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  • 1.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Carrillo, Alejandro Vicente
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Conserved gene expression in sperm reservoirs between birds and mammals in response to mating.2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Spermatozoa are stored in the oviductal functional sperm reservoir in animals with internal fertilization, including zoologically distant classes such as pigs or poultry. They are held fertile in the reservoir for times ranging from a couple of days (in pigs), to several weeks (in chickens), before they are gradually released to fertilize the newly ovulated eggs. It is currently unknown whether females from these species share conserved mechanisms to tolerate such a lengthy presence of immunologically-foreign spermatozoa. Therefore, global gene expression was assessed using cDNA microarrays on tissue collected from the avian utero-vaginal junction (UVJ), and the porcine utero-tubal junction (UTJ) to determine expression changes after mating (entire semen deposition) or in vivo cloacal/cervical infusion of sperm-free seminal fluid (SF)/seminal plasma (SP).

    RESULTS: In chickens, mating changed the expression of 303 genes and SF-infusion changed the expression of 931 genes, as compared to controls, with 68 genes being common to both treatments. In pigs, mating or SP-infusion changed the expressions of 1,722 and 1,148 genes, respectively, as compared to controls, while 592 genes were common to both treatments. The differentially expressed genes were significantly enriched for GO categories related to immune system functions (35.72-fold enrichment). The top 200 differentially expressed genes of each treatment in each animal class were analysed for gene ontology. In both pig and chicken, an excess of genes affecting local immune defence were activated, though frequently these were down-regulated. Similar genes were found in both the chicken and pig, either involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12).

    CONCLUSION: Despite being phylogenetically distant, chicken and pig appear to share some gene functions for the preservation of viable spermatozoa in the female reservoirs.

  • 2.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Correction: Conserved gene expression in sperm reservoirs between birds and mammals in response to mating (vol 18, 98, 2017)2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, article id 563Article in journal (Other academic)
    Abstract [en]

    n/a

  • 3.
    Bresell, Anders
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics . Linköping University, The Institute of Technology.
    Persson, Bengt
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics . Linköping University, The Institute of Technology.
    Characterization of oligopeptide patterns in large protein sets2007In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 8, no 346, p. 1-15Article in journal (Refereed)
    Abstract [en]

    Background: Recent sequencing projects and the growth of sequence data banks enable oligopeptide patterns to be characterized on a genome or kingdom level. Several studies have focused on kingdom or habitat classifications based on the abundance of short peptide patterns. There have also been efforts at local structural prediction based on short sequence motifs. Oligopeptide patterns undoubtedly carry valuable information content. Therefore, it is important to characterize these informational peptide patterns to shed light on possible new applications and the pitfalls implicit in neglecting bias in peptide patterns.

    Results: We have studied four classes of pentapeptide patterns (designated POP, NEP, ORP and URP) in the kingdoms archaea, bacteria and eukaryotes. POP are highly abundant patterns statistically not expected to exist; NEP are patterns that do not exist but are statistically expected to; ORP are patterns unique to a kingdom; and URP are patterns excluded from a kingdom. We used two data sources: the de facto standard of protein knowledge Swiss-Prot, and a set of 386 completely sequenced genomes. For each class of peptides we looked at the 100 most extreme and found both known and unknown sequence features. Most of the known sequence motifs can be explained on the basis of the protein families from which they originate.

    Conclusion: We find an inherent bias of certain oligopeptide patterns in naturally occurring proteins that cannot be explained solely on the basis of residue distribution in single proteins, kingdoms or databases. We see three predominant categories of patterns: (i) patterns widespread in a kingdom such as those originating from respiratory chain-associated proteins and translation machinery; (ii) proteins with structurally and/or functionally favored patterns, which have not yet been ascribed this role; (iii) multicopy species-specific retrotransposons, only found in the genome set. These categories will affect the accuracy of sequence pattern algorithms that rely mainly on amino acid residue usage. Methods presented in this paper may be used to discover targets for antibiotics, as we identify numerous examples of kingdom-specific antigens among our peptide classes. The methods may also be useful for detecting coding regions of genes.

