grid reproducing the true bathymetry of the Pacific Basin and for an idealized one featuring a constant depth of 4000 m and no shorelines. This enables us to study and model separately the influence on the final amplitude of a tsunami wave of effects such as directivity and irregular bathymetry. The contribution of source size directivity and propagation over the sphere are studied using the constant-depth simulations. The influence of distance does not require any dispersive term and is properly modelled by geometrical spreading on the sphere. The directivity term, described classically in the frequency domain by Ben-Menahem & Rosenman can be approximated in the time domain by a moment-dependent linear regression as a function of azimuth. Finally, and after an allowance is made for the effect of receiver bathymetry using Green's law, the effect of irregular bathymetry is found to be generally defocusing, and can be modelled as a linear regression with distance. Once an estimate of the seismic moment of the parent earthquake is known, and under the assumption of a subduction mechanism along a fault of known azimuth, the resulting formula allows to forecast far-field tsunami amplitudes on the high seas. We use a data set of 116 tsunami amplitudes recorded at 51 past and present DART buoys following 21 tsunamigenic events to compare the estimates predicted by our algorithm to the amplitudes actually recorded. The average values of the residuals are 0.00 ± 0.25 logarithmic units, and 0.02 ± 0.20 at distances greater than 20°. An important aspect of our algorithm is that it correctly predicts the DART amplitudes for the 2011 Tohoku tsunami (0.10 ± 0.15 logarithmic units), even though its region was not included when building the algorithm.