Browsing by Subject "GENES"

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  • Mehmood, Furrukh; Abdullah,; Ubaid, Zartasha; Bao, Yiming; Poczai, Péter; Mirza, Bushra (2020)
    Within the family Solanaceae, Withania is a small genus belonging to the Solanoideae subfamily. Here, we report the de novo assembled chloroplast genome sequences of W. coagulans, W. adpressa, and W. riebeckii. The length of these genomes ranged from 154,162 to 154,364 base pairs (bp). These genomes contained a pair of inverted repeats (IRa and IRb) ranging from 25,029 to 25,071 bp that were separated by a large single-copy (LSC) region of 85,635-85,765 bp and a small single-copy (SSC) region of 18,457-18,469 bp. We analyzed the structural organization, gene content and order, guanine-cytosine content, codon usage, RNA-editing sites, microsatellites, oligonucleotide and tandem repeats, and substitutions of Withania plastomes, which revealed high similarities among the species. Comparative analysis among the Withania species also highlighted 10 divergent hotspots that could potentially be used for molecular marker development, phylogenetic analysis, and species identification. Furthermore, our analyses showed that even three mutational hotspots (rps4-trnT, trnM-atpE, and rps15) were sufficient to discriminate the Withania species included in current study.
  • Abdullah,; Henriquez, Claudia L.; Mehmood, Furrukh; Shahzadi, Iram; Ali, Zain; Waheed, Mohammad Tahir; Croat, Thomas B; Poczai, Péter; Ahmed, Ibrar (2020)
    The chloroplast genome provides insight into the evolution of plant species. We de novo assembled and annotated chloroplast genomes of four genera representing three subfamilies of Araceae: Lasia spinosa (Lasioideae), Stylochaeton bogneri, Zamioculcas zamiifolia (Zamioculcadoideae), and Orontium aquaticum (Orontioideae), and performed comparative genomics using these chloroplast genomes. The sizes of the chloroplast genomes ranged from 163,770 bp to 169,982 bp. These genomes comprise 113 unique genes, including 79 protein-coding, 4 rRNA, and 30 tRNA genes. Among these genes, 17–18 genes are duplicated in the inverted repeat (IR) regions, comprising 6–7 protein-coding (including trans-splicing gene rps12), 4 rRNA, and 7 tRNA genes. The total number of genes ranged between 130 and 131. The infA gene was found to be a pseudogene in all four genomes reported here. These genomes exhibited high similarities in codon usage, amino acid frequency, RNA editing sites, and microsatellites. The oligonucleotide repeats and junctions JSB (IRb/SSC) and JSA (SSC/IRa) were highly variable among the genomes. The patterns of IR contraction and expansion were shown to be homoplasious, and therefore unsuitable for phylogenetic analyses. Signatures of positive selection were seen in three genes in S. bogneri, including ycf2, clpP, and rpl36. This study is a valuable addition to the evolutionary history of chloroplast genome structure in Araceae.
  • Frank, Christoph; Sundquist, Jan; Yu, Hongyao; Hemminki, Akseli; Hemminki, Kari (2017)
    Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.
  • Palin, Kimmo; Pitkänen, Esa; Turunen, Mikko; Sahu, Biswajyoti; Pihlajamaa, Päivi; Kivioja, Teemu; Kaasinen, Eevi; Välimäki, Niko; Hänninen, Ulrika A.; Cajuso, Tatiana; Aavikko, Mervi; Tuupanen, Sari; Kilpivaara, Outi; van den Berg, Linda; Kondelin, Johanna; Tanskanen, Tomas; Katainen, Riku; Grau, Marta; Rauanheimo, Heli; Plaketti, Roosa-Maria; Taira, Aurora; Sulo, Päivi; Hartonen, Tuomo; Dave, Kashyap; Schmierer, Bernhard; Botla, Sandeep; Sokolova, Maria; Vähärautio, Anna; Gladysz, Kornelia; Ongen, Halit; Dermitzakis, Emmanouil; Bramsen, Jesper Bertram; Orntoft, Torben Falck; Andersen, Claus Lindbjerg; Ristimäki, Ari; Lepistö, Anna; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Taipale, Jussi; Aaltonen, Lauri A. (2018)
    Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (Al) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible Al targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within Al peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of Al. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between Al target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of Al in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
  • Yeung, Edwina H.; Guan, Weihua; Zeng, Xuehuo; Salas, Lucas A.; Mumford, Sunni L.; de Prado Bert, Paula; van Meel, Evelien R.; Malmberg, Anni; Sunyer, Jordi; Duijts, Liesbeth; Felix, Janine F.; Czamara, Darina; Hämäläinen, Esa; Binder, Elisabeth B.; Räikkönen, Katri; Lahti, Jari; London, Stephanie J.; Silver, Robert M.; Schisterman, Enrique F. (2020)
    Background Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Results Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (<18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p <0.05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Conclusions Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways.
