Science.gov

Sample records for borkumensis sk2 genome

  1. Isolation and characterization of a mutant of the marine bacterium Alcanivorax borkumensis SK2 defective in lipid biosynthesis.

    PubMed

    Manilla-Pérez, Efraín; Lange, Alvin Brian; Hetzler, Stephan; Wältermann, Marc; Kalscheuer, Rainer; Steinbüchel, Alexander

    2010-05-01

    In many microorganisms, the key enzyme responsible for catalyzing the last step in triacylglycerol (TAG) and wax ester (WE) biosynthesis is an unspecific acyltransferase which is also referred to as wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT; AtfA). The importance and function of two AtfA homologues (AtfA1 and AtfA2) in the biosynthesis of TAGs and WEs in the hydrocarbon-degrading marine bacterium Alcanivorax borkumensis SK2 have been described recently. However, after the disruption of both the AtfA1 and AtfA2 genes, reduced but substantial accumulation of TAGs was still observed, indicating the existence of an alternative TAG biosynthesis pathway. In this study, transposon-induced mutagenesis was applied to an atfA1 atfA2 double mutant to screen for A. borkumensis mutants totally defective in biosynthesis of neutral lipids in order to identify additional enzymes involved in the biosynthesis of these lipids. At the same time, we have searched for a totally TAG-negative mutant in order to study the function of TAGs in A. borkumensis. Thirteen fluorescence-negative mutants were identified on Nile red ONR7a agar plates and analyzed for their abilities to synthesize lipids. Among these, mutant 2 M(131) was no longer able to synthesize and accumulate TAGs if pyruvate was used as the sole carbon source. The transposon insertion was localized in a gene encoding a putative cytochrome c family protein (ABO_1185). Growth and TAG accumulation experiments showed that the disruption of this gene resulted in the absence of TAGs in 2 M(131) but that growth was not affected. In cells of A. borkumensis SK2 grown on pyruvate as the sole carbon source, TAGs represented about 11% of the dry weight of the cells, while in the mutant 2 M(131), TAGs were not detected by thin-layer and gas chromatography analyses. Starvation and lipid mobilization experiments revealed that the lipids play an important role in the survival of the cells. The

  2. Osmotic Stress Confers Enhanced Cell Integrity to Hydrostatic Pressure but Impairs Growth in Alcanivorax borkumensis SK2

    PubMed Central

    Scoma, Alberto; Boon, Nico

    2016-01-01

    Alcanivorax is a hydrocarbonoclastic genus dominating oil spills worldwide. While its presence has been detected in oil-polluted seawaters, marine sediment and salt marshes under ambient pressure, its presence in deep-sea oil-contaminated environments is negligible. Recent laboratory studies highlighted the piezosensitive nature of some Alcanivorax species, whose growth yields are highly impacted by mild hydrostatic pressures (HPs). In the present study, osmotic stress was used as a tool to increase HP resistance in the type strain Alcanivorax borkumensis SK2. Control cultures grown under standard conditions of salinity and osmotic pressure with respect to seawater (35.6 ppt or 1136 mOsm kg-1, respectively) were compared with cultures subjected to hypo- and hyperosmosis (330 and 1720 mOsm kg-1, or 18 and 62 ppt in salinity, equivalent to brackish and brine waters, respectively), under atmospheric or increased HP (0.1 and 10 MPa). Osmotic stress had a remarkably positive impact on cell metabolic activity in terms of CO2 production (thus, oil bioremediation) and O2 respiration under hyperosmosis, as acclimation to high salinity enhanced cell activity under 10 MPa by a factor of 10. Both osmotic shocks significantly enhanced cell protection by reducing membrane damage under HP, with cell integrities close to 100% under hyposmosis. The latter was likely due to intracellular water-reclamation as no trace of the piezolyte ectoine was found, contrary to hyperosmosis. Notably, ectoine production was equivalent at 0.1 MPa in hyperosmosis-acclimated cells and at 10 MPa under isosmotic conditions. While stimulating cell metabolism and enhancing cell integrity, osmotic stress had always a negative impact on culture growth and performance. No net growth was observed during 4-days incubation tests, and CO2:O2 ratios and pH values indicated that culture performance in terms of hydrocarbon degradation was lowered by the effects of osmotic stress alone or combined with increased HP

  3. Osmotic Stress Confers Enhanced Cell Integrity to Hydrostatic Pressure but Impairs Growth in Alcanivorax borkumensis SK2.

    PubMed

    Scoma, Alberto; Boon, Nico

    2016-01-01

    Alcanivorax is a hydrocarbonoclastic genus dominating oil spills worldwide. While its presence has been detected in oil-polluted seawaters, marine sediment and salt marshes under ambient pressure, its presence in deep-sea oil-contaminated environments is negligible. Recent laboratory studies highlighted the piezosensitive nature of some Alcanivorax species, whose growth yields are highly impacted by mild hydrostatic pressures (HPs). In the present study, osmotic stress was used as a tool to increase HP resistance in the type strain Alcanivorax borkumensis SK2. Control cultures grown under standard conditions of salinity and osmotic pressure with respect to seawater (35.6 ppt or 1136 mOsm kg(-1), respectively) were compared with cultures subjected to hypo- and hyperosmosis (330 and 1720 mOsm kg(-1), or 18 and 62 ppt in salinity, equivalent to brackish and brine waters, respectively), under atmospheric or increased HP (0.1 and 10 MPa). Osmotic stress had a remarkably positive impact on cell metabolic activity in terms of CO2 production (thus, oil bioremediation) and O2 respiration under hyperosmosis, as acclimation to high salinity enhanced cell activity under 10 MPa by a factor of 10. Both osmotic shocks significantly enhanced cell protection by reducing membrane damage under HP, with cell integrities close to 100% under hyposmosis. The latter was likely due to intracellular water-reclamation as no trace of the piezolyte ectoine was found, contrary to hyperosmosis. Notably, ectoine production was equivalent at 0.1 MPa in hyperosmosis-acclimated cells and at 10 MPa under isosmotic conditions. While stimulating cell metabolism and enhancing cell integrity, osmotic stress had always a negative impact on culture growth and performance. No net growth was observed during 4-days incubation tests, and CO2:O2 ratios and pH values indicated that culture performance in terms of hydrocarbon degradation was lowered by the effects of osmotic stress alone or combined with

  4. Adaptation of the Hydrocarbonoclastic Bacterium Alcanivorax borkumensis SK2 to Alkanes and Toxic Organic Compounds: a Physiological and Transcriptomic Approach

    PubMed Central

    Naether, Daniela J.; Slawtschew, Slavtscho; Stasik, Sebastian; Engel, Maria; Olzog, Martin; Wick, Lukas Y.; Timmis, Kenneth N.

    2013-01-01

    The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is able to degrade mixtures of n-alkanes as they occur in marine oil spills. However, investigations of growth behavior and physiology of these bacteria when cultivated with n-alkanes of different chain lengths (C6 to C30) as the substrates are still lacking. Growth rates increased with increasing alkane chain length up to a maximum between C12 and C19, with no evident difference between even- and odd-numbered chain lengths, before decreasing with chain lengths greater than C19. Surface hydrophobicity of alkane-grown cells, assessed by determination of the water contact angles, showed a similar pattern, with maximum values associated with growth rates on alkanes with chain lengths between C11 and C19 and significantly lower values for cells grown on pyruvate. A. borkumensis was found to incorporate and modify the fatty acid intermediates generated by the corresponding n-alkane degradation pathway. Cells grown on distinct n-alkanes proved that A. borkumensis is able to not only incorporate but also modify fatty acid intermediates derived from the alkane degradation pathway. Comparing cells grown on pyruvate with those cultivated on hexadecane in terms of their tolerance toward two groups of toxic organic compounds, chlorophenols and alkanols, representing intensely studied organic compounds, revealed similar tolerances toward chlorophenols, whereas the toxicities of different n-alkanols were significantly reduced when hexadecane was used as a carbon source. As one adaptive mechanism of A. borkumensis to these toxic organic solvents, the activity of cis-trans isomerization of unsaturated fatty acids was proven. These findings could be verified by a detailed transcriptomic comparison between cultures grown on hexadecane and pyruvate and including solvent stress caused by the addition of 1-octanol as the most toxic intermediate of n-alkane degradation. PMID:23645199

  5. Adaptation of the hydrocarbonoclastic bacterium Alcanivorax borkumensis SK2 to alkanes and toxic organic compounds: a physiological and transcriptomic approach.

    PubMed

    Naether, Daniela J; Slawtschew, Slavtscho; Stasik, Sebastian; Engel, Maria; Olzog, Martin; Wick, Lukas Y; Timmis, Kenneth N; Heipieper, Hermann J

    2013-07-01

    The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is able to degrade mixtures of n-alkanes as they occur in marine oil spills. However, investigations of growth behavior and physiology of these bacteria when cultivated with n-alkanes of different chain lengths (C6 to C30) as the substrates are still lacking. Growth rates increased with increasing alkane chain length up to a maximum between C12 and C19, with no evident difference between even- and odd-numbered chain lengths, before decreasing with chain lengths greater than C19. Surface hydrophobicity of alkane-grown cells, assessed by determination of the water contact angles, showed a similar pattern, with maximum values associated with growth rates on alkanes with chain lengths between C11 and C19 and significantly lower values for cells grown on pyruvate. A. borkumensis was found to incorporate and modify the fatty acid intermediates generated by the corresponding n-alkane degradation pathway. Cells grown on distinct n-alkanes proved that A. borkumensis is able to not only incorporate but also modify fatty acid intermediates derived from the alkane degradation pathway. Comparing cells grown on pyruvate with those cultivated on hexadecane in terms of their tolerance toward two groups of toxic organic compounds, chlorophenols and alkanols, representing intensely studied organic compounds, revealed similar tolerances toward chlorophenols, whereas the toxicities of different n-alkanols were significantly reduced when hexadecane was used as a carbon source. As one adaptive mechanism of A. borkumensis to these toxic organic solvents, the activity of cis-trans isomerization of unsaturated fatty acids was proven. These findings could be verified by a detailed transcriptomic comparison between cultures grown on hexadecane and pyruvate and including solvent stress caused by the addition of 1-octanol as the most toxic intermediate of n-alkane degradation.

  6. Alcanivorax borkumensis produces an extracellular siderophore in iron-limitation condition maintaining the hydrocarbon-degradation efficiency.

    PubMed

    Denaro, R; Crisafi, F; Russo, D; Genovese, M; Messina, E; Genovese, L; Carbone, M; Ciavatta, M L; Ferrer, M; Golyshin, P; Yakimov, M M

    2014-10-01

    Obligate marine hydrocarbonoclastic bacteria possess genetic and physiological features to use hydrocarbons as sole source of carbon and to compete for the uptake of nutrients in usually nutrient-depleted marine habitats. In the present work we have studied the siderophore-based iron uptake systems in Alcanivorax borkumensis SK2 and their functioning during biodegradation of an aliphatic hydrocarbon, tetradecane, under iron limitation conditions. The antiSMASH analysis of SK2 genome revealed the presence of two different putative operons of siderophore synthetases. Search for the predicted core structures indicated that one siderophore is clearly affiliated to the family of complex oligopeptidic siderophores possessing an Orn-Ser-Orn carboxyl motif whereas the second one is likely to belong to the family of SA (salicylic acid)-based siderophores. Analyzing the supernatant of SK2 culture, an extracellular siderophore was identified and its structure was resolved. Thus, along with the recently described membrane-associated amphiphilic tetrapeptidic siderophore amphibactin, strain SK2 additionally produces an extracellular type of iron-chelating molecule with structural similarity to pseudomonins. Comparative Q-PCR analysis of siderophore synthetases demonstrated their significant up-regulation in iron-depleted medium. Different expression patterns were recorded for two operons during the early and late exponential phases of growth, suggesting a different function of these two siderophores under iron-depleted conditions.

  7. An impaired metabolic response to hydrostatic pressure explains Alcanivorax borkumensis recorded distribution in the deep marine water column

    NASA Astrophysics Data System (ADS)

    Scoma, Alberto; Barbato, Marta; Borin, Sara; Daffonchio, Daniele; Boon, Nico

    2016-08-01

    Alcanivorax borkumensis is an ubiquitous model organism for hydrocarbonoclastic bacteria, which dominates polluted surface waters. Its negligible presence in oil-contaminated deep waters (as observed during the Deepwater Horizon accident) raises the hypothesis that it may lack adaptive mechanisms to hydrostatic pressure (HP). The type strain SK2 was tested under 0.1, 5 and 10 MPa (corresponding to surface water, 500 and 1000 m depth, respectively). While 5 MPa essentially inactivated SK2, further increase to 10 MPa triggered some resistance mechanism, as indicated by higher total and intact cell numbers. Under 10 MPa, SK2 upregulated the synthetic pathway of the osmolyte ectoine, whose concentration increased from 0.45 to 4.71 fmoles cell-1. Central biosynthetic pathways such as cell replication, glyoxylate and Krebs cycles, amino acids metabolism and fatty acids biosynthesis, but not β-oxidation, were upregulated or unaffected at 10 MPa, although total cell number was remarkably lower with respect to 0.1 MPa. Concomitantly, expression of more than 50% of SK2 genes was downregulated, including genes related to ATP generation, respiration and protein translation. Thus, A. borkumensis lacks proper adaptation to HP but activates resistance mechanisms. These consist in poorly efficient biosynthetic rather than energy-yielding degradation-related pathways, and suggest that HP does represent a major driver for its distribution at deep-sea.

  8. An impaired metabolic response to hydrostatic pressure explains Alcanivorax borkumensis recorded distribution in the deep marine water column.

    PubMed

    Scoma, Alberto; Barbato, Marta; Borin, Sara; Daffonchio, Daniele; Boon, Nico

    2016-08-12

    Alcanivorax borkumensis is an ubiquitous model organism for hydrocarbonoclastic bacteria, which dominates polluted surface waters. Its negligible presence in oil-contaminated deep waters (as observed during the Deepwater Horizon accident) raises the hypothesis that it may lack adaptive mechanisms to hydrostatic pressure (HP). The type strain SK2 was tested under 0.1, 5 and 10 MPa (corresponding to surface water, 500 and 1000 m depth, respectively). While 5 MPa essentially inactivated SK2, further increase to 10 MPa triggered some resistance mechanism, as indicated by higher total and intact cell numbers. Under 10 MPa, SK2 upregulated the synthetic pathway of the osmolyte ectoine, whose concentration increased from 0.45 to 4.71 fmoles cell(-1). Central biosynthetic pathways such as cell replication, glyoxylate and Krebs cycles, amino acids metabolism and fatty acids biosynthesis, but not β-oxidation, were upregulated or unaffected at 10 MPa, although total cell number was remarkably lower with respect to 0.1 MPa. Concomitantly, expression of more than 50% of SK2 genes was downregulated, including genes related to ATP generation, respiration and protein translation. Thus, A. borkumensis lacks proper adaptation to HP but activates resistance mechanisms. These consist in poorly efficient biosynthetic rather than energy-yielding degradation-related pathways, and suggest that HP does represent a major driver for its distribution at deep-sea.

  9. An impaired metabolic response to hydrostatic pressure explains Alcanivorax borkumensis recorded distribution in the deep marine water column

    PubMed Central

    Scoma, Alberto; Barbato, Marta; Borin, Sara; Daffonchio, Daniele; Boon, Nico

    2016-01-01

    Alcanivorax borkumensis is an ubiquitous model organism for hydrocarbonoclastic bacteria, which dominates polluted surface waters. Its negligible presence in oil-contaminated deep waters (as observed during the Deepwater Horizon accident) raises the hypothesis that it may lack adaptive mechanisms to hydrostatic pressure (HP). The type strain SK2 was tested under 0.1, 5 and 10 MPa (corresponding to surface water, 500 and 1000 m depth, respectively). While 5 MPa essentially inactivated SK2, further increase to 10 MPa triggered some resistance mechanism, as indicated by higher total and intact cell numbers. Under 10 MPa, SK2 upregulated the synthetic pathway of the osmolyte ectoine, whose concentration increased from 0.45 to 4.71 fmoles cell−1. Central biosynthetic pathways such as cell replication, glyoxylate and Krebs cycles, amino acids metabolism and fatty acids biosynthesis, but not β-oxidation, were upregulated or unaffected at 10 MPa, although total cell number was remarkably lower with respect to 0.1 MPa. Concomitantly, expression of more than 50% of SK2 genes was downregulated, including genes related to ATP generation, respiration and protein translation. Thus, A. borkumensis lacks proper adaptation to HP but activates resistance mechanisms. These consist in poorly efficient biosynthetic rather than energy-yielding degradation-related pathways, and suggest that HP does represent a major driver for its distribution at deep-sea. PMID:27515484

  10. Analysis of storage lipid accumulation in Alcanivorax borkumensis: Evidence for alternative triacylglycerol biosynthesis routes in bacteria.

    PubMed

    Kalscheuer, Rainer; Stöveken, Tim; Malkus, Ursula; Reichelt, Rudolf; Golyshin, Peter N; Sabirova, Julia S; Ferrer, Manuel; Timmis, Kenneth N; Steinbüchel, Alexander

    2007-02-01

    Marine hydrocarbonoclastic bacteria, like Alcanivorax borkumensis, play a globally important role in bioremediation of petroleum oil contamination in marine ecosystems. Accumulation of storage lipids, serving as endogenous carbon and energy sources during starvation periods, might be a potential adaptation mechanism for coping with nutrient limitation, which is a frequent stress factor challenging those bacteria in their natural marine habitats. Here we report on the analysis of storage lipid biosynthesis in A. borkumensis strain SK2. Triacylglycerols (TAGs) and wax esters (WEs), but not poly(hydroxyalkanoic acids), are the principal storage lipids present in this and other hydrocarbonoclastic bacterial species. Although so far assumed to be a characteristic restricted to gram-positive actinomycetes, substantial accumulation of TAGs corresponding to a fatty acid content of more than 23% of the cellular dry weight is the first characteristic of large-scale de novo TAG biosynthesis in a gram-negative bacterium. The acyltransferase AtfA1 (ABO_2742) exhibiting wax ester synthase/acyl-coenzyme A:diacylglycerol acyltransferase (WS/DGAT) activity plays a key role in both TAG and WE biosynthesis, whereas AtfA2 (ABO_1804) was dispensable for storage lipid formation. However, reduced but still substantial residual TAG levels in atfA1 and atfA2 knockout mutants compellingly indicate the existence of a yet unknown WS/DGAT-independent alternative TAG biosynthesis route. Storage lipids of A. borkumensis were enriched in saturated fatty acids and accumulated as insoluble intracytoplasmic inclusions exhibiting great structural variety. Storage lipid accumulation provided only a slight growth advantage during short-term starvation periods but was not required for maintaining viability and long-term persistence during extended starvation phases.

  11. Sequencing and molecular dissection of Sk-2 in Neurospora

    USDA-ARS?s Scientific Manuscript database

    Neurospora Spore killer-2 is a selfish meiotic drive element that kills its non-Sk-2 siblings during sexual sporulation. Although the location of Sk-2 has been mapped to a large recombination-suppressed region of chromosome III, the physical length and exact borders of the element have remained unde...

  12. Interaction of Alcanivorax borkumensis with a Surfactant Decorated Oil-Water Interface.

    PubMed

    Bookstaver, Michelle; Bose, Arijit; Tripathi, Anubhav

    2015-06-02

    Alcanivorax borkumensis is a hydrocarbon degrading bacterium linked to oil degradation around oil spill sites. It is known to be a surface bacterium leading to substantial interaction with the oil-water interface. Because of its abundance in oil spill regions, it has great potential to be used actively in oil spill remediation. Dispersants are thought to be important in the creation of oil-in-water emulsions that are meant to aid in the biodegradation process by bacteria. Although it is likely that some sort of dispersant will be used again in the case of another oil spill, to date, no studies have shown the impact of dispersants on the bacteria population. Corexit 9500 was the main dispersant used during the Deepwater Horizon oil spill, but little is known about its effect on the bacteria community. We built an experimental platform to quantitatively measure the transient growth of Alcanivorax borkumensis at the interface of oil and water. To our knowledge, this is the first study of how A. borkumensis interacts with a surfactant decorated oil-water interface. We use COREXIT EC9500A, cetylytrimethylamonium bromide, dioctyl sulfosuccinate sodium salt, l-α-phosphatidylcholine, sodium dodecyl sulfate, and Tween 20 to investigate the impact of dispersants on Alcanivorax borkumensis. We assess the impact of these dispersants on the growth rate, lag time, and maximum concentration of Alcanivorax borkumensis. We show that the charge, structure, and surface activity of these surfactants greatly impact the growth of A. borkumensis. Our results indicated that out of the surfactants tested only Tween 20 assists Acanivorax borkumensis growth. The results of this study will be important in the decision of dispersant use in the future.

  13. Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction*

    PubMed Central

    Dolga, Amalia M.; Netter, Michael F.; Perocchi, Fabiana; Doti, Nunzianna; Meissner, Lilja; Tobaben, Svenja; Grohm, Julia; Zischka, Hans; Plesnila, Nikolaus; Decher, Niels; Culmsee, Carsten

    2013-01-01

    Small conductance calcium-activated potassium (SK2/KCa2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K+ currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction. PMID:23430260

  14. Mitochondrial small conductance SK2 channels prevent glutamate-induced oxytosis and mitochondrial dysfunction.

    PubMed

    Dolga, Amalia M; Netter, Michael F; Perocchi, Fabiana; Doti, Nunzianna; Meissner, Lilja; Tobaben, Svenja; Grohm, Julia; Zischka, Hans; Plesnila, Nikolaus; Decher, Niels; Culmsee, Carsten

    2013-04-12

    Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K(+) currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction.

  15. Increasing SK2 channel activity impairs associative learning

    PubMed Central

    McKay, Bridget M.; Oh, M. Matthew; Galvez, Roberto; Burgdorf, Jeffrey; Kroes, Roger A.; Weiss, Craig; Adelman, John P.; Moskal, Joseph R.

    2012-01-01

    Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning. PMID:22552186

  16. Developmental profile of SK2 channel expression and function in CA1 neurons

    PubMed Central

    Ballesteros-Merino, Carmen; Lin, Mike; Wu, Wendy W.; Ferrandiz-Huertas, Clotilde; Cabañero, María J.; Watanabe, Masahiko; Fukazawa, Yugo; Shigemoto, Ryuichi; Maylie, James; Adelman, John P.; Luján, Rafael

    2012-01-01

    We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal-to-distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum-moleculare in adult. These results show a developmental increase and gradient in SK2-containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development. PMID:22072564

  17. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    PubMed Central

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; Radhakrishnan, Abhijith; Kumar, Nitin; Chou, Tsung-Han; Long, Feng; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2015-01-01

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a reevaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here, we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs. PMID:25892120

  18. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    SciTech Connect

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; Radhakrishnan, Abhijith; Kumar, Nitin; Chou, Tsung-Han; Long, Feng; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2015-04-20

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.

  19. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    NASA Astrophysics Data System (ADS)

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; Radhakrishnan, Abhijith; Kumar, Nitin; Chou, Tsung-Han; Long, Feng; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2015-04-01

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.

  20. UBE3A regulates synaptic plasticity and learning and memory by controlling SK2 channel endocytosis

    PubMed Central

    Sun, Jiandong; Zhu, Guoqi; Liu, Yan; Standley, Steve; Ji, Angela; Tunuguntla, Rashmi; Wang, Yubin; Claus, Chad; Luo, Lyna; Baudry, Michel; Bi, Xiaoning

    2015-01-01

    Summary Gated solely by activity-induced changes in intracellular calcium, small conductance potassium channels (SKs) are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and over-expression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function. PMID:26166566

  1. Localization of SK2 channels relative to excitatory synaptic sites in the mouse developing Purkinje cells

    PubMed Central

    Ballesteros-Merino, Carmen; Martínez-Hernández, José; Aguado, Carolina; Watanabe, Masahiko; Adelman, John P.; Luján, Rafael

    2014-01-01

    Small-conductance, Ca2+-activated K+ (SK) channels regulate neuronal excitability in a variety of ways. To understand their roles in different neuronal subtypes it is important to determine their precise subcellular distribution. Here, we used biochemical, light microscopy immunohistochemical and immunoelectron microscopy techniques, combined with quantitative approaches, to reveal the expression and subcellular localization patterns of SK2 in the developing cerebellum. Using western blots, the SK2 protein showed a progressive increase during postnatal development. At the light microscopic level, SK2 immunoreactivity was very prominent in the developing Purkinje cells (PC), particularly in the molecular layer (ML). Electron microscopy revealed that throughout development SK2 was mostly detected at the extrasynaptic and perisynaptic plasma membrane of dendritic shafts and dendritic spines of PCs. However, there was some localization at axon terminals as well. Quantitative analyses and 3D reconstructions further revealed a progressive developmental change of SK2 on the surface of PCs from dendritic shafts to dendritic spines. Together, these results indicate that SK2 channels undergo dynamic spatial regulation during cerebellar development, and this process is associated with the formation and maturation of excitatory synaptic contacts to PCs. PMID:25565979

  2. Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.

    PubMed

    Wimmer, Ralf D; Astori, Simone; Bond, Chris T; Rovó, Zita; Chatton, Jean-Yves; Adelman, John P; Franken, Paul; Lüthi, Anita

    2012-10-03

    Sleep spindles are synchronized 11-15 Hz electroencephalographic (EEG) oscillations predominant during nonrapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Ca(v)3.3-type Ca(2+) channels and Ca(2+)-dependent small-conductance-type 2 (SK2) K(+) channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-overexpressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared with wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow waves (<4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles.

  3. Sustaining sleep spindles through enhanced SK2 channel activity consolidates sleep and elevates arousal threshold

    PubMed Central

    Wimmer, Ralf D.; Astori, Simone; Bond, Chris T.; Rovó, Zita; Chatton, Jean-Yves; Adelman, John P.; Franken, Paul; Lüthi, Anita

    2013-01-01

    Sleep spindles are synchronized 11–15 Hz electroencephalographic (EEG) oscillations predominant during non-rapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Cav3.3-type Ca2+ channels and Ca2+-dependent small-conductance-type 2 (SK2) K+ channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-over-expressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared to wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow-waves (< 4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles. PMID:23035101

  4. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    DOE PAGES

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; ...

    2015-04-20

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm tomore » halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.« less

  5. Cloning and characterization of SK2 channel from chicken short hair cells.

    PubMed

    Matthews, T M; Duncan, R K; Zidanic, M; Michael, T H; Fuchs, P A

    2005-06-01

    In the inner ear of birds, as in mammals, reptiles and amphibians, acetylcholine released from efferent neurons inhibits hair cells via activation of an apamin-sensitive, calcium-dependent potassium current. The particular potassium channel involved in avian hair cell inhibition is unknown. In this study, we cloned a small-conductance, calcium-sensitive potassium channel (gSK2) from a chicken cochlear library. Using RT-PCR, we demonstrated the presence of gSK2 mRNA in cochlear hair cells. Electrophysiological studies on transfected HEK293 cells showed that gSK2 channels have a conductance of approximately 16 pS and a half-maximal calcium activation concentration of 0.74+/-0.17 microM. The expressed channels were blocked by apamin (IC(50)=73.3+/-5.0 pM) and d-tubocurarine (IC(50)=7.6+/-1.0 microM), but were insensitive to charybdotoxin. These characteristics are consistent with those reported for acetylcholine-induced potassium currents of isolated chicken hair cells, suggesting that gSK2 is involved in efferent inhibition of chicken inner ear. These findings imply that the molecular mechanisms of inhibition are conserved in hair cells of all vertebrates.

  6. Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain.

    PubMed

    Willis, Michael; Trieb, Maria; Leitner, Irmgard; Wietzorrek, Georg; Marksteiner, Josef; Knaus, Hans-Günther

    2017-03-01

    SK2 (KCa2.2) channels are voltage-independent Ca(2+)-activated K(+) channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels.

  7. Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression

    PubMed Central

    Schrecengost, Randy S.; Keller, Staci N.; Schiewer, Matthew J.; Knudsen, Karen E.; Smith, Charles D.

    2015-01-01

    The bioactive sphingolipid sphingosine-1-phosphate (S1P) drives several hallmark processes of cancer, making the enzymes that synthesize S1P, i.e. sphingosine kinase 1 and 2 (SK1 and SK2), important molecular targets for cancer drug development. ABC294640 is a first-in-class SK2 small-molecule inhibitor that effectively inhibits cancer cell growth in vitro and in vivo. Given that AR and Myc are two of the most widely implicated oncogenes in prostate cancer (PCa), and that sphingolipids impact signaling by both proteins, the therapeutic potential for using ABC294640 in the treatment of PCa was evaluated. This study demonstrates that ABC294640 abrogates signaling pathways requisite for PCa growth and proliferation. Key findings validate that ABC294640 treatment of early stage and advanced PCa models downregulate Myc and AR expression and activity. This corresponds with significant inhibition of growth, proliferation, and cell cycle progression. Finally, oral administration of ABC294640 was found to dramatically impede xenograft tumor growth. Together, these pre-clinical findings support the hypotheses that SK2 activity is required for PCa function and that ABC294640 represents a new pharmacological agent for treatment of early stage and aggressive PCa. PMID:26271487

  8. Alternative splice isoforms of small conductance calcium-activated SK2 channels differ in molecular interactions and surface levels.

    PubMed

    Scholl, Elizabeth Storer; Pirone, Antonella; Cox, Daniel H; Duncan, R Keith; Jacob, Michele H

    2014-01-01

    Small conductance Ca(2+)-sensitive potassium (SK2) channels are voltage-independent, Ca(2+)-activated ion channels that conduct potassium cations and thereby modulate the intrinsic excitability and synaptic transmission of neurons and sensory hair cells. In the cochlea, SK2 channels are functionally coupled to the highly Ca(2+) permeant α9/10-nicotinic acetylcholine receptors (nAChRs) at olivocochlear postsynaptic sites. SK2 activation leads to outer hair cell hyperpolarization and frequency-selective suppression of afferent sound transmission. These inhibitory responses are essential for normal regulation of sound sensitivity, frequency selectivity, and suppression of background noise. However, little is known about the molecular interactions of these key functional channels. Here we show that SK2 channels co-precipitate with α9/10-nAChRs and with the actin-binding protein α-actinin-1. SK2 alternative splicing, resulting in a 3 amino acid insertion in the intracellular 3' terminus, modulates these interactions. Further, relative abundance of the SK2 splice variants changes during developmental stages of synapse maturation in both the avian cochlea and the mammalian forebrain. Using heterologous cell expression to separately study the 2 distinct isoforms, we show that the variants differ in protein interactions and surface expression levels, and that Ca(2+) and Ca(2+)-bound calmodulin differentially regulate their protein interactions. Our findings suggest that the SK2 isoforms may be distinctly modulated by activity-induced Ca(2+) influx. Alternative splicing of SK2 may serve as a novel mechanism to differentially regulate the maturation and function of olivocochlear and neuronal synapses.

