Browsing by Subject "ANNOTATION"

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  • Horesh, Gal; Blackwell, Grace A.; Tonkin-Hill, Gerry; Corander, Jukka; Heinz, Eva; Thomson, Nicholas R. (2021)
    Escherichia coli is a highly diverse organism that includes a range of commensal and pathogenic variants found across a range of niches and worldwide. In addition to causing severe intestinal and extraintestinal disease, E. coli is considered a priority pathogen due to high levels of observed drug resistance. The diversity in the E. coli population is driven by high genome plasticity and a very large gene pool. All these have made E. coli one of the most well- studied organisms, as well as a commonly used laboratory strain. Today, there are thousands of sequenced E. coli genomes stored in public databases. While data is widely available, accessing the information in order to perform analyses can still be a challenge. Collecting relevant available data requires accessing different sources, where data may be stored in a range of formats, and often requires further manipulation and processing to apply various analyses and extract useful information. In this study, we collated and intensely curated a collection of over 10 000 E. coli and Shigella genomes to provide a single, uniform, high- quality dataset. Shigella were included as they are considered specialized pathovars of E. coli. We provide these data in a number of easily accessible formats that can be used as the foundation for future studies addressing the biological differences between E. coli lineages and the distribution and flow of genes in the E. coli population at a high resolution. The analysis we present emphasizes our lack of understanding of the true diversity of the E. coli species, and the biased nature of our current understanding of the genetic diversity of such a key pathogen.
  • Haase, Robert; Fazeli, Elnaz; Legland, David; Doube, Michael; Culley, Sian; Belevich, Ilya; Jokitalo, Eija; Schorb, Martin; Klemm, Anna; Tischer, Christian (2022)
    Modern research in the life sciences is unthinkable without computational methods for extracting, quantifying and visualising information derived from microscopy imaging data of biological samples. In the past decade, we observed a dramatic increase in available software packages for these purposes. As it is increasingly difficult to keep track of the number of available image analysis platforms, tool collections, components and emerging technologies, we provide a conservative overview of software that we use in daily routine and give insights into emerging new tools. We give guidance on which aspects to consider when choosing the platform that best suits the user's needs, including aspects such as image data type, skills of the team, infrastructure and community at the institute and availability of time and budget.
  • Majander, Kerttu; Pfrengle, Saskia; Kocher, Arthur; Neukamm, Judith; du Plessis, Louis; Pla-Diaz, Marta; Arora, Natasha; Akgul, Gulfirde; Salo, Kati; Schats, Rachel; Inskip, Sarah; Oinonen, Markku; Valk, Heiki; Malve, Martin; Kriiska, Aivar; Onkamo, Paivi; Gonzalez-Candelas, Fernando; Kuehnert, Denise; Krause, Johannes; Schuenemann, Verena J. (2020)
    Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood.
  • Kankainen, Matti; Ojala, Teija; Holm, Liisa (2012)
  • McNally, Alan; Oren, Yaara; Kelly, Darren; Pascoe, Ben; Dunn, Steven; Sreecharan, Tristan; Vehkala, Minna; Välimäki, Niko; Prentice, Michael B.; Ashour, Amgad; Avram, Oren; Pupko, Tal; Dobrindt, Ulrich; Literak, Ivan; Guenther, Sebastian; Schaufler, Katharina; Wieler, Lothar H.; Zong Zhiyong; Sheppard, Samuel K.; McInerney, James O.; Corander, Jukka (2016)
    The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.