  • 4.
    Caren, Helena
    et al.
    University of Gothenburg, Sweden.
    Erichsen, Jennie
    University of Gothenburg, Sweden.
    Olsson, Linda
    University of Gothenburg, Sweden.
    Enerbäck, Charlotta
    University of Gothenburg, Sweden.
    Sjoberg, Rose-Marie
    University of Gothenburg, Sweden.
    Abrahamsson, Jonas
    University of Gothenburg, Sweden.
    Kogner, Per
    Childhood Canc Res Unit, SE-17176 Stockholm, Sweden .
    Martinsson, Tommy
    University of Gothenburg, Sweden.
    High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: Four cases of homozygous deletions of the CDKN2A gene2008In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 9, no 353Article in journal (Refereed)
    Abstract [en]

    Background: Neuroblastoma is a very heterogeneous pediatric tumor of the sympathetic nervous system showing clinically significant patterns of genetic alterations. Favorable tumors usually have near-triploid karyotypes with few structural rearrangements. Aggressive stage 4 tumors often have near-diploid or near-tetraploid karyotypes and structural rearrangements. Whole genome approaches for analysis of genome-wide copy number have been used to analyze chromosomal abnormalities in tumor samples. We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP) arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets. Results: Ninety-two neuroblastoma tumors were analyzed with 50 K and/or 250 K SNP arrays from Affymetrix, using CNAG3.0 software. Thirty percent of the tumors harbored 1p deletion, 22% deletion of 11q, 26% had MYCN amplification and 45% 17q gain. Most of the tumors with 1p deletion were found among those with MYCN amplification. Loss of 11q was most commonly seen in tumors without MYCN amplification. In the case of MYCN amplification, two types were identified. One type displayed simple continuous amplicons; the other type harbored more complex rearrangements. MYCN was the only common gene in all cases with amplification. Complex amplification on chromosome 12 was detected in two tumors and three different overlapping regions of amplification were identified. Two regions with homozygous deletions, four cases with CDKN2A deletions in 9p and one case with deletion on 3p (the gene RBMS3) were also detected in the tumors. Conclusion: SNP arrays provide useful tools for high-resolution characterization of significant chromosomal rearrangements in neuroblastoma tumors. The mapping arrays from Affymetrix provide both copy number and allele-specific information at a resolution of 10-12 kb. Chromosome 9p, especially the gene CDKN2A, is subject to homozygous (four cases) and heterozygous deletions (five cases) in neuroblastoma tumors.

  • 5.
    Garcia-Sanchez, Susana
    et al.
    University of Basque Country UPV EHU, Spain.
    Bernales, Irantzu
    University of Basque Country UPV EHU, Spain.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. University of Basque Country UPV EHU, Spain.
    Early response to nanoparticles in the Arabidopsis transcriptome compromises plant defence and root-hair development through salicylic acid signalling2015In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, no 341Article in journal (Refereed)
    Abstract [en]

    Background: The impact of nano-scaled materials on photosynthetic organisms needs to be evaluated. Plants represent the largest interface between the environment and biosphere, so understanding how nanoparticles affect them is especially relevant for environmental assessments. Nanotoxicology studies in plants allude to quantum size effects and other properties specific of the nano-stage to explain increased toxicity respect to bulk compounds. However, gene expression profiles after exposure to nanoparticles and other sources of environmental stress have not been compared and the impact on plant defence has not been analysed. Results: Arabidopsis plants were exposed to TiO2-nanoparticles, Ag-nanoparticles, and multi-walled carbon nanotubes as well as different sources of biotic (microbial pathogens) or abiotic (saline, drought, or wounding) stresses. Changes in gene expression profiles and plant phenotypic responses were evaluated. Transcriptome analysis shows similarity of expression patterns for all plants exposed to nanoparticles and a low impact on gene expression compared to other stress inducers. Nanoparticle exposure repressed transcriptional responses to microbial pathogens, resulting in increased bacterial colonization during an experimental infection. Inhibition of root hair development and transcriptional patterns characteristic of phosphate starvation response were also observed. The exogenous addition of salicylic acid prevented some nano-specific transcriptional and phenotypic effects, including the reduction in root hair formation and the colonization of distal leaves by bacteria. Conclusions: This study integrates the effect of nanoparticles on gene expression with plant responses to major sources of environmental stress and paves the way to remediate the impact of these potentially damaging compounds through hormonal priming.

  • 6.
    Iso-Touru, Terhi
    et al.
    Nat Resources Inst Finland Luke, Finland.
    Wurmser, Christine
    Tech Univ Munich, Germany.
    Venhoranta, Heli
    Univ Helsinki, Finland.
    Hiltpold, Maya
    Swiss Fed Inst Technol, Switzerland.
    Savolainen, Tujia
    Univ Helsinki, Finland.
    Sironen, Anu
    Nat Resources Inst Finland Luke, Finland.
    Fischer, Konrad
    Tech Univ Munich, Germany.
    Flisikowski, Krzysztof
    Tech Univ Munich, Germany.
    Fries, Ruedi
    Tech Univ Munich, Germany.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Nagy, Szabolcs
    Univ Pannonia, Hungary.
    Mutikainen, Mervi
    Nat Resources Inst Finland Luke, Finland.
    Peippo, Jaana
    Nat Resources Inst Finland Luke, Finland.
    Taponen, Juhani
    Univ Helsinki, Finland.
    Sahana, Goutam
    Aarhus Univ, Denmark.
    Guldbrandtsen, Bernt
    Aarhus Univ, Denmark.
    Simonen, Henri
    VikingGenet, Finland.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Magnus
    Univ Helsinki, Finland.
    Pausch, Hubert
    Swiss Fed Inst Technol, Switzerland.
    A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle2019In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 20, no 1, article id 286Article in journal (Refereed)
    Abstract [en]

    Background

    Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected.