  • Casar-Borota, Olivera; Boldt, Henning Bünsow; Engstrom, Britt Eden; Andersen, Marianne Skovsager; Baussart, Bertrand; Bengtsson, Daniel; Berinder, Katarina; Ekman, Bertil; Feldt-Rasmussen, Ulla; Hoybye, Charlotte; Jorgensen, Jens Otto L.; Kolnes, Anders Jensen; Korbonits, Marta; Rasmussen, Ase Krogh; Lindsay, John R.; Loughrey, Paul Benjamin; Maiter, Dominique; Manojlovic-Gacic, Emilija; Pahnke, Jens; Poliani, Pietro Luigi; Popovic, Vera; Ragnarsson, Oskar; Schalin-Jäntti, Camilla; Scheie, David; Toth, Miklos; Villa, Chiara; Wirenfeldt, Martin; Kunicki, Jacek; Burman, Pia (2021)
    Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
  • Haapaniemi, Emma; Botla, Sandeep; Persson, Jenna; Schmierer, Bernhard; Taipale, Jussi (2018)
    Here, we report that genome editing by CRISPR-Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR-Cas9.
  • Yohannes, Dawit A.; Freitag, Tobias L.; de Kauwe, Andrea; Kaukinen, Katri; Kurppa, Kalle; Wacklin, Pirjo; Mäki, Markku; Arstila, T. Petteri; Anderson, Robert P.; Greco, Dario; Saavalainen, Päivi (2017)
    Celiac disease (CD) patients mount an abnormal immune response to gluten. T-cell receptor (TCR) repertoires directed to some immunodominant gluten peptides have previously been described, but the global immune response to in vivo gluten exposure in CD has not been systematically investigated yet. Here, we characterized signatures associated with gluten directed immune activity and identified gluten-induced T-cell clonotypes from total blood and gut TCR repertoires in an unbiased manner using immunosequencing. CD patient total TCR repertoires showed increased overlap and substantially altered TRBV-gene usage in both blood and gut samples, and increased diversity in the gut during gluten exposure. Using differential abundance analysis, we identified gluten-induced clonotypes in each patient that were composed of a large private and an important public component. Hierarchical clustering of public clonotypes associated with dietary gluten exposure identified subsets of highly similar clonotypes, the most proliferative of which showing significant enrichment for the motif ASS[LF] R[SW][TD][DT][TE][QA][YF] in PBMC repertoires. These results show that CD-associated clonotypes can be identified and that common gluten associated immune response features can be characterized in vivo from total repertoires, with potential use in disease stratification and monitoring.