  • Pitkanen, Esa; Jouhten, Paula; Hou, Jian; Syed, Muhammad Fahad; Blomberg, Peter; Kludas, Jana; Oja, Merja; Holm, Liisa; Penttila, Merja; Rousu, Juho; Arvas, Mikko (2014)
  • Ouwerkerk, Janneke P.; Tytgat, Hanne L. P.; Elzinga, Janneke; Koehorst, Jasper; Van den Abbeele, Pieter; Henrissat, Bernard; Gueimonde, Miguel; Cani, Patrice D.; Van de Wiele, Tom; Belzer, Clara; de Vos, Willem M. (2022)
    Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila Muc(T) and A. glycaniphila Pyt(T). Complete genome sequencing revealed that, despite their large genomic similarity (>97.6%), the novel isolates clustered into two distinct subspecies of A. muciniphila: Amuc1, which includes the type-strain Muc(T), and AmucU, a cluster of unassigned strains that have not yet been well characterized. CRISPR analysis showed all strains to be unique and confirmed that single healthy subjects can carry more than one A. muciniphila strain. Mucin degradation pathways were strongly conserved amongst all isolates, illustrating the exemplary niche adaptation of A. muciniphila to the mucin interface. This was confirmed by analysis of the predicted glycoside hydrolase profiles and supported by comparing the proteomes of A. muciniphila strain H2, belonging to the AmucU cluster, to Muc(T) and A. glycaniphila Pyt(T) (including 610 and 727 proteins, respectively). While some intrinsic resistance was observed among the A. muciniphila straind, none of these seem to pose strain-specific risks in terms of their antibiotic resistance patterns nor a significant risk for the horizontal transfer of antibiotic resistance determinants, opening the way to apply the type-strain Muc(T) or these new A. muciniphila strains as next generation beneficial microbes.
  • Andreevskaya, Margarita; Hultman, Jenni; Johansson, Per; Laine, Pia; Paulin, Lars; Auvinen, Petri; Björkroth, Johanna (2016)
    Leuconostoc gelidum subsp. gasicomitatum is a predominant lactic acid bacterium (LAB) in spoilage microbial communities of different kinds of modified-atmosphere packaged (MAP) food products. So far, only one genome sequence of a poultry-originating type strain of this bacterium (LMG 18811T) has been available. In the current study, we present the completely sequenced and functionally annotated genome of strain KG16-1 isolated from a vegetable-based product. In addition, six other vegetable-associated strains were sequenced to study possible “niche” specificity suggested by recent multilocus sequence typing. The genome of strain KG16-1 consisted of one circular chromosome and three plasmids, which together contained 2,035 CDSs. The chromosome carried at least three prophage regions and one of the plasmids encoded a galactan degradation cluster, which might provide a survival advantage in plant-related environments. The genome comparison with LMG 18811T and six other vegetable strains suggests no major differences between the meat- and vegetable-associated strains that would explain their “niche” specificity. Finally, the comparison with the genomes of other leuconostocs highlights the distribution of functionally interesting genes across the L. gelidum strains and the genus Leuconostoc.
  • Miyauchi, Shingo; Hage, Hayat; Drula, Elodie; Lesage-Meessen, Laurence; Berrin, Jean-Guy; Navarro, David; Favel, Anne; Chaduli, Delphine; Grisel, Sacha; Haon, Mireille; Piumi, Francois; Levasseur, Anthony; Lomascolo, Anne; Ahrendt, Steven; Barry, Kerrie; LaButti, Kurt M.; Chevret, Didier; Daum, Chris; Mariette, Jerome; Klopp, Christophe; Cullen, Daniel; de Vries, Ronald P.; Gathman, Allen C.; Hainaut, Matthieu; Henrissat, Bernard; Hilden, Kristiina S.; Kuees, Ursula; Lilly, Walt; Lipzen, Anna; Maekelae, Miia R.; Martinez, Angel T.; Morel-Rouhier, Melanie; Morin, Emmanuelle; Pangilinan, Jasmyn; Ram, Arthur F. J.; Woesten, Han A. B.; Ruiz-Duenas, Francisco J.; Riley, Robert; Record, Eric; Grigoriev, Igor; Rosso, Marie-Noelle (2020)
    White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here, we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood-decaying activity within the Basidiomycota genus Pycnoporus. We observed a strong conservation in the genome structures and the repertoires of protein-coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analysed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2-producing enzymes with H2O2-consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 lytic polysaccharide monooxygenase gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood-decaying process.