  9. Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function

    PubMed Central

    Kim, Gukhan; Luján, Rafael; Schwenk, Jochen; Kelley, Melissa H; Aguado, Carolina; Watanabe, Masahiko; Fakler, Bernd; Maylie, James; Adelman, John P

    2016-01-01

    Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synaptically evoked NMDAR-dependent Ca2+ influx, the synaptic SK2-containing channels modulate excitatory post-synaptic responses and the induction of synaptic plasticity. In addition, their activity- and protein kinase A-dependent trafficking contributes to expression of long-term potentiation (LTP). We have identified a novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2; p55), a member of the membrane-associated guanylate kinase (MAGUK) family that interacts with SK2-containing channels. MPP2 and SK2 co-immunopurified from mouse brain, and co-immunoprecipitated when they were co-expressed in HEK293 cells. MPP2 is highly expressed in the post-synaptic density of dendritic spines on CA1 pyramidal neurons. Knocking down MPP2 expression selectively abolished the SK2-containing channel contribution to synaptic responses and decreased LTP. Thus, MPP2 is a novel synaptic scaffold that is required for proper synaptic localization and function of SK2-containing channels. DOI: http://dx.doi.org/10.7554/eLife.12637.001 PMID:26880549

  10. Antioxidative Polyketones from the Mangrove-Derived Fungus Ascomycota sp. SK2YWS-L

    PubMed Central

    Tan, Chunbin; Liu, Zhaoming; Chen, Senhua; Huang, Xishan; Cui, Hui; Long, Yuhua; Lu, Yongjun; She, Zhigang

    2016-01-01

    Three novel 2,3-diaryl indone derivatives, ascomindones A−C (1−3), and two new isobenzofuran derivatives, ascomfurans A (4) and B (5), together with four know compounds (6−9) were isolated from the culture of a mangrove-derived fungus Ascomycota sp. SK2YWS-L. Their structures were elucidated on the interpretation of spectroscopic data. 1 and 4 were further constructed by analysis of X-ray diffraction. Antioxidant properties based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical scavenging activities and the ferric reducing ability power (FRAP) of the new compounds were assayed. All of them exhibited significant effects, of which 1 showed more potent activity than ascorbic acid in scavenging DPPH radical with IC50 value of 18.1 μM. PMID:27811993

  11. Application program of CRUST-1 10km continental scientific drilling rig in SK-2 scientific drilling well

    NASA Astrophysics Data System (ADS)

    Sun, Youhong; Gao, Ke; Yu, Ping; Liu, Baochang; Guo, Wei; Ma, Yinlong; Yang, Yang

    2014-05-01

    SK-2 Well is located in DaQing city,where is site of the largest oil field in China,Heilongjiang province, north-east of China.The objective of SK-2 well is to obtain full cores of cretaceous formation in Song Liao basin,and to build the time tunnel of Cretaceous greenhouse climate change,and to clarify the causes,processes and results of the formations of DaQing oil field. This will ensure to achieve our ultimate goals,to test the CRUST-1 drilling rig and improve China's deep scientific drilling technology,to form the scientific drilling technology,method and system with independent intellectual property rights,and to provide technical knowledge and information for China's ten kilometers super-deep scientific drilling technical resources.SK-2 Well is at 6400 meter depth, where the drilling inclination is 90 degree and the continuous coring length is 3535 meter that from 2865 to 6400 meter,the recovery rate of the core is greater or equal to 95 percent with 100 millimeters core diameter and 3.9 degree per 100 meter geothermal gradient.The CRUST-1 rig is designated with special drilling equipment for continental scientific drilling combined to the oil drilling equipment ability with advanced geological drilling technology which is highly automatic and intelligent. CRUST-1 drilling ability is 10000 meter with the maximum hook load 700 tons, the total power is 4610 Kilowatt.CRUST-1 will be integrated with a complete set of automation equipment,including big torque hydraulic top drive,high accuracy automatic drilling rod feeding system, suspended automatic drill string discharge device,hydraulic intelligent iron roughneck,and hydraulic automatic catwalk to fully meet the drilling process requirements of SK-2.Designed with advanced drilling technique for 260 degree in the bottom of SK-2 well and hard rock,including the drilling tools of high temperature hydraulic hammer,high temperature resistance and high strength aluminum drill pipe,high temperature preparation of mud

  12. T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

    PubMed

    Cueni, Lucius; Canepari, Marco; Luján, Rafael; Emmenegger, Yann; Watanabe, Masahiko; Bond, Chris T; Franken, Paul; Adelman, John P; Lüthi, Anita

    2008-06-01

    T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

  13. Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels

    PubMed Central

    Hougaard, C; Eriksen, B L; Jørgensen, S; Johansen, T H; Dyhring, T; Madsen, L S; Strøbæk, D; Christophersen, P

    2007-01-01

    Background and purpose: Positive modulators of small conductance Ca2+-activated K+ channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1-EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca2+-activated K+ channel (IK). This paper demonstrates, for the first time, subtype-selective positive modulation of SK channels. Experimental approach: Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) on recombinant hSK1-3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells. Key results: CyPPA was found to be a positive modulator of hSK3 (EC50 = 5.6 ± 1.6 μM, efficacy 90 ± 1.8 %) and hSK2 (EC50 = 14 ± 4 μM, efficacy 71 ± 1.8 %) when measured in inside-out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration-dependent increase in the apparent Ca2+-sensitivity of channel activation, changing the EC50(Ca2+) from 429 nM to 59 nM. Conclusions and implications: As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1-EBIO and NS309 to distinguish SK3/SK2- from SK1/IK-mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co-express in certain peripheral tissues. PMID:17486140

  14. [Application of recording SK2 current in human atrial myocytes by perforated patch clamp techniques with the mix of beta-escin and amphotericin B].

    PubMed

    Wang, Hua; Li, Tao; Lei, Ming; Li, Miao-ling; Ding, Yin-yuan; Yang, Yan; Zeng, Xiao-rong

    2012-05-01

    To establish a perforated patch-clamp technology with amphotericin B and beta-escin and to research the regulation of small conductance calcium-activated potassium channel SK2 currents by calcium ions. Single human atrial myocytes were enzymatically isolated from the right atrial appendage. Amphotericin B and / or beta-escin were used by perforated electrode liquid. The regulation of SK2 current by calcium ions in human atrial myocytes was performed with the perforated patch-clamp technique. The intracellular calcium changes were measured by the intracellular calcium test system. Mixed perforated electrode liquid compared with 150 microg/ml amphotericin B or 6.88 microg/ml beta-escin alone, it was easy to seal cells and activate SK2 current by the former method. Moreover, the ration of F340/380 was consistent with the change of intracellular free calcium ion concentration increase after the formation of perforation. The ration of F340/380 was measured by intracellular calcium test system. The appropriate concentration of amphotericin B mixed with beta-escin can form a stable whole-cell patch recording technology that is appropriate for the research of SK2 current regulation by intracellular calcium.

  15. Tremor dominant Kyoto (Trdk) rats carry a missense mutation in the gene encoding the SK2 subunit of small-conductance Ca(2+)-activated K(+) channel.

    PubMed

    Kuramoto, Takashi; Yokoe, Mayuko; Kunisawa, Naofumi; Ohashi, Kana; Miyake, Takahito; Higuchi, Yuki; Yoshimi, Kazuto; Mashimo, Tomoji; Tanaka, Miyuu; Kuwamura, Mitusru; Kaneko, Shuji; Shimizu, Saki; Serikawa, Tadao; Ohno, Yukihiro

    2017-09-13

    Tremor dominant Kyoto (Trdk) is an autosomal dominant mutation that appeared in F344/NSlc rats mutagenized with N-ethyl-N-nitrosourea (ENU). In this study, we characterized and genetically analyzed F344-Trdk/+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344-Trdk/+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson's disease-related tremor, indicating that the pharmacological phenotype of F344-Trdk/+ rats was similar to human ET. Using positional candidate approach, we identified the Trdk mutation as a missense substitution (c. 866 T>A, p. I289N) in Kcnn2, which encodes the SK2 subunit of the small-conductance Ca(2+)-activated K(+) channel. In vitro electrophysiological studies revealed that the I289N mutation diminished SK2 channel activity. These findings demonstrate that F344-Trdk/+ rats represent a novel model of ET, and strongly suggest that Kcnn2 is the causative gene for the tremor phenotype in F344-Trdk/+ rats. Copyright © 2017. Published by Elsevier B.V.

  16. Direct Host Plasminogen Binding to Bacterial Surface M-protein in Pattern D Strains of Streptococcus pyogenes Is Required for Activation by Its Natural Coinherited SK2b Protein.

    PubMed

    Chandrahas, Vishwanatha; Glinton, Kristofor; Liang, Zhong; Donahue, Deborah L; Ploplis, Victoria A; Castellino, Francis J

    2015-07-24

    Streptokinase (SK), secreted by Group A Streptococcus (GAS), is a single-chain ∼47-kDa protein containing three consecutive primary sequence regions that comprise its α, β, and γ modules. Phylogenetic analyses of the variable β-domain sequences from different GAS strains suggest that SKs can be arranged into two clusters, SK1 and SK2, with a subdivision of SK2 into SK2a and SK2b. SK2b is secreted by skin-tropic Pattern D M-protein strains that also express plasminogen (human Pg (hPg)) binding Group A streptococcal M-protein (PAM) as its major cell surface M-protein. SK2a-expressing strains are associated with nasopharynx tropicity, and many of these strains express human fibrinogen (hFg) binding Pattern A-C M-proteins, e.g. M1. PAM interacts with hPg directly, whereas M1 binds to hPg indirectly via M1-bound hFg. Subsequently, SK is secreted by GAS and activates hPg to plasmin (hPm), thus generating a proteolytic surface on GAS that enhances its dissemination. Due to these different modes of hPg/hPm recognition by GAS, full characterizations of the mechanisms of activation of hPg by SK2a and SK2b and their roles in GAS virulence are important topics. To more fully examine these subjects, isogenic chimeric SK- and M-protein-containing GAS strains were generated, and the virulence of these chimeric strains were analyzed in mice. We show that SK and M-protein alterations influenced the virulence of GAS and were associated with the different natures of hPg activation and hPm binding. These studies demonstrate that GAS virulence can be explained by disparate hPg activation by SK2a and SK2b coupled with the coinherited M-proteins of these strains. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Application of geochemical logging for palaeoenvironmental research in the Late Cretaceous Qingshankou Formation from the Chinese Continental Scientific Drilling Project-SK-2e, Songliao Basin, NE China

    NASA Astrophysics Data System (ADS)

    Peng, Cheng; Zou, Changchun; Pan, Li; Niu, Yixiong

    2017-08-01

    The Chinese Continental Scientific Drilling Project of the Cretaceous Songliao Basin (CCSD-SK) provides an excellent opportunity to understand the response of terrestrial environments to greenhouse climate change in the Cretaceous. We conducted a palaeoenvironmental study of the Late Cretaceous Qingshankou Formation (K2qn) based on geochemical log data from the SK-2 east borehole. According to the characteristic of Ti mainly from terrigenous minerals, the content of authigenic elements was calculated. Correlation space was proposed to study the variation of the correlation between two log curves along the depth. Palaeoenvironmental proxies were selected from log data to study the evolution of the climate and lake, productivity of the paleolake, and organic matter deposition. The results demonstrate that the productivity of the paleolake was driven by chemical weathering in K2qn, in which the first section of the Qingshankou Formation (K2qn1) has higher productivity than the second and third sections of the Qingshankou Formation (K2qn2+3). The high content of pyrite in several thin layers reveals lake water of high sulfate concentration. This may have been caused by acid rain related to large volcanic activity. In K2qn2+3, several periods of high productivity without the formation of source rocks and high organic matter content were identified. This may show that organic matter deposition was limited by low accommodation space or oxidation environment. Therefore, the preservation condition is suggested as the main controlling factor of organic matter deposition in K2qn.

  18. Overexpression of CsLEA11, a Y3SK2-type dehydrin gene from cucumber (Cucumis sativus), enhances tolerance to heat and cold in Escherichia coli.

    PubMed

    Zhou, Yong; He, Peng; Xu, Yaping; Liu, Qiang; Yang, Yingui; Liu, Shiqiang

    2017-09-29

    As the group II LEA (late embryogenesis abundant) proteins, dehydrins (DHNs) play an important role in plant growth and development, as well as in response to abiotic or biotic stress challenges. In this study, a DHN gene named CsLEA11 was identified and characterized from Cucumis sativus. Sequence analysis of CsLEA11 showed that it is a Y3SK2-type DHN protein rich in hydrophilic amino acids. Expression analyses revealed that the transcription of CsLEA11 could be significantly induced by heat and cold stress. The recombinant plasmid was transformed into Escherichia coli BL21 and isopropy-β-D-thiogalactoside (IPTG) was used to induce recombinant E. coli to express CsLEA11 gene. Overexpression of CsLEA11 in E. coli enhanced cell viability and conferred tolerance to heat and cold stress. Furthermore, CsLEA11 protein could protect the activity of lactate dehydrogenase (LDH) under heat stress. Taken together, our data demonstrate that CsLEA11 might function in tolerance of cucumber to heat and cold stress.

  19. CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate.

    PubMed

    Herrik, Kjartan F; Redrobe, John P; Holst, Dorte; Hougaard, Charlotte; Sandager-Nielsen, Karin; Nielsen, Alexander N; Ji, Huifang; Holst, Nina M; Rasmussen, Hanne B; Nielsen, Elsebet Ø; Strøbæk, Dorte; Shepard, Paul D; Christophersen, Palle

    2012-01-01

    Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca(2+)-activated K(+) channels (SK channels), in particular the SK3 subtype, are important in the physiology of DA neurons, and agents modifying SK channel activity could potentially affect DA signaling and DA-related behaviors. Here we show that cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), a subtype-selective positive modulator of SK channels (SK3 > SK2 > > > SK1, IK), decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both mouse and rat midbrain slices. Using an immunocytochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. Taken together, the data accentuate the important role played by SK3 channels in the physiology of DA neurons, and indicate that their facilitation by CyPPA profoundly influences physiological as well as pharmacologically induced hyperdopaminergic behavior.

  20. Hydrocarbonoclastic Alcanivorax Isolates Exhibit Different Physiological and Expression Responses to n-dodecane

    PubMed Central

    Barbato, Marta; Scoma, Alberto; Mapelli, Francesca; De Smet, Rebecca; Banat, Ibrahim M.; Daffonchio, Daniele; Boon, Nico; Borin, Sara

    2016-01-01

    Autochthonous microorganisms inhabiting hydrocarbon polluted marine environments play a fundamental role in natural attenuation and constitute promising resources for bioremediation approaches. Alcanivorax spp. members are ubiquitous in contaminated surface waters and are the first to flourish on a wide range of alkanes after an oil-spill. Following oil contamination, a transient community of different Alcanivorax spp. develop, but whether they use a similar physiological, cellular and transcriptomic response to hydrocarbon substrates is unknown. In order to identify which cellular mechanisms are implicated in alkane degradation, we investigated the response of two isolates belonging to different Alcanivorax species, A. dieselolei KS 293 and A. borkumensis SK2 growing on n-dodecane (C12) or on pyruvate. Both strains were equally able to grow on C12 but they activated different strategies to exploit it as carbon and energy source. The membrane morphology and hydrophobicity of SK2 changed remarkably, from neat and hydrophilic on pyruvate to indented and hydrophobic on C12, while no changes were observed in KS 293. In addition, SK2 accumulated a massive amount of intracellular grains when growing on pyruvate, which might constitute a carbon reservoir. Furthermore, SK2 significantly decreased medium surface tension with respect to KS 293 when growing on C12, as a putative result of higher production of biosurfactants. The transcriptomic responses of the two isolates were also highly different. KS 293 changes were relatively balanced when growing on C12 with respect to pyruvate, giving almost the same amount of upregulated (28%), downregulated (37%) and equally regulated (36%) genes, while SK2 transcription was upregulated for most of the genes (81%) when growing on pyruvate when compared to C12. While both strains, having similar genomic background in genes related to hydrocarbon metabolism, retained the same capability to grow on C12, they nevertheless presented very

  1. Hydrocarbonoclastic Alcanivorax Isolates Exhibit Different Physiological and Expression Responses to n-dodecane.

    PubMed

    Barbato, Marta; Scoma, Alberto; Mapelli, Francesca; De Smet, Rebecca; Banat, Ibrahim M; Daffonchio, Daniele; Boon, Nico; Borin, Sara

    2016-01-01

    Autochthonous microorganisms inhabiting hydrocarbon polluted marine environments play a fundamental role in natural attenuation and constitute promising resources for bioremediation approaches. Alcanivorax spp. members are ubiquitous in contaminated surface waters and are the first to flourish on a wide range of alkanes after an oil-spill. Following oil contamination, a transient community of different Alcanivorax spp. develop, but whether they use a similar physiological, cellular and transcriptomic response to hydrocarbon substrates is unknown. In order to identify which cellular mechanisms are implicated in alkane degradation, we investigated the response of two isolates belonging to different Alcanivorax species, A. dieselolei KS 293 and A. borkumensis SK2 growing on n-dodecane (C12) or on pyruvate. Both strains were equally able to grow on C12 but they activated different strategies to exploit it as carbon and energy source. The membrane morphology and hydrophobicity of SK2 changed remarkably, from neat and hydrophilic on pyruvate to indented and hydrophobic on C12, while no changes were observed in KS 293. In addition, SK2 accumulated a massive amount of intracellular grains when growing on pyruvate, which might constitute a carbon reservoir. Furthermore, SK2 significantly decreased medium surface tension with respect to KS 293 when growing on C12, as a putative result of higher production of biosurfactants. The transcriptomic responses of the two isolates were also highly different. KS 293 changes were relatively balanced when growing on C12 with respect to pyruvate, giving almost the same amount of upregulated (28%), downregulated (37%) and equally regulated (36%) genes, while SK2 transcription was upregulated for most of the genes (81%) when growing on pyruvate when compared to C12. While both strains, having similar genomic background in genes related to hydrocarbon metabolism, retained the same capability to grow on C12, they nevertheless presented very

  2. Comparative Genomics of the Ubiquitous, Hydrocarbon-degrading Genus Marinobacter

    NASA Astrophysics Data System (ADS)

    Singer, E.; Webb, E.; Edwards, K. J.

    2012-12-01

    The genus Marinobacter is amongst the most ubiquitous in the global oceans and strains have been isolated from a wide variety of marine environments, including offshore oil-well heads, coastal thermal springs, Antarctic sea water, saline soils and associations with diatoms and dinoflagellates. Many strains have been recognized to be important hydrocarbon degraders in various marine habitats presenting sometimes extreme pH or salinity conditions. Analysis of the genome of M. aquaeolei revealed enormous adaptation versatility with an assortment of strategies for carbon and energy acquisition, sensation, and defense. In an effort to elucidate the ecological and biogeochemical significance of the Marinobacters, seven Marinobacter strains from diverse environments were included in a comparative genomics study. Genomes were screened for metabolic and adaptation potential to elucidate the strategies responsible for the omnipresence of the Marinobacter genus and their remedial action potential in hydrocarbon-polluted waters. The core genome predominantly encodes for key genes involved in hydrocarbon degradation, biofilm-relevant processes, including utilization of external DNA, halotolerance, as well as defense mechanisms against heavy metals, antibiotics, and toxins. All Marinobacter strains were observed to degrade a wide spectrum of hydrocarbon species, including aliphatic, polycyclic aromatic as well as acyclic isoprenoid compounds. Various genes predicted to facilitate hydrocarbon degradation, e.g. alkane 1-monooxygenase, appear to have originated from lateral gene transfer as they are located on gene clusters of 10-20% lower GC-content compared to genome averages and are flanked by transposases. Top ortholog hits are found in other hydrocarbon degrading organisms, e.g. Alcanivorax borkumensis. Strategies for hydrocarbon uptake encoded by various Marinobacter strains include cell surface hydrophobicity adaptation via capsular polysaccharide biosynthesis and attachment

  3. Prophage Genomics

    PubMed Central

    Canchaya, Carlos; Proux, Caroline; Fournous, Ghislain; Bruttin, Anne; Brüssow, Harald

    2003-01-01

    The majority of the bacterial genome sequences deposited in the National Center for Biotechnology Information database contain prophage sequences. Analysis of the prophages suggested that after being integrated into bacterial genomes, they undergo a complex decay process consisting of inactivating point mutations, genome rearrangements, modular exchanges, invasion by further mobile DNA elements, and massive DNA deletion. We review the technical difficulties in defining such altered prophage sequences in bacterial genomes and discuss theoretical frameworks for the phage-bacterium interaction at the genomic level. The published genome sequences from three groups of eubacteria (low- and high-G+C gram-positive bacteria and γ-proteobacteria) were screened for prophage sequences. The prophages from Streptococcus pyogenes served as test case for theoretical predictions of the role of prophages in the evolution of pathogenic bacteria. The genomes from further human, animal, and plant pathogens, as well as commensal and free-living bacteria, were included in the analysis to see whether the same principles of prophage genomics apply for bacteria living in different ecological niches and coming from distinct phylogenetical affinities. The effect of selection pressure on the host bacterium is apparently an important force shaping the prophage genomes in low-G+C gram-positive bacteria and γ-proteobacteria. PMID:12794192

  4. Aquaculture Genomics

    USDA-ARS?s Scientific Manuscript database

    The genomics chapter covers the basics of genome mapping and sequencing and the current status of several relevant species. The chapter briefly describes the development and use of (cDNA, BAC, etc.) libraries for mapping and obtaining specific sequence information. Other topics include comparative ...

  5. Antarctic Genomics

    PubMed Central

    Clarke, Andrew; Cockell, Charles S.; Convey, Peter; Detrich III, H. William; Fraser, Keiron P. P.; Johnston, Ian A.; Methe, Barbara A.; Murray, Alison E.; Peck, Lloyd S.; Römisch, Karin; Rogers, Alex D.

    2004-01-01

    With the development of genomic science and its battery of technologies, polar biology stands on the threshold of a revolution, one that will enable the investigation of important questions of unprecedented scope and with extraordinary depth and precision. The exotic organisms of polar ecosystems are ideal candidates for genomic analysis. Through such analyses, it will be possible to learn not only the novel features that enable polar organisms to survive, and indeed thrive, in their extreme environments, but also fundamental biological principles that are common to most, if not all, organisms. This article aims to review recent developments in Antarctic genomics and to demonstrate the global context of such studies. PMID:18629155

  6. Genome databases

    SciTech Connect

    Courteau, J.

    1991-10-11

    Since the Genome Project began several years ago, a plethora of databases have been developed or are in the works. They range from the massive Genome Data Base at Johns Hopkins University, the central repository of all gene mapping information, to small databases focusing on single chromosomes or organisms. Some are publicly available, others are essentially private electronic lab notebooks. Still others limit access to a consortium of researchers working on, say, a single human chromosome. An increasing number incorporate sophisticated search and analytical software, while others operate as little more than data lists. In consultation with numerous experts in the field, a list has been compiled of some key genome-related databases. The list was not limited to map and sequence databases but also included the tools investigators use to interpret and elucidate genetic data, such as protein sequence and protein structure databases. Because a major goal of the Genome Project is to map and sequence the genomes of several experimental animals, including E. coli, yeast, fruit fly, nematode, and mouse, the available databases for those organisms are listed as well. The author also includes several databases that are still under development - including some ambitious efforts that go beyond data compilation to create what are being called electronic research communities, enabling many users, rather than just one or a few curators, to add or edit the data and tag it as raw or confirmed.

  7. Genome Sequencing.

    PubMed

    Verma, Mansi; Kulshrestha, Samarth; Puri, Ayush

    2017-01-01

    Genome sequencing is an important step toward correlating genotypes with phenotypic characters. Sequencing technologies are important in many fields in the life sciences, including functional genomics, transcriptomics, oncology, evolutionary biology, forensic sciences, and many more. The era of sequencing has been divided into three generations. First generation sequencing involved sequencing by synthesis (Sanger sequencing) and sequencing by cleavage (Maxam-Gilbert sequencing). Sanger sequencing led to the completion of various genome sequences (including human) and provided the foundation for development of other sequencing technologies. Since then, various techniques have been developed which can overcome some of the limitations of Sanger sequencing. These techniques are collectively known as "Next-generation sequencing" (NGS), and are further classified into second and third generation technologies. Although NGS methods have many advantages in terms of speed, cost, and parallelism, the accuracy and read length of Sanger sequencing is still superior and has confined the use of NGS mainly to resequencing genomes. Consequently, there is a continuing need to develop improved real time sequencing techniques. This chapter reviews some of the options currently available and provides a generic workflow for sequencing a genome.

  8. Genome Informatics

    PubMed Central

    Winslow, Raimond L.; Boguski, Mark S.

    2005-01-01

    This article reviews recent advances in genomics and informatics relevant to cardiovascular research. In particular, we review the status of (1) whole genome sequencing efforts in human, mouse, rat, zebrafish, and dog; (2) the development of data mining and analysis tools; (3) the launching of the National Heart, Lung, and Blood Institute Programs for Genomics Applications and Proteomics Initiative; (4) efforts to characterize the cardiac transcriptome and proteome; and (5) the current status of computational modeling of the cardiac myocyte. In each instance, we provide links to relevant sources of information on the World Wide Web and critical appraisals of the promises and the challenges of an expanding and diverse information landscape. PMID:12750305

  9. Listeria Genomics

    NASA Astrophysics Data System (ADS)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

    The opportunistic intracellular foodborne pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens. This chapter provides an overview of progress in the exploration of genomic, transcriptomic, and proteomic data in Listeria spp. to understand genome evolution and diversity, as well as physiological aspects of metabolism used by bacteria when growing in diverse environments, in particular in infected hosts.

  10. Genome mapping

    USDA-ARS?s Scientific Manuscript database

    Genome maps can be thought of much like road maps except that, instead of traversing across land, they traverse across the chromosomes of an organism. Genetic markers serve as landmarks along the chromosome and provide researchers information as to how close they may be to a gene or region of inter...

  11. Personal genomics services: whose genomes?

    PubMed Central

    Gurwitz, David; Bregman-Eschet, Yael

    2009-01-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below. PMID:19259127

  12. Citrus Genomics

    PubMed Central

    Talon, Manuel; Gmitter Jr., Fred G.

    2008-01-01

    Citrus is one of the most widespread fruit crops globally, with great economic and health value. It is among the most difficult plants to improve through traditional breeding approaches. Currently, there is risk of devastation by diseases threatening to limit production and future availability to the human population. As technologies rapidly advance in genomic science, they are quickly adapted to address the biological challenges of the citrus plant system and the world's industries. The historical developments of linkage mapping, markers and breeding, EST projects, physical mapping, an international citrus genome sequencing project, and critical functional analysis are described. Despite the challenges of working with citrus, there has been substantial progress. Citrus researchers engaged in international collaborations provide optimism about future productivity and contributions to the benefit of citrus industries worldwide and to the human population who can rely on future widespread availability of this health-promoting and aesthetically pleasing fruit crop. PMID:18509486

  13. Imaging genomics.

    PubMed

    Hariri, Ahmad R; Weinberger, Daniel R

    2003-01-01

    The recent completion of a working draft of the human genome sequence promises to provide unprecedented opportunities to explore the genetic basis of individual differences in complex behaviours and vulnerability to neuropsychiatric illness. Functional neuroimaging, because of its unique ability to assay information processing at the level of brain within individuals, provides a powerful approach to such functional genomics. Recent fMRI studies have established important physiological links between functional genetic polymorphisms and robust differences in information processing within distinct brain regions and circuits that have been linked to the manifestation of various disease states such as Alzheimer's disease, schizophrenia and anxiety disorders. Importantly, all of these biological relationships have been revealed in relatively small samples of healthy volunteers and in the absence of observable differences at the level of behaviour, underscoring the power of a direct assay of brain physiology like fMRI in exploring the functional impact of genetic variation.

  14. Ancient genomics

    PubMed Central

    Der Sarkissian, Clio; Allentoft, Morten E.; Ávila-Arcos, María C.; Barnett, Ross; Campos, Paula F.; Cappellini, Enrico; Ermini, Luca; Fernández, Ruth; da Fonseca, Rute; Ginolhac, Aurélien; Hansen, Anders J.; Jónsson, Hákon; Korneliussen, Thorfinn; Margaryan, Ashot; Martin, Michael D.; Moreno-Mayar, J. Víctor; Raghavan, Maanasa; Rasmussen, Morten; Velasco, Marcela Sandoval; Schroeder, Hannes; Schubert, Mikkel; Seguin-Orlando, Andaine; Wales, Nathan; Gilbert, M. Thomas P.; Willerslev, Eske; Orlando, Ludovic

    2015-01-01

    The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when testing specific hypotheses related to the past. PMID:25487338

  15. Ancient genomics.

    PubMed

    Der Sarkissian, Clio; Allentoft, Morten E; Ávila-Arcos, María C; Barnett, Ross; Campos, Paula F; Cappellini, Enrico; Ermini, Luca; Fernández, Ruth; da Fonseca, Rute; Ginolhac, Aurélien; Hansen, Anders J; Jónsson, Hákon; Korneliussen, Thorfinn; Margaryan, Ashot; Martin, Michael D; Moreno-Mayar, J Víctor; Raghavan, Maanasa; Rasmussen, Morten; Velasco, Marcela Sandoval; Schroeder, Hannes; Schubert, Mikkel; Seguin-Orlando, Andaine; Wales, Nathan; Gilbert, M Thomas P; Willerslev, Eske; Orlando, Ludovic

    2015-01-19

    The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when testing specific hypotheses related to the past.

  16. Whole Genome Sequencing

    MedlinePlus

    ... you want to learn. Search form Search Whole Genome Sequencing You are here Home Testing & Services Testing ... the full story, click here . What is whole genome sequencing? Whole genome sequencing is the mapping out ...

  17. The platypus genome unraveled.

    PubMed

    O'Brien, Stephen J

    2008-06-13

    The genome of the platypus has been sequenced, assembled, and annotated by an international genomics team. Like the animal itself the platypus genome contains an amalgam of mammal, reptile, and bird-like features.

  18. Genome evolution: the dynamics of static genomes.

    PubMed

    Stechmann, Alexandra

    2004-06-22

    A random survey of a microsporidian genome has revealed some striking features. Although the genomes of microsporidians are among the smallest known for eukaryotes, their organisation appears to be well conserved.

  19. Genome cartography: charting the apicomplexan genome.

    PubMed

    Kissinger, Jessica C; DeBarry, Jeremy

    2011-08-01

    Genes reside in particular genomic contexts that can be mapped at many levels. Historically, 'genetic maps' were used primarily to locate genes. Recent technological advances in the determination of genome sequences have made the analysis and comparison of whole genomes possible and increasingly tractable. What do we see if we shift our focus from gene content (the 'inventory' of genes contained within a genome) to the composition and organization of a genome? This review examines what has been learned about the evolution of the apicomplexan genome as well as the significance and impact of genomic location on our understanding of the eukaryotic genome and parasite biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Genomic selection requires genomic control of inbreeding.

    PubMed

    Sonesson, Anna K; Woolliams, John A; Meuwissen, Theo H E

    2012-08-16

    In the past, pedigree relationships were used to control and monitor inbreeding because genomic relationships among selection candidates were not available until recently. The aim of this study was to understand the consequences for genetic variability across the genome when genomic information is used to estimate breeding values and in managing the inbreeding generated in the course of selection on genome-enhanced estimated breeding values. These consequences were measured by genetic gain, pedigree- and genome-based rates of inbreeding, and local inbreeding across the genome. Breeding schemes were compared by simulating truncation selection or optimum contribution selection with a restriction on pedigree- or genome-based inbreeding, and with selection using estimated breeding values based on genome- or pedigree-based BLUP. Trait information was recorded on full-sibs of the candidates. When the information used to estimate breeding values and to constrain rates of inbreeding were either both pedigree-based or both genome-based, rates of genomic inbreeding were close to the desired values and the identical-by-descent profiles were reasonably uniform across the genome. However, with a pedigree-based inbreeding constraint and genome-based estimated breeding values, genomic rates of inbreeding were much higher than expected. With pedigree-instead of genome-based estimated breeding values, the impact of the largest QTL on the breeding values was much smaller, resulting in a more uniform genome-wide identical-by-descent profile but genomic rates of inbreeding were still higher than expected based on pedigree relationships, because they measure the inbreeding at a neutral locus not linked to any QTL. Neutral loci did not exist here, where there were 100 QTL on each chromosome. With a pedigree-based inbreeding constraint and genome-based estimated breeding values, genomic rates of inbreeding substantially exceeded the value of its constraint. In contrast, with a genome

  1. Plant Genome Duplication Database.

    PubMed

    Lee, Tae-Ho; Kim, Junah; Robertson, Jon S; Paterson, Andrew H

    2017-01-01

    Genome duplication, widespread in flowering plants, is a driving force in evolution. Genome alignments between/within genomes facilitate identification of homologous regions and individual genes to investigate evolutionary consequences of genome duplication. PGDD (the Plant Genome Duplication Database), a public web service database, provides intra- or interplant genome alignment information. At present, PGDD contains information for 47 plants whose genome sequences have been released. Here, we describe methods for identification and estimation of dates of genome duplication and speciation by functions of PGDD.The database is freely available at http://chibba.agtec.uga.edu/duplication/.