  • Feng, Shaohong; Stiller, Josefin; Deng, Yuan; Armstrong, Joel; Fang, Qi; Reeve, Andrew Hart; Xie, Duo; Chen, Guangji; Guo, Chunxue; Faircloth, Brant C.; Petersen, Bent; Wang, Zongji; Zhou, Qi; Diekhans, Mark; Chen, Wanjun; Andreu-Sanchez, Sergio; Margaryan, Ashot; Howard, Jason Travis; Parent, Carole; Pacheco, George; Sinding, Mikkel-Holger S.; Puetz, Lara; Cavill, Emily; Ribeiro, Angela M.; Eckhart, Leopold; Fjeldsa, Jon; Hosner, Peter A.; Brumfield, Robb T.; Christidis, Les; Bertelsen, Mads F.; Sicheritz-Ponten, Thomas; Tietze, Dieter Thomas; Robertson, Bruce C.; Song, Gang; Borgia, Gerald; Claramunt, Santiago; Lovette, Irby J.; Cowen, Saul J.; Njoroge, Peter; Dumbacher, John Philip; Ryder, Oliver A.; Fuchs, Jerome; Bunce, Michael; Burt, David W.; Cracraft, Joel; Meng, Guanliang; Hackett, Shannon J.; Ryan, Peter G.; Jønsson, Knud Andreas; Jamieson, Ian G.; da Fonseca, Rute R.; Braun, Edward L.; Houde, Peter; Mirarab, Siavash; Suh, Alexander; Hansson, Bengt; Ponnikas, Suvi; Sigeman, Hanna; Stervander, Martin; Frandsen, Paul B.; van der Zwan, Henriette; van der Sluis, Rencia; Visser, Carina; Balakrishnan, Christopher N.; Clark, Andrew G.; Fitzpatrick, John W.; Bowman, Reed; Chen, Nancy; Cloutier, Alison; Sackton, Timothy B.; Edwards, Scott V.; Foote, Dustin J.; Shakya, Subir B.; Sheldon, Frederick H.; Vignal, Alain; Soares, Andre E. R.; Shapiro, Beth; Gonzalez-Solis, Jacob; Ferrer-Obiol, Joan; Rozas, Julio; Riutort, Marta; Tigano, Anna; Friesen, Vicki; Dalen, Love; Urrutia, Araxi O.; Szekely, Tamas; Liu, Yang; Campana, Michael G.; Corvelo, Andre; Fleischer, Robert C.; Rutherford, Kim M.; Gemmell, Neil J.; Dussex, Nicolas; Mouritsen, Henrik; Thiele, Nadine; Delmore, Kira; Liedvogel, Miriam; Franke, Andre; Hoeppner, Marc P.; Krone, Oliver; Fudickar, Adam M.; Mila, Borja; Ketterson, Ellen D.; Fidler, Andrew Eric; Friis, Guillermo; Parody-Merino, Angela M.; Battley, Phil F.; Cox, Murray P.; Lima, Nicholas Costa Barroso; Prosdocimi, Francisco; Parchman, Thomas Lee; Schlinger, Barney A.; Loiselle, Bette A.; Blake, John G.; Lim, Haw Chuan; Day, Lainy B.; Fuxjager, Matthew J.; Baldwin, Maude W.; Braun, Michael J.; Wirthlin, Morgan; Dikow, Rebecca B.; Ryder, T. Brandt; Camenisch, Glauco; Keller, Lukas F.; DaCosta, Jeffrey M.; Hauber, Mark E.; Louder, Matthew I. M.; Witt, Christopher C.; McGuire, Jimmy A.; Mudge, Joann; Megna, Libby C.; Carling, Matthew D.; Wang, Biao; Taylor, Scott A.; Del-Rio, Glaucia; Aleixo, Alexandre; Vasconcelos, Ana Tereza Ribeiro; Mello, Claudio V.; Weir, Jason T.; Haussler, David; Li, Qiye; Yang, Huanming; Wang, Jian; Lei, Fumin; Rahbek, Carsten; Gilbert, M. Thomas P.; Graves, Gary R.; Jarvis, Erich D.; Paten, Benedict; Zhang, Guojie (2020)
    Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
  • Liu, Xuanyao; Kanduri, Chakravarthi; Oikkonen, Jaana; Karma, Kai; Raijas, Pirre; Ukkola-Vuoti, Liisa; Teo, Yik-Ying; Jarvela, Irma (2016)
    Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and F-ST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude.