  • Kautt, Andreas F.; Kratochwil, Claudius F.; Nater, Alexander; Machado-Schiaffino, Gonzalo; Olave, Melisa; Henning, Frederico; Torres-Dowdall, Julian; Härer, Andreas; Hulsey, C. Darrin; Franchini, Paolo; Pippel, Martin; Myers, Eugene W.; Meyer, Axel (2020)
    Population genomic analyses of Midas cichlid fishes in young Nicaraguan crater lakes suggest that sympatric speciation is promoted by polygenic architectures. The transition from 'well-marked varieties' of a single species into 'well-defined species'-especially in the absence of geographic barriers to gene flow (sympatric speciation)-has puzzled evolutionary biologists ever since Darwin(1,2). Gene flow counteracts the buildup of genome-wide differentiation, which is a hallmark of speciation and increases the likelihood of the evolution of irreversible reproductive barriers (incompatibilities) that complete the speciation process(3). Theory predicts that the genetic architecture of divergently selected traits can influence whether sympatric speciation occurs(4), but empirical tests of this theory are scant because comprehensive data are difficult to collect and synthesize across species, owing to their unique biologies and evolutionary histories(5). Here, within a young species complex of neotropical cichlid fishes (Amphilophus spp.), we analysed genomic divergence among populations and species. By generating a new genome assembly and re-sequencing 453 genomes, we uncovered the genetic architecture of traits that have been suggested to be important for divergence. Species that differ in monogenic or oligogenic traits that affect ecological performance and/or mate choice show remarkably localized genomic differentiation. By contrast, differentiation among species that have diverged in polygenic traits is genomically widespread and much higher overall, consistent with the evolution of effective and stable genome-wide barriers to gene flow. Thus, we conclude that simple trait architectures are not always as conducive to speciation with gene flow as previously suggested, whereas polygenic architectures can promote rapid and stable speciation in sympatry.
  • Karinen, Sirkku; Heikkinen, Tuomas; Nevanlinna, Heli; Hautaniemi, Sampsa (2011)
  • Horesh, Gal; Taylor-Brown, Alyce; McGimpsey, Stephanie; Lassalle, Florent; Corander, Jukka; Heinz, Eva; Thomson, Nicholas R. (2021)
    The pan-genome is defined as the combined set of all genes in the gene pool of a species. Pan-genome analyses have been very useful in helping to understand different evolutionary dynamics of bacterial species: an open pan-genome often indicates a free-living lifestyle with metabolic versatility, while closed pan-genomes are linked to host-restricted, ecologically specialized bacteria. A detailed understanding of the species pan-genome has also been instrumental in tracking the phylodynamics of emerging drug resistance mechanisms and drug-resistant pathogens. However, current approaches to analyse a species' pan-genome do not take the species population structure into account, nor do they account for the uneven sampling of different lineages, as is commonplace due to over -sampling of clinically relevant representatives. Here we present the application of a population structure- aware approach for classify-ing genes in a pan-genome based on within-species distribution. We demonstrate our approach on a collection of 7500 Escherichia coli genomes, one of the most-studied bacterial species and used as a model for an open pan-genome. We reveal clearly distinct groups of genes, clustered by different underlying evolutionary dynamics, and provide a more biologically informed and accurate description of the species' pan-genome.
  • Aserse, Aregu Amsalu; Woyke, Tanja; Kyrpides, Nikos C.; Whitman, William B.; Lindström, Kristina (2017)
    Rhizobium aethiopicum sp. nov. is a newly proposed species within the genus Rhizobium. This species includes six rhizobial strains; which were isolated from root nodules of the legume plant Phaseolus vulgaris growing in soils of Ethiopia. The species fixes nitrogen effectively in symbiosis with the host plant P. vulgaris, and is composed of aerobic, Gram-negative staining, rod-shaped bacteria. The genome of type strain HBR26(T) of R. aethiopicum sp. nov. was one of the rhizobial genomes sequenced as a part of the DOE JGI 2014 Genomic Encyclopedia project designed for soil and plant-associated and newly described type strains. The genome sequence is arranged in 62 scaffolds and consists of 6,557,588 bp length, with a 61% G + C content and 6221 protein-coding and 86 RNAs genes. The genome of HBR26(T) contains repABC genes (plasmid replication genes) homologous to the genes found in five different Rhizobium etli CFN42(T) plasmids, suggesting that HBR26(T) may have five additional replicons other than the chromosome. In the genome of HBR26(T), the nodulation genes nodB, nodC, nodS, nodI, nodJ and nodD are located in the same module, and organized in a similar way as nod genes found in the genome of other known common bean-nodulating