  2. Ensembl genomes 2016: more genomes, more complexity

    USDA-ARS?s Scientific Manuscript database

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent...

  3. Ensembl Genomes 2016: more genomes, more complexity.

    PubMed

    Kersey, Paul Julian; Allen, James E; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello-Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M; Howe, Kevin L; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M

    2016-01-04

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces.

  4. Ensembl Genomes 2016: more genomes, more complexity

    PubMed Central

    Kersey, Paul Julian; Allen, James E.; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J.; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J.; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K.; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D.; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello–Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M.; Howe, Kevin L.; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M.

    2016-01-01

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces. PMID:26578574

  5. Funding Opportunity: Genomic Data Centers

    Cancer.gov

    Funding Opportunity CCG, Funding Opportunity Center for Cancer Genomics, CCG, Center for Cancer Genomics, CCG RFA, Center for cancer genomics rfa, genomic data analysis network, genomic data analysis network centers,

  6. Ontology for Genome Comparison and Genomic Rearrangements

    PubMed Central

    Flanagan, Keith; Stevens, Robert; Pocock, Matthew; Lee, Pete

    2004-01-01

    We present an ontology for describing genomes, genome comparisons, their evolution and biological function. This ontology will support the development of novel genome comparison algorithms and aid the community in discussing genomic evolution. It provides a framework for communication about comparative genomics, and a basis upon which further automated analysis can be built. The nomenclature defined by the ontology will foster clearer communication between biologists, and also standardize terms used by data publishers in the results of analysis programs. The overriding aim of this ontology is the facilitation of consistent annotation of genomes through computational methods, rather than human annotators. To this end, the ontology includes definitions that support computer analysis and automated transfer of annotations between genomes, rather than relying upon human mediation. PMID:18629137

  7. Enabling functional genomics with genome engineering.

    PubMed

    Hilton, Isaac B; Gersbach, Charles A

    2015-10-01

    Advances in genome engineering technologies have made the precise control over genome sequence and regulation possible across a variety of disciplines. These tools can expand our understanding of fundamental biological processes and create new opportunities for therapeutic designs. The rapid evolution of these methods has also catalyzed a new era of genomics that includes multiple approaches to functionally characterize and manipulate the regulation of genomic information. Here, we review the recent advances of the most widely adopted genome engineering platforms and their application to functional genomics. This includes engineered zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for genome editing, transcription factors for epigenome editing, and other emerging applications. We also present current and potential future applications of these tools, as well as their current limitations and areas for future advances. © 2015 Hilton and Gersbach; Published by Cold Spring Harbor Laboratory Press.

  8. Enabling functional genomics with genome engineering

    PubMed Central

    Hilton, Isaac B.; Gersbach, Charles A.

    2015-01-01

    Advances in genome engineering technologies have made the precise control over genome sequence and regulation possible across a variety of disciplines. These tools can expand our understanding of fundamental biological processes and create new opportunities for therapeutic designs. The rapid evolution of these methods has also catalyzed a new era of genomics that includes multiple approaches to functionally characterize and manipulate the regulation of genomic information. Here, we review the recent advances of the most widely adopted genome engineering platforms and their application to functional genomics. This includes engineered zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for genome editing, transcription factors for epigenome editing, and other emerging applications. We also present current and potential future applications of these tools, as well as their current limitations and areas for future advances. PMID:26430154

  9. Navigating yeast genome maintenance with functional genomics.

    PubMed

    Measday, Vivien; Stirling, Peter C

    2016-03-01

    Maintenance of genome integrity is a fundamental requirement of all organisms. To address this, organisms have evolved extremely faithful modes of replication, DNA repair and chromosome segregation to combat the deleterious effects of an unstable genome. Nonetheless, a small amount of genome instability is the driver of evolutionary change and adaptation, and thus a low level of instability is permitted in populations. While defects in genome maintenance almost invariably reduce fitness in the short term, they can create an environment where beneficial mutations are more likely to occur. The importance of this fact is clearest in the development of human cancer, where genome instability is a well-established enabling characteristic of carcinogenesis. This raises the crucial question: what are the cellular pathways that promote genome maintenance and what are their mechanisms? Work in model organisms, in particular the yeast Saccharomyces cerevisiae, has provided the global foundations of genome maintenance mechanisms in eukaryotes. The development of pioneering genomic tools inS. cerevisiae, such as the systematic creation of mutants in all nonessential and essential genes, has enabled whole-genome approaches to identifying genes with roles in genome maintenance. Here, we review the extensive whole-genome approaches taken in yeast, with an emphasis on functional genomic screens, to understand the genetic basis of genome instability, highlighting a range of genetic and cytological screening modalities. By revealing the biological pathways and processes regulating genome integrity, these analyses contribute to the systems-level map of the yeast cell and inform studies of human disease, especially cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Culex genome is not just another genome for comparative genomics.

    PubMed

    Reddy, B P Niranjan; Labbé, Pierrick; Corbel, Vincent

    2012-03-30

    Formal publication of the Culex genome sequence has closed the human disease vector triangle by meeting the Anopheles gambiae and Aedes aegypti genome sequences. Compared to these other mosquitoes, Culex quinquefasciatus possesses many specific hallmark characteristics, and may thus provide different angles for research which ultimately leads to a practical solution for controlling the ever increasing burden of insect-vector-borne diseases around the globe. We argue the special importance of the cosmopolitan species- Culex genome sequence by invoking many interesting questions and the possible of potential of the Culex genome to answer those.

  11. Culex genome is not just another genome for comparative genomics

    PubMed Central

    2012-01-01

    Formal publication of the Culex genome sequence has closed the human disease vector triangle by meeting the Anopheles gambiae and Aedes aegypti genome sequences. Compared to these other mosquitoes, Culex quinquefasciatus possesses many specific hallmark characteristics, and may thus provide different angles for research which ultimately leads to a practical solution for controlling the ever increasing burden of insect-vector-borne diseases around the globe. We argue the special importance of the cosmopolitan species- Culex genome sequence by invoking many interesting questions and the possible of potential of the Culex genome to answer those. PMID:22463777

  12. GenomeFingerprinter: the genome fingerprint and the universal genome fingerprint analysis for systematic comparative genomics.

    PubMed

    Ai, Yuncan; Ai, Hannan; Meng, Fanmei; Zhao, Lei

    2013-01-01

    No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range. We define it as the systematic comparative genomics and aim to develop the methodology. First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence. Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA). Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories. Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis. Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison. Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy. We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the outcome dataset. These have set

  13. GenomeFingerprinter: The Genome Fingerprint and the Universal Genome Fingerprint Analysis for Systematic Comparative Genomics

    PubMed Central

    Ai, Yuncan; Ai, Hannan; Meng, Fanmei; Zhao, Lei

    2013-01-01

    Background No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range. We define it as the systematic comparative genomics and aim to develop the methodology. Results First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence. Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA). Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories. Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis. Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison. Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy. Conclusions We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the

  14. Exploring Other Genomes: Bacteria.

    ERIC Educational Resources Information Center

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  15. Exploring Other Genomes: Bacteria.

    ERIC Educational Resources Information Center

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  16. Exploiting the Genome

    DTIC Science & Technology

    1998-09-11

    complete human genome sequence . 14. SUBJECT TERMS 15. NUMBER OF PAGES 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY...goal of the project is to ob- tain the complete sequence of the human genome by the year 2005. The genome contains approximately 3.3 Gb (billion base...and second, to consider possible roles for the DOE in the "post- genomic " era, following acquisition of the complete human genome

  17. The kangaroo genome

    PubMed Central

    Wakefield, Matthew J.; Graves, Jennifer A. Marshall

    2003-01-01

    The kangaroo genome is a rich and unique resource for comparative genomics. Marsupial genetics and cytology have made significant contributions to the understanding of gene function and evolution, and increasing the availability of kangaroo DNA sequence information would provide these benefits on a genomic scale. Here we summarize the contributions from cytogenetic and genetic studies of marsupials, describe the genomic resources currently available and those being developed, and explore the benefits of a kangaroo genome project. PMID:12612602

  18. Genome Maps, a new generation genome browser

    PubMed Central

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-01-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org. PMID:23748955

  19. Genome Maps, a new generation genome browser.

    PubMed

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-07-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

  20. Genomic Encyclopedia of Fungi

    SciTech Connect

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  1. JGI Fungal Genomics Program

    SciTech Connect

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  2. Plant genomics: an overview.

    PubMed

    Campos-de Quiroz, Hugo

    2002-01-01

    Recent technological advancements have substantially expanded our ability to analyze and understand plant genomes and to reduce the gap existing between genotype and phenotype. The fast evolving field of genomics allows scientists to analyze thousand of genes in parallel, to understand the genetic architecture of plant genomes and also to isolate the genes responsible for mutations. Furthermore, whole genomes can now be sequenced. This review addresses these issues and also discusses ways to extract biological meaning from DNA data. Although genomic issuesare addressed from a plant perspective, this review provides insights into the genomic analyses of other organisms.

  3. Integrating sequence, evolution and functional genomics in regulatory genomics

    PubMed Central

    Vingron, Martin; Brazma, Alvis; Coulson, Richard; van Helden, Jacques; Manke, Thomas; Palin, Kimmo; Sand, Olivier; Ukkonen, Esko

    2009-01-01

    With genome analysis expanding from the study of genes to the study of gene regulation, 'regulatory genomics' utilizes sequence information, evolution and functional genomics measurements to unravel how regulatory information is encoded in the genome. PMID:19226437

  4. Genomic Data Commons | Office of Cancer Genomics

    Cancer.gov

    The NCI’s Center for Cancer Genomics launches the Genomic Data Commons (GDC), a unified data sharing platform for the cancer research community. The mission of the GDC is to enable data sharing across the entire cancer research community, to ultimately support precision medicine in oncology.

  5. Genomic Data Commons launches

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  6. GENOMICS AND ENVIRONMENTAL RESEARCH

    EPA Science Inventory

    The impact of recently developed and emerging genomics technologies on environmental sciences has significant implications for human and ecological risk assessment issues. The linkage of data generated from genomics, transcriptomics, proteomics, metabalomics, and ecology can be ...

  7. GENOMICS AND ENVIRONMENTAL RESEARCH

    EPA Science Inventory

    The impact of recently developed and emerging genomics technologies on environmental sciences has significant implications for human and ecological risk assessment issues. The linkage of data generated from genomics, transcriptomics, proteomics, metabalomics, and ecology can be ...

  8. Exploiting the genome

    SciTech Connect

    Block, S.; Cornwall, J.; Dyson, F.; Koonin, S.; Lewis, N.; Schwitters, R.

    1998-09-11

    In 1997, JASON conducted a DOE-sponsored study of the human genome project with special emphasis on the areas of technology, quality assurance and quality control, and informatics. The present study has two aims: first, to update the 1997 Report in light of recent developments in genome sequencing technology, and second, to consider possible roles for the DOE in the ''post-genomic" era, following acquisition of the complete human genome sequence.

  9. National Plant Genome Initiative

    DTIC Science & Technology

    2005-01-01

    JAN 2005 2. REPORT TYPE 3. DATES COVERED 00-00-2005 to 00-00-2005 4. TITLE AND SUBTITLE National Plant Genome Initiative. Progress Report 5a...refl ected in future Administration budgets. Cover Photo: National Plant Genome Initiative Progress Report January 2005 National Science and...Technology Council Committee on Science Interagency Working Group on Plant Genomes [Blank Page] Interagency Working Group on Plant Genomes Committee on

  10. GENESIS: genome evolution scenarios.

    PubMed

    Gog, Simon; Bader, Martin; Ohlebusch, Enno

    2008-03-01

    We implemented a software tool called GENESIS for three different genome rearrangement problems: Sorting a unichromosomal genome by weighted reversals and transpositions (SwRT), sorting a multichromosomal genome by reversals, translocations, fusions and fissions (SRTl), and sorting a multichromosomal genome by weighted reversals, translocations, fusions, fissions and transpositions (SwRTTl). Source code can be obtained by the authors, or use the web interface http://www.uni-ulm.de/in/theo/research/genesis.html.

  11. Whole-genome patenting.

    PubMed

    O'Malley, Maureen A; Bostanci, Adam; Calvert, Jane

    2005-06-01

    Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. When these patents are analysed and compared to those for other biological entities, it becomes clear that genome patents seek to exploit the genome as an information base and are part of a broader shift towards intangible intellectual property in genomics.

  12. Office of Cancer Genomics |

    Cancer.gov

    The mission of the NCI’s Office of Cancer Genomics (OCG) is to enhance the understanding of the molecular mechanisms of cancer, advance and accelerate genomics science and technology development, and efficiently translate the genomics data to improve cancer research, prevention, early detection, diagnosis and treatment.

  13. The human genome project

    SciTech Connect

    Yager, T.D.; Zewert, T.E.; Hood, L.E. )

    1994-04-01

    The Human Genome Project (HGP) is a coordinated worldwide effort to precisely map the human genome and the genomes of selected model organisms. The first explicit proposal for this project dates from 1985 although its foundations (both conceptual and technological) can be traced back many years in genetics, molecular biology, and biotechnology. The HGP has matured rapidly and is producing results of great significance.

  14. Office of Cancer Genomics |

    Cancer.gov

    The mission of the NCI’s Office of Cancer Genomics (OCG) is to enhance the understanding of the molecular mechanisms of cancer, advance and accelerate genomics science and technology development, and efficiently translate the genomics data to improve cancer research, prevention, early detection, diagnosis and treatment.

  15. Comparative genomics of Lactobacillus

    PubMed Central

    Kant, Ravi; Blom, Jochen; Palva, Airi; Siezen, Roland J.; de Vos, Willem M.

    2011-01-01

    Summary The genus Lactobacillus includes a diverse group of bacteria consisting of many species that are associated with fermentations of plants, meat or milk. In addition, various lactobacilli are natural inhabitants of the intestinal tract of humans and other animals. Finally, several Lactobacillus strains are marketed as probiotics as their consumption can confer a health benefit to host. Presently, 154 Lactobacillus species are known and a growing fraction of these are subject to draft genome sequencing. However, complete genome sequences are needed to provide a platform for detailed genomic comparisons. Therefore, we selected a total of 20 genomes of various Lactobacillus strains for which complete genomic sequences have been reported. These genomes had sizes varying from 1.8 to 3.3 Mb and other characteristic features, such as G+C content that ranged from 33% to 51%. The Lactobacillus pan genome was found to consist of approximately 14 000 protein‐encoding genes while all 20 genomes shared a total of 383 sets of orthologous genes that defined the Lactobacillus core genome (LCG). Based on advanced phylogeny of the proteins encoded by this LCG, we grouped the 20 strains into three main groups and defined core group genes present in all genomes of a single group, signature group genes shared in all genomes of one group but absent in all other Lactobacillus genomes, and Group‐specific ORFans present in core group genes of one group and absent in all other complete genomes. The latter are of specific value in defining the different groups of genomes. The study provides a platform for present individual comparisons as well as future analysis of new Lactobacillus genomes. PMID:21375712

  16. A genome blogger manifesto.

    PubMed

    Corpas, Manuel

    2012-10-26

    Cheap prices for genomic testing have revolutionized consumers' access to personal genomics. Exploration of personal genomes poses significant challenges for customers wishing to learn beyond provider customer reports. A vibrant community has spontaneously appeared blogging experiences and data as a way to learn about their personal genomes. No set of values has publicly been described to date encapsulating ideals and code of conduct for this community. Here I present a first attempt to address this vacuum based on my own personal experiences as genome blogger.

  17. Chromium and Genomic Stability

    PubMed Central

    Wise, Sandra S.; Wise, John Pierce

    2014-01-01

    Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There are no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as highly toxic and carcinogenic with no nutritional value. Recent data indicate that it causes genomic instability and also has no role in promoting genomic stability. PMID:22192535

  18. The Genomic Medicine Game.

    PubMed

    Tran, Elvis; de Andrés-Galiana, Enrique J; Benitez, Sonia; Martin-Sanchez, Fernando; Lopez-Campos, Guillermo H

    2016-01-01

    With advancements in genomics technology, health care has been improving and new paradigms of medicine such as genomic medicine have evolved. The education of clinicians, researchers and students to face the challenges posed by these new approaches, however, has been often lagging behind. From this the Genomic Medicine Game, an educational tool, was created for the purpose of conceptualizing the key components of Genomic Medicine. A number of phenotype-genotype associations were found through a literature review, which was used to be a base for the concepts the Genomic Medicine Game would focus on. Built in Java, the game was successfully tested with promising results.

  19. The Bluejay genome browser.

    PubMed

    Soh, Jung; Gordon, Paul M K; Sensen, Christoph W

    2012-03-01

    The Bluejay genome browser is a stand-alone visualization tool for the multi-scale viewing of annotated genomes and other genomic elements. Bluejay allows users to customize display features to suit their needs, and produces publication-quality graphics. Bluejay provides a multitude of ways to interrelate biological data at the genome scale. Users can load gene expression data into a genome display for expression visualization in context. Multiple genomes can be compared concurrently, including time series expression data, based on Gene Ontology labels. External, context-sensitive biological Web Services are linked to the displayed genomic elements ad hoc for in-depth genomic data analysis and interpretation. Users can mark multiple points of interest in a genome by creating waypoints, and exploit them for easy navigation of single or multiple genomes. Using this comprehensive visual environment, users can study a gene not just in relation to its genome, but also its transcriptome and evolutionary origins. Written in Java, Bluejay is platform-independent and is freely available from http://bluejay.ucalgary.ca.

  20. Microbial genomic taxonomy

    PubMed Central

    2013-01-01

    A need for a genomic species definition is emerging from several independent studies worldwide. In this commentary paper, we discuss recent studies on the genomic taxonomy of diverse microbial groups and a unified species definition based on genomics. Accordingly, strains from the same microbial species share >95% Average Amino Acid Identity (AAI) and Average Nucleotide Identity (ANI), >95% identity based on multiple alignment genes, <10 in Karlin genomic signature, and > 70% in silico Genome-to-Genome Hybridization similarity (GGDH). Species of the same genus will form monophyletic groups on the basis of 16S rRNA gene sequences, Multilocus Sequence Analysis (MLSA) and supertree analysis. In addition to the established requirements for species descriptions, we propose that new taxa descriptions should also include at least a draft genome sequence of the type strain in order to obtain a clear outlook on the genomic landscape of the novel microbe. The application of the new genomic species definition put forward here will allow researchers to use genome sequences to define simultaneously coherent phenotypic and genomic groups. PMID:24365132

  1. UCSC genome browser tutorial.

    PubMed

    Zweig, Ann S; Karolchik, Donna; Kuhn, Robert M; Haussler, David; Kent, W James

    2008-08-01

    The University of California Santa Cruz (UCSC) Genome Bioinformatics website consists of a suite of free, open-source, on-line tools that can be used to browse, analyze, and query genomic data. These tools are available to anyone who has an Internet browser and an interest in genomics. The website provides a quick and easy-to-use visual display of genomic data. It places annotation tracks beneath genome coordinate positions, allowing rapid visual correlation of different types of information. Many of the annotation tracks are submitted by scientists worldwide; the others are computed by the UCSC Genome Bioinformatics group from publicly available sequence data. It also allows users to upload and display their own experimental results or annotation sets by creating a custom track. The suite of tools, downloadable data files, and links to documentation and other information can be found at http://genome.ucsc.edu/.

  2. Bacterial Genome Instability

    PubMed Central

    Darmon, Elise

    2014-01-01

    SUMMARY Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease. PMID:24600039

  3. Whole-genome alignment.

    PubMed

    Dewey, Colin N

    2012-01-01

    Whole-genome alignment (WGA) is the prediction of evolutionary relationships at the nucleotide level between two or more genomes. It combines aspects of both colinear sequence alignment and gene orthology prediction, and is typically more challenging to address than either of these tasks due to the size and complexity of whole genomes. Despite the difficulty of this problem, numerous methods have been developed for its solution because WGAs are valuable for genome-wide analyses, such as phylogenetic inference, genome annotation, and function prediction. In this chapter, we discuss the meaning and significance of WGA and present an overview of the methods that address it. We also examine the problem of evaluating whole-genome aligners and offer a set of methodological challenges that need to be tackled in order to make the most effective use of our rapidly growing databases of whole genomes.

  4. Genomic Sequencing in Cancer

    PubMed Central

    Tuna, Musaffe; Amos, Christopher I.

    2013-01-01

    Genomic sequencing has provided critical insights into the etiology of both simple and complex diseases. The enormous reductions in cost for whole genome sequencing have allowed this technology to gain increasing use. Whole genome analysis has impacted research of complex diseases including cancer by allowing the systematic analysis of entire genomes in a single experiment, thereby facilitating the discovery of somatic and germline mutations, and identification of the function and impact of the insertions, deletions, and structural rearrangements, including translocations and inversions, in novel disease genes. Whole-genome sequencing can be used to provide the most comprehensive characterization of the cancer genome, the complexity of which we are only beginning to understand. Hence in this review, we focus on whole-genome sequencing in cancer. PMID:23178448

  5. Enabling responsible public genomics.

    PubMed

    Conley, John M; Doerr, Adam K; Vorhaus, Daniel B

    2010-01-01

    As scientific understandings of genetics advance, researchers require increasingly rich datasets that combine genomic data from large numbers of individuals with medical and other personal information. Linking individuals' genetic data and personal information precludes anonymity and produces medically significant information--a result not contemplated by the established legal and ethical conventions governing human genomic research. To pursue the next generation of human genomic research and commerce in a responsible fashion, scientists, lawyers, and regulators must address substantial new issues, including researchers' duties with respect to clinically significant data, the challenges to privacy presented by genomic data, the boundary between genomic research and commerce, and the practice of medicine. This Article presents a new model for understanding and addressing these new challenges--a "public genomics" premised on the idea that ethically, legally, and socially responsible genomics research requires openness, not privacy, as its organizing principle. Responsible public genomics combines the data contributed by informed and fully consenting information altruists and the research potential of rich datasets in a genomic commons that is freely and globally available. This Article examines the risks and benefits of this public genomics model in the context of an ambitious genetic research project currently under way--the Personal Genome Project. This Article also (i) demonstrates that large-scale genomic projects are desirable, (ii) evaluates the risks and challenges presented by public genomics research, and (iii) determines that the current legal and regulatory regimes restrict beneficial and responsible scientific inquiry while failing to adequately protect participants. The Article concludes by proposing a modified normative and legal framework that embraces and enables a future of responsible public genomics.

  6. Whole-exome/genome sequencing and genomics.

    PubMed

    Grody, Wayne W; Thompson, Barry H; Hudgins, Louanne

    2013-12-01

    As medical genetics has progressed from a descriptive entity to one focused on the functional relationship between genes and clinical disorders, emphasis has been placed on genomics. Genomics, a subelement of genetics, is the study of the genome, the sum total of all the genes of an organism. The human genome, which is contained in the 23 pairs of nuclear chromosomes and in the mitochondrial DNA of each cell, comprises >6 billion nucleotides of genetic code. There are some 23,000 protein-coding genes, a surprisingly small fraction of the total genetic material, with the remainder composed of noncoding DNA, regulatory sequences, and introns. The Human Genome Project, launched in 1990, produced a draft of the genome in 2001 and then a finished sequence in 2003, on the 50th anniversary of the initial publication of Watson and Crick's paper on the double-helical structure of DNA. Since then, this mass of genetic information has been translated at an ever-increasing pace into useable knowledge applicable to clinical medicine. The recent advent of massively parallel DNA sequencing (also known as shotgun, high-throughput, and next-generation sequencing) has brought whole-genome analysis into the clinic for the first time, and most of the current applications are directed at children with congenital conditions that are undiagnosable by using standard genetic tests for single-gene disorders. Thus, pediatricians must become familiar with this technology, what it can and cannot offer, and its technical and ethical challenges. Here, we address the concepts of human genomic analysis and its clinical applicability for primary care providers.

  7. HeteroGenome: database of genome periodicity

    PubMed Central

    Chaley, Maria; Kutyrkin, Vladimir; Tulbasheva, Gayane; Teplukhina, Elena; Nazipova, Nafisa

    2014-01-01

    We present the first release of the HeteroGenome database collecting latent periodicity regions in genomes. Tandem repeats and highly divergent tandem repeats along with the regions of a new type of periodicity, known as profile periodicity, have been collected for the genomes of Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans and Drosophila melanogaster. We obtained data with the aid of a spectral-statistical approach to search for reliable latent periodicity regions (with periods up to 2000 bp) in DNA sequences. The original two-level mode of data presentation (a broad view of the region of latent periodicity and a second level indicating conservative fragments of its structure) was further developed to enable us to obtain the estimate, without redundancy, that latent periodicity regions make up ∼10% of the analyzed genomes. Analysis of the quantitative and qualitative content of located periodicity regions on all chromosomes of the analyzed organisms revealed dominant characteristic types of periodicity in the genomes. The pattern of density distribution of latent periodicity regions on chromosome unambiguously characterizes each chromosome in genome. Database URL: http://www.jcbi.ru/lp_baze/ PMID:24857969

  8. State of cat genomics.

    PubMed

    O'Brien, Stephen J; Johnson, Warren; Driscoll, Carlos; Pontius, Joan; Pecon-Slattery, Jill; Menotti-Raymond, Marilyn

    2008-06-01

    Our knowledge of cat family biology was recently expanded to include a genomics perspective with the completion of a draft whole genome sequence of an Abyssinian cat. The utility of the new genome information has been demonstrated by applications ranging from disease gene discovery and comparative genomics to species conservation. Patterns of genomic organization among cats and inbred domestic cat breeds have illuminated our view of domestication, revealing linkage disequilibrium tracks consequent of breed formation, defining chromosome exchanges that punctuated major lineages of mammals and suggesting ancestral continental migration events that led to 37 modern species of Felidae. We review these recent advances here. As the genome resources develop, the cat is poised to make a major contribution to many areas in genetics and biology.

  9. Genomics of oral bacteria.

    PubMed

    Duncan, Margaret J

    2003-01-01

    Advances in bacterial genetics came with the discovery of the genetic code, followed by the development of recombinant DNA technologies. Now the field is undergoing a new revolution because of investigators' ability to sequence and assemble complete bacterial genomes. Over 200 genome projects have been completed or are in progress, and the oral microbiology research community has benefited through projects for oral bacteria and their non-oral-pathogen relatives. This review describes features of several oral bacterial genomes, and emphasizes the themes of species relationships, comparative genomics, and lateral gene transfer. Genomics is having a broad impact on basic research in microbial pathogenesis, and will lead to new approaches in clinical research and therapeutics. The oral microbiota is a unique community especially suited for new challenges to sequence the metagenomes of microbial consortia, and the genomes of uncultivable bacteria.

  10. Querying genomic databases

    SciTech Connect

    Baehr, A.; Hagstrom, R.; Joerg, D.; Overbeek, R.

    1991-09-01

    A natural-language interface has been developed that retrieves genomic information by using a simple subset of English. The interface spares the biologist from the task of learning database-specific query languages and computer programming. Currently, the interface deals with the E. coli genome. It can, however, be readily extended and shows promise as a means of easy access to other sequenced genomic databases as well.

  11. Genomes by design

    PubMed Central

    Haimovich, Adrian D.; Muir, Paul; Isaacs, Farren J.

    2016-01-01

    Next-generation DNA sequencing has revealed the complete genome sequences of numerous organisms, establishing a fundamental and growing understanding of genetic variation and phenotypic diversity. Engineering at the gene, network and whole-genome scale aims to introduce targeted genetic changes both to explore emergent phenotypes and to introduce new functionalities. Expansion of these approaches into massively parallel platforms establishes the ability to generate targeted genome modifications, elucidating causal links between genotype and phenotype, as well as the ability to design and reprogramme organisms. In this Review, we explore techniques and applications in genome engineering, outlining key advances and defining challenges. PMID:26260262

  12. Genomics of Clostridium tetani.

    PubMed

    Brüggemann, Holger; Brzuszkiewicz, Elzbieta; Chapeton-Montes, Diana; Plourde, Lucile; Speck, Denis; Popoff, Michel R

    2015-05-01

    Genomic information about Clostridium tetani, the causative agent of the tetanus disease, is scarce. The genome of strain E88, a strain used in vaccine production, was sequenced about 10 years ago. One additional genome (strain 12124569) has recently been released. Here we report three new genomes of C. tetani and describe major differences among all five C. tetani genomes. They all harbor tetanus-toxin-encoding plasmids that contain highly conserved genes for TeNT (tetanus toxin), TetR (transcriptional regulator of TeNT) and ColT (collagenase), but substantially differ in other plasmid regions. The chromosomes share a large core genome that contains about 85% of all genes of a given chromosome. The non-core chromosome comprises mainly prophage-like genomic regions and genes encoding environmental interaction and defense functions (e.g. surface proteins, restriction-modification systems, toxin-antitoxin systems, CRISPR/Cas systems) and other fitness functions (e.g. transport systems, metabolic activities). This new genome information will help to assess the level of genome plasticity of the species C. tetani and provide the basis for detailed comparative studies.

  13. Filarial and Wolbachia genomics

    PubMed Central

    SCOTT, A. L.; GHEDIN, E.; NUTMAN, T. B.; McREYNOLDS, L. A.; POOLE, C. B.; SLATKO, B. E.; FOSTER, J. M.

    2012-01-01

    SUMMARY Filarial nematode parasites, the causative agents for a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the well-being and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95-Mb genome of the human filarial parasite Brugia malayi – representing the first helminth parasite genome to be sequenced – has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven nonfilarial nematode parasites of animals and nearly 30 plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial–Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics. PMID:22098559

  14. Fungal Genomics Program

    SciTech Connect

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  15. Between Two Fern Genomes

    PubMed Central

    2014-01-01

    Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves. PMID:25324969

  16. [Landscape and ecological genomics].

    PubMed

    Tetushkin, E Ia

    2013-10-01

    Landscape genomics is the modern version of landscape genetics, a discipline that arose approximately 10 years ago as a combination of population genetics, landscape ecology, and spatial statistics. It studies the effects of environmental variables on gene flow and other microevolutionary processes that determine genetic connectivity and variations in populations. In contrast to population genetics, it operates at the level of individual specimens rather than at the level of population samples. Another important difference between landscape genetics and genomics and population genetics is that, in the former, the analysis of gene flow and local adaptations takes quantitative account of landforms and features of the matrix, i.e., hostile spaces that separate species habitats. Landscape genomics is a part of population ecogenomics, which, along with community genomics, is a major part of ecological genomics. One of the principal purposes of landscape genomics is the identification and differentiation of various genome-wide and locus-specific effects. The approaches and computation tools developed for combined analysis of genomic and landscape variables make it possible to detect adaptation-related genome fragments, which facilitates the planning of conservation efforts and the prediction of species' fate in response to expected changes in the environment.

  17. Between two fern genomes.

    PubMed

    Sessa, Emily B; Banks, Jo Ann; Barker, Michael S; Der, Joshua P; Duffy, Aaron M; Graham, Sean W; Hasebe, Mitsuyasu; Langdale, Jane; Li, Fay-Wei; Marchant, D Blaine; Pryer, Kathleen M; Rothfels, Carl J; Roux, Stanley J; Salmi, Mari L; Sigel, Erin M; Soltis, Douglas E; Soltis, Pamela S; Stevenson, Dennis W; Wolf, Paul G

    2014-01-01

    Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves.

