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  • 1101. Wennerstrom, Lovisa
    et al.
    Ryman, Nils
    Tison, Jean-Luc
    Hasslow, Anna
    Dalén, Love
    Swedish Museum of Natural History, Department of Bioinformatics and Genetics.
    Laikre, Linda
    Genetic landscape with sharp discontinuities shaped by complex demographic history in moose (Alces alces)2016In: Journal of Mammalogy, ISSN 0022-2372, E-ISSN 1545-1542, Vol. 97, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    The moose (Alces alces) is the most intensely managed game species in Fennoscandia; approximately one-third of the population, ca. 160,000 animals, is harvested annually. Despite the species' biological and socioeconomic importance, there are knowledge gaps with respect to its intraspecific diversity and genetic structure. Recent studies of moose in neighboring countries report 2 genetic groups in Finland, 3 in Norway with one of them suggested to be of ancient origin, and no indications of bottlenecks. To delineate the spatial genetic landscape of the Swedish moose, we used allozyme variability from over 20,000 georeferenced moose collected all over Sweden in combination with 12 microsatellites (n = 1,200) and mitochondrial DNA (mtDNA) sequences (n = 44). We combined individual-based and traditional statistical approaches with coalescence-based simulations. The results indicate a complex history with bottlenecks and recent expansions that is consistent with historical records. Swedish moose are separated into 2 major genetic groups, a northern and a southern one, where the southern group is further divided into 3 subgroups. The 2 main subpopulations are moderately differentiated (F-ST = 0.1; R-ST = 0.07) and separated by sharp genetic discontinuities occurring over a relatively narrow transition zone in central Sweden that coincides with a similar, previously reported transition zone in Norway. This differentiation is not reflected in mtDNA variation, where no significant divergence was observed. Together with the F-ST andR(ST) similarities, this suggests that the 2 major subpopulations in Sweden reflect divergence shaped after the postglacial recolonization of Scandinavia. Neighborhood size assessments indicate that gene flow is relatively restricted with an estimated average dispersal distance of 3.5-11.1 km, and spatial autocorrelograms suggest that genetic similarity decreases almost linearly over space resulting in continuous genetic clines within major subgroups. Management areas largely coincide with genetic clusters, simplifying the integration of genetic information into management.

  • 1102. Westin, M A K
    et al.
    Hunt, M C
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Genetik.
    Alexson, S E H
    Short- and medium-chain carnitine acyltransferases and acyl-CoA thioesterases in mouse provide complementary systems for transport of beta-oxidation products out of peroxisomes.2008In: Cell Mol Life Sci, ISSN 1420-682X, Vol. 65, no 6, p. 982-90Article in journal (Refereed)
  • 1103.
    Westman, Anna-Karin
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences, Engineering and Mathematics.
    Investigation of Progress in Peer Discussions Regarding Genetic ConceptsManuscript (preprint) (Other academic)
  • 1104.
    Wetterbom, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sevov, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Cavelier, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bergström, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Comparative genomic analysis of human and chimpanzee indicates a key role for indels in primate evolution2006In: Journal of Molecular Evolution, ISSN 0022-2844, E-ISSN 1432-1432, Vol. 63, no 5, p. 682-690Article in journal (Refereed)
    Abstract [en]

    Sequence comparison of humans and chimpanzees is of interest to understand the mechanisms behind primate evolution. Here we present an independent analysis of human chromosome 21 and the high-quality BAC clone sequences of the homologous chimpanzee chromosome 22. In contrast to previous studies, we have used global alignment methods and Ensembl predictions of protein coding genes (n = 224) for the analysis. Divergence due to insertions and deletions (indels) along with substitutions was examined separately for different genomic features (coding, noncoding genic, and intergenic sequence). The major part of the genomic divergence could be attributed to indels (5.07%), while the nucleotide divergence was estimated as 1.52%. Thus the total divergence was estimated as 6.58%. When excluding repeats and low-complexity DNA the total divergence decreased to 2.37%. The chromosomal distribution of nucleotide substitutions and indel events was significantly correlated. To further examine the role of indels in primate evolution we focused on coding sequences. Indels were found within the coding sequence of 13% of the genes and approximately half of the indels have not been reported previously. In 5% of the chimpanzee genes, indels or substitutions caused premature stop codons that rendered the affected transcripts nonfunctional. Taken together, our findings demonstrate that indels comprise the majority of the genomic divergence. Furthermore, indels occur frequently in coding sequences. Our results thereby support the hypothesis that indels may have a key role in primate evolution.

  • 1105.
    Wheatcroft, David
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Genetic divergence of early song discrimination between two young songbird species2017In: NATURE ECOLOGY & EVOLUTION, ISSN 2397-334X, Vol. 1, no 7, article id UNSP 0192Article in journal (Refereed)
    Abstract [en]

    Juvenile songbirds express species-specific song discrimination from an early age, which focuses learning onto the songs of their parental species. However, it remains unknown whether this early song discrimination is influenced by early social experience or maternal effects or whether it is instead largely genetically determined. We manipulated early social experience by swapping young embryos between the nests of two co-occurring songbird species-pied and collared flycatchers. We show that nestlings are more active in response to playbacks of conspecific songs, even when raised by adults from the other species, thus enabling us to reject social experience as the main determinant of early song discrimination. We then crossed the two species in captivity and showed that the song responses of hybrid nestlings do not depend on social experience or maternal species, implying genetic divergence of early song discrimination. Our results provide conclusive evidence that early song discrimination has a largely genetic component, which can stabilize reproductive isolation by reducing song learning across closely related species.

  • 1106.
    Widell, Paulina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Genetiken bakom artbildning: fokus på Leptidea Sinapis2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Artbildning, det vill säga uppkomst av nya arter, är ett centralt ämne inom evolutionsbiologinoch en process som kan fortskrida på ett flertal olika sätt. Reproduktiva barriärer som är nödvändiga för artbildningsprocessen kan utvecklas mellan populationer och verkar antingen så att individer hindras från att para sig med varandra (prezygotisk isolering) eller så att överlevnad eller reproduktionsframgång hos avkomman är reducerad (postzygotisk isolering).Syftet men där här studien är att först beskriva dessa olika typer av isoleringar och sedan summera den aktuella kunskapen om hur själva artbildningsprocessen kan fortgå. Avslutningvis beskrivs ett exempelsystem med tre geografiskt separerade populationer avarten skogsvitsvinge (Leptidea sinapis). Skillnader i kromosomantal och ekologi mellan vissa av populationerna kan potentiellt vara faktorer som har lett till begränsat genflöde och som i slutänden kan leda till att fullständigt reproduktivt isolerade arter uppkommer.

  • 1107. Willems, Sara M.
    et al.
    Wright, Daniel J.
    Day, Felix R.
    Trajanoska, Katerina
    Joshi, Peter K.
    Morris, John A.
    Matteini, Amy M.
    Garton, Fleur C.
    Grarup, Niels
    Oskolkov, Nikolay
    Thalamuthu, Anbupalam
    Mangino, Massimo
    Liu, Jun
    Demirkan, Ayse
    Lek, Monkol
    Xu, Liwen
    Wang, Guan
    Oldmeadow, Christopher
    Gaulton, Kyle J.
    Lotta, Luca A.
    Miyamoto-Mikami, Eri
    Rivas, Manuel A.
    White, Tom
    Loh, Po-Ru
    Aadahl, Mette
    Amin, Najaf
    Attia, John R.
    Austin, Krista
    Benyamin, Beben
    Brage, Soren
    Cheng, Yu-Ching
    Cieszczyk, Pawel
    Derave, Wim
    Eriksson, Karl-Fredrik
    Eynon, Nir
    Linneberg, Allan
    Lucia, Alejandro
    Massidda, Myosotis
    Mitchell, Braxton D.
    Miyachi, Motohiko
    Murakami, Haruka
    Padmanabhan, Sandosh
    Pandey, Ashutosh
    Papadimitriou, Loannis
    Rajpal, Deepak K.
    Sale, Craig
    Schnurr, Theresia M.
    Sessa, Francesco
    Shrine, Nick
    Tobin, Martin D.
    Varley, Ian
    Wain, Louise V.
    Wray, Naomi R.
    Lindgren, Cecilia M.
    MacArthur, Daniel G.
    Waterworth, Dawn M.
    McCarthy, Mark I.
    Pedersen, Oluf
    Khaw, Kay-Tee
    Kie, Douglas P.
    Pitsiladis, Yannis
    Fuku, Noriyuki
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skånes University Hospital, 222 41 Lund, Sweden.
    North, Kathryn N.
    van Duijn, Cornelia M.
    Mather, Karen A.
    Hansen, Torben
    Hansson, Ola
    Spector, Tim
    Murabito, Joanne M.
    Richards, J. Brent
    Rivadeneira, Fernando
    Langenberg, Claudia
    Perry, John R. B.
    Wareham, Nick J.
    Scott, Robert A.
    Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 16015Article in journal (Refereed)
    Abstract [en]

    Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 x 10(-8)) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

  • 1108. Williams, Jessica S
    et al.
    Clausen, Anders R
    Nick McElhinny, Stephanie A
    Watts, Brian E
    Johansson, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kunkel, Thomas A
    Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase ɛ.2012In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 11, no 8, p. 649-656Article in journal (Refereed)
    Abstract [en]

    We have investigated the ability of the 3' exonuclease activity of Saccharomyces cerevisiae DNA polymerase ɛ (Pol ɛ) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol ɛ proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2-4-fold in pol2-4 rnh201Δ strains that are also defective in Pol ɛ proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an 'incorrect' sugar is less efficient than is proofreading of an incorrect base, Pol ɛ does proofread newly inserted rNMPs to enhance genome stability.