rhizobial species. nodA gene is found in a different scaffold, but it is also very similar to nodA genes of other bean-nodulating rhizobial strains. Though HBR26(T) is distinct on the phylogenetic tree and based on ANI analysis (the highest value 90.2% ANI with CFN42(T)) from other bean-nodulating species, these nod genes and most nitrogen-fixing genes found in the genome of HBR26(T) share high identity with the corresponding genes of known bean-nodulating rhizobial species (96-100% identity). This suggests that symbiotic genes might be shared between bean-nodulating rhizobia through horizontal gene transfer. R. aethiopicum sp. nov. was grouped into the genus Rhizobium but was distinct from all recognized species of that genus by phylogenetic analyses of combined sequences of the housekeeping genes recA and glnII. The closest reference type strains for HBR26(T) were R. etli CFN42(T) (94% similarity of the combined recA and glnII sequences) and Rhizobium bangladeshense BLR175(T) (93%). Genomic ANI calculation based on protein-coding genes also revealed that the closest reference strains were R. bangladeshense BLR175(T) and R. etli CFN42(T) with ANI values 91.8 and 90.2%, respectively. Nevertheless, the ANI values between HBR26(T) and BLR175(T) or CFN42(T) are far lower than the cutoff value of ANI (> = 96%) between strains in the same species, confirming that HBR26(T) belongs to a novel species. Thus, on the basis of phylogenetic, comparative genomic analyses and ANI results, we formally propose the creation of R. aethiopicum sp. nov. with strain HBR26(T) (= HAMBI 3550(T)= LMG 29711(T)) as the type strain. The genome assembly and annotation data is deposited in the DOE JGI portal and also available at European Nucleotide Archive under accession numbers FMAJ01000001-FMAJ01000062.
  • Groussin, Mathieu; Poyet, Mathilde; Sistiaga, Ainara; Kearney, Sean M.; Moniz, Katya; Noel, Mary; Hooker, Jeff; Gibbons, Sean M.; Segurel, Laure; Froment, Alain; Mohamed, Rihlat Said; Fezeu, Alain; Juimo, Vanessa A.; Lafosse, Sophie; Tabe, Francis E.; Girard, Catherine; Iqaluk, Deborah; Nguyen, Le Thanh Tu; Shapiro, B. Jesse; Lehtimaki, Jenni; Ruokolainen, Lasse; Kettunen, Pinja P.; Vatanen, Tommi; Sigwazi, Shani; Mabulla, Audax; Dominguez-Rodrigo, Manuel; Nartey, Yvonne A.; Agyei-Nkansah, Adwoa; Duah, Amoako; Awuku, Yaw A.; Valles, Kenneth A.; Asibey, Shadrack O.; Afihene, Mary Y.; Roberts, Lewis R.; Plymoth, Amelie; Onyekwere, Charles A.; Summons, Roger E.; Xavier, Ramnik J.; Alm, Eric J. (2021)
    Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.
  • Alvarenga, Danillo O.; Franco, Maione W.; Sivonen, Kaarina; Fiore, Marli F.; Varani, Alessandro M. (2020)
    Background. Brasilonema is a cyanobacterial genus found on the surface of mineral substrates and plants such as bromeliads, orchids and eucalyptus. B. octagenarum stands out among cyanobacteria due to causing damage to the leaves of its host in an interaction not yet observed in other cyanobacteria. Previous studies revealed that B. octagenaum UFV-E1 is capable of leading eucalyptus leaves to suffer internal tissue damage and necrosis by unknown mechanisms. This work aimed to investigate the effects of B. octagenarum UFV-E1 inoculation on Eucalyptus urograndis and to uncover molecular mechanisms potentially involved in leaf damage by these cyanobacteria using a comparative genomics approach. Results. Leaves from E. urograndis saplings were exposed for 30 days to B. octagenarum UFV-E1, which was followed by the characterization of its genome and its comparison with the genomes of four other Brasilonema strains isolated from phyllosphere and the surface of mineral substrates. While UFV-E1 inoculation caused an increase in root and stem dry mass of the host plants, the sites colonized by cyanobacteria on leaves presented a significant decrease in pigmentation, showing that the cyanobacterial mats have an effect on leaf cell structure. Genomic analyses revealed that all evaluated Brasilonema genomes harbored genes encoding molecules possibly involved in plant-pathogen interactions, such as hydrolases targeting plant cell walls and proteins similar to known virulence factors from plant pathogens. However, sequences related to the type III secretory system and effectors were not detected, suggesting that, even if any virulence factors could be expressed in contact with their hosts, they would not have the structural means to actively reach plant cytoplasm. Conclusions. Leaf damage by this species is likely related to the blockage of access to sunlight by the efficient growth of cyanobacterial mats on the phyllosphere, which may hinder the photosynthetic machinery and prevent access to some essential molecules. These results reveal that the presence of cyanobacteria on leaf surfaces is not as universally beneficial as previously thought, since they may not merely provide the products of nitrogen fixation to their hosts in exchange for physical support, but in some cases also hinder regular leaf physiology leading to tissue damage.