  18. MIPS plant genome information resources.

    PubMed

    Spannagl, Manuel; Haberer, Georg; Ernst, Rebecca; Schoof, Heiko; Mayer, Klaus F X

    2007-01-01

    The Munich Institute for Protein Sequences (MIPS) has been involved in maintaining plant genome databases since the Arabidopsis thaliana genome project. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable data sets for model plant genomes as a backbone against which experimental data, for example from high-throughput functional genomics, can be organized and evaluated. In addition, model genomes also form a scaffold for comparative genomics, and much can be learned from genome-wide evolutionary studies.

  19. Home - The Cancer Genome Atlas - Cancer Genome - TCGA

    Cancer.gov

    The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

  20. Automated Microbial Genome Annotation

    SciTech Connect

    Land, Miriam

    2009-05-29

    Miriam Land of the DOE Joint Genome Institute at Oak Ridge National Laboratory gives a talk on the current state and future challenges of moving toward automated microbial genome annotation at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  1. Phanerochaete chrysosporium genomics

    Treesearch

    Luis F. Larrondo; Rafael Vicuna; Dan Cullen

    2005-01-01

    A high quality draft genome sequence has been generated for the lignocellulose-degrading basidiomycete Phanerochaete chrysosporium (Martinez et al. 2004). Analysis of the genome in the context of previously established genetics and physiology is presented. Transposable elements and their potential relationship to genes involved in lignin degradation are systematically...

  2. Unlocking the bovine genome

    USDA-ARS?s Scientific Manuscript database

    The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries. ...

  3. Genomics for Weed Science

    USDA-ARS?s Scientific Manuscript database

    Numerous genomic-based studies have provided insight to the physiological and evolutionary processes involved in developmental and environmental processes of model plants such as arabidopsis and rice. However, far fewer efforts have been attempted to use genomic resources to study physiological and ...

  4. The cybernetic genome

    NASA Astrophysics Data System (ADS)

    Ben-Jacob, Eshel

    We propose a new picture of the genome as an adaptive cybernetic unit with self-awareness. We further propose that under colonial stress bacteria employ genetic communication which leads to the emergence of creative genomic web or “global brain”.

  5. Genetics and Genomics

    USDA-ARS?s Scientific Manuscript database

    Good progress is being made on genetics and genomics of sugar beet, however it is in process and the tools are now being generated and some results are being analyzed. The GABI BeetSeq project released a first draft of the sugar beet genome of KWS2320, a dihaploid (see http://bvseq.molgen.mpg.de/Gen...

  6. Breeding-assisted genomics.

    PubMed

    Poland, Jesse

    2015-04-01

    The revolution of inexpensive sequencing has ushered in an unprecedented age of genomics. The promise of using this technology to accelerate plant breeding is being realized with a vision of genomics-assisted breeding that will lead to rapid genetic gain for expensive and difficult traits. The reality is now that robust phenotypic data is an increasing limiting resource to complement the current wealth of genomic information. While genomics has been hailed as the discipline to fundamentally change the scope of plant breeding, a more symbiotic relationship is likely to emerge. In the context of developing and evaluating large populations needed for functional genomics, none excel in this area more than plant breeders. While genetic studies have long relied on dedicated, well-structured populations, the resources dedicated to these populations in the context of readily available, inexpensive genotyping is making this philosophy less tractable relative to directly focusing functional genomics on material in breeding programs. Through shifting effort for basic genomic studies from dedicated structured populations, to capturing the entire scope of genetic determinants in breeding lines, we can move towards not only furthering our understanding of functional genomics in plants, but also rapidly improving crops for increased food security, availability and nutrition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Genomics of Disease

    USDA-ARS?s Scientific Manuscript database

    This edited book represents the 23rd symposium in the Stadler Genetics Symposia series, and the general theme of this conference was "The Genomics of Disease." The 24 national and international speakers were invited to discuss their world-class research into the advances that genomics has made on c...

  8. The Future of Microbial Genomics

    SciTech Connect

    Kyrpides, Nikos

    2010-06-02

    Nikos Kyrpides, head of the Genome Biology group at the DOE Joint Genome Institute discusses current challenges in the field of microbial genomics on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  9. AutoGenomics, Inc.

    PubMed

    Vairavan, Ram

    2004-07-01

    AutoGenomics has created an automated multiplexing microarray platform to make genomic and proteomic analyses routine and efficient for clinical and research laboratories. While the emergence of microarrays has advanced genomic analyses, a number of underlying issues, such as cross-hybridization, poor spot morphology and intrinsic fluorescence of the solid substrate, have yet to be fully resolved. Current methods use discrete instrumentation, are manual and require highly skilled labor, which leads to inconsistent results. AutoGenomics' automated platform uses a three-dimensional BioFilmChip microarray to circumvent these issues, providing optimal spot morphology and utilizing solution-based hybridization with allele-specific primer extension to improve single-base discrimination. AutoGenomics is developing applications for the early detection and management of complex disease states in oncology, cardiology, and mental disorders. Customers include clinical reference laboratories, hospitals, academic institutions, and pharmaceutical and biotech companies. Founded in 1999, the company is headquartered in Carlsbad, California, USA.

  10. Microbial Genomes Multiply

    NASA Technical Reports Server (NTRS)

    Doolittle, Russell F.

    2002-01-01

    The publication of the first complete sequence of a bacterial genome in 1995 was a signal event, underscored by the fact that the article has been cited more than 2,100 times during the intervening seven years. It was a marvelous technical achievement, made possible by automatic DNA-sequencing machines. The feat is the more impressive in that complete genome sequencing has now been adopted in many different laboratories around the world. Four years ago in these columns I examined the situation after a dozen microbial genomes had been completed. Now, with upwards of 60 microbial genome sequences determined and twice that many in progress, it seems reasonable to assess just what is being learned. Are new concepts emerging about how cells work? Have there been practical benefits in the fields of medicine and agriculture? Is it feasible to determine the genomic sequence of every bacterial species on Earth? The answers to these questions maybe Yes, Perhaps, and No, respectively.

  11. The UCSC Genome Browser

    PubMed Central

    Karolchik, Donna; Hinrichs, Angie S.; Kent, W. James

    2011-01-01

    The University of California Santa Cruz (UCSC) Genome Browser is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation “tracks.” The annotations generated by the UCSC Genome Bioinformatics Group and external collaborators include gene predictions, mRNA and expressed sequence tag alignments, simple nucleotide polymorphisms, expression and regulatory data, phenotype and variation data, and pairwise and multiple-species comparative genomics data. All information relevant to a region is presented in one window, facilitating biological analysis and interpretation. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser. Users can upload personal datasets in a wide variety of formats as custom annotation tracks in both browsers for research or educational purposes. PMID:21975940

  12. Microbial Genomes Multiply

    NASA Technical Reports Server (NTRS)

    Doolittle, Russell F.

    2002-01-01

    The publication of the first complete sequence of a bacterial genome in 1995 was a signal event, underscored by the fact that the article has been cited more than 2,100 times during the intervening seven years. It was a marvelous technical achievement, made possible by automatic DNA-sequencing machines. The feat is the more impressive in that complete genome sequencing has now been adopted in many different laboratories around the world. Four years ago in these columns I examined the situation after a dozen microbial genomes had been completed. Now, with upwards of 60 microbial genome sequences determined and twice that many in progress, it seems reasonable to assess just what is being learned. Are new concepts emerging about how cells work? Have there been practical benefits in the fields of medicine and agriculture? Is it feasible to determine the genomic sequence of every bacterial species on Earth? The answers to these questions maybe Yes, Perhaps, and No, respectively.

  13. Comparative genomics of nematodes.

    PubMed

    Mitreva, Makedonka; Blaxter, Mark L; Bird, David M; McCarter, James P

    2005-10-01

    Recent transcriptome and genome projects have dramatically expanded the biological data available across the phylum Nematoda. Here we summarize analyses of these sequences, which have revealed multiple unexpected results. Despite a uniform body plan, nematodes are more diverse at the molecular level than was previously recognized, with many species- and group-specific novel genes. In the genus Caenorhabditis, changes in chromosome arrangement, particularly local inversions, are also rapid, with breakpoints occurring at 50-fold the rate in vertebrates. Tylenchid plant parasitic nematode genomes contain several genes closely related to genes in bacteria, implicating horizontal gene transfer events in the origins of plant parasitism. Functional genomics techniques are also moving from Caenorhabditis elegans to application throughout the phylum. Soon, eight more draft nematode genome sequences will be available. This unique resource will underpin both molecular understanding of these most abundant metazoan organisms and aid in the examination of the dynamics of genome evolution in animals.

  14. Phytozome Comparative Plant Genomics Portal

    SciTech Connect

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  15. Evolution of Genome Architecture

    PubMed Central

    Koonin, Eugene V.

    2012-01-01

    Charles Darwin believed that all traits of organisms have been honed to near perfection by natural selection. The empirical basis underlying Darwin’s conclusions consisted of numerous observations made by him and other naturalists on the exquisite adaptations of animals and plants to their natural habitats and on the impressive results of artificial selection. Darwin fully appreciated the importance of heredity but was unaware of the nature and, in fact, the very existence of genomes. A century and a half after the publication of the “Origin”, we have the opportunity to draw conclusions from the comparisons of hundreds of genome sequences from all walks of life. These comparisons suggest that the dominant mode of genome evolution is quite different from that of the phenotypic evolution. The genomes of vertebrates, those purported paragons of biological perfection, turned out to be veritable junkyards of selfish genetic elements where only a small fraction of the genetic material is dedicated to encoding biologically relevant information. In sharp contrast, genomes of microbes and viruses are incomparably more compact, with most of the genetic material assigned to distinct biological functions. However, even in these genomes, the specific genome organization (gene order) is poorly conserved. The results of comparative genomics lead to the conclusion that the genome architecture is not a straightforward result of continuous adaptation but rather is determined by the balance between the selection pressure, that is itself dependent on the effective population size and mutation rate, the level of recombination, and the activity of selfish elements. Although genes and, in many cases, multigene regions of genomes possess elaborate architectures that ensure regulation of expression, these arrangements are evolutionarily volatile and typically change substantially even on short evolutionary scales when gene sequences diverge minimally. Thus, the observed genome

  16. The banana genome hub.

    PubMed

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D'Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world's favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/

  17. The Banana Genome Hub

    PubMed Central

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D’Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world’s favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/ PMID:23707967

  18. Genomic Insights into Bifidobacteria

    PubMed Central

    Lee, Ju-Hoon; O'Sullivan, Daniel J.

    2010-01-01

    Summary: Since the discovery in 1899 of bifidobacteria as numerically dominant microbes in the feces of breast-fed infants, there have been numerous studies addressing their role in modulating gut microflora as well as their other potential health benefits. Because of this, they are frequently incorporated into foods as probiotic cultures. An understanding of their full interactions with intestinal microbes and the host is needed to scientifically validate any health benefits they may afford. Recently, the genome sequences of nine strains representing four species of Bifidobacterium became available. A comparative genome analysis of these genomes reveals a likely efficient capacity to adapt to their habitats, with B. longum subsp. infantis exhibiting more genomic potential to utilize human milk oligosaccharides, consistent with its habitat in the infant gut. Conversely, B. longum subsp. longum exhibits a higher genomic potential for utilization of plant-derived complex carbohydrates and polyols, consistent with its habitat in an adult gut. An intriguing observation is the loss of much of this genome potential when strains are adapted to pure culture environments, as highlighted by the genomes of B. animalis subsp. lactis strains, which exhibit the least potential for a gut habitat and are believed to have evolved from the B. animalis species during adaptation to dairy fermentation environments. PMID:20805404

  19. NCBI viral genomes resource.

    PubMed

    Brister, J Rodney; Ako-Adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by US Government employees and is in the public domain in the US.

  20. NCBI Viral Genomes Resource

    PubMed Central

    Brister, J. Rodney; Ako-adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. PMID:25428358

  1. Ensembl comparative genomics resources

    PubMed Central

    Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J.; Searle, Stephen M. J.; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

    2016-01-01

    Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. PMID:26896847

  2. Toward 959 nematode genomes

    PubMed Central

    Kumar, Sujai; Koutsovoulos, Georgios; Kaur, Gaganjot; Blaxter, Mark

    2012-01-01

    The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organisms to approach genome sequencing of their species. The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla. PMID:24058822

  3. Ensembl comparative genomics resources.

    PubMed

    Herrero, Javier; Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J; Searle, Stephen M J; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

    2016-01-01

    Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. © The Author(s) 2016. Published by Oxford University Press.

  4. Traditional medicine and genomics

    PubMed Central

    Joshi, Kalpana; Ghodke, Yogita; Shintre, Pooja

    2010-01-01

    ‘Omics’ developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics. PMID:21829298

  5. Human Genome Program

    SciTech Connect

    Not Available

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  6. Genetics and genomic medicine.

    PubMed

    Bogaard, Kali; Johnson, Marlene

    2009-01-01

    Genetics is playing an increasingly important role in the diagnosis, monitoring and treatment of diseases, and the expansion of genetics into health care has generated the field of genomic medicine. Health care delivery is shifting away from general diagnostic evaluation toward a generation of therapeutics based on a patient's genetic makeup. Meanwhile, the scientific community debates how best to incorporate genetics and genomic medicine into practice. While obstacles remain, the ultimate goal is to use information generated from the study of human genetics to improve disease treatment, cure and prevention. As the use of genetics in medical diagnosis and treatment increases, health care workers will require an understanding of genetics and genomic medicine.

  7. Genomic variation in maize

    SciTech Connect

    Rivin, C.J.

    1990-01-01

    We have endeavored to learn to learn how different DNA sequences and sequence arrangements contribute to genome plasticity in maize. We describe quantitative variation among maize inbred lines for tandemly arrayed and dispersed repeated DNA sequences and gene families, and qualitative variation for sequences homologous to the Mutator family of transposons. The potential of these sequences to undergo unequal crossing over, non-allelic (ectopic) recombination and transposition makes them a source of genome instability. We have found examples of rapid genomic change involving these sequences in F1 hybrids, tissue culture cells and regenerated plants.

  8. What Is a Genome?

    PubMed Central

    Goldman, Aaron David; Landweber, Laura F.

    2016-01-01

    The genome is often described as the information repository of an organism. Whether millions or billions of letters of DNA, its transmission across generations confers the principal medium for inheritance of organismal traits. Several emerging areas of research demonstrate that this definition is an oversimplification. Here, we explore ways in which a deeper understanding of genomic diversity and cell physiology is challenging the concepts of physical permanence attached to the genome as well as its role as the sole information source for an organism. PMID:27442251

  9. Human Genome Project

    SciTech Connect

    Block, S.; Cornwall, J.; Dally, W.; Dyson, F.; Fortson, N.; Joyce, G.; Kimble, H. J.; Lewis, N.; Max, C.; Prince, T.; Schwitters, R.; Weinberger, P.; Woodin, W. H.

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  10. Center for Cancer Genomics | Office of Cancer Genomics

    Cancer.gov

    The Center for Cancer Genomics (CCG) was established to unify the National Cancer Institute's activities in cancer genomics, with the goal of advancing genomics research and translating findings into the clinic to improve the precise diagnosis and treatment of cancers. In addition to promoting genomic sequencing app

  11. Comparative primate genomics: emerging patterns of genome content and dynamics.

    PubMed

    Rogers, Jeffrey; Gibbs, Richard A

    2014-05-01

    Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for various primate species, and analyses of several others are underway. Whole-genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other non-human primates offer valuable insights into genetic similarities and differences among species that are used as models for disease-related research. This Review summarizes current knowledge regarding primate genome content and dynamics, and proposes a series of goals for the near future.

  12. Comparative primate genomics: emerging patterns of genome content and dynamics

    PubMed Central

    Rogers, Jeffrey; Gibbs, Richard A.

    2014-01-01

    Preface Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for several primates, with analyses of several others underway. Whole genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other nonhuman primates provide valuable insight into genetic similarities and differences among species used as models for disease-related research. This review summarizes current knowledge regarding primate genome content and dynamics and offers a series of goals for the near future. PMID:24709753

  13. Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine

    PubMed Central

    Elsik, Christine G.; Tayal, Aditi; Diesh, Colin M.; Unni, Deepak R.; Emery, Marianne L.; Nguyen, Hung N.; Hagen, Darren E.

    2016-01-01

    We report an update of the Hymenoptera Genome Database (HGD) (http://HymenopteraGenome.org), a model organism database for insect species of the order Hymenoptera (ants, bees and wasps). HGD maintains genomic data for 9 bee species, 10 ant species and 1 wasp, including the versions of genome and annotation data sets published by the genome sequencing consortiums and those provided by NCBI. A new data-mining warehouse, HymenopteraMine, based on the InterMine data warehousing system, integrates the genome data with data from external sources and facilitates cross-species analyses based on orthology. New genome browsers and annotation tools based on JBrowse/WebApollo provide easy genome navigation, and viewing of high throughput sequence data sets and can be used for collaborative genome annotation. All of the genomes and annotation data sets are combined into a single BLAST server that allows users to select and combine sequence data sets to search. PMID:26578564

  14. Genomic definition of species

    SciTech Connect

    Crkvenjakov, R.; Drmanac, R.

    1991-07-01

    The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

  15. Human genomic variation

    PubMed Central

    Disotell, Todd R

    2000-01-01

    The recent completion and assembly of the first draft of the human genome, which combines samples from several ethnically diverse males and females, provides preliminary data on the extent of human genetic variation. PMID:11178257

  16. The rise of genomics.

    PubMed

    Weissenbach, Jean

    2016-01-01

    A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis. Initial analyses focused on the inventory of genes encoding proteins. Completeness and quality of gene prediction remains crucial. Genome analyses profoundly modified our views on evolution, biodiversity and contributed to the detection of new functions, yet to be fully elucidated, such as those fulfilled by non-coding RNAs. Genomics has become the basis for the study of biology and provides the molecular support for a bunch of large-scale studies, the omics.

  17. Rubicon Genomics, Inc.

    PubMed

    Langmore, John P

    2002-07-01

    Rubicon Genomics, Inc. is a leader in development and application of effective methods to analyze human DNA for genome-wide genotyping and haplotyping. The company is developing its proprietary OmniPlex technology as an integrated platform for archiving, amplifying and analyzing patient DNA for drug target discovery, pharmacogenomics and diagnostics. Single-site, multiple-site or whole genome amplification can be done using small samples of DNA that have been archived as OmniPlex DNA. Rubicon technology will make genome-wide SNP scoring faster, more accurate, more robust and less expensive. Rubicon will partner with pharmaceutical and diagnostic companies, as well as the makers of instruments and reagents to bring OmniPlex technology to the widest market - increasing the pipeline of more effective and safer drugs and ushering in the practice of gene-based medicine.

  18. The genomics of adaptation.

    PubMed

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation.

  19. The genomics of Colletotrichum

    USDA-ARS?s Scientific Manuscript database

    Colletotrichum are devastating fungal pathogens of major crop plants worldwide. This book chapter provides an overview of the genomics and transcriptomics of Colletotrichum. Included is an overview of the agricultural relevance of the genus Colletotrichum, the taxonomic position, information about ...

  20. Genomics of Aspergillus oryzae.

    PubMed

    Kobayashi, Tetsuo; Abe, Keietsu; Asai, Kiyoshi; Gomi, Katsuya; Juvvadi, Praveen Rao; Kato, Masashi; Kitamoto, Katsuhiko; Takeuchi, Michio; Machida, Masayuki

    2007-03-01

    The genome sequence of Aspergillus oryzae, a fungus used in the production of the traditional Japanese fermentation foods sake (rice wine), shoyu (soy sauce), and miso (soybean paste), has revealed prominent features in its gene composition as compared to those of Saccharomyces cerevisiae and Neurospora crassa. The A. oryzae genome is extremely enriched with genes involved in biomass degradation, primary and secondary metabolism, transcriptional regulation, and cell signaling. Even compared to the related species A. nidulans and A. fumigatus, an abundance of metabolic genes is apparent, with acquisition of more than 6 Mb of sequence in the A. oryzae lineage, interspersed throughout the A. oryzae genome. Besides the various already established merits of A. oryzae for industrial uses, the genome sequence and the abundance of metabolic genes should significantly accelerate the biotechnological use of A. oryzae in industry.

  1. Genomic imprinting and reproduction.

    PubMed

    Swales, A K E; Spears, N

    2005-10-01

    Genomic imprinting is the parent-of-origin specific gene expression which is a vital mechanism through both development and adult life. One of the key elements of the imprinting mechanism is DNA methylation, controlled by DNA methyltransferase enzymes. Germ cells undergo reprogramming to ensure that sex-specific genomic imprinting is initiated, thus allowing normal embryo development to progress after fertilisation. In some cases, errors in genomic imprinting are embryo lethal while in others they lead to developmental disorders and disease. Recent studies have suggested a link between the use of assisted reproductive techniques and an increase in normally rare imprinting disorders. A greater understanding of the mechanisms of genomic imprinting and the factors that influence them are important in assessing the safety of these techniques.

  2. Lophotrochozoan mitochondrial genomes

    SciTech Connect

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  3. Platyzoan mitochondrial genomes.

    PubMed

    Wey-Fabrizius, Alexandra R; Podsiadlowski, Lars; Herlyn, Holger; Hankeln, Thomas

    2013-11-01

    Platyzoa is a putative lophotrochozoan (spiralian) subtaxon within the protostome clade of Metazoa, comprising a range of biologically diverse, mostly small worm-shaped animals. The monophyly of Platyzoa, the relationships between the putative subgroups Platyhelminthes, Gastrotricha and Gnathifera (the latter comprising at least Gnathostomulida, "Rotifera" and Acanthocephala) as well as some aspects of the internal phylogenies of these subgroups are highly debated. Here we review how complete mitochondrial (mt) genome data contribute to these debates. We highlight special features of the mt genomes and discuss problems in mtDNA phylogenies of the clade. Mitochondrial genome data seem to be insufficient to resolve the position of the platyzoan clade within the Spiralia but can help to address internal phylogenetic questions. The present review includes a tabular survey of all published platyzoan mt genomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Epidemiology & Genomics Research Program

    Cancer.gov

    The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

  5. Mouse genome database 2016

    PubMed Central

    Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E.

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  6. Biobanks for Genomics and Genomics for Biobanks

    PubMed Central

    Ducournau, Pascal; Gourraud, Pierre-Antoine; Pontille, David

    2003-01-01

    Biobanks include biological samples and attached databases. Human biobanks occur in research, technological development and medical activities. Population genomics is highly dependent on the availability of large biobanks. Ethical issues must be considered: protecting the rights of those people whose samples or data are in biobanks (information, autonomy, confidentiality, protection of private life), assuring the non-commercial use of human body elements and the optimal use of samples and data. They balance other issues, such as protecting the rights of researchers and companies, allowing long-term use of biobanks while detailed information on future uses is not available. At the level of populations, the traditional form of informed consent is challenged. Other dimensions relate to the rights of a group as such, in addition to individual rights. Conditions of return of results and/or benefit to a population need to be defined. With ‘large-scale biobanking’ a marked trend in genomics, new societal dimensions appear, regarding communication, debate, regulation, societal control and valorization of such large biobanks. Exploring how genomics can help health sector biobanks to become more rationally constituted and exploited is an interesting perspective. For example, evaluating how genomic approaches can help in optimizing haematopoietic stem cell donor registries using new markers and high-throughput techniques to increase immunogenetic variability in such registries is a challenge currently being addressed. Ethical issues in such contexts are important, as not only individual decisions or projects are concerned, but also national policies in the international arena and organization of democratic debate about science, medicine and society. PMID:18629026

  7. Bacteriophage T4 genome.

    PubMed

    Miller, Eric S; Kutter, Elizabeth; Mosig, Gisela; Arisaka, Fumio; Kunisawa, Takashi; Rüger, Wolfgang

    2003-03-01

    Phage T4 has provided countless contributions to the paradigms of genetics and biochemistry. Its complete genome sequence of 168,903 bp encodes about 300 gene products. T4 biology and its genomic sequence provide the best-understood model for modern functional genomics and proteomics. Variations on gene expression, including overlapping genes, internal translation initiation, spliced genes, translational bypassing, and RNA processing, alert us to the caveats of purely computational methods. The T4 transcriptional pattern reflects its dependence on the host RNA polymerase and the use of phage-encoded proteins that sequentially modify RNA polymerase; transcriptional activator proteins, a phage sigma factor, anti-sigma, and sigma decoy proteins also act to specify early, middle, and late promoter recognition. Posttranscriptional controls by T4 provide excellent systems for the study of RNA-dependent processes, particularly at the structural level. The redundancy of DNA replication and recombination systems of T4 reveals how phage and other genomes are stably replicated and repaired in different environments, providing insight into genome evolution and adaptations to new hosts and growth environments. Moreover, genomic sequence analysis has provided new insights into tail fiber variation, lysis, gene duplications, and membrane localization of proteins, while high-resolution structural determination of the "cell-puncturing device," combined with the three-dimensional image reconstruction of the baseplate, has revealed the mechanism of penetration during infection. Despite these advances, nearly 130 potential T4 genes remain uncharacterized. Current phage-sequencing initiatives are now revealing the similarities and differences among members of the T4 family, including those that infect bacteria other than Escherichia coli. T4 functional genomics will aid in the interpretation of these newly sequenced T4-related genomes and in broadening our understanding of the complex

  8. Molluscan Evolutionary Genomics

    SciTech Connect

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  9. An Introduction to Genome Annotation.

    PubMed

    Campbell, Michael S; Yandell, Mark

    2015-12-17

    Genome projects have evolved from large international undertakings to tractable endeavors for a single lab. Accurate genome annotation is critical for successful genomic, genetic, and molecular biology experiments. These annotations can be generated using a number of approaches and available software tools. This unit describes methods for genome annotation and a number of software tools commonly used in gene annotation.

  10. Ebolavirus comparative genomics

    DOE PAGES

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; ...

    2015-07-14

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. We examine the dynamics of this genome, comparing more than one hundred currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus, and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of themore » same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP), and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. In conclusion, this information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies.« less

  11. Human Social Genomics

    PubMed Central

    Cole, Steven W.

    2014-01-01

    A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural “social signal transduction” pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving. PMID:25166010

  12. An archaeal genomic signature

    NASA Technical Reports Server (NTRS)

    Graham, D. E.; Overbeek, R.; Olsen, G. J.; Woese, C. R.

    2000-01-01

    Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal "design fabric." Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org).

  13. Genomic Instability in Cancer

    PubMed Central

    Abbas, Tarek; Keaton, Mignon A.; Dutta, Anindya

    2013-01-01

    One of the fundamental challenges facing the cell is to accurately copy its genetic material to daughter cells. When this process goes awry, genomic instability ensues in which genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Organisms have developed multiple mechanisms that can be classified into two major classes to ensure the fidelity of DNA replication. The first class includes mechanisms that prevent premature initiation of DNA replication and ensure that the genome is fully replicated once and only once during each division cycle. These include cyclin-dependent kinase (CDK)-dependent mechanisms and CDK-independent mechanisms. Although CDK-dependent mechanisms are largely conserved in eukaryotes, higher eukaryotes have evolved additional mechanisms that seem to play a larger role in preventing aberrant DNA replication and genome instability. The second class ensures that cells are able to respond to various cues that continuously threaten the integrity of the genome by initiating DNA-damage-dependent “checkpoints” and coordinating DNA damage repair mechanisms. Defects in the ability to safeguard against aberrant DNA replication and to respond to DNA damage contribute to genomic instability and the development of human malignancy. In this article, we summarize our current knowledge of how genomic instability arises, with a particular emphasis on how the DNA replication process can give rise to such instability. PMID:23335075

  14. An archaeal genomic signature.

    PubMed

    Graham, D E; Overbeek, R; Olsen, G J; Woese, C R

    2000-03-28

    Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal "design fabric." Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org).

  15. An archaeal genomic signature

    PubMed Central

    Graham, David E.; Overbeek, Ross; Olsen, Gary J.; Woese, Carl R.

    2000-01-01

    Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal “design fabric.” Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org). PMID:10716711

  16. An archaeal genomic signature

    NASA Technical Reports Server (NTRS)

    Graham, D. E.; Overbeek, R.; Olsen, G. J.; Woese, C. R.

    2000-01-01

    Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal "design fabric." Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org).

  17. How the genome folds

    NASA Astrophysics Data System (ADS)

    Lieberman Aiden, Erez

    2012-02-01

    I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  18. Human Genome Annotation

    NASA Astrophysics Data System (ADS)

    Gerstein, Mark

    A central problem for 21st century science is annotating the human genome and making this annotation useful for the interpretation of personal genomes. My talk will focus on annotating the 99% of the genome that does not code for canonical genes, concentrating on intergenic features such as structural variants (SVs), pseudogenes (protein fossils), binding sites, and novel transcribed RNAs (ncRNAs). In particular, I will describe how we identify regulatory sites and variable blocks (SVs) based on processing next-generation sequencing experiments. I will further explain how we cluster together groups of sites to create larger annotations. Next, I will discuss a comprehensive pseudogene identification pipeline, which has enabled us to identify >10K pseudogenes in the genome and analyze their distribution with respect to age, protein family, and chromosomal location. Throughout, I will try to introduce some of the computational algorithms and approaches that are required for genome annotation. Much of this work has been carried out in the framework of the ENCODE, modENCODE, and 1000 genomes projects.

  19. WheatGenome.info: A Resource for Wheat Genomics Resource.

    PubMed

    Lai, Kaitao

    2016-01-01

    An integrated database with a variety of Web-based systems named WheatGenome.info hosting wheat genome and genomic data has been developed to support wheat research and crop improvement. The resource includes multiple Web-based applications, which are implemented as a variety of Web-based systems. These include a GBrowse2-based wheat genome viewer with BLAST search portal, TAGdb for searching wheat second generation genome sequence data, wheat autoSNPdb, links to wheat genetic maps using CMap and CMap3D, and a wheat genome Wiki to allow interaction between diverse wheat genome sequencing activities. This portal provides links to a variety of wheat genome resources hosted at other research organizations. This integrated database aims to accelerate wheat genome research and is freely accessible via the web interface at http://www.wheatgenome.info/ .

  20. Genome size analyses of Pucciniales reveal the largest fungal genomes.

    PubMed

    Tavares, Sílvia; Ramos, Ana Paula; Pires, Ana Sofia; Azinheira, Helena G; Caldeirinha, Patrícia; Link, Tobias; Abranches, Rita; Silva, Maria do Céu; Voegele, Ralf T; Loureiro, João; Talhinhas, Pedro

    2014-01-01

    Rust fungi (Basidiomycota, Pucciniales) are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 225.3 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi). In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp). Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94%). The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  1. Genomes to Proteomes

    SciTech Connect

    Panisko, Ellen A.; Grigoriev, Igor; Daly, Don S.; Webb-Robertson, Bobbie-Jo; Baker, Scott E.

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  2. Genomics and drug discovery.

    PubMed

    Haseltine, W A

    2001-09-01

    Genomics, the systematic study of all the genes of an organism, offers a new and much-needed source of systematic productivity for the pharmaceutical industry. The isolation of the majority of human genes in their most useful form is leading to the creation of new drugs based on human proteins, antibodies, peptides, and genes. Human Genome Sciences, Inc, was the first company to use the systematic, genomics approach to discovering drugs, and we have placed 4 of these in clinical trials. Two are described: repifermin (keratinocyte growth factor-2, KGF-2) for wound healing and treatment of mucositis caused by cancer therapy, and B lymphocyte stimulator (BLyS) for stimulation of the immune system. An anti-BLyS antibody drug is in advanced preclinical development for treatment of autoimmune diseases.