  • 1109. Wilsker, Deborah
    et al.
    Chung, Jon H.
    Pradilla, Ivan
    Petermann, Eva
    Helleday, Thomas
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Bunz, Fred
    Targeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and Survival2012In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 11, no 1, p. 98-107Article in journal (Refereed)
    Abstract [en]

    Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a subset of the drugs tested. These results show that specifically inhibiting the Cdk2/ATR/Chk1 pathway via distinct regulators can differentially sensitize cancer cells to a wide range of therapeutic agents.

  • 1110. Wind, Julia J.
    et al.
    Peviani, Alessia
    Snel, Berend
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Smeekens, Sjef C.
    ABI4: versatile activator and repressor2013In: Trends in Plant Science, ISSN 1360-1385, E-ISSN 1878-4372, Vol. 18, no 3, p. 125-132Article in journal (Refereed)
    Abstract [en]

    The ABSCISIC ACID INSENSITIVE4 (ABI4) gene was discovered to be an abscisic acid (ABA) signaling responsive transcription factor active during seed germination. The evolutionary history of the ABI4 gene supports its role as an ABA signaling intermediate in land plants. Investigating the ABI4 protein-cis element interaction supports the proposal that ABI4 binding to its known CE1 cis-element competes with transcription factor binding to the overlapping G-Box element. Recent publications report on ABI4 as a regulatory factor in diverse processes. In developing seedlings, ABI4 mediates sugar signaling, lipid breakdown, and plastid-to-nucleus signaling. Moreover, ABI4 is a regulator of rosette growth, redox signaling, cell wall metabolism and the effect of nitrate on lateral root development.

  • 1111.
    Wittenburg, Dörte
    et al.
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Melzer, Nina
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Willmitzer, Lothar
    Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Lisec, Jan
    Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Kesting, U
    Landeskontrollverband für Leistungs, Qualitätsprüfung Mecklenburg-Vorpommern e.V. (LKV), Güstrow, Germany .
    Reinsch, Norbert
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Repsilber, Dirk
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Milk metabolites and their genetic variability2013In: Journal of Dairy Science, ISSN 0022-0302, E-ISSN 1525-3198, Vol. 96, no 4, p. 2557-69Article in journal (Refereed)
    Abstract [en]

    The composition of milk is crucial to evaluate milk performance and quality measures. Milk components partly contribute to breeding scores, and they can be assessed to judge metabolic and energy status of the cow as well as to serve as predictive markers for diseases. In addition to the milk composition measures (e.g., fat, protein, lactose) traditionally recorded during milk performance test via infrared spectroscopy, novel techniques, such as gas chromatography-mass spectrometry, allow for a further analysis of milk into its metabolic components. Gas chromatography-mass spectrometry is suitable for measuring several hundred metabolites with high throughput, and thus it is applicable to study sources of genetic and nongenetic variation of milk metabolites in dairy cows. Heritability and mode of inheritance of metabolite measurements were studied in a linear mixed model approach including expected (pedigree) and realized (genomic) relationship between animals. The genetic variability of 190 milk metabolite intensities was analyzed from 1,295 cows held on 18 farms in Mecklenburg-Western Pomerania, Germany. Besides extensive pedigree information, genotypic data comprising 37,180 single nucleotide polymorphism markers were available. Goodness of fit and significance of genetic variance components based on likelihood ratio tests were investigated with a full model, including marker- and pedigree-based genetic effects. Broad-sense heritability varied from zero to 0.699, with a median of 0.125. Significant additive genetic variance was observed for highly heritable metabolites, but dominance variance was not significantly present. As some metabolites are particularly favorable for human nutrition, for instance, future research should address the identification of locus-specific genetic effects and investigate metabolites as the molecular basis of traditional milk performance test traits.

  • 1112.
    Wolf, Jochen B. W.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Ludwig Maximilian Univ Munich, Dept Biol 2, Sect Evolutionary Biol, Grosshaderner Str 2, D-82152 Planegg Martinsried, Germany..
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Making sense of genomic islands of differentiation in light of speciation2017In: Nature reviews genetics, ISSN 1471-0056, E-ISSN 1471-0064, Vol. 18, no 2, p. 87-100Article, review/survey (Refereed)
    Abstract [en]

    As populations diverge, genetic differences accumulate across the genome. Spurred by rapid developments in sequencing technology, genome-wide population surveys of natural populations promise insights into the evolutionary processes and the genetic basis underlying speciation. Although genomic regions of elevated differentiation are the focus of searches for 'speciation genes', there is an increasing realization that such genomic signatures can also arise by alternative processes that are not related to population divergence, such as linked selection. In this Review, we explore methodological trends in speciation genomic studies, highlight the difficulty in separating processes related to speciation from those emerging from genome-wide properties that are not related to reproductive isolation, and provide a set of suggestions for future work in this area.

  • 1113. Wong, Gane Ka-Shu
    et al.
    Liu, Bin
    Wang, Jun
    Zhang, Yong
    Yang, Xu
    Zhang, Zengjin
    Meng, Qingshun
    Zhou, Jun
    Li, Dawei
    Zhang, Jingjing
    Ni, Peixiang
    Li, Songgang
    Ran, Longhua
    Li, Heng
    Zhang, Jianguo
    Li, Ruiqiang
    Li, Shengting
    Zheng, Hongkun
    Lin, Wei
    Li, Guangyuan
    Wang, Xiaoling
    Zhao, Wenming
    Li, Jun
    Ye, Chen
    Dai, Mingtao
    Ruan, Jue
    Zhou, Yan
    Li, Yuanzhe
    He, Ximiao
    Zhang, Yunze
    Wang, Jing
    Huang, Xiangang
    Tong, Wei
    Chen, Jie
    Ye, Jia
    Chen, Chen
    Wei, Ning
    Li, Guoqing
    Dong, Le
    Lan, Fengdi
    Sun, Yongqiao
    Zhang, Zhenpeng
    Yang, Zheng
    Yu, Yingpu
    Huang, Yanqing
    He, Dandan
    Xi, Yan
    Wei, Dong
    Qi, Qiuhui
    Li, Wenjie
    Shi, Jianping
    Wang, Miaoheng
    Xie, Fei
    Wang, Jianjun
    Zhang, Xiaowei
    Wang, Pei
    Zhao, Yiqiang
    Li, Ning
    Yang, Ning
    Dong, Wei
    Hu, Songnian
    Zeng, Changqing
    Zheng, Weimou
    Hao, Bailin
    Hillier, Ladeana W
    Yang, Shiaw-Pyng
    Warren, Wesley C
    Wilson, Richard K
    Brandström, Mikael
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Ellegren, Hans
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Crooijmans, Richard P M A
    van der Poel, Jan J
    Bovenhuis, Henk
    Groenen, Martien A M
    Ovcharenko, Ivan
    Gordon, Laurie
    Stubbs, Lisa
    Lucas, Susan
    Glavina, Tijana
    Aerts, Andrea
    Kaiser, Pete
    Rothwell, Lisa
    Young, John R
    Rogers, Sally
    Walker, Brian A
    van Hateren, Andy
    Kaufman, Jim
    Bumstead, Nat
    Lamont, Susan J
    Zhou, Huaijun
    Hocking, Paul M
    Morrice, David
    de Koning, Dirk-Jan
    Law, Andy
    Bartley, Neil
    Burt, David W
    Hunt, Henry
    Cheng, Hans H
    Gunnarsson, Ulrika
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Wahlberg, Per
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Andersson, Leif
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Kindlund, Ellen
    Tammi, Martti T
    Andersson, Björn
    Webber, Caleb
    Ponting, Chris P
    Overton, Ian M
    Boardman, Paul E
    Tang, Haizhou
    Hubbard, Simon J
    Wilson, Stuart A
    Yu, Jun
    Wang, Jian
    Yang, Huanming
    A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.2004In: Nature, ISSN 1476-4687, Vol. 432, no 7018, p. 717-22Article in journal (Refereed)
  • 1114.
    Woronik, Alyssa
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Neethiraj, Ramprasad
    Stockholm University, Faculty of Science, Department of Zoology.
    Lehmann, Philipp
    Stockholm University, Faculty of Science, Department of Zoology.
    Maria, de la Paz Celorio Mancera
    Stockholm University, Faculty of Science, Department of Zoology.
    Stefanescu, Constanti
    Hill, Jason
    Stockholm University, Faculty of Science, Department of Zoology.
    Käkelä, Reijo
    Brattstrom, Oskar
    Wheat, Christopher
    Stockholm University, Faculty of Science, Department of Zoology.
    A transposable element insertion is associated with a female-limited, alternative life history strategyManuscript (preprint) (Other academic)
  • 1115. Wrzaczek, Michael
    et al.
    Vainonen, Julia P.
    Stael, Simon
    Tsiatsiani, Liana
    Help-Rinta-Rahko, Hanna
    Gauthier, Adrien
    Kaufholdt, David
    Bollhöner, Benjamin
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lamminmaki, Airi
    Staes, An
    Gevaert, Kris
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Van Breusegem, Frank
    Helariutta, Yka
    Kangasjarvi, Jaakko
    GRIM REAPER peptide binds to receptor kinase PRK5 to trigger cell death in Arabidopsis2015In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 31, no 1, p. 55-66Article in journal (Refereed)
    Abstract [en]

