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  • 1051.
    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, 303- p., 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.

  • 1052. 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, 657-666 p.Article 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.

  • 1053.
    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, 1444-1453 p.Article 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.

  • 1054.
    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, 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.

  • 1055.
    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, 666-674 p.Article 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.

  • 1056.
    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, 1193-1204 p.Article 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.

  • 1057.
    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, 2319-2328 p.Article 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.

  • 1058.
    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.

  • 1059.
    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. 

  • 1060.
    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, 7-17 p.Article in journal (Other (popular science, discussion, etc.))
  • 1061.
    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.

  • 1062. 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, 105-12 p.Article 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.

  • 1063. 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, 659-668 p.Article 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.

  • 1064.
    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.

  • 1065.
    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, Vol. 440, no 7087, 1045-1049 p.Article 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.

  • 1066.
    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, Vol. 440, no 7084, 671-675 p.Article 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.

  • 1067. 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, 51-57 p.Article 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.

  • 1068.
    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, 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.

  • 1069. 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, 89-99 p.Article 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.

  • 1070. 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, Vol. 14, 242- p.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.

  • 1071. Zulfugarov, Ismayil S.
    et al.
    Tovuu, Altanzaya
    Kim, Chi-Yeol
    Vo, Kieu Thi Xuan
    Ko, Soo Yeon
    Hall, Michael
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Seok, Hye-Yeon
    Kim, Yeon-Ki
    Skogström, Oscar
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Moon, Yong-Hwan
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jeon, Jong-Seong
    Lee, Choon-Hwan
    Enhanced resistance of PsbS-deficient rice (Oryza sativa L.) to fungal and bacterial pathogens2016In: Journal of Plant Biology, ISSN 1226-9239, Vol. 59, no 6, 616-626 p.Article in journal (Refereed)
    Abstract [en]

    The 22-kDa PsbS protein of Photosystem II is involved in nonphotochemical quenching (NPQ) of chlorophyll fluorescence. Genome-wide analysis of the expression pattern in PsbS knockout (KO) rice plants showed that a lack of this protein led to changes in the transcript levels of 406 genes, presumably a result of superoxide produced in the chloroplasts. The top Gene Ontology categories, in which expression was the most differential, included 'Immune response', 'Response to jasmonic acid', and 'MAPK cascade'. From those genes, we randomly selected nine that were up-regulated. Our microarray results were confirmed by quantitative RT-PCR analysis. The KO and PsbS RNAi (knockdown) plants were more resistant to pathogens Magnaporthe oryzae PO6-6 and Xanthomonas oryzae pv. oryzae than either the wild-type plants or PsbS-overexpressing transgenic line. These findings suggest that superoxide production might be the reason that these plants have greater pathogen resistance to fungal and bacterial pathogens in the absence of energy-dependent NPQ. For example, a high level of cell wall lignification in the KO mutants was possibly due to enhanced superoxide production. Our data indicate that certain abiotic stress-induced reactive oxygen species can promote specific signaling pathways, which then activate a defense mechanism against biotic stress in PsbS-KO rice plants.

  • 1072.
    Zwoinska, Martyna K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology. Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland..
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Kawecki, Tadeusz J.
    Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland..
    Hollis, Brian
    Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.;Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland..
    Experimental evolution of slowed cognitive aging in Drosophila melanogaster2017In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 3, 662-670 p.Article in journal (Refereed)
    Abstract [en]

    Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories.

  • 1073.
    Åberg, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Lindholm, Eva
    Saetre, Peter
    Wetterberg, Lennart
    Pettersson, Ulf
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Genome Wide Investigation of an Isolated Schizophrenia Population Using a Dense Map of Microsatellites and SNPs in CombinationManuscript (Other (popular science, discussion, etc.))
  • 1074.
    Åberg, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Saetre, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Lindholm, Eva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Ekholm, Birgit
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adolfsson, Rolf
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Human QKI, a New Candidate Gene for Schizophrenia Involved in Myelination2005In: American journal of medical genetics. Part B, Neuropsychiatric genetics, ISSN 1552-4841, Vol. 141B, no 1, 84-90 p.Article in journal (Refereed)
    Abstract [en]

    We have previously shown that chromosome 6q25-6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine-mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%). A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P-value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI), was investigated in human brain autopsies from 55 cases and 55 controls using a high-resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients (P-value 0.0004 and 0.03, respectively). The function of QKI has not been studied in humans, but the mouse homolog is involved in neural development and myelination. In conclusion, we present evidence from three unrelated sample-sets that propose the involvement of the QKI gene in schizophrenia. The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case-control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins. Taken together, we propose QKI as a possible target for functional studies related to the role of myelination in schizophrenia.

  • 1075.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Carling, T.
    Endocrine Research Unit, Yale University, New Haven, CT, USA..
    Beuschlein, F.
    Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany..
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Genetics of adrenocortical tumours2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 6, 540-550 p.Article in journal (Refereed)
    Abstract [en]

    The recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease-causing mutations have been described for aldosterone-producing adenomas, cortisol-producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation. Moreover, compounds that bind specifically to altered proteins may be used as screening targets or therapeutic agents. Regulation of cortisol release by interaction with an altered subunit in adenylate cyclase may be more complex, but may provide a new option for regulating steroid release. Information about derangements in adrenocortical carcinoma is already helpful for determining patient prognosis. With further knowledge, we may be able to identify novel biomarkers that effectively and noninvasively help in differentiating between benign and malignant disease. It is clear that the next few years will provide much novel information that hopefully will aid in the treatment of patients with adrenocortical tumours.