  3. Calibrating the genome.

    PubMed

    Markward, Nathan J; Fisher, William P

    2004-01-01

    This project demonstrates how to calibrate different samples and scales of genomic information to a common scale of genomic measurement. 1,113 persons were genotyped at the 13 Combined DNA Index System (CODIS) short tandem repeat (STR) marker loci used by the Federal Bureau of Investigation (FBI) for human identity testing. A measurement model of form ln[(P(nik))/(1-P(nik))] = B(n)-D(i)-L(k) is used to construct person measures and locus calibrations from information contained in the CODIS database. Winsteps (Wright and Linacre, 2003) is employed to maximize initial estimates and to investigate the necessity and sufficiency of different rating classification schema. Model fit is satisfactory in all analyses. Study outcomes are found in Tables 1-6. Additive, divisible, and interchangeable measures and calibrations can be created from raw genomic information that transcend sample- and scale-dependencies associated with racial and ethnic descent, chromosomal location, and locus-specific allele expansion structures.

  4. Genomics of Preterm Birth

    PubMed Central

    Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

    2015-01-01

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

  5. Genes, genome and Gestalt.

    PubMed

    Grisolia, Cesar Koppe

    2005-03-31

    According to Gestalt thinking, biological systems cannot be viewed as the sum of their elements, but as processes of the whole. To understand organisms we must start from the whole, observing how the various parts are related. In genetics, we must observe the genome over and above the sum of its genes. Either loss or addition of one gene in a genome can change the function of the organism. Genomes are organized in networks of genes, which need to be well integrated. In the case of genetically modified organisms (GMOs), for example, soybeans, rats, Anopheles mosquitoes, and pigs, the insertion of an exogenous gene into a receptive organism generally causes disturbance in the networks, resulting in the breakdown of gene interactions. In these cases, genetic modification increased the genetic load of the GMO and consequently decreased its adaptability (fitness). Therefore, it is hard to claim that the production of such organisms with an increased genetic load does not have ethical implications.

  6. Genomics of Salmonella Species

    NASA Astrophysics Data System (ADS)

    Canals, Rocio; McClelland, Michael; Santiviago, Carlos A.; Andrews-Polymenis, Helene

    Progress in the study of Salmonella survival, colonization, and virulence has increased rapidly with the advent of complete genome sequencing and higher capacity assays for transcriptomic and proteomic analysis. Although many of these techniques have yet to be used to directly assay Salmonella growth on foods, these assays are currently in use to determine Salmonella factors necessary for growth in animal models including livestock animals and in in vitro conditions that mimic many different environments. As sequencing of the Salmonella genome and microarray analysis have revolutionized genomics and transcriptomics of salmonellae over the last decade, so are new high-throughput sequencing technologies currently accelerating the pace of our studies and allowing us to approach complex problems that were not previously experimentally tractable.

  7. Genomic Imprinting in Mammals

    PubMed Central

    Barlow, Denise P.

    2014-01-01

    Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs (lncRNAs). To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure. Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation. PMID:24492710

  8. Genomics for weed science.

    PubMed

    Horvath, David

    2010-03-01

    Numerous genomic-based studies have provided insight to the physiological and evolutionary processes involved in developmental and environmental processes of model plants such as arabidopsis and rice. However, far fewer efforts have been attempted to use genomic resources to study physiological and evolutionary processes of weedy plants. Genomics-based tools such as extensive EST databases and microarrays have been developed for a limited number of weedy species, although application of information and resources developed for model plants and crops are possible and have been exploited. These tools have just begun to provide insights into the response of these weeds to herbivore and pathogen attack, survival of extreme environmental conditions, and interaction with crops. The potential of these tools to illuminate mechanisms controlling the traits that allow weeds to invade novel habitats, survive extreme environments, and that make weeds difficult to eradicate have potential for both improving crops and developing novel methods to control weeds.

  9. Genomics of preterm birth.

    PubMed

    Swaggart, Kayleigh A; Pavlicev, Mihaela; Muglia, Louis J

    2015-02-02

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. Genomics for Weed Science

    PubMed Central

    Horvath, David

    2010-01-01

    Numerous genomic-based studies have provided insight to the physiological and evolutionary processes involved in developmental and environmental processes of model plants such as arabidopsis and rice. However, far fewer efforts have been attempted to use genomic resources to study physiological and evolutionary processes of weedy plants. Genomics-based tools such as extensive EST databases and microarrays have been developed for a limited number of weedy species, although application of information and resources developed for model plants and crops are possible and have been exploited. These tools have just begun to provide insights into the response of these weeds to herbivore and pathogen attack, survival of extreme environmental conditions, and interaction with crops. The potential of these tools to illuminate mechanisms controlling the traits that allow weeds to invade novel habitats, survive extreme environments, and that make weeds difficult to eradicate have potential for both improving crops and developing novel methods to control weeds. PMID:20808523

  11. Genomics of Volvocine Algae

    PubMed Central

    Umen, James G.; Olson, Bradley J.S.C.

    2015-01-01

    Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics. PMID:25883411

  12. Ebolavirus comparative genomics

    PubMed Central

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S.; Pedersen, Thomas D.; Wassenaar, Trudy M.; Ussery, David W.

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). PMID:26175035

  13. Ebolavirus comparative genomics.

    PubMed

    Jun, Se-Ran; Leuze, Michael R; Nookaew, Intawat; Uberbacher, Edward C; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S; Pedersen, Thomas D; Wassenaar, Trudy M; Ussery, David W

    2015-09-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies.This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).

  14. The cancer genome

    PubMed Central

    Stratton, Michael R.; Campbell, Peter J.; Futreal, P. Andrew

    2010-01-01

    All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells. Over the past quarter of a century much has been learnt about these mutations and the abnormal genes that operate in human cancers. We are now, however, moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes. These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed. PMID:19360079

  15. The genomics of mycobacteria.

    PubMed

    Viale, M N; Zumárraga, M J; Araújo, F R; Zarraga, A M; Cataldi, A A; Romano, M I; Bigi, F

    2016-04-01

    The species Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis are the causal agents, respectively, of tuberculosis and paratuberculosis in animals. Both mycobacteria, especially M. bovis, are also important to public health because they can infect humans. In recent years, this and the impact of tuberculosis and paratuberculosis on animal production have led to significant advances in knowledge about both pathogens and their host interactions. This article describes the contribution of genomics and functional genomics to studies of the evolution, virulence, epidemiology and diagnosis of both these pathogenic mycobacteria.

  16. Landscape evolutionary genomics.

    PubMed

    Lowry, David B

    2010-08-23

    Tremendous advances in genetic and genomic techniques have resulted in the capacity to identify genes involved in adaptive evolution across numerous biological systems. One of the next major steps in evolutionary biology will be to determine how landscape-level geographical and environmental features are involved in the distribution of this functional adaptive genetic variation. Here, I outline how an emerging synthesis of multiple disciplines has and will continue to facilitate a deeper understanding of the ways in which heterogeneity of the natural landscapes mould the genomes of organisms.

  17. Methanococcus jannaschii genome: revisited

    NASA Technical Reports Server (NTRS)

    Kyrpides, N. C.; Olsen, G. J.; Klenk, H. P.; White, O.; Woese, C. R.

    1996-01-01

    Analysis of genomic sequences is necessarily an ongoing process. Initial gene assignments tend (wisely) to be on the conservative side (Venter, 1996). The analysis of the genome then grows in an iterative fashion as additional data and more sophisticated algorithms are brought to bear on the data. The present report is an emendation of the original gene list of Methanococcus jannaschii (Bult et al., 1996). By using a somewhat more updated database and more relaxed (and operator-intensive) pattern matching methods, we were able to add significantly to, and in a few cases amend, the gene identification table originally published by Bult et al. (1996).

  18. Genomic standards consortium projects.

    PubMed

    Field, Dawn; Sterk, Peter; Kottmann, Renzo; De Smet, J Wim; Amaral-Zettler, Linda; Cochrane, Guy; Cole, James R; Davies, Neil; Dawyndt, Peter; Garrity, George M; Gilbert, Jack A; Glöckner, Frank Oliver; Hirschman, Lynette; Klenk, Hans-Peter; Knight, Rob; Kyrpides, Nikos; Meyer, Folker; Karsch-Mizrachi, Ilene; Morrison, Norman; Robbins, Robert; San Gil, Inigo; Sansone, Susanna; Schriml, Lynn; Tatusova, Tatiana; Ussery, Dave; Yilmaz, Pelin; White, Owen; Wooley, John; Caporaso, Gregory

    2014-06-15

    The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

  19. Methanococcus jannaschii genome: revisited.

    PubMed

    Kyrpides, N C; Olsen, G J; Klenk, H P; White, O; Woese, C R

    1996-01-01

    Analysis of genomic sequences is necessarily an ongoing process. Initial gene assignments tend (wisely) to be on the conservative side (Venter, 1996). The analysis of the genome then grows in an iterative fashion as additional data and more sophisticated algorithms are brought to bear on the data. The present report is an emendation of the original gene list of Methanococcus jannaschii (Bult et al., 1996). By using a somewhat more updated database and more relaxed (and operator-intensive) pattern matching methods, we were able to add significantly to, and in a few cases amend, the gene identification table originally published by Bult et al. (1996).

  20. Brief Guide to Genomics: DNA, Genes and Genomes

    MedlinePlus

    ... guía de genómica A Brief Guide to Genomics DNA, Genes and Genomes Deoxyribonucleic acid (DNA) is the ... and lead to a disease such as cancer. DNA Sequencing Sequencing simply means determining the exact order ...

  1. Haemonchus contortus: Genome Structure, Organization and Comparative Genomics.

    PubMed

    Laing, R; Martinelli, A; Tracey, A; Holroyd, N; Gilleard, J S; Cotton, J A

    2016-01-01

    One of the first genome sequencing projects for a parasitic nematode was that for Haemonchus contortus. The open access data from the Wellcome Trust Sanger Institute provided a valuable early resource for the research community, particularly for the identification of specific genes and genetic markers. Later, a second sequencing project was initiated by the University of Melbourne, and the two draft genome sequences for H. contortus were published back-to-back in 2013. There is a pressing need for long-range genomic information for genetic mapping, population genetics and functional genomic studies, so we are continuing to improve the Wellcome Trust Sanger Institute assembly to provide a finished reference genome for H. contortus. This review describes this process, compares the H. contortus genome assemblies with draft genomes from other members of the strongylid group and discusses future directions for parasite genomics using the H. contortus model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Visualizing Genomic Annotations with the UCSC Genome Browser.

    PubMed

    Hung, Jui-Hung; Weng, Zhiping

    2016-11-01

    Genomic data and annotations are rapidly accumulating in databases such as the UCSC Genome Browser, NCBI, and Ensembl. Given the massive scale of these genomic databases, it is important to be able to easily retrieve known data and annotations of a specified genomic locus. For example, for a newly identified cis-regulatory element bound by a transcription factor, questions that immediately come to mind include whether the element is near a transcriptional start site and, if so, the name of the corresponding gene, and whether the histones or DNA at the locus are modified. The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. This protocol describes how to use the UCSC Genome Browser to visualize selected tracks at specified genomic regions, download the data and annotations for further analysis, and retrieve multiple sequence alignments and their conservation scores.

  3. Center for Cancer Genomics | Office of Cancer Genomics

    Cancer.gov

    The Center for Cancer Genomics (CCG) was established to unify the National Cancer Institute's activities in cancer genomics, with the goal of advancing genomics research and translating findings into the clinic to improve the precise diagnosis and treatment of cancers. In addition to promoting genomic sequencing approaches, CCG aims to accelerate structural, functional and computational research to explore cancer mechanisms, discover new cancer targets, and develop new therapeutics.

  4. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

    PubMed

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur, amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

  5. Genomic Advances to Improve Biomass for Biofuels (Genomics and Bioenergy)

    SciTech Connect

    Rokhsar, Daniel

    2008-02-11

    Lawrence Berkeley National Lab bioscientist Daniel Rokhsar discusses genomic advances to improve biomass for biofuels. He presented his talk Feb. 11, 2008 in Berkeley, California as part of Berkeley Lab's community lecture series. Rokhsar works with the U.S. Department of Energy's Joint Genome Institute and Berkeley Lab's Genomics Division.

  6. Dynamic evolution of genomes and the concept of genome space.

    PubMed

    Bellgard, M I; Itoh, T; Watanabe, H; Imanishi, T; Gojobori, T

    1999-05-18

    A new era in the elucidation of genome evolution has been heralded with the availability of numerous genome sequences. With these data, it has been possible to study evolutionary processes at a greater level of detail in order to characterize features such as gene shuffling, genome rearrangements, base bias composition, and horizontal gene transfer. In this paper, we discuss the evolutionary implications of significant rearrangements within genomes as well as characteristic genomic regions that have been conserved across genomes. This is based on our analysis of orthologous and paralogous genes. We argue that genome plasticity has most likely contributed substantially to the dynamic evolution of genomes. We also describe the characteristic mosaic features of an archaea genome that is comprised of both bacterial and eukaryal elements. Here we investigate base compositional differences as well as the similarity of this species' genes to either bacteria or eukarya. We conclude that these features can be largely explained by the mechanism of horizontal gene transfer. Finally, we introduce the concept of genome space which is defined as the entire set of genomes of all living organisms. We explain its usefulness to describe as well as to gain deeper insight into the general features of the dynamic genomic evolutionary process.

  7. The tomato genome: implications for plant breeding, genomics and evolution

    PubMed Central

    2012-01-01

    The genome sequence of tomato (Solanum lycopersicum), one of the most important vegetable crops, has recently been decoded. We address implications of the tomato genome for plant breeding, genomics and evolutionary studies, and its potential to fuel future crop biology research. PMID:22943138

  8. The Brachypodium genome sequence: a resource for oat genomics research

    USDA-ARS?s Scientific Manuscript database

    Oat (Avena sativa) is an important cereal crop used as both an animal feed and for human consumption. Genetic and genomic research on oat is hindered because it is hexaploid and possesses a large (13 Gb) genome. Diploid Avena relatives have been employed for genetic and genomic studies, but only mod...

  9. Genomic Data Commons launches - TCGA

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  10. On genomics, kin, and privacy

    PubMed Central

    Telenti, Amalio; Ayday, Erman; Hubaux, Jean Pierre

    2014-01-01

    The storage of greater numbers of exomes or genomes raises the question of loss of privacy for the individual and for families if genomic data are not properly protected. Access to genome data may result from a personal decision to disclose, or from gaps in protection. In either case, revealing genome data has consequences beyond the individual, as it compromises the privacy of family members. Increasing availability of genome data linked or linkable to metadata through online social networks and services adds one additional layer of complexity to the protection of genome privacy.  The field of computer science and information technology offers solutions to secure genomic data so that individuals, medical personnel or researchers can access only the subset of genomic information required for healthcare or dedicated studies. PMID:25254097

  11. Sixty years of genome biology

    PubMed Central

    2013-01-01

    Sixty years after Watson and Crick published the double helix model of DNA's structure, thirteen members of Genome Biology's Editorial Board select key advances in the field of genome biology subsequent to that discovery. PMID:23651518

  12. Better chocolate through genomics

    USDA-ARS?s Scientific Manuscript database

    Theobroma cacao, the cacao or chocolate tree, is a tropical understory tree whose seeds are used to make chocolate. And like any important crop, cacao is the subject of much research. On September 15, 2010, scientists publicly released a preliminary sequence of the cacao genome--which contains all o...

  13. The Nostoc punctiforme Genome

    SciTech Connect

    John C. Meeks

    2001-12-31

    Nostoc punctiforme is a filamentous cyanobacterium with extensive phenotypic characteristics and a relatively large genome, approaching 10 Mb. The phenotypic characteristics include a photoautotrophic, diazotrophic mode of growth, but N. punctiforme is also facultatively heterotrophic; its vegetative cells have multiple development alternatives, including terminal differentiation into nitrogen-fixing heterocysts and transient differentiation into spore-like akinetes or motile filaments called hormogonia; and N. punctiforme has broad symbiotic competence with fungi and terrestrial plants, including bryophytes, gymnosperms and an angiosperm. The shotgun-sequencing phase of the N. punctiforme strain ATCC 29133 genome has been completed by the Joint Genome Institute. Annotation of an 8.9 Mb database yielded 7432 open reading frames, 45% of which encode proteins with known or probable known function and 29% of which are unique to N. punctiforme. Comparative analysis of the sequence indicates a genome that is highly plastic and in a state of flux, with numerous insertion sequences and multilocus repeats, as well as genes encoding transposases and DNA modification enzymes. The sequence also reveals the presence of genes encoding putative proteins that collectively define almost all characteristics of cyanobacteria as a group. N. punctiforme has an extensive potential to sense and respond to environmental signals as reflected by the presence of more than 400 genes encoding sensor protein kinases, response regulators and other transcriptional factors. The signal transduction systems and any of the large number of unique genes may play essential roles in the cell differentiation and symbiotic interaction properties of N. punctiforme.

  14. The G4 Genome

    PubMed Central

    Maizels, Nancy; Gray, Lucas T.

    2013-01-01

    Recent experiments provide fascinating examples of how G4 DNA and G4 RNA structures—aka quadruplexes—may contribute to normal biology and to genomic pathologies. Quadruplexes are transient and therefore difficult to identify directly in living cells, which initially caused skepticism regarding not only their biological relevance but even their existence. There is now compelling evidence for functions of some G4 motifs and the corresponding quadruplexes in essential processes, including initiation of DNA replication, telomere maintenance, regulated recombination in immune evasion and the immune response, control of gene expression, and genetic and epigenetic instability. Recognition and resolution of quadruplex structures is therefore an essential component of genome biology. We propose that G4 motifs and structures that participate in key processes compose the G4 genome, analogous to the transcriptome, proteome, or metabolome. This is a new view of the genome, which sees DNA as not only a simple alphabet but also a more complex geography. The challenge for the future is to systematically identify the G4 motifs that form quadruplexes in living cells and the features that confer on specific G4 motifs the ability to function as structural elements. PMID:23637633

  15. [Genomic instability in atherosclerosis].

    PubMed

    Dzhokhadze, T A; Buadze, T Zh; Gaiozishvili, M N; Kakauridze, N G; Lezhava, T A

    2014-11-01

    A comparative study of the level of genomic instability, parameters of quantitative and structural mutations of chromosomes (aberration, aneuploidy, polyploidy) in lymphocyte cultures from patients with atherosclerosis of age 80 years and older (control group - 30-35 years old) was conducted. The possibility of correction of disturbed genomic indicators by peptide bioregulators - Livagen (Lys-Glu-Asp-Ala) and cobalt ions with separate application or in combination was also studied. Control was lymphocyte culture of two healthy respective age groups. It was also shown that patients with atherosclerosis exhibit high level of genomic instability in all studied parameters, regardless of age, which may suggest that there is marked increase in chromatin condensation in atherosclerosis. It was also shown that Livagen (characterized by modifying influence on chromatin) separately and in combination with cobalt ions, promotes normalization of altered genomic indicators of atherosclerosis in both age groups. The results show that Livagen separately and in combination with cobalt ions has impact on chromatin of patients with atherosclerosis. The identified protective action of Livagen proves its efficacy in prevention of atherosclerosis.

  16. Poster: the macaque genome.

    PubMed

    2007-04-13

    The rhesus macaque (Macaca mulatta) facilitates an extraordinary range of biomedical and basic research, and the publication of the genome only makes it a more powerful model for studies of human disease; moreover, the macaque's position relative to humans and chimpanzees affords the opportunity to learn about the processes that have shaped the last 25 million years of primate evolution. To allow users to explore these themes of the macaque genome, Science has created a special interactive version of the poster published in the print edition of the 13 April 2007 issue. The interactive version includes additional text and exploration, as well as embedded video featuring seven scientists discussing the importance of the macaque and its genome sequence in studies of biomedicine and evolution. We have also created an accompanying teaching resource, including a lesson plan aimed at teachers of advanced high school life science students, for exploring what a comparison of the macaque and human genomes can tell us about human biology and evolution. These items are free to all site visitors.

  17. The tomato genome

    USDA-ARS?s Scientific Manuscript database

    The tomato genome sequence was undertaken at a time when state-of-the-art sequencing methodologies were undergoing a transition to co-called next generation methodologies. The result was an international consortium undertaking a strategy merging both old and new approaches. Because biologists were...

  18. Ascaris suum draft genome.

    PubMed

    Jex, Aaron R; Liu, Shiping; Li, Bo; Young, Neil D; Hall, Ross S; Li, Yingrui; Yang, Linfeng; Zeng, Na; Xu, Xun; Xiong, Zijun; Chen, Fangyuan; Wu, Xuan; Zhang, Guojie; Fang, Xiaodong; Kang, Yi; Anderson, Garry A; Harris, Todd W; Campbell, Bronwyn E; Vlaminck, Johnny; Wang, Tao; Cantacessi, Cinzia; Schwarz, Erich M; Ranganathan, Shoba; Geldhof, Peter; Nejsum, Peter; Sternberg, Paul W; Yang, Huanming; Wang, Jun; Wang, Jian; Gasser, Robin B

    2011-10-26

    Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America. In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years. Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death. Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality. The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 megabase draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases.

  19. RIKEN mouse genome encyclopedia.

    PubMed

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  20. The genomics of LUCA.

    PubMed

    Mat, Wai-Kin; Xue, Hong; Wong, Jeffrey Tze-Fei

    2008-05-01

    To understand the nature and evolution of LUCA, or Last Universal Common Ancestor, the minimum genome of LUCA has been identified based on the genes common to the eight primitive Euryarchaea and Crenarchaea species Methanopyrus kandleri, Methanothermobacter thermautotrophicum, Methanococcus jannaschii, Pyrococcus abyssi, Pyrococcus furiosus, Pyrococcus horikoshii, Aeropyrum pernix and Pyrobaculum aerophilum, together with the methanogenesis genes of the primitive methanogens. The 424 protein encoding genes in the minimum LUCA genome exceed significantly the 150-340 genes estimated to be present in a minimal proteome compatible with life. Thus LUCA was not a minimal organism but the first modern organism equipped with a DNA genome and the universal genetic code. The hyperthermophilic, Methanopyrus-proximal LUCA is consistent with a Hot Cross Origin of life which proposes that early heterotrophic life forms in the cooler temperature zones invented methanogenesis and a DNA genome upon their adaptation to the hydrothermal vents, where life flourished massively on lithoautotrophy supported by carbon dioxide and hydrogen, thereby leading to the rise of LUCA.

  1. (Genomic variation in maize)

    SciTech Connect

    Rivin, C.J.

    1991-01-01

    These studies have sought to learn how different DNA sequences and sequence arrangements contribute to genome plasticity in maize. We describe quantitative variation among maize inbred lines for tandemly arrayed and dispersed repeated DNA sequences and gene families, and qualitative variation for sequences homologous to the Mutator family of transposons. The potential of these sequences to undergo unequal crossing over, non-allelic (ectopic) recombination and transposition makes them a source of genome instability. We have found examples of rapid genomic change involving these sequences in Fl hybrids, tissue culture cells and regenerated plants. We describe the repetitive portion of the maize genome as composed primarily of sequences that vary markedly in copy number among different genetic stocks. The most highly variable is the 185 bp repeat associated with the heterochromatic chromosome knobs. Even in lines without visible knobs, there is a considerable quantity of tandemly arrayed repeats. We also found a high degree of variability for the tandemly arrayed 5S and ribosomal DNA repeats. While such variation might be expected as the result of unequal cross-over, we were surprised to find considerable variation among lower copy number, dispersed repeats as well. One highly repeated sequence that showed a complex tandem and dispersed arrangement stood out as showing no detectable variability among the maize lines. In striking contrast to the variability seen between the inbred stocks, individuals within a stock were indistinguishable with regard to their repeated sequence multiplicities.

  2. Dairy genomics in application

    USDA-ARS?s Scientific Manuscript database

    Implementation of genomic evaluation has caused profound changes in dairy cattle breeding. All young bulls bought by major artificial-insemination organizations now are selected based on these evaluation. Evaluation reliability can reach ~75% for yield traits, which is adequate for marketing semen o...

  3. Prenatal Whole Genome Sequencing

    PubMed Central

    Donley, Greer; Hull, Sara Chandros; Berkman, Benjamin E.

    2014-01-01

    With whole genome sequencing set to become the preferred method of prenatal screening, we need to pay more attention to the massive amount of information it will deliver to parents—and the fact that we don't yet understand what most of it means. PMID:22777977

  4. [RadGenomics project].

    PubMed

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu; Ban, Sadayuki; Michikawa, Yu-ichi; Saegusa, Kumiko; Sagara, Masasi; Tsuji, Atsushi; Noda, Shuhei; Ishikawa, Atsuko

    2002-08-01

    Human health conditions are largely determined by a complex interplay among genetic susceptibility, environmental factors, and aging. The RadGenomics project, which began in April 2001, promotes analysis of genes in response to irradiation, identification of their allelic variants in the human population, development of an effective procedure for quantitating individual radio-sensitivity, and analysis of the interrelationship between genetic heterogeneity and susceptibility to irradiation. Major groups of genes with which the project will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor suppressor genes, genes for programmed cell death, genes for signal transduction, and genes for oxidative processes. The outcome of the RadGenomics project should lead to improved protocols for personalized radiotherapy and reduce the possible side effects of treatment. The project will contribute to future research on the molecular mechanisms of radiation sensitivity in humans and stimulate the development of new high-throughput technology for a broader application of the biological and medical sciences. Identification of functionally important polymorphisms in the radiation response genes may determine individual differences in sensitivity to radiation exposure. The staff members, who are specialists in a variety of fields including genome science, radiation biology, medical science, molecular biology, and bioinformatics, have come to the RadGenomics project from various universities, companies, and research institutes.

  5. The human genome project.

    PubMed Central

    Olson, M V

    1993-01-01

    The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities in the present phase of the project. Advances in mapping techniques have allowed good progress toward the specific goals of the project and are also providing strong corollary benefits throughout biomedical research. Actual DNA sequencing of the genomes of the human and model organisms is still at an early stage. There has been little progress in the intrinsic efficiency of DNA-sequence determination. However, refinements in experimental protocols, instrumentation, and project management have made it practical to acquire sequence data on an enlarged scale. It is also increasingly apparent that DNA-sequence data provide a potent means of relating knowledge gained from the study of model organisms to human biology. There is as yet little indication that the infusion of technology from outside biology into the Human Genome Project has been effectively stimulated. Opportunities in this area remain large, posing substantial technical and policy challenges. PMID:8506271

  6. The Human Genome Program

    SciTech Connect

    Bell, G.I.

    1989-01-01

    Early in 1986, Charles DeLisi, then head of the Office of Health and Environmental Research at the Department of Energy (DOE) requested the Los Alamos National Laboratory (LANL) to organize a workshop charged with inquiring whether the state of technology and potential payoffs in biological knowledge and medical practice were such as to justify an organized program to map and sequence the human genome. The DOE's interest arose from its mission to assess the effects of radiation and other products of energy generation on human health in general and genetic material in particular. The workshop concluded that the technology was ripe, the benefits would be great, and a national program should be promptly initiated. Later committees, reporting to DOE, to the NIH, to the Office of Technology Assessment of the US Congress, and to the National Academy of Science have reviewed these issues more deliberately and come to the same conclusion. As a consequence, there has been established in the United States, a Human Genome Program, with funding largely from the NIH and the DOE, as indicated in Table 1. Moreover, the Program has attracted international interest, and Great Britain, France, Italy, and the Soviet Union, among other countries, have been reported to be starting human genome initiatives. Coordination of these programs, clearly in the interests of each, remains to be worked out, although an international Human Genome Organization (HUGO) is considering such coordination. 5 refs., 1 fig., 2 tabs.

  7. Genetics, genomics and fertility

    USDA-ARS?s Scientific Manuscript database

    In order to enhance the sustainability of dairy businesses, new management tools are needed to increase the fertility of dairy cattle. Genomic selection has been successfully used by AI studs to screen potential sires and significantly decrease the generation interval of bulls. Buoyed by the success...

  8. Genomics in Cardiovascular Disease

    PubMed Central

    Roberts, Robert; Marian, A.J.; Dandona, Sonny; Stewart, Alexandre F.R.

    2013-01-01

    A paradigm shift towards biology occurred in the 1990’s subsequently catalyzed by the sequencing of the human genome in 2000. The cost of DNA sequencing has gone from millions to thousands of dollars with sequencing of one’s entire genome costing only $1,000. Rapid DNA sequencing is being embraced for single gene disorders, particularly for sporadic cases and those from small families. Transmission of lethal genes such as associated with Huntington’s disease can, through in-vitro fertilization, avoid passing it on to one’s offspring. DNA sequencing will meet the challenge of elucidating the genetic predisposition for common polygenic diseases, especially in determining the function of the novel common genetic risk variants and identifying the rare variants, which may also partially ascertain the source of the missing heritability. The challenge for DNA sequencing remains great, despite human genome sequences being 99.5% identical, the 3 million single nucleotide polymorphisms (SNPs) responsible for most of the unique features add up to 60 new mutations per person which, for 7 billion people, is 420 billion mutations. It is claimed that DNA sequencing has increased 10,000 fold while information storage and retrieval only 16 fold. The physician and health user will be challenged by the convergence of two major trends, whole genome sequencing and the storage/retrieval and integration of the data. PMID:23524054

  9. Genomic imprinting: parental influence on the genome.

    PubMed

    Reik, W; Walter, J

    2001-01-01

    Genomic imprinting affects several dozen mammalian genes and results in the expression of those genes from only one of the two parental chromosomes. This is brought about by epigenetic instructions--imprints--that are laid down in the parental germ cells. Imprinting is a particularly important genetic mechanism in mammals, and is thought to influence the transfer of nutrients to the fetus and the newborn from the mother. Consistent with this view is the fact that imprinted genes tend to affect growth in the womb and behaviour after birth. Aberrant imprinting disturbs development and is the cause of various disease syndromes. The study of imprinting also provides new insights into epigenetic gene modification during development.

  10. Statistical Methods in Integrative Genomics.

    PubMed

    Richardson, Sylvia; Tseng, George C; Sun, Wei

    2016-06-01

    Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions.

  11. Statistical Methods in Integrative Genomics

    PubMed Central

    Richardson, Sylvia; Tseng, George C.; Sun, Wei

    2016-01-01

    Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions. PMID:27482531

  12. TUTORIAL ON NETWORK GENOMICS.

    SciTech Connect

    Forst, C.

    2001-01-01

    With the ever-increasing genomic information pouring into the databases researchers start to look for pattern in genomes. Key questions are the identification of function. In the past function was mainly understood to be assigned to a single gene isolated from other cellular components or mechanisms. Sequence comparison fo single genes and their products (proteins) as well as of intergenic space are a consequence of a well established one-gene one-function interpretation. prediction of function solely by sequence similarity searches are powerful techniques that initiated the advent of bioinformatics and computational biology. Seminal work on sequence alignment by Temple Smith and Michael Waterman [33] and sequence searches with the BLAST algorithm by Altschul et al. [2] provide essential methods for sequence based determination of function. Similar outstanding contributions to determination of function have been archived in the area of structure prediction, molecular modeling and molecular dynamics. Techniques covering ab initio and homology modeling up to biophysical interpretation of long-run molecular dynamics simulations are mentioned ehre. With the ever-increasing number of information of different genetic/genomic origin, new aspect are looked for that deviate from the single gene at a time method. Especially with the identification of surprisingly few human genes the emerging perception in the scientific community that the concept of function has to be extended to include other sequence based as well as non-sequenced based information. A schema of determination of function by different concepts is shown in Figure 1. The tutorial is comprised of the following sections: The first two sections discuss the differences between genomic and non-genomic based context information, section three will cover combined methods. Finally, section four lsits web-resources and databases. All presented approaches extensively employ comparative methods.