    Recognition of extracellular peptides by plasma membrane-localized receptor proteins is commonly used in signal transduction. In plants, very little is known about how extracellular peptides are processed and activated in order to allow recognition by receptors. Here, we show that induction of cell death in planta by a secreted plant protein GRIM REAPER (GRI) is dependent on the activity of the type II metacaspase METACASPASE-9. GRI is cleaved by METACASPASE-9 in vitro resulting in the release of an 11 amino acid peptide. This peptide bound in vivo to the extracellular domain of the plasma membrane-localized, atypical leucine-rich repeat receptor-like kinase POLLEN-SPECIFIC RECEPTOR-LIKE KINASE 5 (PRK5) and was sufficient to induce oxidative stress/ROS-dependent cell death. This shows a signaling pathway in plants from processing and activation of an extracellular protein to recognition by its receptor.

  • 1116. Wu, Chenglin
    et al.
    Mignardi, Marco
    chen, lei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landegren, Ulf
    Nilsson, Mats
    Profiling and genotyping individual mRNA molecules through in situ sequencing of super rolling circle amplification productsManuscript (preprint) (Other academic)
    Abstract [en]

    We have recently developed a technology for localized sequence library preparation with rolling-circle amplification (RCA) as an approach for in situ sequencing. This method involves generation of clonally amplified and specially confined substrates for next-generation sequencing within the preserved context of cells and tissues. Our approach combines padlock probing, RCA, and sequencing-by-ligation chemistry that can resolve expression profiles of sets of genes and mutations in tissues without loss of histological context. Like other fluorescence-based assays, it can be hindered by high level of background fluorescence. To achieve high signal-to-noise ratios, we now describe a method to boost the amplification generated by RCA of padlock probes in situ by super RCA (sRCA). In this technique, a second padlock probe is hybridized, ligated and amplified on the first RCA product for enhanced, localized amplification. We describe and compare different sRCA strategies where gap-fill ligation was showed to be most efficient. The sRCA products co-localize and have comparable sizes as RCA products but they display at least two fold higher signal intensity. This increase in signal to noise also proved to result in two folds increase in the number of sRCA products detected. By combining sRCA with in situ sequencing for highly multiplex detection in tissue a four-time increase was seen. In summary, we demonstrate that sRCA can significantly increase the performance of padlock-based in situ sequencing for gene expression profiling of tissue sections, enabling detection of low abundant transcripts and the analysis of also highly auto-fluorescent samples. 

  • 1117.
    Wu, Cuiyan
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Liu, Huan
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhang, Feng'e
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Shao, Wanzhen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Yang, Lei
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Ning, Yujie
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Wang, Sen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhao, Guanghui
    Department of Knee Joint, Xi'an Hong Hui Hospital, Xi'an, P.R. China.
    Lee, Byeong Jae
    Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, Korea.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Guo, Xiong
    Long noncoding RNA expression profile reveals lncRNAs signature associated with extracellular matrix degradation in kashin-beck disease2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17553Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.

  • 1118. Wu, Xiaofen
    et al.
    Pedersen, Karsten
    Edlund, Johanna
    Eriksson, Lena
    Astrom, Mats
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Bertilsson, Stefan
    Dopson, Mark
    Potential for hydrogen-oxidizing chemolithoautotrophic and diazotrophic populations to initiate biofilm formation in oligotrophic, deep terrestrial subsurface waters2017In: Microbiome, ISSN 0026-2633, E-ISSN 2049-2618, Vol. 5, article id 37Article in journal (Refereed)
    Abstract [en]

    Background: Deep terrestrial biosphere waters are separated from the light-driven surface by the time required to percolate to the subsurface. Despite biofilms being the dominant form of microbial life in many natural environments, they have received little attention in the oligotrophic and anaerobic waters found in deep bedrock fractures. This study is the first to use community DNA sequencing to describe biofilm formation under in situ conditions in the deep terrestrial biosphere. Results: In this study, flow cells were attached to boreholes containing either "modern marine" or "old saline" waters of different origin and degree of isolation from the light-driven surface of the earth. Using 16S rRNA gene sequencing, we showed that planktonic and attached populations were dissimilar while gene frequencies in the metagenomes suggested that hydrogen-fed, carbon dioxide-and nitrogen-fixing populations were responsible for biofilm formation across the two aquifers. Metagenome analyses further suggested that only a subset of the populations were able to attach and produce an extracellular polysaccharide matrix. Initial biofilm formation is thus likely to be mediated by a few bacterial populations which were similar to Epsilonproteobacteria, Deltaproteobacteria, Betaproteobacteria, Verrucomicrobia, and unclassified bacteria. Conclusions: Populations potentially capable of attaching to a surface and to produce extracellular polysaccharide matrix for attachment were identified in the terrestrial deep biosphere. Our results suggest that the biofilm populations were taxonomically distinct from the planktonic community and were enriched in populations with a chemolithoautotrophic and diazotrophic metabolism coupling hydrogen oxidation to energy conservation under oligotrophic conditions.

  • 1119.
    Wuolikainen, Anna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    ALS patients with mutations in the SOD1 gene have an unique metabolomic profile in the cerebrospinal fluid compared with ALS patients without mutations2012In: Molecular Genetics and Metabolism, ISSN 1096-7192, E-ISSN 1096-7206, Vol. 105, no 3, p. 472-478Article in journal (Refereed)
    Abstract [en]

    A specific biochemical marker for early diagnosing and for monitoring disease progression in amyotrophic lateral sclerosis (ALS) will have important clinical applications. ALS is a heterogeneous syndrome with multiple subtypes with ill-defined borders. A minority of patients carries mutations in the Cu/Zn-superoxide dismutase (SOD1) gene but the disease mechanism remains unknown for all types of ALS. Using a GC-TOFMS platform we studied the cerebrospinal fluid (CSF) metabolome in 16 ALS patients with six different mutations in the SOD1 gene and compared with ALS-patients without such mutations. OPLS-DA was used for classification modeling. We find that patients with a SOD1 mutation have a distinct metabolic profile in the CSF. In particular, the eight patients homozygous for the D90A SOD1 mutation showed a distinctively different signature when modeled against ALS patients with other SOD1 mutations and sporadic and familial ALS patients without a SOD1 gene mutation. This was found irrespective of medication with riluzole and survival time. Among the metabolites that contributed most to the CSF signature were arginine, lysine, ornithine, serine, threonine and pyroglutamic acid, all found to be reduced in patients carrying a D90A SOD1 mutation. ALS-patients with a SOD1 gene mutation appear as a distinct metabolic entity in the CSF, in particular in patients with the D90A mutation, the most frequently identified cause of ALS. The findings suggest that metabolomic profiling using GC-TOFMS and multivariate data analysis may be a future tool for diagnosing and monitoring disease progression, and may cast light on the disease mechanisms in ALS.

  • 1120. Wärmländer, Sebastian
    Struktur och dynamik hos DNA studerad med KSR och optisk spektroskopi = Structure and dynamics of DNA studied by NMR and optical spectroscopy2003Doctoral thesis, comprehensive summary (Other academic)
  • 1121. Xenikoudakis, G.
    et al.
    Ersmark, E.
    Tison, J. -L
    Waits, L.
    Kindberg, J.
    Swenson, J. E.
    Dalen, L.
    Consequences of a demographic bottleneck on geneticstructure and variation in the Scandinavian brown bear2015In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 24, no 13, p. 3441-3454Article in journal (Refereed)
  • 1122. Xie, Peiwu
    et al.
    Tu, Tieyao
    Razafimandimbison, Sylvain G.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Faculty of Science, The Bergius Botanical Garden Museum.
    Zhu, Chengjie
    Zhang, Dianxiang
    Phylogenetic position of Guihaiothamnus (Rubiaceae): Its evolutionary and ecological implications2014In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 78, p. 375-385Article in journal (Refereed)
    Abstract [en]

    Guihaiothamnus (Rubiaceae) is an enigmatic, monotypic genus endemic to southwestern China. Its generic status has never been doubted because it is morphologically unique by having rosette habit, showy, long-corolla-tubed flowers, and multi-seeded indehiscent berry-like fruits. The genus has been postulated to be a relict in the broad-leaved forests of China, and to be related to the genus Wendlandia, which was placed in the subfamily Cinchonoideae and recently classified in the tribe Augusteae of the subfamily Dialypetalanthoideae. Using combined evidence from palynology, cytology, and DNA sequences of nuclear ITS and four plastid markers (rps16, trnT-F, ndhF, rbcL), we assessed the phylogenetic position of Guihaiothamnus in Rubiaceae. Our molecular phylogenetic analyses placed the genus deeply nested within Wendlandia. This relationship is corroborated by evidence from palynology and cytology. Using a relaxed molecular clock method based on five fossil records, we dated the stem age of Wendlandia to be 17.46 my and, the split between G. acaulis and related Wendlandia species in southwestern China to be 2.11 mya. This young age, coupled with the derived position in Wendlandia, suggests an evolutionary derivation rather than an evolutionary relict of G. acaulis. Its rosette habit and large showy flowers, which are very distinctive from other Wendlandias, are interpreted as a result of recent rapid adaptation to rock and cliff habitats.