  • Tomppo, Liisa; Ekelund, Jesper; Lichtermann, Dirk; Veijola, Juha; Jaervelin, Marjo-Riitta; Hennah, William (2012)
  • Ma, Liang; Chen, Zehua; Huang, Da Wei; Cisse, Ousmane H.; Rothenburger, Jamie L.; Latinne, Alice; Bishop, Lisa; Blair, Robert; Brenchley, Jason M.; Chabe, Magali; Deng, Xilong; Hirsch, Vanessa; Keesler, Rebekah; Kutty, Geetha; Liu, Yueqin; Margolis, Daniel; Morand, Serge; Pahar, Bapi; Peng, Li; Van Rompay, Koen K. A.; Song, Xiaohong; Song, Jun; Sukura, Antti; Thapar, Sabrina; Wang, Honghui; Weissenbacher-Lang, Christiane; Xu, Jie; Lee, Chao-Hung; Jardine, Claire; Lempicki, Richard A.; Cushion, Melanie T.; Cuomo, Christina A.; Kovacs, Joseph A. (2020)
    Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.
  • Dayeh, Tasnim; Tuomi, Tiinamaija; Almgren, Peter; Perfilyev, Alexander; Jansson, Per-Anders; de Mello, Vanessa D.; Pihlajamaki, Jussi; Vaag, Allan; Groop, Leif; Nilsson, Emma; Ling, Charlotte (2016)
    Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.
  • Impola, Ulla; Turpeinen, Hannu; Alakulppi, Noora; Linjama, Tiina; Volin, Liisa; Niittyvuopio, Riitta; Partanen, Jukka; Koskela, Satu (2014)
    Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GyL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GyL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients.
  • Zhang, Teng; Elomaa, Paula (2021)
    The sunflower or daisy family, Asteraceae, comprises of approximately 10% of all angiosperm species. Their inflorescences form dense flower-like structures, pseudanthia or false flowers that may combine hundreds of individual flowers into a single structure. Recent data suggest that pseudanthia are analogs of single flowers not only morphologically but also at developmental and genetic level, and cannot merely be considered as condensed inflorescences. The large meristem size provides an advantage to study basic principles of patterning as well as inflorescence diversity in this evolutionary successful family. This knowledge has also practical importance in the commercially important crops of the family.
  • Pacwa-Plociniczak, Magdalena; Plociniczak, Tomasz; Yu, Dan; Kurola, Jukka Mikael; Sinkkonen, Aki Tapio; Piotrowska-Seget, Zofia; Romantschuk, Martin L. (2018)
    In this study, we analysed the impact of heavy metals and plant rhizodeposition on the structure of indigenous microbial communities in rhizosphere and bulk soil that had been exposed to heavy metals for more than 150 years. Samples of the rhizosphere of Silene vulgaris and non-rhizosphere soils 250 and 450 m from the source of emission that had different metal concentrations were collected for analyses. The results showed that soils were collected 250 m from the smelter had a higher number of Cd-resistant CFU compared with the samples that were collected from 450 m, but no significant differences were observed in the number of total and oligotrophic CFU or the equivalent cell numbers between rhizosphere and non-rhizosphere soils that were taken 250 and 450 m from the emitter. Unweighted pair group method with arithmetic mean (UPGMA) cluster analysis of the denaturing gradient gel electrophoresis (DGGE) profiles, as well as a cluster analysis that was generated on the phospholipid fatty acid (PLFA) profiles, showed that the bacterial community structure of rhizosphere soils depended more on the plant than on the distance and metal concentrations. The sequencing of the 16S rDNA fragments that were excised from the DGGE gel revealed representatives of the phyla Bacteroidetes, Acidobacteria, Gemmatimonadetes, Actinobacteria and Betaproteobacteria in the analysed soil with a predominance of the first three groups. The obtained results demonstrated that the presence of S. vulgaris did not affect the number of CFUs, except for those of Cd-resistant bacteria. However, the presence of S. vulgaris altered the soil bacterial community structure, regardless of the sampling site, which supported the thesis that plants have a higher impact on soil microbial community than metal contamination.