  13. Plant functional genomics

    NASA Astrophysics Data System (ADS)

    Holtorf, Hauke; Guitton, Marie-Christine; Reski, Ralf

    2002-04-01

    Functional genome analysis of plants has entered the high-throughput stage. The complete genome information from key species such as Arabidopsis thaliana and rice is now available and will further boost the application of a range of new technologies to functional plant gene analysis. To broadly assign functions to unknown genes, different fast and multiparallel approaches are currently used and developed. These new technologies are based on known methods but are adapted and improved to accommodate for comprehensive, large-scale gene analysis, i.e. such techniques are novel in the sense that their design allows researchers to analyse many genes at the same time and at an unprecedented pace. Such methods allow analysis of the different constituents of the cell that help to deduce gene function, namely the transcripts, proteins and metabolites. Similarly the phenotypic variations of entire mutant collections can now be analysed in a much faster and more efficient way than before. The different methodologies have developed to form their own fields within the functional genomics technological platform and are termed transcriptomics, proteomics, metabolomics and phenomics. Gene function, however, cannot solely be inferred by using only one such approach. Rather, it is only by bringing together all the information collected by different functional genomic tools that one will be able to unequivocally assign functions to unknown plant genes. This review focuses on current technical developments and their impact on the field of plant functional genomics. The lower plant Physcomitrella is introduced as a new model system for gene function analysis, owing to its high rate of homologous recombination.

  14. Towards Sequencing Cotton (Gossypium) Genomes

    USDA-ARS?s Scientific Manuscript database

    Despite rapidly decreasing costs and innovative technologies, sequencing of angiosperm genomes is not yet undertaken lightly. Generating larger amounts of sequence data more quickly does not address the difficulties of sequencing and assembling complex genomes de novo. The cotton genomes represent a...

  15. Comprehensive genome sequencing of the liver cancer genome.

    PubMed

    Nakagawa, Hidewaki; Shibata, Tatsuhiro

    2013-11-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Recently, comprehensive whole genome and exome sequencing analyses for HCC revealed new cancer-associated genes and a variety of genomic alterations. In particular, frequent genetic alterations of the chromatin remodeling genes were observed, suggesting a new potential therapeutic target for HCC. Sequencing analysis has further identified the molecular complexities of multicentric lesions and intratumoral heterogeneity. Detailed analyses of the somatic substitution pattern of the cancer genome and the HBV virus genome integration sites by using whole-genome sequencing will elucidate the molecular basis and diverse etiological factors involved in liver cancer development.

  16. From human genome to cancer genome: The first decade

    PubMed Central

    Wheeler, David A.; Wang, Linghua

    2013-01-01

    The realization that cancer progression required the participation of cellular genes provided one of several key rationales, in 1986, for embarking on the human genome project. Only with a reference genome sequence could the full spectrum of somatic changes leading to cancer be understood. Since its completion in 2003, the human reference genome sequence has fulfilled its promise as a foundational tool to illuminate the pathogenesis of cancer. Herein, we review the key historical milestones in cancer genomics since the completion of the genome, and some of the novel discoveries that are shaping our current understanding of cancer. PMID:23817046

  17. Genome of Crocodilepox Virus

    PubMed Central

    Afonso, C. L.; Tulman, E. R.; Delhon, G.; Lu, Z.; Viljoen, G. J.; Wallace, D. B.; Kutish, G. F.; Rock, D. L.

    2006-01-01

    Here, we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (crocodilepox virus; CRV). The genome is 190,054 bp (62% G+C) and predicted to contain 173 genes encoding proteins of 53 to 1,941 amino acids. The central genomic region contains genes conserved and generally colinear with those of other chordopoxviruses (ChPVs). CRV is distinct, as the terminal 33-kbp (left) and 13-kbp (right) genomic regions are largely CRV specific, containing 48 unique genes which lack similarity to other poxvirus genes. Notably, CRV also contains 14 unique genes which disrupt ChPV gene colinearity within the central genomic region, including 7 genes encoding GyrB-like ATPase domains similar to those in cellular type IIA DNA topoisomerases, suggestive of novel ATP-dependent functions. The presence of 10 CRV proteins with similarity to components of cellular multisubunit E3 ubiquitin-protein ligase complexes, including 9 proteins containing F-box motifs and F-box-associated regions and a homologue of cellular anaphase-promoting complex subunit 11 (Apc11), suggests that modification of host ubiquitination pathways may be significant for CRV-host cell interaction. CRV encodes a novel complement of proteins potentially involved in DNA replication, including a NAD+-dependent DNA ligase and a protein with similarity to both vaccinia virus F16L and prokaryotic serine site-specific resolvase-invertases. CRV lacks genes encoding proteins for nucleotide metabolism. CRV shares notable genomic similarities with molluscum contagiosum virus, including genes found only in these two viruses. Phylogenetic analysis indicates that CRV is quite distinct from other ChPVs, representing a new genus within the subfamily Chordopoxvirinae, and it lacks recognizable homologues of most ChPV genes involved in virulence and host range, including those involving interferon response, intracellular signaling, and host immune response modulation. These data reveal

  18. Nongenetic functions of the genome.

    PubMed

    Bustin, Michael; Misteli, Tom

    2016-05-06

    The primary function of the genome is to store, propagate, and express the genetic information that gives rise to a cell's architectural and functional machinery. However, the genome is also a major structural component of the cell. Besides its genetic roles, the genome affects cellular functions by nongenetic means through its physical and structural properties, particularly by exerting mechanical forces and by serving as a scaffold for binding of cellular components. Major cellular processes affected by nongenetic functions of the genome include establishment of nuclear structure, signal transduction, mechanoresponses, cell migration, and vision in nocturnal animals. We discuss the concept, mechanisms, and implications of nongenetic functions of the genome.

  19. Genomics and the immune system.

    PubMed

    Pipkin, Matthew E; Monticelli, Silvia

    2008-05-01

    While the hereditary information encoded in the Watson-Crick base pairing of genomes is largely static within a given individual, access to this information is controlled by dynamic mechanisms. The human genome is pervasively transcribed, but the roles played by the majority of the non-protein-coding genome sequences are still largely unknown. In this review we focus on insights to gene transcriptional regulation by placing special emphasis on genome-wide approaches, and on how non-coding RNAs, which derive from global transcription of the genome, in turn control gene expression. We review recent progress in the field with highlights on the immune system.

  20. The perennial ryegrass GenomeZipper: targeted use of genome resources for comparative grass genomics.

    PubMed

    Pfeifer, Matthias; Martis, Mihaela; Asp, Torben; Mayer, Klaus F X; Lübberstedt, Thomas; Byrne, Stephen; Frei, Ursula; Studer, Bruno

    2013-02-01

    Whole-genome sequences established for model and major crop species constitute a key resource for advanced genomic research. For outbreeding forage and turf grass species like ryegrasses (Lolium spp.), such resources have yet to be developed. Here, we present a model of the perennial ryegrass (Lolium perenne) genome on the basis of conserved synteny to barley (Hordeum vulgare) and the model grass genome Brachypodium (Brachypodium distachyon) as well as rice (Oryza sativa) and sorghum (Sorghum bicolor). A transcriptome-based genetic linkage map of perennial ryegrass served as a scaffold to establish the chromosomal arrangement of syntenic genes from model grass species. This scaffold revealed a high degree of synteny and macrocollinearity and was then utilized to anchor a collection of perennial ryegrass genes in silico to their predicted genome positions. This resulted in the unambiguous assignment of 3,315 out of 8,876 previously unmapped genes to the respective chromosomes. In total, the GenomeZipper incorporates 4,035 conserved grass gene loci, which were used for the first genome-wide sequence divergence analysis between perennial ryegrass, barley, Brachypodium, rice, and sorghum. The perennial ryegrass GenomeZipper is an ordered, information-rich genome scaffold, facilitating map-based cloning and genome assembly in perennial ryegrass and closely related Poaceae species. It also represents a milestone in describing synteny between perennial ryegrass and fully sequenced model grass genomes, thereby increasing our understanding of genome organization and evolution in the most important temperate forage and turf grass species.

  1. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    PubMed

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so.

  2. Evolution of small prokaryotic genomes

    PubMed Central

    Martínez-Cano, David J.; Reyes-Prieto, Mariana; Martínez-Romero, Esperanza; Partida-Martínez, Laila P.; Latorre, Amparo; Moya, Andrés; Delaye, Luis

    2015-01-01

    As revealed by genome sequencing, the biology of prokaryotes with reduced genomes is strikingly diverse. These include free-living prokaryotes with ∼800 genes as well as endosymbiotic bacteria with as few as ∼140 genes. Comparative genomics is revealing the evolutionary mechanisms that led to these small genomes. In the case of free-living prokaryotes, natural selection directly favored genome reduction, while in the case of endosymbiotic prokaryotes neutral processes played a more prominent role. However, new experimental data suggest that selective processes may be at operation as well for endosymbiotic prokaryotes at least during the first stages of genome reduction. Endosymbiotic prokaryotes have evolved diverse strategies for living with reduced gene sets inside a host-defined medium. These include utilization of host-encoded functions (some of them coded by genes acquired by gene transfer from the endosymbiont and/or other bacteria); metabolic complementation between co-symbionts; and forming consortiums with other bacteria within the host. Recent genome sequencing projects of intracellular mutualistic bacteria showed that previously believed universal evolutionary trends like reduced G+C content and conservation of genome synteny are not always present in highly reduced genomes. Finally, the simplified molecular machinery of some of these organisms with small genomes may be used to aid in the design of artificial minimal cells. Here we review recent genomic discoveries of the biology of prokaryotes endowed with small gene sets and discuss the evolutionary mechanisms that have been proposed to explain their peculiar nature. PMID:25610432

  3. Sequencing technologies and genome sequencing.

    PubMed

    Pareek, Chandra Shekhar; Smoczynski, Rafal; Tretyn, Andrzej

    2011-11-01

    The high-throughput - next generation sequencing (HT-NGS) technologies are currently the hottest topic in the field of human and animals genomics researches, which can produce over 100 times more data compared to the most sophisticated capillary sequencers based on the Sanger method. With the ongoing developments of high throughput sequencing machines and advancement of modern bioinformatics tools at unprecedented pace, the target goal of sequencing individual genomes of living organism at a cost of $1,000 each is seemed to be realistically feasible in the near future. In the relatively short time frame since 2005, the HT-NGS technologies are revolutionizing the human and animal genome researches by analysis of chromatin immunoprecipitation coupled to DNA microarray (ChIP-chip) or sequencing (ChIP-seq), RNA sequencing (RNA-seq), whole genome genotyping, genome wide structural variation, de novo assembling and re-assembling of genome, mutation detection and carrier screening, detection of inherited disorders and complex human diseases, DNA library preparation, paired ends and genomic captures, sequencing of mitochondrial genome and personal genomics. In this review, we addressed the important features of HT-NGS like, first generation DNA sequencers, birth of HT-NGS, second generation HT-NGS platforms, third generation HT-NGS platforms: including single molecule Heliscope™, SMRT™ and RNAP sequencers, Nanopore, Archon Genomics X PRIZE foundation, comparison of second and third HT-NGS platforms, applications, advances and future perspectives of sequencing technologies on human and animal genome research.

  4. Informational laws of genome structures

    PubMed Central

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-01-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined. PMID:27354155

  5. Evolution of small prokaryotic genomes.

    PubMed

    Martínez-Cano, David J; Reyes-Prieto, Mariana; Martínez-Romero, Esperanza; Partida-Martínez, Laila P; Latorre, Amparo; Moya, Andrés; Delaye, Luis

    2014-01-01

    As revealed by genome sequencing, the biology of prokaryotes with reduced genomes is strikingly diverse. These include free-living prokaryotes with ∼800 genes as well as endosymbiotic bacteria with as few as ∼140 genes. Comparative genomics is revealing the evolutionary mechanisms that led to these small genomes. In the case of free-living prokaryotes, natural selection directly favored genome reduction, while in the case of endosymbiotic prokaryotes neutral processes played a more prominent role. However, new experimental data suggest that selective processes may be at operation as well for endosymbiotic prokaryotes at least during the first stages of genome reduction. Endosymbiotic prokaryotes have evolved diverse strategies for living with reduced gene sets inside a host-defined medium. These include utilization of host-encoded functions (some of them coded by genes acquired by gene transfer from the endosymbiont and/or other bacteria); metabolic complementation between co-symbionts; and forming consortiums with other bacteria within the host. Recent genome sequencing projects of intracellular mutualistic bacteria showed that previously believed universal evolutionary trends like reduced G+C content and conservation of genome synteny are not always present in highly reduced genomes. Finally, the simplified molecular machinery of some of these organisms with small genomes may be used to aid in the design of artificial minimal cells. Here we review recent genomic discoveries of the biology of prokaryotes endowed with small gene sets and discuss the evolutionary mechanisms that have been proposed to explain their peculiar nature.

  6. Advances in plant chromosome genomics.

    PubMed

    Doležel, Jaroslav; Vrána, Jan; Cápal, Petr; Kubaláková, Marie; Burešová, Veronika; Simková, Hana

    2014-01-01

    Next generation sequencing (NGS) is revolutionizing genomics and is providing novel insights into genome organization, evolution and function. The number of plant genomes targeted for sequencing is rising. For the moment, however, the acquisition of full genome sequences in large genome species remains difficult, largely because the short reads produced by NGS platforms are inadequate to cope with repeat-rich DNA, which forms a large part of these genomes. The problem of sequence redundancy is compounded in polyploids, which dominate the plant kingdom. An approach to overcoming some of these difficulties is to reduce the full nuclear genome to its individual chromosomes using flow-sorting. The DNA acquired in this way has proven to be suitable for many applications, including PCR-based physical mapping, in situ hybridization, forming DNA arrays, the development of DNA markers, the construction of BAC libraries and positional cloning. Coupling chromosome sorting with NGS offers opportunities for the study of genome organization at the single chromosomal level, for comparative analyses between related species and for the validation of whole genome assemblies. Apart from the primary aim of reducing the complexity of the template, taking a chromosome-based approach enables independent teams to work in parallel, each tasked with the analysis of a different chromosome(s). Given that the number of plant species tractable for chromosome sorting is increasing, the likelihood is that chromosome genomics - the marriage of cytology and genomics - will make a significant contribution to the field of plant genetics.

  7. Informational laws of genome structures

    NASA Astrophysics Data System (ADS)

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-06-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined.

  8. Advances on Genome Duplication Distances

    NASA Astrophysics Data System (ADS)

    Gagnon, Yves; Savard, Olivier Tremblay; Bertrand, Denis; El-Mabrouk, Nadia

    Given a phylogenetic tree involving Whole Genome Duplication events, we contribute to the problem of computing the rearrangement distance on a branch of a tree linking a duplication node d to a speciation node or a leaf s. In the case of a genome G at s containing exactly two copies of each gene, the genome halving problem is to find a perfectly duplicated genome D at d minimizing the rearrangement distance with G. We generalize the existing exact linear-time algorithm for genome halving to the case of a genome G with missing gene copies. In the case of a known ancestral duplicated genome D, we develop a greedy approach for computing the distance between G and D that is shown time-efficient and very accurate for both the rearrangement and DCJ distances.

  9. Comparative genomics of Brassicaceae crops

    PubMed Central

    Sharma, Ashutosh; Li, Xiaonan; Lim, Yong Pyo

    2014-01-01

    The family Brassicaceae is one of the major groups of the plant kingdom and comprises diverse species of great economic, agronomic and scientific importance, including the model plant Arabidopsis. The sequencing of the Arabidopsis genome has revolutionized our knowledge in the field of plant biology and provides a foundation in genomics and comparative biology. Genomic resources have been utilized in Brassica for diversity analyses, construction of genetic maps and identification of agronomic traits. In Brassicaceae, comparative sequence analysis across the species has been utilized to understand genome structure, evolution and the detection of conserved genomic segments. In this review, we focus on the progress made in genetic resource development, genome sequencing and comparative mapping in Brassica and related species. The utilization of genomic resources and next-generation sequencing approaches in improvement of Brassica crops is also discussed. PMID:24987286

  10. Toward genome-enabled mycology.

    PubMed

    Hibbett, David S; Stajich, Jason E; Spatafora, Joseph W

    2013-01-01

    Genome-enabled mycology is a rapidly expanding field that is characterized by the pervasive use of genome-scale data and associated computational tools in all aspects of fungal biology. Genome-enabled mycology is integrative and often requires teams of researchers with diverse skills in organismal mycology, bioinformatics and molecular biology. This issue of Mycologia presents the first complete fungal genomes in the history of the journal, reflecting the ongoing transformation of mycology into a genome-enabled science. Here, we consider the prospects for genome-enabled mycology and the technical and social challenges that will need to be overcome to grow the database of complete fungal genomes and enable all fungal biologists to make use of the new data.

  11. Multiple genome rearrangement by reversals.

    PubMed

    Wu, Shiquan; Gu, Xun

    2002-01-01

    In this paper, we discuss a multiple genome rearrangement problem: Given a collection of genomes represented by permutations, we generate the collection from some fixed genome, e.g., the identity permutation, in a minimum number of signed reversals. It is NP-hard, so efficient heuristics is important for finding its optimal solution. We at first discuss how to generate two and three genomes from a fixed genome by polynomial algorithms for some special cases. Then based on the polynomial algorithms, we obtain some approximation algorithms for generating two and three genomes in general, respectively. Finally, we apply these approximation algorithms to design a new approximation algorithm for generating more genomes. We also show by some experimental examples that the algorithms are efficient.

  12. Viruses within animal genomes.

    PubMed

    De Brognier, A; Willems, L

    2016-04-01

    Viruses and their hosts can co-evolve to reach a fragile equilibrium that allows the survival of both. An excess of pathogenicity in the absence of a reservoir would be detrimental to virus survival. A significant proportion of all animal genomes has been shaped by the insertion of viruses that subsequently became 'fossilised'. Most endogenous viruses have lost the capacity to replicate via an infectious cycle and now replicate passively. The insertion of endogenous viruses has contributed to the evolution of animal genomes, for example in the reproductive biology of mammals. However, spontaneous viral integration still occasionally occurs in a number of virus-host systems. This constitutes a potential risk to host survival but also provides an opportunity for diversification and evolution.

  13. Manipulating the Plasmodium genome.

    PubMed

    Carvalho, Teresa Gil; Ménard, Robert

    2005-01-01

    Genome manipulation, the primary tool for assigning function to sequence, will be essential for understanding Plasmodium biology and malaria pathogenesis in molecular terms. The first success in transfecting Plasmodium was reported almost ten years ago. Gene-targeting studies have since flourished, as Plasmodium is haploid and integrates DNA only by homologous recombination. These studies have shed new light on the function of many proteins, including vaccine candidates and drug resistance factors. However, many essential proteins, including those involved in parasite invasion of erythrocytes, cannot be characterized in the absence of conditional mutagenesis. Proteins also cannot be identified on a functional basis as random DNA integration has not been achieved. We overview here the ways in which the Plasmodium genome can be manipulated. We also point to the tools that should be established if our goal is to address parasite infectivity in a systematic way and to conduct refined structure-function analysis of selected products.

  14. Bacterial genome annotation.

    PubMed

    Beckloff, Nicholas; Starkenburg, Shawn; Freitas, Tracey; Chain, Patrick

    2012-01-01

    Annotation of prokaryotic sequences can be separated into structural and functional annotation. Structural annotation is dependent on algorithmic interrogation of experimental evidence to discover the physical characteristics of a gene. This is done in an effort to construct accurate gene models, so understanding function or evolution of genes among organisms is not impeded. Functional annotation is dependent on sequence similarity to other known genes or proteins in an effort to assess the function of the gene. Combining structural and functional annotation across genomes in a comparative manner promotes higher levels of accurate annotation as well as an advanced understanding of genome evolution. As the availability of bacterial sequences increases and annotation methods improve, the value of comparative annotation will increase.

  15. Big cat genomics.

    PubMed

    O'Brien, Stephen J; Johnson, Warren E

    2005-01-01

    Advances in population and quantitative genomics, aided by the computational algorithms that employ genetic theory and practice, are now being applied to biological questions that surround free-ranging species not traditionally suitable for genetic enquiry. Here we review how applications of molecular genetic tools have been used to describe the natural history, present status, and future disposition of wild cat species. Insight into phylogenetic hierarchy, demographic contractions, geographic population substructure, behavioral ecology, and infectious diseases have revealed strategies for survival and adaptation of these fascinating predators. Conservation, stabilization, and management of the big cats are important areas that derive benefit from the genome resources expanded and applied to highly successful species, imperiled by an expanding human population.

  16. [Genomics in medicine].

    PubMed

    Ruiz Esparza-Garrido, Ruth; Velázquez-Flores, Miguel Angel; Arenas-Aranda, Diego Julio; Salamanca-Gómez, Fabio

    2014-01-01

    The development of new fields of study in genetics, as the -omic sciences (transcriptomics, proteomics, metabolomics), has allowed the study of the regulation and expression of genomes. Therefore, nowadays it is possible to study global alterations--in the whole genome--and their effect at the protein and metabolic levels. Importantly, this new way of studying genetics has opened new areas of knowledge, and new cellular mechanisms that regulate the functioning of biological systems have been elucidated. In the clinical field, in the last years new molecular tools have been implemented. These tools are favorable to a better classification, diagnosis and prognosis of several human diseases. Additionally, in some cases best treatments, which improve the quality of life of patients, have been established. Due to the previous assertion, it is important to review and divulge changes in the study of genetics as a result of the development of the -omic sciences, which is the aim of this review.

  17. Genome size analyses of Pucciniales reveal the largest fungal genomes

    PubMed Central

    Tavares, Sílvia; Ramos, Ana Paula; Pires, Ana Sofia; Azinheira, Helena G.; Caldeirinha, Patrícia; Link, Tobias; Abranches, Rita; Silva, Maria do Céu; Voegele, Ralf T.; Loureiro, João; Talhinhas, Pedro

    2014-01-01

    Rust fungi (Basidiomycota, Pucciniales) are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 225.3 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi). In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp). Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94%). The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research. PMID:25206357

  18. Human Germline Genome Editing.

    PubMed

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  19. Microarray Genomic Systems Development

    DTIC Science & Technology

    2008-06-01

    D Canada Contract Report DRDC Suffield CR 2009-145 June 2008 V. Lam, M. Crichton , T. Dickinson Laing, and D.C. Mah Canada West Biosciences Inc...Genomic Systems Development V. Lam, M. Crichton , T. Dickinson Laing, and D.C. Mah Canada West Biosciences Inc. Canada West Biosciences Inc. 5429... Crichton , M.; Dickinson Laing, T.; Mah, D.C.; DRDC Suffield CR 2009- 145; Defence R&D Canada – Suffield; June 2008. Introduction: Conventional

  20. Automated Microfluidics for Genomics

    DTIC Science & Technology

    2001-10-25

    Abstract--The Genomation Laboratory at the University of Washington is developing an automated fluid handling system called " Acapella " to prepare...Photonic Systems, Inc. (Redmond, WA), an automated submicroliter fluid sample preparation system called ACAPELLA is being developed. Reactions such...technology include minimal residual disease quantification and sample preparation for DNA. Preliminary work on the ACAPELLA is presented in [4][5]. This

  1. [Synthesizing a human genome?

    PubMed

    Jordan, Bertrand

    2016-10-01

    The recently proposed « HGP-write » project aims to synthetize a full human genome and to introduce it into cells. This ambitious endeavour is fraught with financial and technical uncertainties and, if successful, would make « synthetic humans » a definite possibility even though this is not part of its announced goals. Accordingly, it has not been received with enthusiasm. © 2016 médecine/sciences – Inserm.

  2. Genomic landscape of liposarcoma

    PubMed Central

    Kanojia, Deepika; Nagata, Yasunobu; Garg, Manoj; Lee, Dhong Hyun; Sato, Aiko; Yoshida, Kenichi; Sato, Yusuke; Sanada, Masashi; Mayakonda, Anand; Bartenhagen, Christoph; Klein, Hans-Ulrich; Doan, Ngan B.; Said, Jonathan W.; Mohith, S.; Gunasekar, Swetha; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Myklebost, Ola; Yang, Henry; Dugas, Martin; Meza-Zepeda, Leonardo A.; Silberman, Allan W.; Forscher, Charles; Tyner, Jeffrey W.; Ogawa, Seishi; Koeffler, H. Phillip

    2015-01-01

    Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach. PMID:26643872

  3. Genomics of cellulosic biofuels.

    PubMed

    Rubin, Edward M

    2008-08-14

    The development of alternatives to fossil fuels as an energy source is an urgent global priority. Cellulosic biomass has the potential to contribute to meeting the demand for liquid fuel, but land-use requirements and process inefficiencies represent hurdles for large-scale deployment of biomass-to-biofuel technologies. Genomic information gathered from across the biosphere, including potential energy crops and microorganisms able to break down biomass, will be vital for improving the prospects of significant cellulosic biofuel production.

  4. Genome Wide Association Studies

    NASA Astrophysics Data System (ADS)

    Sebastiani, Paola; Solovieff, Nadia

    The availability of high throughput technology for parallel genotyping has opened the field of genetics to genome-wide association studies (GWAS). These studies generate massive amount of genetic data that challenge investigators with issues related to data management, statistical analysis of large data sets, visualization, and annotation of results. We will review the common approach to analysis of GWAS data and then discuss options to learn more from these data.

  5. Mapping the human genome

    SciTech Connect

    Annas, G.C.; Elias, S.

    1992-01-01

    This article is a review of the book Mapping the Human Genome: Using Law and Ethics as Guides, edited by George C. Annas and Sherman Elias. The book is a collection of essays on the subject of using ethics and laws as guides to justify human gene mapping. It addresses specific issues such problems related to eugenics, patents, insurance as well as broad issues such as the societal definitions of normality.

  6. Personalized Genomic Medicine with a Patchwork, Partially Owned Genome

    PubMed Central

    Mason, Christopher E.; Seringhaus, Michael R.; Sattler de Sousa e Brito, Clara

    2008-01-01

    “His book was known as the Book of Sand, because neither the book nor the sand have any beginning or end.” — Jorge Luis Borges The human genome is a three billion-letter recipe for the genesis of a human being, directing development from a single-celled embryo to the trillions of adult cells. Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to genomic medicine, aimed at detecting and understanding all genetic variations of the human genome that contribute to the manifestation and progression of disease. The overarching vision of genomic (or “personalized”) medicine is to custom-tailor each treatment for maximum effectiveness in an individual patient. Detecting the variation in a patient’s deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein structures is no longer an insurmountable hurdle. Today, the challenge for genomic medicine lies in contextualizing those myriad genetic variations in terms of their functional consequences for a person’s health and development throughout life and in terms of that patient’s susceptibility to disease and differential clinical responses to medication. Additionally, several recent developments have complicated our understanding of the nominal human genome and, thereby, altered the progression of genomic medicine. In this brief review, we shall focus on these developments and examine how they are changing our understanding of our genome. PMID:18449389

  7. Conditioned genome reconstruction: how to avoid choosing the conditioning genome.

    PubMed

    Spencer, Matthew; Bryant, David; Susko, Edward

    2007-02-01

    Genome phylogenies can be inferred from data on the presence and absence of genes across taxa. Logdet distances may be a good method, because they allow expected genome size to vary across the tree. Recently, Lake and Rivera proposed conditioned genome reconstruction (calculation of logdet distances using only those genes present in a conditioning genome) to deal with unobservable genes that are absent from every taxon of interest. We prove that their method can consistently estimate the topology for almost any choice of conditioning genome. Nevertheless, the choice of conditioning genome is important for small samples. For real bacterial genome data, different choices of conditioning genome can result in strong bootstrap support for different tree topologies. To overcome this problem, we developed supertree methods that combine information from all choices of conditioning genome. One of these methods, based on the BIONJ algorithm, performs well on simulated data and may have applications to other supertree problems. However, an analysis of 40 bacterial genomes using this method supports an incorrect clade of parasites. This is a common feature of model-based gene content methods and is due to parallel gene loss.

  8. Genomics Portals: integrative web-platform for mining genomics data

    PubMed Central

    2010-01-01

    Background A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Results Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis. Conclusion The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org. PMID:20070909

  9. Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine.

    PubMed

    Elsik, Christine G; Tayal, Aditi; Diesh, Colin M; Unni, Deepak R; Emery, Marianne L; Nguyen, Hung N; Hagen, Darren E

    2016-01-04

    We report an update of the Hymenoptera Genome Database (HGD) (http://HymenopteraGenome.org), a model organism database for insect species of the order Hymenoptera (ants, bees and wasps). HGD maintains genomic data for 9 bee species, 10 ant species and 1 wasp, including the versions of genome and annotation data sets published by the genome sequencing consortiums and those provided by NCBI. A new data-mining warehouse, HymenopteraMine, based on the InterMine data warehousing system, integrates the genome data with data from external sources and facilitates cross-species analyses based on orthology. New genome browsers and annotation tools based on JBrowse/WebApollo provide easy genome navigation, and viewing of high throughput sequence data sets and can be used for collaborative genome annotation. All of the genomes and annotation data sets are combined into a single BLAST server that allows users to select and combine sequence data sets to search. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. The canine genome.

    PubMed

    Ostrander, Elaine A; Wayne, Robert K

    2005-12-01

    The dog has emerged as a premier species for the study of morphology, behavior, and disease. The recent availability of a high-quality draft sequence lifts the dog system to a new threshold. We provide a primer to use the dog genome by first focusing on its evolutionary history. We overview the relationship of dogs to wild canids and discuss their origin and domestication. Dogs clearly originated from a substantial number of gray wolves and dog breeds define distinct genetic units that can be divided into at least four hierarchical groupings. We review evidence showing that dogs have high levels of linkage disequilibrium. Consequently, given that dog breeds express specific phenotypic traits and vary in behavior and the incidence of genetic disease, genomic-wide scans for linkage disequilibrium may allow the discovery of genes influencing breed-specific characteristics. Finally, we review studies that have utilized the dog to understand the genetic underpinning of several traits, and we summarize genomic resources that can be used to advance such studies. We suggest that given these resources and the unique characteristics of breeds, that the dog is a uniquely valuable resource for studying the genetic basis of complex traits.

  11. Mapping the human genome

    SciTech Connect

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  12. Cancer Genome Landscapes

    PubMed Central

    Vogelstein, Bert; Papadopoulos, Nickolas; Velculescu, Victor E.; Zhou, Shibin; Diaz, Luis A.; Kinzler, Kenneth W.

    2013-01-01

    Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality. PMID:23539594

  13. Family genome browser: visualizing genomes with pedigree information.

    PubMed

    Juan, Liran; Liu, Yongzhuang; Wang, Yongtian; Teng, Mingxiang; Zang, Tianyi; Wang, Yadong

    2015-07-15

    Families with inherited diseases are widely used in Mendelian/complex disease studies. Owing to the advances in high-throughput sequencing technologies, family genome sequencing becomes more and more prevalent. Visualizing family genomes can greatly facilitate human genetics studies and personalized medicine. However, due to the complex genetic relationships and high similarities among genomes of consanguineous family members, family genomes are difficult to be visualized in traditional genome visualization framework. How to visualize the family genome variants and their functions with integrated pedigree information remains a critical challenge. We developed the Family Genome Browser (FGB) to provide comprehensive analysis and visualization for family genomes. The FGB can visualize family genomes in both individual level and variant level effectively, through integrating genome data with pedigree information. Family genome analysis, including determination of parental origin of the variants, detection of de novo mutations, identification of potential recombination events and identical-by-decent segments, etc., can be performed flexibly. Diverse annotations for the family genome variants, such as dbSNP memberships, linkage disequilibriums, genes, variant effects, potential phenotypes, etc., are illustrated as well. Moreover, the FGB can automatically search de novo mutations and compound heterozygous variants for a selected individual, and guide investigators to find high-risk genes with flexible navigation options. These features enable users to investigate and understand family genomes intuitively and systematically. The FGB is available at http://mlg.hit.edu.cn/FGB/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Genome of Horsepox Virus

    PubMed Central

    Tulman, E. R.; Delhon, G.; Afonso, C. L.; Lu, Z.; Zsak, L.; Sandybaev, N. T.; Kerembekova, U. Z.; Zaitsev, V. L.; Kutish, G. F.; Rock, D. L.