  • 1123. Xing, Fangqian
    et al.
    Mao, Jian-Feng
    Meng, Jingxiang
    Dai, Jianfeng
    Zhao, Wei
    Liu, Hao
    Xing, Zhen
    Zhang, Hua
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Li, Yue
    Needle morphological evidence of the homoploid hybrid origin of Pinus densata based on analysis of artificial hybrids and the putative parents, Pinus tabuliformis and Pinus yunnanensis2014In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 4, no 10, p. 1890-1902Article in journal (Refereed)
    Abstract [en]

    Genetic analyses indicate that Pinus densata is a natural homoploid hybrid originating from Pinus tabuliformis and Pinus yunnanensis. Needle morphological and anatomical features show relative species stability and can be used to identify coniferous species. Comparative analyses of these needle characteristics and phenotypic differences between the artificial hybrids, P.densata, and parental species can be used to determine the genetic and phenotypic evolutionary consequences of natural hybridization. Twelve artificial hybrid families, the two parental species, and P.densata were seeded in a high-altitude habitat in Linzhi, Tibet. The needles of artificial hybrids and the three pine species were collected, and 24 needle morphological and anatomical traits were analyzed. Based on these results, variations in 10 needle traits among artificial hybrid families and 22 traits among species and artificial hybrids were predicted and found to be under moderate genetic control. Nineteen needle traits in artificial hybrids were similar to those in P.densata and between the two parental species, P.tabuliformis and P.yunnanensis. The ratio of plants with three needle clusters in artificial hybrids was 22.92%, which was very similar to P.densata. The eight needle traits (needle length, the mean number of stomata in sections 2mm in length of the convex and flat sides of the needle, mean stomatal density, mesophyll/vascular bundle area ratio, mesophyll/resin canal area ratio, mesophyll/(resin canals and vascular bundles) area ratio, vascular bundle/resin canal area ratio) relative to physiological adaptability were similar to the artificial hybrids and P.densata. The similar needle features between the artificial hybrids and P.densata could be used to verify the homoploid hybrid origin of P.densata and helps to better understand of the hybridization roles in adaptation and speciation in plants.

  • 1124.
    Xochelli, Aliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. ..
    Kavakiotis, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Agathangelidis, Andreas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ntoufa, Stavroula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Yan, Xiao-Jie
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait
    Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Rossi, Davide
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Navarro, Alba
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Sandberg, Yorick
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Scarfo, Lydia
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast, Antrim, North Ireland..
    Kienle, Dirk
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Facco, Monica
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Bahlo, Jasmin
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Pedersen, Lone Bredo
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Chu, Charles C.
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Giudicelli, Veronique
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Lefranc, Marie-Paule
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Vlahavas, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Antic, Darko
    Ctr Clin, Clin Hematol, Belgrade, Serbia.;Univ Belgrade, Fac Med, Belgrade, Serbia..
    Trentin, Livio
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Montillo, Marco
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Niemann, Carsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Doehner, Hartmut
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hallek, Michael
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Campo, Elias
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Chiorazzi, Nicholas
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Maglaveras, Nikos
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, Gianluca
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chouvarda, Ioanna
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece ;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 17, p. 5292-5301Article in journal (Refereed)
    Abstract [en]

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.  

  • 1125.
    Xu, Dongqing
    et al.
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.;Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Lin, Fang
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Jiang, Yan
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.;Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Ling, Junjie
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Hettiarachchi, Chamari
    Univ Colombo, Dept Chem, Colombo, Sri Lanka..
    Tellgren-Roth, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Holm, Magnus
    Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Wei, Ning
    Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA..
    Deng, Xing Wang
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Arabidopsis COP1 SUPPRESSOR 2 Represses COP1 E3 Ubiquitin Ligase Activity through Their Coiled-Coil Domains Association2015In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 12, article id e1005747Article in journal (Refereed)
    Abstract [en]

    CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) functions as an E3 ubiquitin ligase and mediates a variety of developmental processes in Arabidopsis by targeting a number of key regulators for ubiquitination and degradation. Here, we identify a novel COP1 interacting protein, COP1 SUPPRESSOR 2 (CSU2). Loss of function mutations in CSU2 suppress the constitutive photomorphogenic phenotype of cop1-6 in darkness. CSU2 directly interacts with COP1 via their coiled-coil domains and is recruited by COP1 into nuclear speckles in living plant cells. Furthermore, CSU2 inhibits COP1 E3 ubiquitin ligase activity in vitro, and represses COP1 mediated turnover of HY5 in cell-free extracts. We propose that in csu2 cop1-6 mutants, the lack of CSU2's repression of COP1 allows the low level of COP1 to exhibit higher activity that is sufficient to prevent accumulation of HY5 in the dark, thus restoring the etiolated phenotype. In addition, CSU2 is required for primary root development under normal light growth condition.

  • 1126.
    Xu, Feifei
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jerlström-Hultqvist, Jon
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Einarsson, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Astvaldsson, Asgeir
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svärd, Staffan G
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 2, p. e1004053-Article in journal (Refereed)
    Abstract [en]

    Spironucleus salmonicida causes systemic infections in salmonid fish. It belongs to the group diplomonads, binucleated heterotrophic flagellates adapted to micro-aerobic environments. Recently we identified energy-producing hydrogenosomes in S. salmonicida. Here we present a genome analysis of the fish parasite with a focus on the comparison to the more studied diplomonad Giardia intestinalis. We annotated 8067 protein coding genes in the ∼12.9 Mbp S. salmonicida genome. Unlike G. intestinalis, promoter-like motifs were found upstream of genes which are correlated with gene expression, suggesting a more elaborate transcriptional regulation. S. salmonicida can utilise more carbohydrates as energy sources, has an extended amino acid and sulfur metabolism, and more enzymes involved in scavenging of reactive oxygen species compared to G. intestinalis. Both genomes have large families of cysteine-rich membrane proteins. A cluster analysis indicated large divergence of these families in the two diplomonads. Nevertheless, one of S. salmonicida cysteine-rich proteins was localised to the plasma membrane similar to G. intestinalis variant-surface proteins. We identified S. salmonicida homologs to cyst wall proteins and showed that one of these is functional when expressed in Giardia. This suggests that the fish parasite is transmitted as a cyst between hosts. The extended metabolic repertoire and more extensive gene regulation compared to G. intestinalis suggest that the fish parasite is more adapted to cope with environmental fluctuations. Our genome analyses indicate that S. salmonicida is a well-adapted pathogen that can colonize different sites in the host.

  • 1127. Xue, Weiya
    et al.
    Ruprecht, Colin
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hematy, Kian
    Chang, Christine
    Frommer, Wolf B
    Persson, Staffan
    Niittyla, Totte
    Paramutation-like interaction of T-DNA loci in arabidopsis2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51651-Article in journal (Refereed)
    Abstract [en]

    In paramutation, epigenetic information is transferred from one allele to another to create a gene expression state which is stably inherited over generations. Typically, paramutation describes a phenomenon where one allele of a gene down-regulates the expression of another allele. Paramutation has been described in several eukaryotes and is best understood in plants. Here we describe an unexpected paramutation-like trans SALK T-DNA interaction in Arabidopsis. Unlike most of the previously described paramutations, which led to gene silencing, the trans SALK T-DNA interaction caused an increase in the transcript levels of the endogenous gene (COBRA) where the T-DNA was inserted. This increased COBRA expression state was stably inherited for several generations and led to the partial suppression of the cobra phenotype. DNA methylation was implicated in this trans SALK T-DNA interaction since mutation of the DNA methyltransferase 1 in the suppressed cobra caused a reversal of the suppression. In addition, null mutants of the DNA demethylase ROS1 caused a similar COBRA transcript increase in the cobra SALK T-DNA mutant as the trans T-DNA interaction. Our results provide a new example of a paramutation-like trans T-DNA interaction in Arabidopsis, and establish a convenient hypocotyl elongation assay to study this phenomenon. The results also alert to the possibility of unexpected endogenous transcript increase when two T-DNAs are combined in the same genetic background. Citation: Xue W, Ruprecht C, Street N, Hematy K, Chang C, et al. (2012) Paramutation-Like Interaction of T-DNA Loci in Arabidopsis. PLoS ONE 7(12): e51651. doi:10.1371/journal.pone.0051651