  • Qiao, Wanjin; Qiao, Yu; Liu, Fulu; Zhang, Yating; Li, Ran; Wu, Zhenzhou; Xu, Haijin; Saris, Per Erik Joakim; Qiao, Mingqiang (2020)
    Background In bioengineering, growth of microorganisms is limited because of environmental and industrial stresses during fermentation. This study aimed to construct a nisin-producing chassis Lactococcus lactis strain with genome-streamlined, low metabolic burden, and multi-stress tolerance characteristics. Results The Cre-loxP recombination system was applied to reduce the genome and obtain the target chassis strain. A prophage-related fragment (PRF; 19,739 bp) in the L. lactis N8 genome was deleted, and the mutant strain L. lactis N8-1 was chosen for multi-stress tolerance studies. Nisin immunity of L. lactis N8-1 was increased to 6500 IU/mL, which was 44.44% higher than that of the wild-type L. lactis N8 (4500 IU/mL). The survival rates of L. lactis N8-1 treated with lysozyme for 2 h and lactic acid for 1 h were 1000- and 10,000-fold higher than that of the wild-type strain, respectively. At 39 celcius, the L. lactis N8-1 could still maintain its growth, whereas the growth of the wild-type strain dramatically dropped. Scanning electron microscopy showed that the cell wall integrity of L. lactis N8-1 was well maintained after lysozyme treatment. Tandem mass tags labeled quantitative proteomics revealed that 33 and 9 proteins were significantly upregulated and downregulated, respectively, in L. lactis N8-1. These differential proteins were involved in carbohydrate and energy transport/metabolism, biosynthesis of cell wall and cell surface proteins. Conclusions PRF deletion was proven to be an efficient strategy to achieve multi-stress tolerance and nisin immunity in L. lactis, thereby providing a new perspective for industrially obtaining engineered strains with multi-stress tolerance and expanding the application of lactic acid bacteria in biotechnology and synthetic biology. Besides, the importance of PRF, which can confer vital phenotypes to bacteria, was established.
  • Roman, Veronica L.; Merlin, Christophe; Virta, Marko P. J.; Bellanger, Xavier (2021)
    EpicPCR (Emulsion, Paired Isolation and Concatenation PCR) is a recent single-cell genomic method based on a fusion-PCR allowing us to link a functional sequence of interest to a 16S rRNA gene fragment and use the mass sequencing of the resulting amplicons for taxonomic assignment of the functional sequence-carrying bacteria. Although it is interesting because it presents the highest efficiency for assigning a bacterial host to a marker, epicPCR remains a complex multistage procedure with technical difficulties that may easily impair the approach depth and quality. Here, we described how to adapt epicPCR to new gene targets and environmental matrices while identifying the natural host range of SXT/R391 integrative and conjugative elements in water microbial communities from the Meurthe River (France). We notably show that adding a supplementary PCR step allowed us to increase the amplicon yield and thus the number of reads obtained after sequencing. A comparison of operational taxonomic unit (OTU) identification approaches when using biological and technical replicates demonstrated that, although OTUs can be validated when obtained from three out of three technical replicates, up to now, results obtained from two or three biological replicates give a similar and even a better confidence level in OTU identification, while allowing us to detect poorly represented SXT/R391 hosts in microbial communities.
  • 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.
  • Heinonsalo, Jussi; Sun, Hui; Santalahti, Minna; Bäcklund, Kirsi; Hari, Pertti; Pumpanen, Jukka (2015)
    Ectomycorrhizal (ECM) symbiosis has been proposed to link plant photosynthesis and soil organic matter (SOM) decomposition through the production of fungal enzymes which promote SOM degradation and nitrogen (N) uptake. However, laboratory and field evidence for the existence of these processes are rare. Piloderma sp., a common ECM genus in boreal forest soil, was chosen as model mycorrhiza for this study. The abundance of Piloderma sp. was studied in root tips and soil over one growing season and in winter. Protease production was measured from ectomycorrhiza and soil solution in the field and pure fungal cultures. We also tested the effect of Piloderma olivaceum on host plant organic N nutrition in the laboratory. The results showed that Piloderma sp. was highly abundant in the field and produced extracellular proteases, which correlated positively with the gross primary production, temperature and soil respiration. In the laboratory, Piloderma olivaceum could improve the ability of Pinus sylvestris L. to utilize N from extragenous proteins. We suggest that ECM fungi, although potentially retaining N in their hyphae, are important in forest C and N cycling due to their ability to access proteinaeous N. As Piloderma sp. abundance appeared to be seasonally highly variable, recycling of fungal-bound N after hyphal death may therefore be of primary importance for the N cycling in boreal ecosystems.