    Results

    Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle.

    Conclusions

    Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

  • 7.
    Johnsson, Martin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Univ Edinburgh, England; Swedish Univ Agr Sci, Sweden.
    Henriksen, Rie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Höglund, Andrey
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Fogelholm, Jesper
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Genetical genomics of growth in a chicken model2018In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 19, article id 72Article in journal (Refereed)
    Abstract [en]

    Background: The genetics underlying body mass and growth are key to understanding a wide range of topics in biology, both evolutionary and developmental. Body mass and growth traits are affected by many genetic variants of small effect. This complicates genetic mapping of growth and body mass. Experimental intercrosses between individuals from divergent populations allows us to map naturally occurring genetic variants for selected traits, such as body mass by linkage mapping. By simultaneously measuring traits and intermediary molecular phenotypes, such as gene expression, one can use integrative genomics to search for potential causative genes. Results: In this study, we use linkage mapping approach to map growth traits (N = 471) and liver gene expression (N = 130) in an advanced intercross of wild Red Junglefowl and domestic White Leghorn layer chickens. We find 16 loci for growth traits, and 1463 loci for liver gene expression, as measured by microarrays. Of these, the genes TRAK1, OSBPL8, YEATS4, CEP55, and PIP4K2B are identified as strong candidates for growth loci in the chicken. We also show a high degree of sex-specific gene-regulation, with almost every gene expression locus exhibiting sex-interactions. Finally, several trans-regulatory hotspots were found, one of which coincides with a major growth locus. Conclusions: These findings not only serve to identify several strong candidates affecting growth, but also show how sex-specificity and local gene-regulation affect growth regulation in the chicken.

  • 8.
    Nelander, S
    et al.
    Sahlgrenska Academy.
    Larsson, E
    Sahlgrenska Academy.
    Kristiansson, E
    Chalmers Technical University.
    Månsson, R
    Lund Strategic Research Center for Stem Cell Biology and Cell Therapy.
    Nerman, O
    Chalmers Technical University.
    Sigvardsson, Mikael
    Lund Strategic Research Center for Stem Cell Biology and Cell Therapy.
    Mostad, P
    Chalmers Technical University.
    Lindahl, P
    Sahlgrenska Academy.
    Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals2005In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 6, no 68Article in journal (Refereed)
    Abstract [en]

    Background: The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation. Results: In a screen that covered andSIM; 40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis- regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in andSIM; 10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in andSIM; 30% of all kidney specific genes respectively. The results are publicly available at http://www.wlab.gu.se/lindahl/genebatteries. Conclusion: 21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design.

  • 9.
    Nätt, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Rubin, Carl-Johan
    Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Beltéky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Andersson, Leif
    Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, no 59Article in journal (Refereed)
    Abstract [en]

    Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation. Here, we show that in Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differ substantially from that of a domesticated egg laying breed. Expression as well as methylation differences are largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences are tissue-specific, and the differential methylation at specific loci are little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication. Hence, our results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.

  • 10.
    Rubin, Carl-Johan
    et al.
    Department of Medical Sciences Uppsala University.
    Lindberg, Johan
    Department of Gene Technology Royal Institute of Technology, Stockholm.
    Fitzsimmons, Carolyn
    Department of Animal Breeding and Genetics Swedish University of Agricultural Sciences, Uppsala.
    Savolainen, Peter
    Department of Gene Technology Royal Institute of Technology, Stockholm.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Lundeberg, Joakim
    Department of Gene Technology Royal Institute of Technology, Stockholm.
    Andersson, Leif
    Department of Animal Breeding and Genetics Swedish University of Agricultural Sciences, Uppsala.
    Kindmark, Andreas
    Department of Medical Sciences Uppsala University.
    Differential gene expression in femoral bone from red junglefowl and domestic chicken, differing for bone phenotypic traits2007In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 8Article in journal (Refereed)
  • 11.
    Skarp-de Haan, Caroline P. A.
    et al.
    University of Helsinki, Finland .
    Culebro, Alejandra
    University of Helsinki, Finland .
    Schott, Thomas
    University of Helsinki, Finland .
    Revez, Joana
    University of Helsinki, Finland .
    Schweda, Elke
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Hanninen, Marja-Liisa
    University of Helsinki, Finland .
    Rossi, Mirko
    University of Helsinki, Finland .
    Comparative genomics of unintrogressed Campylobacter coli clades 2 and 32014In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, no 129Article in journal (Refereed)
    Abstract [en]