  • 1128.
    Xue-Franzen, Yongtao
    et al.
    Södertörn University, School of Life Sciences. Karolinska Institutet.
    Kjaerulff, Soren
    University of Copenhagen, Copenhagen, Denmark.
    Holmberg, Christian
    University of Copenhagen, Copenhagen, Denmark.
    Wright, Anthony
    Södertörn University, School of Life Sciences. Karolinska Institutet.
    Nielsen, Olaf
    University of Copenhagen, Copenhagen, Denmark.
    Genomewide identification of pheromone-targeted transcription in fission yeast2006In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 7, p. 303-, article id 303Article in journal (Refereed)
    Abstract [en]

    Background: Fission yeast cells undergo sexual differentiation in response to nitrogen starvation. In this process haploid M and P cells first mate to form diploid zygotes, which then enter meiosis and sporulate. Prior to mating, M and P cells communicate with diffusible mating pheromones that activate a signal transduction pathway in the opposite cell type. The pheromone signalling orchestrates mating and is also required for entry into meiosis. Results: Here we use DNA microarrays to identify genes that are induced by M-factor in P cells and by P-factor in M-cells. The use of a cyr1 genetic background allowed us to study pheromone signalling independently of nitrogen starvation. We identified a total of 163 genes that were consistently induced more than two-fold by pheromone stimulation. Gene disruption experiments demonstrated the involvement of newly discovered pheromone-induced genes in the differentiation process. We have mapped Gene Ontology ( GO) categories specifically associated with pheromone induction. A direct comparison of the M- and P-factor induced expression pattern allowed us to identify cell-type specific transcripts, including three new M- specific genes and one new P-specific gene. Conclusion: We found that the pheromone response was very similar in M and P cells. Surprisingly, pheromone control extended to genes fulfilling their function well beyond the point of entry into meiosis, including numerous genes required for meiotic recombination. Our results suggest that the SteII transcription factor is responsible for the majority of pheromone-induced transcription. Finally, most cell-type specific genes now appear to be identified in fission yeast.

  • 1129. Xun, Wei Wei
    et al.
    Brennan, Paul
    Tjonneland, Anne
    Vogel, Ulla
    Overvad, Kim
    Kaaks, Rudolf
    Canzian, Federico
    Boeing, Heiner
    Trichopoulou, Antonia
    Oustoglou, Erifili
    Giotaki, Zoi
    Johansson, Mattias
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H M
    Lund, Eiliv
    Kumle, Merethe
    Rodríguez, Laudina
    Agudo, Antonio
    Sánchez, Maria-José
    Arriola, Larraitz
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Key, Tim
    Riboli, Elio
    Vineis, Paolo
    Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).2011In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 26, no 5, p. 657-666Article in journal (Refereed)
    Abstract [en]

    The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

  • 1130.
    Yazdi, Homa Papoli
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Old but Not (So) Degenerated-Slow Evolution of Largely Homomorphic Sex Chromosomes in Ratites2014In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 6, p. 1444-1453Article in journal (Refereed)
    Abstract [en]

    Degeneration of the nonrecombining chromosome is a common feature of sex chromosome evolution, readily evident by the presence of a pair of largely heteromorphic chromosomes, like in eutherian mammals and birds. However, in ratites (order Palaeognathae, including, e.g., ostrich), the Z and W chromosomes are similar in size and largely undifferentiated, despite avian sex chromosome evolution was initiated > 130 Ma. To better understand what may limit sex chromosome evolution, we performed ostrich transcriptome sequencing and studied genes from the nonrecombining region of the W chromosome. Fourteen gametologous gene pairs present on the W chromosome and Z chromosome were identified, with synonymous sequence divergence of 0.027-0.177. The location of these genes on the Z chromosome was consistent with a sequential increase in divergence, starting 110-157 and ending 24-30 Ma. On the basis of the occurrence of Z-linked genes hemizygous in females, we estimate that about one-third of the Z chromosome does not recombine with the W chromosome in female meiosis. Pairwise d(N)/d(S) between gametologs decreased with age, suggesting strong evolutionary constraint in old gametologs. Lineage-specific d(N)/d(S) was consistently higher in W-linked genes, in accordance with the lower efficacy of selection expected in nonrecombining chromosomes. A higher ratio of GC > AT:AT > GC substitutions in W-linked genes supports a role for GC-biased gene conversion in differentially driving base composition on the two sex chromosomes. A male-to-female (M:F) expression ratio of close to one for recombining genes and close to two for Z-linked genes lacking a W copy show that dosage compensation is essentially absent. Some gametologous genes have retained active expression of the W copy in females (giving a M:F ratio of 1 for the gametologous gene pair), whereas for others W expression has become severely reduced resulting in a M:F ratio of close to 2. These observations resemble the patterns of sex chromosome evolution seen in other avian and mammalian lineages, suggesting similar underlying evolutionary processes, although the rate of sex chromosome differentiation has been atypically low. Lack of dosage compensation may be a factor hindering sex chromosome evolution in this lineage.

  • 1131.
    Yurova Axelsson, Ekaterina
    Linnaeus University, Faculty of Technology, Department of Mathematics.
    On the representation of the genetic code by the attractors of 2-adic function2015In: Physica scripta. T, ISSN 0281-1847, Vol. 2015, no T 165, article id 014043Article in journal (Refereed)
    Abstract [en]

    The genetic code is a map which gives the correspondence between codons in DNA and amino acids. As a continuation of the study made by Khrennikov and Kozyrev on the genetic code, we consider a construction, where amino acids are associated to the attractors of some two-adic function. In this paper, we give an explicit form of representations for the standard nuclear and vertebrate mitochondrial genetics codes. To set these functions we use a van der Put representation. The usage of the van der Put series reduces the complexity of computation for explicit form of the functions for the genetic codes.

  • 1132.
    Zajitschek, Felix
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Jin, Tuo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Colchero, Fernando
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Aging Differently: Diet- and Sex-Dependent Late-Life Mortality Patterns in Drosophila melanogaster2014In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 69, no 6, p. 666-674Article in journal (Refereed)
    Abstract [en]

    Diet effects on age-dependent mortality patterns are well documented in a large number of animal species, but studies that look at the effects of nutrient availability on late-life mortality plateaus are lacking. Here, we focus on the effect of dietary protein content (low, intermediate, and high) on mortality trajectories in late life in the fruit fly Drosophila melanogaster. According to the two theories that are mainly implicated in explaining the deceleration of mortality rate in late life (the heterogeneity/frailty theory and the Hamiltonian theory), we predict, in general, the occurrence of late-life mortality deceleration under most circumstances, independent of sex and dietary regime. However, the heterogeneity theory of late life is more flexible in allowing no mortality deceleration to occur under certain circumstances compared with the Hamiltonian theory. We applied a novel statistical approach based on Bayesian inference of age-specific mortality rates and found a deceleration of late-life mortality rates on all diets in males but only on the intermediate (standard) diet in females. The difference in mortality rate deceleration between males and females on extreme diets suggests that the existence of mortality plateaus in late life is sex and diet dependent and, therefore, not a universal characteristic of large enough cohorts.

  • 1133.
    Zajitschek, Felix
    et al.
    Department of Animal Ecology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Zajitschek, Susanne R. K.
    Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Friberg, Urban
    Department of Evolutionary Biology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Maklakov, Alexei A.
    Department of Animal Ecology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies2013In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 35, no 4, p. 1193-1204Article in journal (Refereed)
    Abstract [en]

    For the evolution of life histories, the trade-off between survival and reproduction is fundamental. Because sexes optimize fitness in different ways, this trade-off is expected to be resolved differently by males and females. Consequently, the sexes are predicted to respond differently to changes in resource availability. In fruit flies, research on dietary restriction has focused largely on females maintained in the absence of males, thereby neglecting sexual interactions that affect reproductive behavior of both sexes under more natural conditions. Here, we tested for the interactive effects of diet (40, 60, 100, and 300 % of standard yeast concentrations) and social environment (separate-sex vs. mixed-sex groups) on male and female Drosophila melanogaster life histories. Additionally, we evaluated the essential amino acid methionine as an agent that can uncouple the survival-reproduction trade-off. We show sex differences in the effect of social environment on survival patterns, but not on reproductive fitness. In females, yeast had a positive effect on reproduction and a negative effect on survival. In males, yeast had a negative effect on reproduction and the effect on survival depended on the social environment. Methionine reduced survival, but had no effect on reproduction. Our findings highlight the need to include both sexes and to vary social environments in research programs aimed at lifespan extension and call for further evaluation of the fecundity-restoring effect of methionine.