    2006-01-01

    Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. HSPV contained 236 open reading frames (ORFs) with similarity to those in other OPVs, with those in the central 100-kbp region most conserved relative to other OPVs. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-four HSPV ORFs likely represented fragments of 25 orthologous OPV genes, including in the central region the only known fragmented form of an OPV ribonucleotide reductase large subunit gene. In terminal genomic regions, HSPV lacked full-length homologues of genes variably fragmented in other VACV-like viruses but was unique in fragmentation of the homologue of VACV strain Copenhagen B6R, a gene intact in other known VACV-like viruses. Notably, HSPV contained in terminal genomic regions 17 kbp of OPV-like sequence absent in known VACV-like viruses, including fragments of genes intact in other OPVs and approximately 1.4 kb of sequence present only in cowpox virus (CPXV). HSPV also contained seven full-length genes fragmented or missing in other VACV-like viruses, including intact homologues of the CPXV strain GRI-90 D2L/I4R CrmB and D13L CD30-like tumor necrosis factor receptors, D3L/I3R and C1L ankyrin repeat proteins, B19R kelch-like protein, D7L BTB/POZ domain protein, and B22R variola virus B22R-like protein. These results indicated that HSPV contains unique genomic features likely contributing to a unique virulence/host range phenotype. They also indicated that while closely related to known VACV-like viruses, HSPV contains additional, potentially ancestral sequences absent in other VACV-like viruses. PMID:16940536

  15. Whole-genome sequencing for comparative genomics and de novo genome assembly.

    PubMed

    Benjak, Andrej; Sala, Claudia; Hartkoorn, Ruben C

    2015-01-01

    Next-generation sequencing technologies for whole-genome sequencing of mycobacteria are rapidly becoming an attractive alternative to more traditional sequencing methods. In particular this technology is proving useful for genome-wide identification of mutations in mycobacteria (comparative genomics) as well as for de novo assembly of whole genomes. Next-generation sequencing however generates a vast quantity of data that can only be transformed into a usable and comprehensible form using bioinformatics. Here we describe the methodology one would use to prepare libraries for whole-genome sequencing, and the basic bioinformatics to identify mutations in a genome following Illumina HiSeq or MiSeq sequencing, as well as de novo genome assembly following sequencing using Pacific Biosciences (PacBio).

  16. An Analysis of Adenovirus Genomes Using Whole Genome Software Tools

    PubMed Central

    Mahadevan, Padmanabhan

    2016-01-01

    The evolution of sequencing technology has lead to an enormous increase in the number of genomes that have been sequenced. This is especially true in the field of virus genomics. In order to extract meaningful biological information from these genomes, whole genome data mining software tools must be utilized. Hundreds of tools have been developed to analyze biological sequence data. However, only some of these tools are user-friendly to biologists. Several of these tools that have been successfully used to analyze adenovirus genomes are described here. These include Artemis, EMBOSS, pDRAW, zPicture, CoreGenes, GeneOrder, and PipMaker. These tools provide functionalities such as visualization, restriction enzyme analysis, alignment, and proteome comparisons that are extremely useful in the bioinformatics analysis of adenovirus genomes. PMID:28293072

  17. Translational genomics for plant breeding with the genome sequence explosion.

    PubMed

    Kang, Yang Jae; Lee, Taeyoung; Lee, Jayern; Shim, Sangrea; Jeong, Haneul; Satyawan, Dani; Kim, Moon Young; Lee, Suk-Ha

    2016-04-01

    The use of next-generation sequencers and advanced genotyping technologies has propelled the field of plant genomics in model crops and plants and enhanced the discovery of hidden bridges between genotypes and phenotypes. The newly generated reference sequences of unstudied minor plants can be annotated by the knowledge of model plants via translational genomics approaches. Here, we reviewed the strategies of translational genomics and suggested perspectives on the current databases of genomic resources and the database structures of translated information on the new genome. As a draft picture of phenotypic annotation, translational genomics on newly sequenced plants will provide valuable assistance for breeders and researchers who are interested in genetic studies. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. The UCSC Ebola Genome Portal

    PubMed Central

    Haeussler, Maximilian; Karolchik, Donna; Clawson, Hiram; Raney, Brian J; Rosenbloom, Kate R.; Fujita, Pauline A.; Hinrichs, Angie S.; Speir, Matthew L; Eisenhart, Chris; Zweig, Ann S.; Haussler, David; Kent, W. James

    2014-01-01

    Background: With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in the generation of much genomic data. Methods: In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have created the University of California Santa Cruz (UCSC) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser web tool, which can be used to view the Ebola virus genome sequence from GenBank and nearly 30 annotation tracks generated by mapping external data to the reference sequence. Significant annotations include a multiple alignment comprising 102 Ebola genomes from the current outbreak, 56 from previous outbreaks, and 2 Marburg genomes as an outgroup; a gene track curated by NCBI; protein annotations curated by UniProt and antibody-binding epitopes curated by IEDB. We have extended the Genome Browser’s multiple alignment color-coding scheme to distinguish mutations resulting from non-synonymous coding changes, synonymous changes, or changes in untranslated regions. Discussion: Our Ebola Genome portal at http://genome.ucsc.edu/ebolaPortal/ links to the Ebola virus Genome Browser and an aggregate of useful information, including a collection of Ebola antibodies we are curating. PMID:25685613

  19. Efficient Breeding by Genomic Mating.

    PubMed

    Akdemir, Deniz; Sánchez, Julio I

    2016-01-01

    Selection in breeding programs can be done by using phenotypes (phenotypic selection), pedigree relationship (breeding value selection) or molecular markers (marker assisted selection or genomic selection). All these methods are based on truncation selection, focusing on the best performance of parents before mating. In this article we proposed an approach to breeding, named genomic mating, which focuses on mating instead of truncation selection. Genomic mating uses information in a similar fashion to genomic selection but includes information on complementation of parents to be mated. Following the efficiency frontier surface, genomic mating uses concepts of estimated breeding values, risk (usefulness) and coefficient of ancestry to optimize mating between parents. We used a genetic algorithm to find solutions to this optimization problem and the results from our simulations comparing genomic selection, phenotypic selection and the mating approach indicate that current approach for breeding complex traits is more favorable than phenotypic and genomic selection. Genomic mating is similar to genomic selection in terms of estimating marker effects, but in genomic mating the genetic information and the estimated marker effects are used to decide which genotypes should be crossed to obtain the next breeding population.

  20. Efficient Breeding by Genomic Mating

    PubMed Central

    Akdemir, Deniz; Sánchez, Julio I.

    2016-01-01

    Selection in breeding programs can be done by using phenotypes (phenotypic selection), pedigree relationship (breeding value selection) or molecular markers (marker assisted selection or genomic selection). All these methods are based on truncation selection, focusing on the best performance of parents before mating. In this article we proposed an approach to breeding, named genomic mating, which focuses on mating instead of truncation selection. Genomic mating uses information in a similar fashion to genomic selection but includes information on complementation of parents to be mated. Following the efficiency frontier surface, genomic mating uses concepts of estimated breeding values, risk (usefulness) and coefficient of ancestry to optimize mating between parents. We used a genetic algorithm to find solutions to this optimization problem and the results from our simulations comparing genomic selection, phenotypic selection and the mating approach indicate that current approach for breeding complex traits is more favorable than phenotypic and genomic selection. Genomic mating is similar to genomic selection in terms of estimating marker effects, but in genomic mating the genetic information and the estimated marker effects are used to decide which genotypes should be crossed to obtain the next breeding population. PMID:27965707

  1. Genome-wide association and genomic selection in animal breeding.

    PubMed

    Hayes, Ben; Goddard, Mike

    2010-11-01

    Results from genome-wide association studies in livestock, and humans, has lead to the conclusion that the effect of individual quantitative trait loci (QTL) on complex traits, such as yield, are likely to be small; therefore, a large number of QTL are necessary to explain genetic variation in these traits. Given this genetic architecture, gains from marker-assisted selection (MAS) programs using only a small number of DNA markers to trace a limited number of QTL is likely to be small. This has lead to the development of alternative technology for using the available dense single nucleotide polymorphism (SNP) information, called genomic selection. Genomic selection uses a genome-wide panel of dense markers so that all QTL are likely to be in linkage disequilibrium with at least one SNP. The genomic breeding values are predicted to be the sum of the effect of these SNPs across the entire genome. In dairy cattle breeding, the accuracy of genomic estimated breeding values (GEBV) that can be achieved and the fact that these are available early in life have lead to rapid adoption of the technology. Here, we discuss the design of experiments necessary to achieve accurate prediction of GEBV in future generations in terms of the number of markers necessary and the size of the reference population where marker effects are estimated. We also present a simple method for implementing genomic selection using a genomic relationship matrix. Future challenges discussed include using whole genome sequence data to improve the accuracy of genomic selection and management of inbreeding through genomic relationships.

  2. The coffee genome hub: a resource for coffee genomes

    PubMed Central

    Dereeper, Alexis; Bocs, Stéphanie; Rouard, Mathieu; Guignon, Valentin; Ravel, Sébastien; Tranchant-Dubreuil, Christine; Poncet, Valérie; Garsmeur, Olivier; Lashermes, Philippe; Droc, Gaëtan

    2015-01-01

    The whole genome sequence of Coffea canephora, the perennial diploid species known as Robusta, has been recently released. In the context of the C. canephora genome sequencing project and to support post-genomics efforts, we developed the Coffee Genome Hub (http://coffee-genome.org/), an integrative genome information system that allows centralized access to genomics and genetics data and analysis tools to facilitate translational and applied research in coffee. We provide the complete genome sequence of C. canephora along with gene structure, gene product information, metabolism, gene families, transcriptomics, syntenic blocks, genetic markers and genetic maps. The hub relies on generic software (e.g. GMOD tools) for easy querying, visualizing and downloading research data. It includes a Genome Browser enhanced by a Community Annotation System, enabling the improvement of automatic gene annotation through an annotation editor. In addition, the hub aims at developing interoperability among other existing South Green tools managing coffee data (phylogenomics resources, SNPs) and/or supporting data analyses with the Galaxy workflow manager. PMID:25392413

  3. Genomic Data Commons and Genomic Cloud Pilots - Google Hangout

    Cancer.gov

    Join us for a live, moderated discussion about two NCI efforts to expand access to cancer genomics data: the Genomic Data Commons and Genomic Cloud Pilots. NCI subject matters experts will include Louis M. Staudt, M.D., Ph.D., Director Center for Cancer Genomics, Warren Kibbe, Ph.D., Director, NCI Center for Biomedical Informatics and Information Technology, and moderated by Anthony Kerlavage, Ph.D., Chief, Cancer Informatics Branch, Center for Biomedical Informatics and Information Technology. We welcome your questions before and during the Hangout on Twitter using the hashtag #AskNCI.

  4. The coffee genome hub: a resource for coffee genomes.

    PubMed

    Dereeper, Alexis; Bocs, Stéphanie; Rouard, Mathieu; Guignon, Valentin; Ravel, Sébastien; Tranchant-Dubreuil, Christine; Poncet, Valérie; Garsmeur, Olivier; Lashermes, Philippe; Droc, Gaëtan

    2015-01-01

    The whole genome sequence of Coffea canephora, the perennial diploid species known as Robusta, has been recently released. In the context of the C. canephora genome sequencing project and to support post-genomics efforts, we developed the Coffee Genome Hub (http://coffee-genome.org/), an integrative genome information system that allows centralized access to genomics and genetics data and analysis tools to facilitate translational and applied research in coffee. We provide the complete genome sequence of C. canephora along with gene structure, gene product information, metabolism, gene families, transcriptomics, syntenic blocks, genetic markers and genetic maps. The hub relies on generic software (e.g. GMOD tools) for easy querying, visualizing and downloading research data. It includes a Genome Browser enhanced by a Community Annotation System, enabling the improvement of automatic gene annotation through an annotation editor. In addition, the hub aims at developing interoperability among other existing South Green tools managing coffee data (phylogenomics resources, SNPs) and/or supporting data analyses with the Galaxy workflow manager. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Shrinking genomes? Evidence from genome size variation in Crepis (Compositae).

    PubMed

    Enke, N; Fuchs, J; Gemeinholzer, B

    2011-01-01

    Large-scale surveys of genome size evolution in angiosperms show that the ancestral genome was most likely small, with a tendency towards an increase in DNA content during evolution. Due to polyploidisation and self-replicating DNA elements, angiosperm genomes were considered to have a 'one-way ticket to obesity' (Bennetzen & Kellogg 1997). New findings on how organisms can lose DNA challenged the hypotheses of unidirectional evolution of genome size. The present study is based on the classical work of Babcock (1947a) on karyotype evolution within Crepis and analyses karyotypic diversification within the genus in a phylogenetic context. Genome size of 21 Crepis species was estimated using flow cytometry. Additional data of 17 further species were taken from the literature. Within 30 diploid Crepis species there is a striking trend towards genome contraction. The direction of genome size evolution was analysed by reconstructing ancestral character states on a molecular phylogeny based on ITS sequence data. DNA content is correlated to distributional aspects as well as life form. Genome size is significantly higher in perennials than in annuals. Within sampled species, very small genomes are only present in Mediterranean or European species, whereas their Central and East Asian relatives have larger 1C values.

  6. Genome instability mechanisms and the structure of cancer genomes.

    PubMed

    Cassidy, Liam D; Venkitaraman, Ashok R

    2012-02-01

    Genomic instability is a hallmark of cancer cells, and arises from the aberrations that these cells exhibit in the normal biological mechanisms that repair and replicate the genome, or ensure its accurate segregation during cell division. Increasingly detailed descriptions of cancer genomes have begun to emerge from next-generation sequencing (NGS), providing snapshots of their nature and heterogeneity in different cancers at different stages in their evolution. Here, we attempt to extract from these sequencing studies insights into the role of genome instability mechanisms in carcinogenesis, and to identify challenges impeding further progress.

  7. The Anolis Lizard Genome: An Amniote Genome without Isochores?

    PubMed Central

    Costantini, Maria; Greif, Gonzalo; Alvarez-Valin, Fernando; Bernardi, Giorgio

    2016-01-01

    Two articles published 5 years ago concluded that the genome of the lizard Anolis carolinensis is an amniote genome without isochores. This claim was apparently contradicting previous results on the general presence of an isochore organization in all vertebrate genomes tested (including Anolis). In this investigation, we demonstrate that the Anolis genome is indeed heterogeneous in base composition, since its macrochromosomes comprise isochores mainly from the L2 and H1 families (a moderately GC-poor and a moderately GC-rich family, respectively), and since the majority of the sequenced microchromosomes consists of H1 isochores. These families are associated with different features of genome structure, including gene density and compositional correlations (e.g., GC3 vs flanking sequence GC and intron GC), as in the case of mammalian and avian genomes. Moreover, the assembled Anolis chromosomes have an enormous number of gaps, which could be due to sequencing problems in GC-rich regions of the genome. In conclusion, the Anolis genome is no exception to the general rule of an isochore organization in the genomes of vertebrates (and other eukaryotes). PMID:26992416

  8. Big Data: Astronomical or Genomical?

    PubMed

    Stephens, Zachary D; Lee, Skylar Y; Faghri, Faraz; Campbell, Roy H; Zhai, Chengxiang; Efron, Miles J; Iyer, Ravishankar; Schatz, Michael C; Sinha, Saurabh; Robinson, Gene E

    2015-07-01

    Genomics is a Big Data science and is going to get much bigger, very soon, but it is not known whether the needs of genomics will exceed other Big Data domains. Projecting to the year 2025, we compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Our estimates show that genomics is a "four-headed beast"--it is either on par with or the most demanding of the domains analyzed here in terms of data acquisition, storage, distribution, and analysis. We discuss aspects of new technologies that will need to be developed to rise up and meet the computational challenges that genomics poses for the near future. Now is the time for concerted, community-wide planning for the "genomical" challenges of the next decade.

  9. The Giardia genome project database.

    PubMed

    McArthur, A G; Morrison, H G; Nixon, J E; Passamaneck, N Q; Kim, U; Hinkle, G; Crocker, M K; Holder, M E; Farr, R; Reich, C I; Olsen, G E; Aley, S B; Adam, R D; Gillin, F D; Sogin, M L

    2000-08-15

    The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.

  10. The genome of Eucalyptus grandis.

    PubMed

    Myburg, Alexander A; Grattapaglia, Dario; Tuskan, Gerald A; Hellsten, Uffe; Hayes, Richard D; Grimwood, Jane; Jenkins, Jerry; Lindquist, Erika; Tice, Hope; Bauer, Diane; Goodstein, David M; Dubchak, Inna; Poliakov, Alexandre; Mizrachi, Eshchar; Kullan, Anand R K; Hussey, Steven G; Pinard, Desre; van der Merwe, Karen; Singh, Pooja; van Jaarsveld, Ida; Silva-Junior, Orzenil B; Togawa, Roberto C; Pappas, Marilia R; Faria, Danielle A; Sansaloni, Carolina P; Petroli, Cesar D; Yang, Xiaohan; Ranjan, Priya; Tschaplinski, Timothy J; Ye, Chu-Yu; Li, Ting; Sterck, Lieven; Vanneste, Kevin; Murat, Florent; Soler, Marçal; Clemente, Hélène San; Saidi, Naijib; Cassan-Wang, Hua; Dunand, Christophe; Hefer, Charles A; Bornberg-Bauer, Erich; Kersting, Anna R; Vining, Kelly; Amarasinghe, Vindhya; Ranik, Martin; Naithani, Sushma; Elser, Justin; Boyd, Alexander E; Liston, Aaron; Spatafora, Joseph W; Dharmwardhana, Palitha; Raja, Rajani; Sullivan, Christopher; Romanel, Elisson; Alves-Ferreira, Marcio; Külheim, Carsten; Foley, William; Carocha, Victor; Paiva, Jorge; Kudrna, David; Brommonschenkel, Sergio H; Pasquali, Giancarlo; Byrne, Margaret; Rigault, Philippe; Tibbits, Josquin; Spokevicius, Antanas; Jones, Rebecca C; Steane, Dorothy A; Vaillancourt, René E; Potts, Brad M; Joubert, Fourie; Barry, Kerrie; Pappas, Georgios J; Strauss, Steven H; Jaiswal, Pankaj; Grima-Pettenati, Jacqueline; Salse, Jérôme; Van de Peer, Yves; Rokhsar, Daniel S; Schmutz, Jeremy

    2014-06-19

    Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.

  11. Phage genomics: small is beautiful.

    PubMed

    Brüssow, Harald; Hendrix, Roger W

    2002-01-11

    The Age of Genomics dawned only gradually for bacteriophages. It was 1977 when the genome of phage phi X174 was published and 1983 when the "large" genome of phage lambda hit the streets. More recently, the pace has quickened, so that we now have over 100 complete phage genomes and can expect thousands in a very few years. These sequences have been marvelously informative for the biology of the individual phages, but with the advent of high volume sequencing technology, the real excitement for phage biology is that it is now possible to analyze the sequences together and thereby address--for the first time at whole genome resolution--a set of fundamental biological questions related to populations: What is the structure of the global phage population? What are its dynamics? How do phages evolve? This is Comparative Genomics with a capital "C".

  12. Genomics of Bacillus Species

    NASA Astrophysics Data System (ADS)

    Økstad, Ole Andreas; Kolstø, Anne-Brit

    Members of the genus Bacillus are rod-shaped spore-forming bacteria belonging to the Firmicutes, the low G+C gram-positive bacteria. The Bacillus genus was first described and classified by Ferdinand Cohn in Cohn (1872), and Bacillus subtilis was defined as the type species (Soule, 1932). Several Bacilli may be linked to opportunistic infections. However, pathogenicity among Bacillus spp. is mainly a feature of bacteria belonging to the Bacillus cereus group, including B. cereus, Bacillus anthracis, and Bacillus thuringiensis. Here we review the genomics of B. cereus group bacteria in relation to their roles as etiological agents of two food poisoning syndromes (emetic and diarrhoeal).

  13. Toward nanoscale genome sequencing.

    PubMed

    Ryan, Declan; Rahimi, Maryam; Lund, John; Mehta, Ranjana; Parviz, Babak A

    2007-09-01

    This article reports on the state-of-the-art technologies that sequence DNA using miniaturized devices. The article considers the miniaturization of existing technologies for sequencing DNA and the opportunities for cost reduction that 'on-chip' devices can deliver. The ability to construct nano-scale structures and perform measurements using novel nano-scale effects has provided new opportunities to identify nucleotides directly using physical, and not chemical, methods. The challenges that these technologies need to overcome to provide a US$1000-genome sequencing technology are also presented.

  14. Programs | Office of Cancer Genomics

    Cancer.gov

    OCG facilitates cancer genomics research through a series of highly-focused programs. These programs generate and disseminate genomic data for use by the cancer research community. OCG programs also promote advances in technology-based infrastructure and create valuable experimental reagents and tools. OCG programs encourage collaboration by interconnecting with other genomics and cancer projects in order to accelerate translation of findings into the clinic. Below are OCG’s current, completed, and initiated programs:

  15. Programs | Office of Cancer Genomics

    Cancer.gov

    OCG facilitates cancer genomics research through a series of highly-focused programs. These programs generate and disseminate genomic data for use by the cancer research community. OCG programs also promote advances in technology-based infrastructure and create valuable experimental reagents and tools. OCG programs encourage collaboration by interconnecting with other genomics and cancer projects in order to accelerate translation of findings into the clinic. Below are OCG’s current, completed, and initiated programs:

  16. Datasets for evolutionary comparative genomics

    PubMed Central

    Liberles, David A

    2005-01-01

    Many decisions about genome sequencing projects are directed by perceived gaps in the tree of life, or towards model organisms. With the goal of a better understanding of biology through the lens of evolution, however, there are additional genomes that are worth sequencing. One such rationale for whole-genome sequencing is discussed here, along with other important strategies for understanding the phenotypic divergence of species. PMID:16086856

  17. DNA clustering and genome complexity.

    PubMed

    Dios, Francisco; Barturen, Guillermo; Lebrón, Ricardo; Rueda, Antonio; Hackenberg, Michael; Oliver, José L

    2014-12-01

    Early global measures of genome complexity (power spectra, the analysis of fluctuations in DNA walks or compositional segmentation) uncovered a high degree of complexity in eukaryotic genome sequences. The main evolutionary mechanisms leading to increases in genome complexity (i.e. gene duplication and transposon proliferation) can all potentially produce increases in DNA clustering. To quantify such clustering and provide a genome-wide description of the formed clusters, we developed GenomeCluster, an algorithm able to detect clusters of whatever genome element identified by chromosome coordinates. We obtained a detailed description of clusters for ten categories of human genome elements, including functional (genes, exons, introns), regulatory (CpG islands, TFBSs, enhancers), variant (SNPs) and repeat (Alus, LINE1) elements, as well as DNase hypersensitivity sites. For each category, we located their clusters in the human genome, then quantifying cluster length and composition, and estimated the clustering level as the proportion of clustered genome elements. In average, we found a 27% of elements in clusters, although a considerable variation occurs among different categories. Genes form the lowest number of clusters, but these are the longest ones, both in bp and the average number of components, while the shortest clusters are formed by SNPs. Functional and regulatory elements (genes, CpG islands, TFBSs, enhancers) show the highest clustering level, as compared to DNase sites, repeats (Alus, LINE1) or SNPs. Many of the genome elements we analyzed are known to be composed of clusters of low-level entities. In addition, we found here that the clusters generated by GenomeCluster can be in turn clustered into high-level super-clusters. The observation of 'clusters-within-clusters' parallels the 'domains within domains' phenomenon previously detected through global statistical methods in eukaryotic sequences, and reveals a complex human genome landscape dominated

  18. Genomics Nursing Faculty Champion Initiative

    PubMed Central

    Jenkins, Jean; Calzone, Kathleen A.

    2016-01-01

    Nurse faculty are challenged to keep up with the emerging and fast-paced field of genomics and the mandate to prepare the nursing workforce to be able to translate genomic research advances into routine clinical care. Using Faculty Champions and other options, the initiative stimulated curriculum development and promoted genomics curriculum integration. The authors summarize this yearlong initiative for undergraduate and graduate nursing faculty. PMID:24300251

  19. Fungal Genome Sequencing and Bioenergy

    SciTech Connect

    Baker, Scott E.; Thykaer, Jette; Adney, William S.; Brettin, T.; Brockman, Fred J.; D'haeseleer, Patrik; Martinez, Antonio D.; Miller, R. M.; Rokhsar, Daniel S.; Schadt, Christopher W.; Torok, Tamas; Tuskan, Gerald; Bennett, Joan W.; Berka, Randy; Briggs, Steve; Heitman, Joseph; Taylor, John; Turgeon, Barbara G.; Werner-Washburne, Maggie; Himmel, Michael E.

    2008-09-30

    To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We advocate an ambitious, forward-looking phylogenetic-based genome sequencing program, designed to capture metabolic diversity within the fungal kingdom, thereby enhancing research into alternative bioenergy sources, bioremediation, and fungal-environment interactions.

  20. Evolutionary patterns in prokaryotic genomes.

    PubMed

    Rocha, Eduardo Pc

    2008-10-01

    Prokaryotic genomics is shifting towards comparative approaches to unravel how and why genomes change over time. Both phylogenetic and population genetics approaches are required to dissect the relative roles of selection and drift under these conditions. Lineages evolve adaptively by selection of changes in extant genomes and the way this occurs is being explored from a systemic and evolutionary perspective to understand how mutations relate with gene repertoire changes and how both are contextualized in cellular networks. Through an increased appreciation of genome dynamics in given ecological contexts, a more detailed picture of the genetic basis of prokaryotic evolution is emerging.

  1. Organizational heterogeneity of vertebrate genomes.

    PubMed

    Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

    2012-01-01

    Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  2. Phototroph genomics ten years on.

    PubMed

    Raymond, Jason; Swingley, Wesley D

    2008-07-01

    The onset of the genome era means different things to different people, but it is clear that this new age brings with it paradigm shifts that will forever affect biological research. Less clear is just how these shifts are changing the scope and scale of research. Are gigabases of raw data more useful than a single well-understood gene? Do we really need a full genome to understand the physiology of a single organism? The photosynthetic field is poised at the periphery of the bulk of genome sequencing work--understandably skewed toward health-related disciplines--and, as such, is subject to different motivations, limitations, and primary focus for each new genome. To understand some of these differences, we focus here on various indicators of the impact that genomics has had on the photosynthetic community, now a full decade since the publication of the first photosynthetic genome. Many useful indicators are indexed in public databases, providing pre- and post-genome sequence snapshots of changes in factors such as publication rate, number of proteins characterized, and sequenced genome coverage versus known diversity. As more genomes are sequenced and metagenomic projects begin to pour out billions of bases, it becomes crucial to understand how to harness this data in order to accumulate possible benefits and avoid possible pitfalls, especially as resources become increasingly directed toward natural environments governed by photosynthetic activity, ranging from hot springs to tropical forest ecosystems to the open ocean.

  3. Genome walking by Klenow polymerase.

    PubMed

    Volpicella, Mariateresa; Leoni, Claudia; Fanizza, Immacolata; Rius, Sebastian; Gallerani, Raffaele; Ceci, Luigi R

    2012-11-15

    Genome walking procedures are all based on a final polymerase chain reaction amplification, regardless of the strategy employed for the synthesis of the substrate molecule. Here we report a modification of an already established genome walking strategy in which a single-strand DNA substrate is obtained by primer extension driven by Klenow polymerase and which results suitable for the direct sequencing of complex eukaryotic genomes. The efficacy of the method is demonstrated by the identification of nucleotide sequences in the case of two gene families (chiA and P1) in the genomes of several maize species. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Comparative Microbial Genomics and Forensics.

    PubMed

    Massey, Steven E

    2016-08-01

    Forensic science concerns the application of scientific techniques to questions of a legal nature and may also be used to address questions of historical importance. Forensic techniques are often used in legal cases that involve crimes against persons or property, and they increasingly may involve cases of bioterrorism, crimes against nature, medical negligence, or tracing the origin of food- and crop-borne disease. Given the rapid advance of genome sequencing and comparative genomics techniques, we ask how these might be used to address cases of a forensic nature, focusing on the use of microbial genome sequence analysis. Such analyses rely on the increasingly large numbers of microbial genomes present in public databases, the ability of individual investigators to rapidly sequence whole microbial genomes, and an increasing depth of understanding of their evolution and function. Suggestions are made as to how comparative microbial genomics might be applied forensically and may represent possibilities for the future development of forensic techniques. A particular emphasis is on the nascent field of genomic epidemiology, which utilizes rapid whole-genome sequencing to identify the source and spread of infectious outbreaks. Also discussed is the application of comparative microbial genomics to the study of historical epidemics and deaths and how the approaches developed may also be applicable to more recent and actionable cases.

  5. Theory of prokaryotic genome evolution.

    PubMed

    Sela, Itamar; Wolf, Yuri I; Koonin, Eugene V

    2016-10-11

    Bacteria and archaea typically possess small genomes that are tightly packed with protein-coding genes. The compactness of prokaryotic genomes is commonly perceived as evidence of adaptive genome streamlining caused by strong purifying selection in large microbial populations. In such populations, even the small cost incurred by nonfunctional DNA because of extra energy and time expenditure is thought to be sufficient for this extra genetic material to be eliminated by selection. However, contrary to the predictions of this model, there exists a consistent, positive correlation between the strength of selection at the protein sequence level, measured as the ratio of nonsynonymous to synonymous substitution rates, and microbial genome size. Here, by fitting the genome size distributions in multiple groups of prokaryotes to predictions of mathematical models of population evolution, we show that only models in which acquisition of additional genes is, on average, slightly beneficial yield a good fit to genomic data. These results suggest that the number of genes in prokaryotic genomes reflects the equilibrium between the benefit of additional genes that diminishes as the genome grows and deletion bias (i.e., the rate of deletion of genetic material being slightly greater than the rate of acquisition). Thus, new genes acquired by microbial genomes, on average, appear to be adaptive. The tight spacing of protein-coding genes likely results from a combination of the deletion bias and purifying selection that efficiently eliminates nonfunctional, noncoding sequences.

  6. Genomic medicine and neurological disease.

    PubMed

    Boone, Philip M; Wiszniewski, Wojciech; Lupski, James R

    2011-07-01

    "Genomic medicine" refers to the diagnosis, optimized management, and treatment of disease--as well as screening, counseling, and disease gene identification--in the context of information provided by an individual patient's personal genome. Genomic medicine, to some extent synonymous with "personalized medicine," has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occur sporadically in association with a new mutation in a single gene. Heritability also contributes to other neurological conditions that appear to exhibit more complex genetics. In addition to discussing current knowledge in this field, we offer suggestions for maximizing the utility of genomic information in clinical practice as the field of genomic medicine unfolds.

  7. Genomic medicine and neurological disease

    PubMed Central

    Boone, Philip M.; Wiszniewski, Wojciech; Lupski, James R.

    2011-01-01

    Genomic medicine” refers to the diagnosis, optimized management, and treatment of disease—as well as screening, counseling, and disease gene identification—in the context of information provided by an individual patient’s personal genome. Genomic medicine, to some extent synonymous with “personalized medicine,” has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occur sporadically in association with a new mutation in a single gene. Heritability also contributes to other neurological conditions that appear to exhibit more complex genetics. In addition to discussing current knowledge in this field, we offer suggestions for maximizing the utility of genomic information in clinical practice as the field of genomic medicine unfolds. PMID:21594611

  8. Parsing of genomic graffiti

    SciTech Connect

    Tibbetts, C.; Golden, J. III; Torgersen, D.

    1996-12-31

    A focal point of modern biology is investigation of wide varieties of phenomena at the level of molecular genetics. The nucleotide sequences of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) define the ultimate resolution of this reductionist approach to understand the determinants of heritable traits. The structure and function of genes, their composite genomic organization, and their regulated expression have been studied in systems representing every class of organism. Many human diseases or pathogenic syndromes can be directly attributed to inherited defects in either the regulated expression, or the quality of the products of specific genes. Genetic determinants of susceptibility to infectious agents or environmental hazards are amply documented. Mapping and sequencing of the DNA molecules encoding human genes have provided powerful technology for pharmaceutical bioengineering and forensic investigations. From an alternative perspective, we may anticipate that voluminous archives of singular DNA sequences alone will not suffice to define and understand the functional determinants of genome organization, allelic diversity and evolutionary plasticity of living organisms. New insights will accumulate pertaining to human evolutionary origins and relationships of human biology to models based on other mammals. Investigators of population genetics and epidemiology now exploit the technology of molecular genetics to more powerfully probe variation within the human gene pool at the level of DNA sequences. 40 refs., 7 figs., 2 tabs.