    Background: Campylobacter jejuni and C. coli share a multitude of risk factors associated with human gastrointestinal disease, yet their phylogeny differs significantly. C. jejuni is scattered into several lineages, with no apparent linkage, whereas C. coli clusters into three distinct phylogenetic groups (clades) of which clade 1 has shown extensive genome-wide introgression with C. jejuni, yet the other two clades (2 and 3) have less than 2% of C. jejuni ancestry. We characterized a C. coli strain (76339) with four novel multilocus sequence type alleles (ST-5088) and having the capability to express gamma-glutamyltranspeptidase (GGT); an accessory feature in C. jejuni. Our aim was to further characterize unintrogressed C. coli clades 2 and 3, using comparative genomics and with additional genome sequences available, to investigate the impact of horizontal gene transfer in shaping the accessory and core gene pools in unintrogressed C. coli. Results: Here, we present the first fully closed C. coli clade 3 genome (76339). The phylogenomic analysis of strain 76339, revealed that it belonged to clade 3 of unintrogressed C. coli. A more extensive respiratory metabolism among unintrogressed C. coli strains was found compared to introgressed C. coli (clade 1). We also identified other genes, such as serine proteases and an active sialyltransferase in the lipooligosaccharide locus, not present in C. coli clade 1 and we further propose a unique scenario for the evolution of Campylobacter ggt. Conclusions: We propose new insights into the evolution of the accessory genome of C. coli clade 3 and C. jejuni. Also, in silico analysis of the gene content revealed that C. coli clades 2 and 3 have genes associated with infection, suggesting they are a potent human pathogen, and may currently be underreported in human infections due to niche separation.

  • 12.
    Skinner, Michael K.
    et al.
    Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, USA.
    Guerrero-Bosagna, Carlos
    Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, USA.
    Role of CpG deserts in the epigenetic transgenerational inheritance of differential DNA methylation regions2014In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, no 692Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Previously a variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated.

    RESULTS:

    The epimutations from six different environmental exposures were found to be predominantly exposure specific with negligible overlap. The current report describes a major genomic feature of all the unique epimutations identified (535) as a very low (<10 CpG/100 bp) CpG density in sperm and somatic cells associated with transgenerational disease. The genomic locations of these epimutations were found to contain DMRs with small clusters of CpG within a general region of very low density CpG. The potential role of these epimutations on gene expression is suggested to be important.

    CONCLUSIONS:

    Observations suggest a potential regulatory role for lower density CpG regions termed "CpG deserts". The potential evolutionary origins of these regions is also discussed.

  • 13.
    Zetterblad, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
    Qian, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
    Zandi, Sasan
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
    Mansson, Robert
    Lund Stem Cell Centre.
    Lagergren, Anna
    Lund Stem Cell Centre.
    Hansson, Frida
    Lund Stem Cell Centre.
    Bryder, David
    Lund University.
    Paulsson, Nils
    Lund Stem Cell Centre.
    Sigvardsson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
    Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication2010In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 11, no 108Article in journal (Refereed)
    Abstract [en]

    Background: The use of functional genomics has largely increased our understanding of cell biology and promises to help the development of systems biology needed to understand the complex order of events that regulates cellular differentiation in vivo. One model system clearly dependent on the integration of extra and intra cellular signals is the development of B-lymphocytes from hematopoietic stem cells in the bone marrow. This developmental pathway involves several defined differentiation stages associated with specific expression of genes including surface markers that can be used for the prospective isolation of the progenitor cells directly from the bone marrow to allow for ex vivo gene expression analysis. The developmental process can be simulated in vitro making it possible to dissect information about cell/cell communication as well as to address the relevance of communication pathways in a rather direct manner. Thus we believe that B-lymphocyte development represents a useful model system to take the first steps towards systems biology investigations in the bone marrow. Results: In order to identify extra cellular signals that promote B lymphocyte development we created a database with approximately 400 receptor ligand pairs and software matching gene expression data from two cell populations to obtain information about possible communication pathways. Using this database and gene expression data from NIH3T3 cells (unable to support B cell development), OP-9 cells (strongly supportive of B cell development), pro-B and pre-B cells as well as mature peripheral B-lineage cells, we were able to identify a set of potential stage and stromal cell restricted communication pathways. Functional analysis of some of these potential ways of communication allowed us to identify BMP-4 as a potent stimulator of B-cell development in vitro. Further, the analysis suggested that there existed possibilities for progenitor B cells to send signals to the stroma. The functional consequences of this were investigated by co-culture experiments revealing that the co-incubation of stromal cells with B cell progenitors altered both the morphology and the gene expression pattern in the stromal cells. Conclusions: We believe that this gene expression data analysis method allows for the identification of functionally relevant interactions and therefore could be applied to other data sets to unravel novel communication pathways.

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