  • 1134.
    Zan, Yanjun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Div Computat Genet, Dept Clin Sci, SE-75651 Uppsala, Sweden.
    Shen, Xia
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH16 4UX, Midlothian, Scotland; Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH16 4UX, Midlothian, Scotland; Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
    Forsberg, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Div Computat Genet, Dept Clin Sci, SE-75651 Uppsala, Sweden.
    Carlborg, Orjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Div Computat Genet, Dept Clin Sci, SE-75651 Uppsala, Sweden.
    Genetic Regulation of Transcriptional Variation in Natural Arabidopsis thaliana Accessions2016In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 6, no 8, p. 2319-2328Article in journal (Refereed)
    Abstract [en]

    An increased knowledge of the genetic regulation of expression in Arabidopsis thaliana is likely to provide important insights about the basis of the plant's extensive phenotypic variation. Here, we reanalysed two publicly available datasets with genome-wide data on genetic and transcript variation in large collections of natural A. thaliana accessions. Transcripts from more than half of all genes were detected in the leaf of all accessions, and from nearly all annotated genes in at least one accession. Thousands of genes had high transcript levels in some accessions but no transcripts at all in others and this pattern was correlated with the genome-wide genotype. In total, 2,669 eQTL were mapped in the largest population, and 717 of them were replicated in the other population. 646 cis-eQTLs regulated genes that lacked detectable transcripts in some accessions, and for 159 of these we identified one, or several, common structural variants in the populations that were shown to be likely contributors to the lack of detectable RNA-transcripts for these genes. This study thus provides new insights on the overall genetic regulation of global gene-expression diversity in the leaf of natural A. thaliana accessions. Further, it also shows that strong cis-acting polymorphisms, many of which are likely to be structural variations, make important contributions to the transcriptional variation in the worldwide A. thaliana population.

  • 1135.
    Zan, Yanjun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sheng, Zheya
    Lillie, Mette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rönnegård, Lars
    Honaker, Christa F
    Siegel, Paul B
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. SLU.
    Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 10, p. 2678-2689Article in journal (Refereed)
    Abstract [en]

    The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity.

  • 1136.
    Zarif Saffari, Amin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Exploring the diversity of unmapped reads from human deep sequencing2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    currently DNA and RNA sequencing are performed as standard parts of many scientific experiments. While the majority of the reads produced in these experiments do map to the genome of the organism of interest there are a significant fraction that do not. These reads have often been viewed as uninteresting and thus discarded, sometimes explained as errors created in the sequencing process. However, there may be a real possibility that these reads actually contain genomic sequences belonging to, but not currently in the genome ofthe organism investigated, as well as information about other organisms which live and thrivein the sample material. Considering this, it is of great interest to investigate these reads to see if they contain any usable information. In this project the unmapped reads from SOLiD sequencing of blood and saliva from a twin pair were assembled. The assembled parts were thencompared to different blast databases to investigate if similar genomic regions are reported inother species. We can conclude that indeed a large fraction of the contigs found in this assemblyhave homology to bacterial genes while other contigs share similarity to genomic regions foundin apes and other species closely related to us. All in all the results show that there is more to the unmapped reads than just sequencing errors.

  • 1137. Zas, Rafael
    et al.
    Björklund, Niklas
    Sampedro, Luis
    Hellqvist, Claes
    Karlsson, Bo
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Nordlander, Göran
    Genetic variation in resistance of Norway spruce seedlings to damage by the pine weevil Hylobius abietis2017In: Tree Genetics & Genomes, ISSN 1614-2942, E-ISSN 1614-2950, Vol. 13, no 5, article id 111Article in journal (Refereed)
    Abstract [en]

    Regeneration of northern conifer forests is commonly performed by reforestation with genetically improved materials obtained from long-term breeding programs focused on productivity and timber quality. Sanitary threats can, however, compromise the realization of the expected genetic gain. Including pest resistance traits in the breeding programs may contribute to a sustainable protection. Here we quantified the variation in different components of resistance of Norway spruce to its main pest, the pine weevil Hylobius abietis. We followed insect damage in two large progeny trials (52 open-pollinated families with 100-200 individuals per family and trial) naturally infested by the pine weevil. Pine weevils damaged between 17 and 48% of the planted seedlings depending on the trial and year, and mortality due to weevil damage was up to 11.4%. The results indicate significant genetic variation in resistance to the pine weevil, and importantly, the variation was highly consistent across trials irrespective of contrasting incidence levels. Individual heritability estimates for the different components of seedling resistance were consistently low, but family heritabilities were moderate (0.53 to 0.81). While forward selections and breeding for higher resistance seem not feasible, backwards selections of the best parent trees emerge as a putative alternative to reduce weevil damage. A positive genetic correlation between early growth potential and probability of being attacked by the weevil was also observed, but the relationship was weak and appeared only in one of the trials. Overall, results presented here open the door to a new attractive way for reducing damage caused by this harmful pest.

  • 1138.
    Zhang, Jiazhuo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Isolation and Characterization of Uncultured Freshwater Bacterioplankton from Lake Ekoln and Lake Erken through Dilution-to-Extinction Approach and Molecular Analysis Tools2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Not many of the abundant freshwater bacterial groups have a representative cultured isolate. In this master thesis project, some abundant bacterioplankton from two lakes (Lake Ekoln and Lake Erken) could be isolated by a dilution-to-extinction approach. Sterilized lake water which was obtained through an ultrafiltration system was used resembling a natural medium. Specific fragments of 16s rRNA of the isolates were amplified by universal bacterial primers (27f and 1492r, 341f and 805r.) for genotyping against a freshwater sequence database and RDP training set (Version 7). A total of 33 isolates from the two lakes were taxonomically classified and revealed the isolation of typical and abundant freshwater bacteria. Original bacterial community of Lake Ekoln was also analyzed by 16S rRNA clone library construction for diversity study. Phylogenetic trees were built through neighbor-joining method by Mega (Version 5) to reveal the evolutionary relationships among database entries, obtained isolates and clones. 

  • 1139.
    Zhang, Jingpu
    et al.
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Rasmuson-Lestander, Åsa
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Expression preference of the S-adenosylmethionine synthetase (SamS) gene in Drosophila melanogaster1997In: Dev Rep Biol, Vol. 6, p. 7-17Article in journal (Other (popular science, discussion, etc.))
  • 1140.
    Zhao, Jin J.
    et al.
    Uppsala University, Sweden.
    Halvardson, Jonatan
    Uppsala University, Sweden.
    Zander, Cecilia S.
    Uppsala University, Sweden.
    Zaghlool, Ammar
    Uppsala University, Sweden.
    Georgii-Hemming, Patrik
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Mansson, Else
    Örebro University Hospital, Sweden.
    Brandberg, Göran
    Pediat Clin, Falun, Sweden.
    Savmarker, Helena E.
    Gävle Central Hospital, Sweden.
    Frykholm, Carina
    Uppsala University, Sweden.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Thuresson, Ann-Charlotte
    Uppsala University, Sweden.
    Feuk, Lars
    Uppsala University, Sweden.
    Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability2018In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 177, no 1, p. 10-20Article in journal (Refereed)
    Abstract [en]

    Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.

  • 1141.
    Zheng, Ning
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Mediation modeling and analysis forhigh-throughput omics data2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    There is a strong need for powerful unified statistical methods for discovering underlying genetic architecture of complex traits with the assistance of omics information. In this paper, two methods aiming to detect novel association between the human genome and complex traits using intermediate omics data are developed based on statistical mediation modeling. We demonstrate theoretically that given proper mediators, the proposed statistical mediation models have better power than genome-wide association studies (GWAS) to detect associations missed in standard GWAS that ignore the mediators. For each ofthe modeling methods in this paper, an empirical example is given, where the association between a SNP and BMI missed by standard GWAS can be discovered by mediation analysis.

  • 1142. Zhou, G Q
    et al.
    Zhang, Y
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The carcinoembryonic antigen (CEA) gene family in non-human primates.2001In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 264, no 1, p. 105-12Article in journal (Refereed)
    Abstract [en]

    Carcinoembryonic antigen (CEA) is a tumor marker of wide clinical use though its function remains unknown. The CEA counterpart and some related macromolecules cannot be demonstrated in mice, thus prohibiting studies of CEA function by gene disruption strategies. In an attempt to find a relevant animal model for functional studies of CEA we have investigated the occurrence of CEA subgroup members in baboon and African green monkey at the genomic and mRNA levels. The investigation was focused on the characteristic immunoglobulin-variable region-like (IgV-like) N-terminal domain of the family members. Based on N-domain sequences 3 and 4 different CEA subgroup genes, respectively, were identified. One sequence in each monkey species corresponded to human CEACAM8, while it was not possible to assign an obvious human counterpart for the other N-domain sequences. However, studies of cDNAs from African green monkey COS-1 cells identified one of the sequences as CEACAM1. Expression of CEACAM1 mRNA and protein was upregulated by IFNgamma as has previously been demonstrated for human CEACAM1. Presence of GPI-linked CEA subgroup members in African green monkey was suggested by sequencing. Both monkey species would thus seem suitable for functional studies of selected CEA subgroup members.