  • 1076.
    Åslund, Sven-Eric
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Mating behaviour in Drosophila melanogaster and its implication to genetic variation1978Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Not much is known about the mechanisms affecting the genetic composition of populations of different species. To investi­gate one of these potential mechanisms, mating behaviour, the fruit fly Drosophila melanogaster, was chosen as an experimen­tal animal.

    To quantify mating behaviour in easily measurable parameters, it was subdivided into several distinct components; mating activity, mating time, mating competition ability and male mating capacity. As behavioural components to a great extent are influenced by environmental conditions all experiments were performed under controlled temperature and humidity. All components of mating behaviour were estimated by introducing females and males into mating chambers.

    Mating behaviour seems to be one of the major factors affect­ing the genetic composition of Drosophila melanogaster popula­tions. The experiments performed showed that differences in mating properties led to a substantial sexual selection among the genotypes. This selection was of a stabilizing type with regard to characters associated to bristle number and Y chromo­somal chromatin. This selection situation seems to warrant the retention of intermediate phenotypes in a population and will therefore contribute to the genetic variation present. Differences in mating properties were also shown to be able to maintain a balanced polymorphism for allozyme variants in populations. This maintenance was obtained through different forms of balancing selection as heterozygous superiority in sexual activity and balancing selection between female and male genotypes. Heterozygous superiority or overdominance in fitness always leads to balanced polymorphism through segre­gation of individuals with lowered fitness. The balancing selection between the female and male genotypes is best looked upon as a form of marginal overdominance, conferring the aver­aged highest fitness to the heterozygous genotype, thereby maintaining the polymorphism of the population.

  • 1077.
    Ödling, Sara
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Is there a correlation between the nutrient content and variation in the HvNAM-2 gene in Hordeum vulgare?2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Barley is one of the most important cereal crops in the world and a better understanding of the factors that regulates the nutrient content in the grain is of high interest. The industrial breeding during the last century has led to bigger yield but possibly a decrease in nutrient content. In wheat, the NAM-B1 gene is a well-studied gene that affects the grain protein and micronutrient content. Two orthologue genes in barley HvNAM-1 and HvNAM-2 are candidate genes to play a similar role in the barley senescence process.

    I have looked for a correlation between the diversity in the HvNAM-2 gene and nutrient content in 37 Nordic barley accessions. The samples were sequenced and then aligned and analyzed for variation. I found three haplotypes which were compared in nutrient content and in micronutrient content. No significant difference between the haplotypes was found, which can be due to small sample size or that no correlation exists between the grain protein content and the HvNAM-2 gene variation. Significant correlation was however found between the nitrogen content and the micronutrient contents that indicate that the pathways of all the nutrients’ mobilizations are tightly coupled. For future research a bigger number of accessions, preferably at least 100, need to be analyzed to be able to give any conclusions. The molecular mechanisms in the cells during senescence also need further investigation.

  • 1078. Örmälä-Odegrip, Anni-Maria
    et al.
    Eriksson, Harald
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mikonranta, Lauri
    Ruotsalainen, Pilvi
    Mattila, Sari
    Hoikkala, Ville
    Nilsson, Anders
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bamford, Jaana K. H.
    Laakso, Jouni
    Evolution of virulence in Klebsiella pneumoniae treated with phage cocktailsManuscript (preprint) (Other academic)
    Abstract [en]

    The worldwide emergence and spread of multidrug-resistant bacteria is a major concern in modern medicine, and threatens the once established control over bacterial infections. Phage therapy has been suggested as one potential solution to the problem of finding new antibacterial agents. Bacteria are known to evolve resistance against bacteriophages but in many cases phage-resistance comes with a cost on bacterial virulence in multicellular hosts. We investigated how the virulence of a clinical isolate of K. pneumoniae Kpn524 evolves in response to exposure to phage cocktails in the phage-resistant bacteria that would potentially survive the phage treatment. We found that the exposure to multiple phages was linked to lowered virulence in the phage-resistant bacteria, when measured in vivo with Galleria mellonella. However, two phages were found to increase the bacterial virulence when they were administered on the bacteria individually, and this was associated with an increased growth rate. Across all treatments, biofilm production was negatively correlated with virulence, whereas growth rate had a positive correlation with bacterial virulence. Our findings suggest that bacterial virulence is attenuated in the presence of multiple phages, possibly due to a trade-off between phage resistance andrate of replication. However, this is dependent on the composition of the phage cocktail.This is the first study to report increased bacterial virulence associated with exposure tolytic bacteriophages and our results call for meticulous consideration when choosingphages for phage cocktails, as phages with certain identity could have detrimentally adverse effects on the success of the treatment.

19202122 1051 - 1078 of 1078
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