  • Kiiski, Johanna; Pelttari, Liisa M.; Khan, Sofia; Freysteinsdottir, Edda S.; Reynisdottir, Inga; Hart, Steven N.; Shimelis, Hermela; Vilske, Sara; Kallioniemi, Anne; Schleutker, Johanna; Leminen, Arto; Butzow, Ralf; Blomqvist, Carl; Barkardottir, Rosa B.; Couch, Fergus J.; Aittomaki, Kristiina; Nevanlinna, Heli (2014)
  • Behanova, Andrea; Abdollahzadeh, Ali; Belevich, Ilya; Jokitalo, Eija; Sierra, Alejandra; Tohka, Jussi (2022)
    Background and Objective: Advances in electron microscopy (EM) now allow three-dimensional (3D) imaging of hundreds of micrometers of tissue with nanometer-scale resolution, providing new opportunities to study the ultrastructure of the brain. In this work, we introduce a freely available Matlab-based gACSON software for visualization, segmentation, assessment, and morphology analysis of myelinated axons in 3D-EM volumes of brain tissue samples. Methods: The software is equipped with a graphical user interface (GUI). It automatically segments the intra-axonal space of myelinated axons and their corresponding myelin sheaths and allows manual segmentation, proofreading, and interactive correction of the segmented components. gACSON analyzes the morphology of myelinated axons, such as axonal diameter, axonal eccentricity, myelin thickness, or gratio. Results: We illustrate the use of the software by segmenting and analyzing myelinated axons in six 3DEM volumes of rat somatosensory cortex after sham surgery or traumatic brain injury (TBI). Our results suggest that the equivalent diameter of myelinated axons in somatosensory cortex was decreased in TBI animals five months after the injury. Conclusion: Our results indicate that gACSON is a valuable tool for visualization, segmentation, assessment, and morphology analysis of myelinated axons in 3D-EM volumes. It is freely available at under the MIT license. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( )
  • FinnGen research group; Strausz, Satu; Ruotsalainen, Sanni; Ollila, Hanna M.; Karjalainen, Juha; Kiiskinen, Tuomo; Reeve, Mary; Kurki, Mitja; Mars, Nina; Havulinna, Aki S.; Luonsi, Elina; Mansour-Aly, Dina; Ahlqvist, Emma; Teder-Laving, Maris; Palta, Priit; Groop, Leif; Magi, Reedik; Mäkitie, Antti; Salomaa, Veikko; Bachour, Adel; Tuomi, Tiinamaija; Palotie, Aarno; Palotie, Tuula; Ripatti, Samuli (2021)
    There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217955 individuals) with 16761 OSA patients identified using nationwide health registries. We estimated 0.08 (95% CI 0.06-0.11) heritability and identified five loci associated with OSA (p < 5.0x10(-8)): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains 1), rs10928560 near CXCR4 (C-X-C motif chemokine receptor type 4), rs185932673 near CAMK1D (calcium/calmodulindependent protein kinase ID) and rs9937053 near FTO (fat mass and obesity-associated protein; a variant previously associated with body mass index (BMI)). In a BMI-adjusted analysis, an association was observed for rs10507084 near RMST/NEDD1 (rhabdomyosarcoma 2 associated transcript/NEDD1 gamma tubulin ring complex targeting factor). We found high genetic correlations between OSA and BMI (r(g)=0.72 (95% CI 0.62-0.83)), and with comorbidities including hypertension, type 2 diabetes, coronary heart disease, stroke, depression, hypothyroidism, asthma and inflammatory rheumatic disease (rg > 0.30). The polygenic risk score for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile, and Mendelian randomisation supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA, and the joint genetic basis between OSA and comorbidities.