  • 1143. Zieba, A.
    et al.
    Sjöstedt, Evelina
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Olovsson, M.
    Fagerberg, Linn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Oskarsson, L.
    Edlund, K.
    Tolf, A.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ponten, F.
    The Human Endometrium-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling2015In: Omics, ISSN 1536-2310, E-ISSN 1557-8100, Vol. 19, no 11, p. 659-668Article in journal (Refereed)
    Abstract [en]

    The human uterus includes the complex endometrial mucosa, the endometrium that undergoes dynamic, hormone-dependent alterations throughout the life of fertile females. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to analyze gene expression patterns in the normal endometrium. Human endometrial tissues from five women were used for deep sequencing (RNA-Seq). The mRNA and protein expression data from the endometrium were compared to 31 (RNA) and 44 (protein) other normal tissue types, to identify genes with elevated expression in the endometrium and to localize the expression of corresponding proteins at a cellular resolution. Based on the expression levels of transcripts, we could classify all putative human protein coding genes into categories defined by expression patterns and found altogether 101 genes that showed an elevated pattern of expression in the endometrium, with only four genes showing more than five-fold higher expression levels in the endometrium compared to other tissues. In conclusion, our analysis based on transcriptomics and antibody-based protein profiling reports here comprehensive lists of genes with elevated expression levels in the endometrium, providing important starting points for a better molecular understanding of human reproductive biology and disease.

  • 1144.
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Investigation of Mechanics of Mutation and Selection by Comparative Sequencing2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The process of evolution is of both scientific and medical interest. This thesis presents several studies using complete genomic reference sequences, comparative genomic data, and intraspecific diversity data to study the two key processes of evolution: mutation and selection.

    Large duplications, deletions, inversions, and translocations of DNA contribute to genomic variation both between and within species. Human chromosomes 15 and 17 contain a high percentage of dispersed, recently duplicated sequences. Examination of the relationships between these sequences showed that the majority of all duplications within each chromosome could be linked through core sequences that are prone to duplication. Comparison to orthologous sequences in other mammals allowed a reconstruction of the ancestral state of the human chromosomes, revealing that regions of rearrangement specific to the human lineage are highly enriched in chromosome-specific duplications. Comparison to copy number variation data from other studies also shows that these regions are enriched in current human structural variation. One specific region, the MAPT locus at 17q21.31, known to contain an inversion polymorphism in Europeans, was resequenced completely across both human orientation haplotypes and in chimpanzee and orangutan, revealing complex duplication structures at the inversion breakpoints, with the human region being more complex than chimpanzee or orangutan. Fluorescent in-situ hybridization analysis of human, chimpanzee, and orangutan chromosomes showed inversion polymorphisms of independent origin in all three species, demonstrating that this region has been a hotspot of genomic rearrangement for at least twelve million years. These results reveal a mechanistic relationship between sequence duplication and rearrangement in the great apes.

    We also generated a draft sequence of the chimpanzee genome and compared it to that of the human. Among other findings, this showed that CpG dinucleotides contribute 25% of all single base mutations, with a rate of mutation ~10-fold that of other bases, and that the male mutation rate in great apes is ~5-6 times the female rate, a higher ratio than had been observed in comparisons of primates and rodents. We detected six regions of probable recent positive selection in humans with a statistical method relying on chimpanzee sequence to control for regional variation in mutation rates.

    Finally, resequencing of several lines of domestic chicken and comparison to the reference chicken genome identified a number of gene deletions fixed in domestic lines and also several potential selective sweeps. Of particular interest are a missense mutation in TSHR nearly fixed in all domestic chickens and a partial deletion of SH3RF2 fixed in a high growth line. The TSHR mutation may play a role in relaxation of seasonal reproduction. A high-resolution QTL mapping experiment showed that the SH3RF2 deletion is significantly associated with increased growth.

    This work provides important new insights into the mechanics of evolutionary change at both the single nucleotide and structural level and identifies potential targets of natural and artificial selection in humans and chickens.

  • 1145.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Adams, David
    The Wellcome Trust Sanger Institute.
    Sharpe, Ted
    Broad Institute.
    Harrow, Jennifer
    The Wellcome Trust Sanger Institute.
    Lupski, James
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Nicholson, Christine
    The Wellcome Trust Sanger Institute.
    Searle, Steven
    The Wellcome Trust Sanger Institute.
    Wilming, Laurens
    The Wellcome Trust Sanger Institute.
    Young, Sarah
    Broad Institute.
    Abouelleil, Amr
    Broad Institute.
    Allen, Nicole
    Broad Institute.
    Bi, Weimin
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Bugalter, Boris
    Broad Institute.
    Butler, Jonathan
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Chen, Chao-Kung
    The Wellcome Trust Sanger Institute.
    Cook, April
    Broad Institute.
    Corum, Benjamin
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    de Jong, Pieter
    Children's Hospital Oakland Research Institute.
    DeCaprio, David
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Gilbert, James
    The Wellcome Trust Sanger Institute.
    Gibson, Richard
    The Wellcome Trust Sanger Institute.
    Gnerre, Sante
    Broad Institute.
    Goldstein, Steven
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Grafham, Darren
    The Wellcome Trust Sanger Institute.
    Grocock, Russell
    The Wellcome Trust Sanger Institute.
    Hafez, Nabil
    Broad Institute.
    Hagopian, Daniel
    Broad Institute.
    Hart, Elizabeth
    The Wellcome Trust Sanger Institute.
    Hosage Norman, Catherine
    Broad Institute.
    Humphray, Sean
    The Wellcome Trust Sanger Institute.
    Jaffe, David
    Broad Institute.
    Jones, Matt
    The Wellcome Trust Sanger Institute.
    Kamal, Michael
    Broad Institute.
    Khodiyan, Varsha
    University College London, Department of Biology.
    LaButti, Kurt
    Broad Institute.
    Laird, Gavin
    The Wellcome Trust Sanger Institute.
    Lehoczky, Jessica
    Broad Institute.
    Liu, Xiaohong
    Broad Institute.
    Lokyitsang, Tashi
    Broad Institute.
    Loveland, Jane
    The Wellcome Trust Sanger Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Major, John
    Broad Institute.
    Matthews, Lucy
    The Wellcome Trust Sanger Institute.
    Mauceli, Evan
    Broad Institute.
    McCarroll, Steven
    Broad Institute.
    Mihalev, Atanas
    Broad Institute.
    Mudge, Jonathan
    The Wellcome Trust Sanger Institute.
    Nguyen, Cindy
    Broad Institute.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Osoegawa, Kazutoyo
    Children's Hospital Oakland Research Institute.
    Schwartz, David
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Shaw-Smith, Charles
    The Wellcome Trust Sanger Institute.
    Stankiewicz, Pawel
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Steward, Charles
    The Wellcome Trust Sanger Institute.
    Swarbreck, David
    The Wellcome Trust Sanger Institute.
    Venkataraman, Vijay
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Yang, Xiaoping
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Bradley, Allan
    The Wellcome Trust Sanger Institute.
    Hubbard, Tim
    The Wellcome Trust Sanger Institute.
    Birren, Bruce
    Broad Institute.
    Rogers, Jane
    The Wellcome Trust Sanger Institute.
    Lander, Eric
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 440, no 7087, p. 1045-1049Article in journal (Refereed)
    Abstract [en]

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

  • 1146.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Sharpe, Ted
    Broad Institute.
    Young, Sarah
    Broad Institute.
    Rowen, Lee
    Institute for Systems Biology.
    O'Neill, Keith
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Kamal, Michael
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Kodira, Chinnappa
    Broad Institute.
    Madan, Anup
    Institute for Systems Biology.
    Qin, Shizhen
    Institute for Systems Biology.
    Yang, Xiaoping
    Broad Institute.
    Abbasi, Nissa
    Institute for Systems Biology.
    Abouelleil, Amr
    Broad Institute.
    Arachchi, Harindra
    Broad Institute.
    Baradarani, Lida
    Institute for Systems Biology.
    Birditt, Brian
    Institute for Systems Biology.
    Bloom, Scott
    Institute for Systems Biology.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Burke, Jeremy
    Institute for Systems Biology.
    Butler, Jonathan
    Broad Institute.
    Cook, April
    Broad Institute.
    DeArellano, Kurt
    Broad Institute.
    DeCaprio, David
    Broad Institute.
    Dorris, Lester
    Broad Institute.
    Dors, Monica
    Institute for Systems Biology.
    Eichler, Evan
    University of Washington, Department of Genome Sciences.
    Engels, Reinhard
    Broad Institute.
    Fahey, Jessica
    Institute for Systems Biology.
    Fleetwood, Peter
    Institute for Systems Biology.
    Friedman, Cynthia
    Fred Hutchinson Cancer Research Center, Division of Human Biology.
    Gearin, Gary
    Broad Institute.
    Hall, Jennifer
    Broad Institute.
    Hensley, Grace
    Institute for Systems Biology.
    Johnson, Ericka
    Institute for Systems Biology.
    Jones, Charlien
    Broad Institute.
    Kamat, Asha
    Broad Institute.
    Kaur, Amardeep
    Institute for Systems Biology.
    Locke, Devin
    University of Washington, Department of Genome Sciences.
    Madan, Anuradha
    Institute for Systems Biology.
    Munson, Glen
    Broad Institute.
    Jaffe, David
    Broad Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Mauceli, Evan
    Broad Institute.
    Naylor, Jerome
    Broad Institute.
    Nesbitt, Ryan
    Institute for Systems Biology.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Ratcliffe, Amber
    Institute for Systems Biology.
    Rounsley, Steven
    Broad Institute.
    She, Xinwei
    University of Washington, Department of Genome Sciences.
    Sneddon, Katherine
    University College London, Department of Biology.
    Stewart, Sandra
    Institute for Systems Biology.
    Sougnez, Carrie
    Broad Institute.
    Stone, Sabrina
    Broad Institute.
    Topham, Kerri
    Broad Institute.
    Vincent, Dascena
    Institute for Systems Biology.
    Wang, Shunguang
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Birren, Bruce
    Broad Institute.
    Hood, Leroy
    Institute for Systems Biology.
    Lander, ic
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    Analysis of the DNA sequence and duplication history of human chromosome 152006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 440, no 7084, p. 671-675Article in journal (Refereed)
    Abstract [en]

    Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

  • 1147. Zouganelis, George D.
    et al.
    Ogden, Rob
    Nahar, Niru
    Runfola, Valeria
    Bonab, Maziar
    Ardalan, Arman
    KTH, School of Biotechnology (BIO), Gene Technology.
    Radford, David
    Barnett, Ross
    Larson, Greger
    Hildred, Alex
    Jones, Mark
    Scarlett, Garry
    An old dog and new tricks: Genetic analysis of a Tudor dog recovered from the Mary Rose wreck2014In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 245, p. 51-57Article in journal (Refereed)
    Abstract [en]

    The Tudor warship the Mary Rose sank in the Solent waters between Portsmouth and the Isle of Wight on the 19th of July 1545, whilst engaging a French invasion fleet. The ship was rediscovered in 1971 and between 1979 and 1982 the entire contents of the ship were excavated resulting in the recovery of over 25,000 objects, including the skeleton of a small to medium sized dog referred to as the Mary Rose Dog (MRD). Here we report the extraction and analysis of both mitochondrial and genomic DNA from a tooth of this animal. Our results show that the MRD was a young male of a terrier type most closely related to modern Jack Russell Terriers with a light to dark brown coat colour. Interestingly, given the antiquity of the sample, the dog was heterozygotic for the SLC2A9 gene variant that leads to hyperuricosuria when found in modern homozygotic animals. These findings help shed light on a notable historical artefact from an important period in the development of modern dog breeds.

  • 1148.
    Zubair, Saima
    et al.
    Swedish Univ Agr Sci, SLU Global Bioinformat Ctr, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Fischer, Anne
    Int Livestock Res Inst, Nairobi, Kenya.;Int Ctr Insect Physiol & Ecol, Nairobi, Kenya..
    Liljander, Anne
    Int Livestock Res Inst, Nairobi, Kenya..
    Meens, Jochen
    Univ Vet Med Hannover, Inst Microbiol, Dept Infect Dis, Hannover, Germany..
    Hegerman, Jan
    Hannover Med Sch, Inst Funct & Appl Anat, Hannover, Germany.;Biomed Res Endstage & Obstruct Lung Dis Hannover, Hannover, Germany.;REBIRTH Cluster Excellence, Hannover, Germany..
    Gourle, Hadrien
    Swedish Univ Agr Sci, SLU Global Bioinformat Ctr, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Bishop, Richard P.
    Int Livestock Res Inst, Nairobi, Kenya..
    Roebbelen, Ina
    Int Livestock Res Inst, Nairobi, Kenya..
    Younan, Mario
    Vet Sans Frontieres Germany, Nairobi, Kenya..
    Mustafa, Mudassir Imran
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Mushtaq, Mamoona
    Swedish Univ Agr Sci, SLU Global Bioinformat Ctr, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Bongcam-Rudloff, Erik
    Swedish Univ Agr Sci, SLU Global Bioinformat Ctr, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Jores, Joerg
    Int Livestock Res Inst, Nairobi, Kenya..
    Complete genome sequence of Staphylococcus aureus, strain ILRI_Eymole1/1, isolated from a Kenyan dromedary camel2015In: Standards in Genomic Sciences, ISSN 1944-3277, E-ISSN 1944-3277, Vol. 10, article id 109Article in journal (Refereed)
    Abstract [en]

    We report the genome of a Staphylococcus aureus strain (ILRI_Eymole1/1) isolated from a nasal swab of a dromedary camel (Camelus dromedarius) in North Kenya. The complete genome sequence of this strain consists of a circular chromosome of 2,874,302 bp with a GC-content of 32.88 %. In silico annotation predicted 2755 protein-encoding genes and 76 non-coding genes. This isolate belongs to MLST sequence type 30 (ST30). Phylogenetic analysis based on a subset of 283 core genes revealed that it falls within the human clonal complex 30 (CC30) S. aureus isolate cluster but is genetically distinct. About 79 % of the protein encoding genes are part of the CC30 core genome (genes common to all CC30 S. aureus isolates), similar to 18 % were within the variable genome (shared among multiple but not all isolates) and similar to 3 % were found only in the genome of the camel isolate. Among the 85 isolate-specific genes, 79 were located within putative phages and pathogenicity islands. Protein encoding genes associated with bacterial adhesion, and secretory proteins that are essential components of the type VII secretion system were also identified. The complete genome sequence of S. aureus strain ILRI_Eymole1/1 has been deposited in the European Nucleotide Archive under the accession no LN626917.1.

  • 1149. Zuccolo, Andrea
    et al.
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    De Paoli, Emanuele
    Morgante, Michele
    The Ty1-copia LTR retroelement family PARTC is highly conserved in conifers over 200 MY of evolution2015In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 568, no 1, p. 89-99Article in journal (Refereed)
    Abstract [en]

    Long Terminal Repeat retroelements (LTR-RTs) are a major component of many plant genomes. Although well studied and described in angiosperms, their features and dynamics are poorly understood in gymnosperms. Representative complete copies of a Ty1-copia element isolate in Picea abies and named PARTC were identified in six other conifer species (Picea glauca, Pinus sylvestris, Pinus taeda, Abies sibirica, Taxus baccata and Juniperus communis) covering more than 200 million years of evolution. Here we characterized the structure of this element, assessed its abundance across conifers, studied the modes and timing of its amplification, and evaluated the degree of conservation of its extant copies at nucleotide level over distant species. We demonstrated that the element is ancient, abundant, widespread and its paralogous copies are present in the genera Picea, Pinus and Abies as an LTR-RT family. The amplification leading to the extant copies of PARTC occurred over long evolutionary times spanning 10 s of MY and mostly took place after the speciation of the conifers analyzed. The level of conservation of PARTC is striking and may be explained by low substitution rates and limited removal mechanisms for LTR-RTs. These PARTC features and dynamics are representative of a more general scenario for LTR-RTs in gymnosperms quite different from that characterizing the vast majority of LTR-RT elements in angiosperms. (C) 2015 Elsevier B.V. All rights reserved.

  • 1150. Zulfugarov, Ismayil S.
    et al.
    Tovuu, Altanzaya
    Eu, Young-Jae
    Dogsom, Bolormaa
    Poudyal, Roshan Sharma
    Nath, Krishna
    Hall, Michael
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Banerjee, Mainak
    Yoon, Ung Chan
    Moon, Yong-Hwan
    An, Gynheung
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lee, Choon-Hwan
    Production of superoxide from Photosystem II in a rice (Oryza sativa L.) mutant lacking PsbS2014In: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 14, p. 242-Article in journal (Refereed)
    Abstract [en]

    Background: PsbS is a 22-kDa Photosystem (PS) II protein involved in non-photochemical quenching (NPQ) of chlorophyll fluorescence. Rice (Oryza sativa L.) has two PsbS genes, PsbS1 and PsbS2. However, only inactivation of PsbS1, through a knockout (PsbS1-KO) or in RNAi transgenic plants, results in plants deficient in qE, the energy-dependent component of NPQ. Results: In studies presented here, under fluctuating high light, growth of young seedlings lacking PsbS is retarded, and PSII in detached leaves of the mutants is more sensitive to photoinhibitory illumination compared with the wild type. Using both histochemical and fluorescent probes, we determined the levels of reactive oxygen species, including singlet oxygen, superoxide, and hydrogen peroxide, in leaves and thylakoids. The PsbS-deficient plants generated more superoxide and hydrogen peroxide in their chloroplasts. PSII complexes isolated from them produced more superoxide compared with the wild type, and PSII-driven superoxide production was higher in the mutants. However, we could not observe such differences either in isolated PSI complexes or through PSI-driven electron transport. Time-course experiments using isolated thylakoids showed that superoxide production was the initial event, and that production of hydrogen peroxide proceeded from that. Conclusion: These results indicate that at least some of the photoprotection provided by PsbS and qE is mediated by preventing production of superoxide released from PSII under conditions of excess excitation energy.

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