  • DCCT EDIC Res Grp; FinnDiane Study Grp; Syreeni, Anna; Sandholm, Niina; Cao, Jingjing; Toppila, Iiro; Maahs, David M.; Rewers, Marian J.; Snell-Bergeon, Janet K.; Costacou, Tina; Orchard, Trevor J.; Caramori, M. Luiza; Mauer, Michael; Klein, Barbara E. K.; Klein, Ronald; Valo, Erkka; Parkkonen, Maija; Forsblom, Carol; Harjutsalo, Valma; Paterson, Andrew D.; Groop, Per-Henrik (2019)
    Glycated hemoglobin (HbA(1c)) is an important measure of glycemia in diabetes. HbA(1c) is influenced by environmental and genetic factors both in people with and in people without diabetes. We performed a genome-wide association study (GWAS) for HbA(1c) in a Finnish type 1 diabetes (T1D) cohort, FinnDiane. Top results were examined for replication in T1D cohorts DCCT/EDIC, WESDR, CACTI, EDC, and RASS, and a meta-analysis was performed. Three SNPs in high linkage disequilibrium on chromosome 13 near relaxin family peptide receptor 2 (RXFP2) were associated with HbA(1c) in FinnDiane at genome-wide significance (P <5 x 10(-8)). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA(1c) also in the meta-analysis with RASS (P <5 x 10(-8)), where these variants had minor allele frequencies 1%. Furthermore, these SNPs were associated with HbA(1c) in an East Asian population without diabetes (P 0.013). A weighted genetic risk score created from 55 HbA(1c)-associated variants from the literature was associated with HbA(1c) in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA(1c) may lead to better prevention of diabetes complications.
  • Mäkinen, Mari; Kuuskeri, Jaana; Laine, Pia; Smolander, Olli-Pekka; Kovalchuk, Andriy; Zeng, Zhen; Asiegbu, Fred; Paulin, Lars; Auvinen, Petri; Lundell, Taina (2019)
    Background The white rot fungus Phlebia radiata, a type species of the genus Phlebia, is an efficient decomposer of plant cell wall polysaccharides, modifier of softwood and hardwood lignin, and is able to produce ethanol from various waste lignocellulose substrates. Thus, P. radiata is a promising organism for biotechnological applications aiming at sustainable utilization of plant biomass. Here we report the genome sequence of P. radiata isolate 79 originally isolated from decayed alder wood in South Finland. To better understand the evolution of wood decay mechanisms in this fungus and the Polyporales phlebioid clade, gene content and clustering of genes encoding specific carbohydrate-active enzymes (CAZymes) in seven closely related fungal species was investigated. In addition, other genes encoding proteins reflecting the fungal lifestyle including peptidases, transporters, small secreted proteins and genes involved in secondary metabolism were identified in the genome assembly of P. radiata. Results The PACBio sequenced nuclear genome of P. radiata was assembled to 93 contigs with 72X sequencing coverage and annotated, revealing a dense genome of 40.4 Mbp with approximately 14 082 predicted protein-coding genes. According to functional annotation, the genome harbors 209 glycoside hydrolase, 27 carbohydrate esterase, 8 polysaccharide lyase, and over 70 auxiliary redox enzyme-encoding genes. Comparisons with the genomes of other phlebioid fungi revealed shared and specific properties among the species with seemingly similar saprobic wood-decay lifestyles. Clustering of especially GH10 and AA9 enzyme-encoding genes according to genomic localization was discovered to be conserved among the phlebioid species. In P. radiata genome, a rich repertoire of genes involved in the production of secondary metabolites was recognized. In addition, 49 genes encoding predicted ABC proteins were identified in P. radiata genome together with 336 genes encoding peptidases, and 430 genes encoding small secreted proteins. Conclusions The genome assembly of P. radiata contains wide array of carbohydrate polymer attacking CAZyme and oxidoreductase genes in a composition identifiable for phlebioid white rot lifestyle in wood decomposition, and may thus serve as reference for further studies. Comparative genomics also contributed to enlightening fungal decay mechanisms in conversion and cycling of recalcitrant organic carbon in the forest ecosystems.