  9. The Structural Genomics Consortium

    PubMed Central

    Jones, Molly Morgan; Castle-Clarke, Sophie; Brooker, Daniel; Nason, Edward; Huzair, Farah; Chataway, Joanna

    2014-01-01

    Abstract The Structural Genomics Consortium (SGC) supports drug discovery efforts through a unique, open access model of public-private collaboration. This study presents the results of an independent evaluation of the Structural Genomics Consortium, conducted by RAND Europe with the Institute on Governance. The evaluation aimed to establish the role of the SGC within the wider drug discovery and PPP landscape, assessing the merits of the SGC open access model relative to alternative models of funding R&D in this space, as well as the key trends and opportunities in the external environment that may impact on the future of the SGC. It also established the incentives and disincentives for investment, strengths and weaknesses of the SGC's model, and the opportunities and threats the SGC will face in the future. This enabled us to assess the most convincing arguments for funding the SGC at present; important trade-offs or limitations that should be addressed in moving towards the next funding phase; and whether funders are anticipating changes either to the SGC or the wider PPP landscape. Finally, we undertook a quantitative analysis to ascertain what judgements can be made about the SGC's past and current performance track record, before unpacking the role of the external environment and particular actors within the SGC in developing scenarios for the future. PMID:28560088

  10. Histones and genome integrity.

    PubMed

    Williamson, Wes D; Pinto, Ines

    2012-01-01

    Chromosomes undergo extensive structural rearrangements during the cell cycle, from the most open chromatin state required for DNA replication to the highest level of compaction and condensation essential for mitotic segregation of sister chromatids. It is now widely accepted that chromatin is a highly dynamic structure that participates in all DNA-related functions, including transcription, DNA replication, repair, and mitosis; hence, histones have emerged as key players in these cellular processes. We review here the studies that implicate histones in functions that affect the chromosome cycle, defined as the cellular processes involved in the maintenance, replication, and segregation of chromosomal DNA. Disruption of the chromosome cycle affects the integrity of the cellular genome, leading to aneuploidy, polyploidy or cell death. Histone stoichiometry, mutations that affect the structure of the nucleosome core particle, and mutations that affect the structure and/or modifications of the histone tails, all have a direct impact on the fidelity of chromosome transmission and the integrity of the genome.

  11. Finding the Alloy Genome

    NASA Astrophysics Data System (ADS)

    Hart, Gus L. W.; Nelson, Lance J.; Zhou, Fei; Ozolins, Vidvuds

    2012-10-01

    First-principles codes can nowadays provide hundreds of high-fidelity enthalpies on thousands of alloy systems with a modest investment of a few tens of millions of CPU hours. But a mere database of enthalpies provides only the starting point for uncovering the ``alloy genome.'' What one needs to fundamentally change alloy discovery and design are complete searches over candidate structures (not just hundreds of known experimental phases) and models that can be used to simulate both kinetics and thermodynamics. Despite more than a decade of effort by many groups, developing robust models for these simulations is still a human-time-intensive endeavor. Compressive sensing solves this problem in dramatic fashion by automatically extracting the ``sparse model'' of an alloy in only minutes. This new paradigm to model building has enabled a new framework that will uncover, automatically and in a general way across the periodic table, the important components of such models and reveal the underlying ``genome'' of alloy physics.

  12. Genomics of apicomplexan parasites.

    PubMed

    Swapna, Lakshmipuram Seshadri; Parkinson, John

    2017-02-22

    The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.

  13. Genomics of Myeloproliferative Neoplasms.

    PubMed

    Zoi, Katerina; Cross, Nicholas C P

    2017-03-20

    Myeloproliferative neoplasms (MPNs) are a group of related clonal hematologic disorders characterized by excess accumulation of one or more myeloid cell lineages and a tendency to transform to acute myeloid leukemia. Deregulated JAK2 signaling has emerged as the central phenotypic driver of BCR -ABL1-negative MPNs and a unifying therapeutic target. In addition, MPNs show unexpected layers of genetic complexity, with multiple abnormalities associated with disease progression, interactions between inherited factors and phenotype driver mutations, and effects related to the order in which mutations are acquired. Although morphology and clinical laboratory analysis continue to play an important role in defining these conditions, genomic analysis is providing a platform for better disease definition, more accurate diagnosis, direction of therapy, and refined prognostication. There is an emerging consensus with regard to many prognostic factors, but there is a clear need to synthesize genomic findings into robust, clinically actionable and widely accepted scoring systems as well as the need to standardize the laboratory methodologies that are used.

  14. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    PubMed

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy.

    PubMed

    Rittmann, Bruce E; Krajmalnik-Brown, Rosa; Halden, Rolf U

    2008-08-01

    Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.

  16. GenomeD3Plot: a library for rich, interactive visualizations of genomic data in web applications.

    PubMed

    Laird, Matthew R; Langille, Morgan G I; Brinkman, Fiona S L

    2015-10-15

    A simple static image of genomes and associated metadata is very limiting, as researchers expect rich, interactive tools similar to the web applications found in the post-Web 2.0 world. GenomeD3Plot is a light weight visualization library written in javascript using the D3 library. GenomeD3Plot provides a rich API to allow the rapid visualization of complex genomic data using a convenient standards based JSON configuration file. When integrated into existing web services GenomeD3Plot allows researchers to interact with data, dynamically alter the view, or even resize or reposition the visualization in their browser window. In addition GenomeD3Plot has built in functionality to export any resulting genome visualization in PNG or SVG format for easy inclusion in manuscripts or presentations. GenomeD3Plot is being utilized in the recently released Islandviewer 3 (www.pathogenomics.sfu.ca/islandviewer/) to visualize predicted genomic islands with other genome annotation data. However, its features enable it to be more widely applicable for dynamic visualization of genomic data in general. GenomeD3Plot is licensed under the GNU-GPL v3 at https://github.com/brinkmanlab/GenomeD3Plot/. brinkman@sfu.ca. © The Author 2015. Published by Oxford University Press.

  17. Human Genome Program Image Gallery (from genomics.energy.gov)

    DOE Data Explorer

    This collection contains approximately 240 images from the genome programs of DOE's Office of Science. The images are divided into galleries related to biofuels research, systems biology, and basic genomics. Each image has a title, a basic citation, and a credit or source. Most of the images are original graphics created by the Genome Management Information System (GMIS). GMIS images are recognizable by their credit line. Permission to use these graphics is not needed, but please credit the U.S. Department of Energy Genome Programs and provide the website http://genomics.energy.gov. Other images were provided by third parties and not created by the U.S. Department of Energy. Users must contact the person listed in the credit line before using those images. The high-resolution images can be downloaded.

  18. A Taste of Algal Genomes from the Joint Genome Institute

    SciTech Connect

    Kuo, Alan; Grigoriev, Igor

    2012-06-17

    Algae play profound roles in aquatic food chains and the carbon cycle, can impose health and economic costs through toxic blooms, provide models for the study of symbiosis, photosynthesis, and eukaryotic evolution, and are candidate sources for bio-fuels; all of these research areas are part of the mission of DOE's Joint Genome Institute (JGI). To date JGI has sequenced, assembled, annotated, and released to the public the genomes of 18 species and strains of algae, sampling almost all of the major clades of photosynthetic eukaryotes. With more algal genomes currently undergoing analysis, JGI continues its commitment to driving forward basic and applied algal science. Among these ongoing projects are the pan-genome of the dominant coccolithophore Emiliania huxleyi, the interrelationships between the 4 genomes in the nucleomorph-containing Bigelowiella natans and Guillardia theta, and the search for symbiosis genes of lichens.

  19. Neuropeptides of the beetle, Tenebrio molitor identified using MALDI-TOF mass spectrometry and deduced sequences from the Tribolium castaneum genome.

    PubMed

    Weaver, Robert J; Audsley, Neil

    2008-02-01

    Four neuropeptides were identified from the brain and corpora cardiaca-corpora allata (CC-CA) of the mealworm beetle Tenebrio molitor using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and information derived from the genome of the red flour beetle, Tribolium castaneum. Leucomyosuppressin (a FLRFamide), previously associated with cockroaches, but also subsequently identified from honey bee seen as a prominent peptide in both brain and CC-CA of T.molitor. A coding sequence for this peptide is found in the genome of T. castaneum. In addition, three FXPRLamides (pyrokinins), provisionally Tenmo-PK-1, Tenmo-PK-2 and Tenmo-PK-3 (HVVNFTPRLamide, SPPFAPRLamide, HL(I)SPFSPRLamide) were identified in both CC-CA and brain of T. molitor, again on the basis of predicted occurrence or similarity in T. castaneum. The sequence of Tenmo-PK-2 is the same as the PK-2 of the cockroach, Periplaneta americana. Other peptides readily predicted from the genome of T. castaneum include two AKH/HrTH peptides (Trica-AKH-1; pELNFSTDWamide and Trica-AKH-2; pELNFTPNWamide), the second of which is identical to Pyrap-AKH, an AKH-related peptide (Trica AKH-L; pEVTFSRDWPamide), two CRF-related diuretic factors (Trica-DH 37 and Trica-DH 47), the latter identical to Tenmo-DH 47, a putative antidiuretic factor (Trica-ADFb; LYDDGSYKPHVYGF-OH), two sulfakinin-like peptides (Trica-SK-1; pETSDDY(SO(3))GHLRFamide, and Trica SK-2; GEEPFDDYGHMRFamide), a potential allatostatin-C (Trica-AS; pESRYRQCYFNPISCF-OH), six allatostatin-B/myoinhibitory peptides (Trica-AST-B-1,2,3,4,5 & 6; DWNKDLHIWamide, GWNNLHEGWamide, AWQSLQSGWamide, NWGQFHGGWamide, SKWDNFRGSWamide, EPAWSNLGIWamide), an allatotropin-like peptide (Trica-ATL; GIEALKYHNMDLGTARGYamide), four 'CAPA'-related peptides (Trica-CAPA-1,2,3,4; NKLASVYALTPSLRVamide, RIGKMVSFPRIamide, PGANSGGMWFGPRLamide, SENFTPWAYIILNGEAPIIREVHYSPRLamide), proctolin (RYLPT), a potential SIFamide (Trica-SIFa; TYRKPPFNGSIFamide), an

  20. OryzaGenome: Genome Diversity Database of Wild Oryza Species.

    PubMed

    Ohyanagi, Hajime; Ebata, Toshinobu; Huang, Xuehui; Gong, Hao; Fujita, Masahiro; Mochizuki, Takako; Toyoda, Atsushi; Fujiyama, Asao; Kaminuma, Eli; Nakamura, Yasukazu; Feng, Qi; Wang, Zi-Xuan; Han, Bin; Kurata, Nori

    2016-01-01

    The species in the genus Oryza, encompassing nine genome types and 23 species, are a rich genetic resource and may have applications in deeper genomic analyses aiming to understand the evolution of plant genomes. With the advancement of next-generation sequencing (NGS) technology, a flood of Oryza species reference genomes and genomic variation information has become available in recent years. This genomic information, combined with the comprehensive phenotypic information that we are accumulating in our Oryzabase, can serve as an excellent genotype-phenotype association resource for analyzing rice functional and structural evolution, and the associated diversity of the Oryza genus. Here we integrate our previous and future phenotypic/habitat information and newly determined genotype information into a united repository, named OryzaGenome, providing the variant information with hyperlinks to Oryzabase. The current version of OryzaGenome includes genotype information of 446 O. rufipogon accessions derived by imputation and of 17 accessions derived by imputation-free deep sequencing. Two variant viewers are implemented: SNP Viewer as a conventional genome browser interface and Variant Table as a text-based browser for precise inspection of each variant one by one. Portable VCF (variant call format) file or tab-delimited file download is also available. Following these SNP (single nucleotide polymorphism) data, reference pseudomolecules/scaffolds/contigs and genome-wide variation information for almost all of the closely and distantly related wild Oryza species from the NIG Wild Rice Collection will be available in future releases. All of the resources can be accessed through http://viewer.shigen.info/oryzagenome/.

  1. Fueling Future with Algal Genomics

    SciTech Connect

    Grigoriev, Igor

    2012-07-05

    Algae constitute a major component of fundamental eukaryotic diversity, play profound roles in the carbon cycle, and are prominent candidates for biofuel production. The US Department of Energy Joint Genome Institute (JGI) is leading the world in algal genome sequencing (http://jgi.doe.gov/Algae) and contributes of the algal genome projects worldwide (GOLD database, 2012). The sequenced algal genomes offer catalogs of genes, networks, and pathways. The sequenced first of its kind genomes of a haptophyte E.huxleyii, chlorarachniophyte B.natans, and cryptophyte G.theta fill the gaps in the eukaryotic tree of life and carry unique genes and pathways as well as molecular fossils of secondary endosymbiosis. Natural adaptation to conditions critical for industrial production is encoded in algal genomes, for example, growth of A.anophagefferens at very high cell densities during the harmful algae blooms or a global distribution across diverse environments of E.huxleyii, able to live on sparse nutrients due to its expanded pan-genome. Communications and signaling pathways can be derived from simple symbiotic systems like lichens or complex marine algae metagenomes. Collectively these datasets derived from algal genomics contribute to building a comprehensive parts list essential for algal biofuel development.

  2. Future Health Applications of Genomics

    PubMed Central

    McBride, Colleen M.; Bowen, Deborah; Brody, Lawrence C.; Condit, Celeste M.; Croyle, Robert T.; Gwinn, Marta; Khoury, Muin J.; Koehly, Laura M.; Korf, Bruce R.; Marteau, Theresa M.; McLeroy, Kenneth; Patrick, Kevin; Valente, Thomas W.

    2014-01-01

    Despite the quickening momentum of genomic discovery, the communication, behavioral, and social sciences research needed for translating this discovery into public health applications has lagged behind. The National Human Genome Research Institute held a 2-day workshop in October 2008 convening an interdisciplinary group of scientists to recommend forward-looking priorities for translational research. This research agenda would be designed to redress the top three risk factors (tobacco use, poor diet, and physical inactivity) that contribute to the four major chronic diseases (heart disease, type 2 diabetes, lung disease, and many cancers) and account for half of all deaths worldwide. Three priority research areas were identified: (1) improving the public’s genetic literacy in order to enhance consumer skills; (2) gauging whether genomic information improves risk communication and adoption of healthier behaviors more than current approaches; and (3) exploring whether genomic discovery in concert with emerging technologies can elucidate new behavioral intervention targets. Important crosscutting themes also were identified, including the need to: (1) anticipate directions of genomic discovery; (2) take an agnostic scientific perspective in framing research questions asking whether genomic discovery adds value to other health promotion efforts; and (3) consider multiple levels of influence and systems that contribute to important public health problems. The priorities and themes offer a framework for a variety of stakeholders, including those who develop priorities for research funding, interdisciplinary teams engaged in genomics research, and policymakers grappling with how to use the products born of genomics research to address public health challenges. PMID:20409503

  3. Comparative Genomics of the Cucurbitaceae

    USDA-ARS?s Scientific Manuscript database

    The genome size for watermelon, melon, cucumber, and pumpkin is 425, 454, 367, and 502 Mbp, respectively, and considered medium size as compared with most other crops. Whole-genome duplication is common in angiosperm plants. Research has revealed a paleohexaploidy (') event in the common ancestor of...

  4. Crop genomics: advances and applications

    USDA-ARS?s Scientific Manuscript database

    The completion of reference genome sequences for many important crops and the ability to perform high-throughput resequencing are providing opportunities for improving our understanding of the history of plant domestication and to accelerate crop improvement. Crop plant comparative genomics is being...

  5. The Atlas Genome Assembly System

    PubMed Central

    Havlak, Paul; Chen, Rui; Durbin, K. James; Egan, Amy; Ren, Yanru; Song, Xing-Zhi; Weinstock, George M.; Gibbs, Richard A.

    2004-01-01

    Atlas is a suite of programs developed for assembly of genomes by a “combined approach” that uses DNA sequence reads from both BACs and whole-genome shotgun (WGS) libraries. The BAC clones afford advantages of localized assembly with reduced computational load, and provide a robust method for dealing with repeated sequences. Inclusion of WGS sequences facilitates use of different clone insert sizes and reduces data production costs. A core function of Atlas software is recruitment of WGS sequences into appropriate BACs based on sequence overlaps. Because construction of consensus sequences is from local assembly of these reads, only small (<0.1%) units of the genome are assembled at a time. Once assembled, each BAC is used to derive a genomic layout. This “sequence-based” growth of the genome map has greater precision than with non-sequence-based methods. Use of BACs allows correction of artifacts due to repeats at each stage of the process. This is aided by ancillary data such as BAC fingerprint, other genomic maps, and syntenic relations with other genomes. Atlas was used to assemble a draft DNA sequence of the rat genome; its major components including overlapper and split-scaffold are also being used in pure WGS projects. PMID:15060016

  6. Genomics and proteomics in cancer.

    PubMed

    Baak, J P A; Path, F R C; Hermsen, M A J A; Meijer, G; Schmidt, J; Janssen, E A M

    2003-06-01

    Cancer development is driven by the accumulation of DNA changes in the approximately 40000 chromosomal genes. In solid tumours, chromosomal numerical/structural aberrations are common. DNA repair defects may lead to genome-wide genetic instability, which can drive further cancer progression. The genes code the actual players in the cellular processes, the 100000-10 million proteins, which in (pre)malignant cells can also be altered in a variety of ways. Over the past decade, our knowledge of the human genome and Genomics (the study of the human genome) in (pre)malignancies has increased enormously and Proteomics (the analysis of the protein complement of the genome) has taken off as well. Both will play an increasingly important role. In this article, a short description of the essential molecular biological cell processes is given. Important genomic and proteomic research methods are described and illustrated. Applications are still limited, but the evidence so far is exciting. Will genomics replace classical diagnostic or prognostic procedures? In breast cancers, the gene expression array is stronger than classical criteria, but in endometrial hyperplasia, quantitative morphological features are more cost-effective than genetic testing. It is still too early to make strong statements, the more so because it is expected that genomics and proteomics will expand rapidly. However, it is likely that they will take a central place in the understanding, diagnosis, monitoring and treatment of (pre)cancers of many different sites.

  7. Genome rearrangements: mother knows best!

    PubMed

    Chalker, Douglas L

    2005-10-25

    In Paramecium, developmentally programmed genome rearrangements can be altered by the presence of homologous sequences within the maternal somatic nucleus. Newly identified RNA-binding proteins appear to mediate the transfer of homologous sequence information from the maternal to the developing somatic nucleus, facilitating epigenetic regulation of this large-scale genome reorganization.

  8. Who owns the human genome

    SciTech Connect

    Roberts, L.

    1987-07-24

    Questions are mounting about whether anyone can own the human genome - whether it can be copyrighted or patented - and what effect that might have on a federal collaboration. This article explores current developments in the initiative to map and sequence the human genome.

  9. How Can Genomics Inform Education?

    ERIC Educational Resources Information Center

    Grigorenko, Elena L.

    2007-01-01

    This article offers some thoughts on possible connections between genomics and education. Genomics is already revolutionizing the way medical care is delivered and distributed; it will inevitably affect children's developmental trajectories by introducing more pharmacological and behavioral therapies. Educators should be prepared to understand the…

  10. How Can Genomics Inform Education?

    ERIC Educational Resources Information Center

    Grigorenko, Elena L.

    2007-01-01

    This article offers some thoughts on possible connections between genomics and education. Genomics is already revolutionizing the way medical care is delivered and distributed; it will inevitably affect children's developmental trajectories by introducing more pharmacological and behavioral therapies. Educators should be prepared to understand the…

  11. Multiplexed fragaria chloroplast genome sequencing

    Treesearch

    W. Njuguna; A. Liston; R. Cronn; N.V. Bassil

    2010-01-01

    A method to sequence multiple chloroplast genomes using ultra high throughput sequencing technologies was recently described. Complete chloroplast genome sequences can resolve phylogenetic relationships at low taxonomic levels and identify informative point mutations and indels. The objective of this research was to sequence multiple Fragaria...

  12. Surveying Breast Cancer's Genomic Landscape.

    PubMed

    2016-07-01

    An in-depth analysis has produced the most comprehensive portrait to date of the myriad genomic alterations involved in breast cancer. In sequencing the whole genomes of 560 breast cancers and combining this information with published data from another 772 breast tumors, the research team uncovered several new genes and mutational signatures that potentially influence this disease.

  13. Cloud computing for comparative genomics.

    PubMed

    Wall, Dennis P; Kudtarkar, Parul; Fusaro, Vincent A; Pivovarov, Rimma; Patil, Prasad; Tonellato, Peter J

    2010-05-18

    Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems.

  14. Cocoa/Cotton Comparative Genomics

    USDA-ARS?s Scientific Manuscript database

    With genome sequence from two members of the Malvaceae family recently made available, we are exploring syntenic relationships, gene content, and evolutionary trajectories between the cacao and cotton genomes. An assembly of cacao (Theobroma cacao) using Illumina and 454 sequence technology yielded ...

  15. Venturia carpophila draft genome sequence

    USDA-ARS?s Scientific Manuscript database

    Venturia carpophila causes peach scab, a disease that renders peach fruit unmarketable. We report a high-quality draft genome sequence (36.9 Mb) of V. carpophila from an isolate collected from a peach tree in central Georgia in the United States. The genome sequence described will be a useful resour...

  16. Cloud computing for comparative genomics

    PubMed Central

    2010-01-01

    Background Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. Results We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. Conclusions The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems. PMID:20482786

  17. Genome editing in cardiovascular diseases.

    PubMed

    Strong, Alanna; Musunuru, Kiran

    2017-01-01

    Genome-editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems, have emerged as an invaluable technology to achieve somatic and germline genomic manipulation in cells and model organisms for multiple applications, including the creation of knockout alleles, introducing desired mutations into genomic DNA, and inserting novel transgenes. Genome editing is being rapidly adopted into all fields of biomedical research, including the cardiovascular field, where it has facilitated a greater understanding of lipid metabolism, electrophysiology, cardiomyopathies, and other cardiovascular disorders, has helped to create a wider variety of cellular and animal models, and has opened the door to a new class of therapies. In this Review, we discuss the applications of genome-editing technology throughout cardiovascular disease research and the prospect of in vivo genome-editing therapies in the future. We also describe some of the existing limitations of genome-editing tools that will need to be addressed if cardiovascular genome editing is to achieve its full scientific and therapeutic potential.

  18. All about the Human Genome Project (HGP)

    MedlinePlus

    ... Genome Resources Access to the full human sequence All About The Human Genome Project (HGP) The Human ... an international research effort to sequence and map all of the genes - together known as the genome - ...

  19. International genomic evaluation methods for dairy cattle

    USDA-ARS?s Scientific Manuscript database

    Background Genomic evaluations are rapidly replacing traditional evaluation systems used for dairy cattle selection. Economies of scale in genomics promote cooperation across country borders. Genomic information can be transferred across countries using simple conversion equations, by modifying mult...

  20. Epistasis correlates to genomic complexity

    PubMed Central

    Sanjuán, Rafael; Elena, Santiago F.

    2006-01-01

    Whether systematic genetic interactions (epistasis) occur at the genomic scale remains a challenging topic in evolutionary biology. Epistasis should make a significant contribution to variation in complex traits and influence the evolution of genetic systems as sex, diploidy, dominance, or the contamination of genomes with deleterious mutations. We have collected data from widely different organisms and quantified epistasis in a common, per-generation scale. Simpler genomes, such as those of RNA viruses, display antagonistic epistasis (mutations have smaller effects together than expected); bacterial microorganisms do not apparently deviate from independent effects, whereas in multicellular eukaryotes, a transition toward synergistic epistasis occurs (mutations have larger effects together than expected). We propose that antagonistic epistasis might be a property of compact genomes with few nonpleiotropic biological functions, whereas in complex genomes, synergism might emerge from mutational robustness. PMID:16983079

  1. Pathophysiology of MDS: genomic aberrations.

    PubMed

    Ichikawa, Motoshi

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  2. Advances in targeted genome editing.

    PubMed

    Perez-Pinera, Pablo; Ousterout, David G; Gersbach, Charles A

    2012-08-01

    New technologies have recently emerged that enable targeted editing of genomes in diverse systems. This includes precise manipulation of gene sequences in their natural chromosomal context and addition of transgenes to specific genomic loci. This progress has been facilitated by advances in engineering targeted nucleases with programmable, site-specific DNA-binding domains, including zinc finger proteins and transcription activator-like effectors (TALEs). Recent improvements have enhanced nuclease performance, accelerated nuclease assembly, and lowered the cost of genome editing. These advances are driving new approaches to many areas of biotechnology, including biopharmaceutical production, agriculture, creation of transgenic organisms and cell lines, and studies of genome structure, regulation, and function. Genome editing is also being investigated in preclinical and clinical gene therapies for many diseases.

  3. Big Data: Astronomical or Genomical?

    PubMed Central

    Stephens, Zachary D.; Lee, Skylar Y.; Faghri, Faraz; Campbell, Roy H.; Zhai, Chengxiang; Efron, Miles J.; Iyer, Ravishankar; Schatz, Michael C.; Sinha, Saurabh; Robinson, Gene E.

    2015-01-01

    Genomics is a Big Data science and is going to get much bigger, very soon, but it is not known whether the needs of genomics will exceed other Big Data domains. Projecting to the year 2025, we compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Our estimates show that genomics is a “four-headed beast”—it is either on par with or the most demanding of the domains analyzed here in terms of data acquisition, storage, distribution, and analysis. We discuss aspects of new technologies that will need to be developed to rise up and meet the computational challenges that genomics poses for the near future. Now is the time for concerted, community-wide planning for the “genomical” challenges of the next decade. PMID:26151137

  4. Genomics of sex determination.

    PubMed

    Zhang, Jisen; Boualem, Adnane; Bendahmane, Abdelhafid; Ming, Ray

    2014-04-01

    Sex determination is a major switch in the evolutionary history of angiosperm, resulting 11% monoecious and dioecious species. The genomic sequences of papaya sex chromosomes unveiled the molecular basis of recombination suppression in the sex determination region, and candidate genes for sex determination. Identification and analyses of sex determination genes in cucurbits and maize demonstrated conservation of sex determination mechanism in one lineage and divergence between the two systems. Epigenetic control and hormonal influence of sex determination were elucidated in both plants and animals. Intensive investigation of potential sex determination genes in model species will improve our understanding of sex determination gene network. Such network will in turn accelerate the identification of sex determination genes in dioecious species with sex chromosomes, which are burdensome due to no recombination in sex determining regions. The sex determination genes in dioecious species are crucial for understanding the origin of dioecy and sex chromosomes, particularly in their early stage of evolution.

  5. Materials Genome Initiative

    NASA Technical Reports Server (NTRS)

    Vickers, John

    2015-01-01

    The Materials Genome Initiative (MGI) project element is a cross-Center effort that is focused on the integration of computational tools to simulate manufacturing processes and materials behavior. These computational simulations will be utilized to gain understanding of processes and materials behavior to accelerate process development and certification to more efficiently integrate new materials in existing NASA projects and to lead to the design of new materials for improved performance. This NASA effort looks to collaborate with efforts at other government agencies and universities working under the national MGI. MGI plans to develop integrated computational/experimental/ processing methodologies for accelerating discovery and insertion of materials to satisfy NASA's unique mission demands. The challenges include validated design tools that incorporate materials properties, processes, and design requirements; and materials process control to rapidly mature emerging manufacturing methods and develop certified manufacturing processes

  6. The South Asian genome.

    PubMed

    Chambers, John C; Abbott, James; Zhang, Weihua; Turro, Ernest; Scott, William R; Tan, Sian-Tsung; Afzal, Uzma; Afaq, Saima; Loh, Marie; Lehne, Benjamin; O'Reilly, Paul; Gaulton, Kyle J; Pearson, Richard D; Li, Xinzhong; Lavery, Anita; Vandrovcova, Jana; Wass, Mark N; Miller, Kathryn; Sehmi, Joban; Oozageer, Laticia; Kooner, Ishminder K; Al-Hussaini, Abtehale; Mills, Rebecca; Grewal, Jagvir; Panoulas, Vasileios; Lewin, Alexandra M; Northwood, Korrinne; Wander, Gurpreet S; Geoghegan, Frank; Li, Yingrui; Wang, Jun; Aitman, Timothy J; McCarthy, Mark I; Scott, James; Butcher, Sarah; Elliott, Paul; Kooner, Jaspal S

    2014-01-01

    The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

  7. Genomics in neurological disorders.

    PubMed

    Han, Guangchun; Sun, Jiya; Wang, Jiajia; Bai, Zhouxian; Song, Fuhai; Lei, Hongxing

    2014-08-01

    Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center (i.e., the brain) in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be discussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer's disease and autism spectrum disorder.

  8. Sequencing the maize genome.

    PubMed

    Martienssen, Robert A; Rabinowicz, Pablo D; O'Shaughnessy, Andrew; McCombie, W Richard

    2004-04-01

    Sequencing of complex genomes can be accomplished by enriching shotgun libraries for genes. In maize, gene-enrichment by copy-number normalization (high C(0)t) and methylation filtration (MF) have been used to generate up to two-fold coverage of the gene-space with less than 1 million sequencing reads. Simulations using sequenced bacterial artificial chromosome (BAC) clones predict that 5x coverage of gene-rich regions, accompanied by less than 1x coverage of subclones from BAC contigs, will generate high-quality mapped sequence that meets the needs of geneticists while accommodating unusually high levels of structural polymorphism. By sequencing several inbred strains, we propose a strategy for capturing this polymorphism to investigate hybrid vigor or heterosis.

  9. Wheat Landrace Genome Diversity

    PubMed Central

    Wingen, Luzie U.; West, Claire; Leverington-Waite, Michelle; Collier, Sarah; Orford, Simon; Goram, Richard; Yang, Cai-Yun; King, Julie; Allen, Alexandra M.; Burridge, Amanda; Edwards, Keith J.; Griffiths, Simon

    2017-01-01

    Understanding the genomic complexity of bread wheat (Triticum aestivum L.) is a cornerstone in the quest to unravel the processes of domestication and the following adaptation of domesticated wheat to a wide variety of environments across the globe. Additionally, it is of importance for future improvement of the crop, particularly in the light of climate change. Focusing on the adaptation after domestication, a nested association mapping (NAM) panel of 60 segregating biparental populations was developed, mainly involving landrace accessions from the core set of the Watkins hexaploid wheat collection optimized for genetic diversity. A modern spring elite variety, “Paragon,” was used as common reference parent. Genetic maps were constructed following identical rules to make them comparable. In total, 1611 linkage groups were identified, based on recombination from an estimated 126,300 crossover events over the whole NAM panel. A consensus map, named landrace consensus map (LRC), was constructed and contained 2498 genetic loci. These newly developed genetics tools were used to investigate the rules underlying genome fluidity or rigidity, e.g., by comparing marker distances and marker orders. In general, marker order was highly correlated, which provides support for strong synteny between bread wheat accessions. However, many exceptional cases of incongruent linkage groups and increased marker distances were also found. Segregation distortion was detected for many markers, sometimes as hot spots present in different populations. Furthermore, evidence for translocations in at least 36 of the maps was found. These translocations fell, in general, into many different translocation classes, but a few translocation classes were found in several accessions, the most frequent one being the well-known T5B:7B translocation. Loci involved in recombination rate, which is an interesting trait for plant breeding, were identified by QTL analyses using the crossover counts as a

  10. Wheat Landrace Genome Diversity.

    PubMed

    Wingen, Luzie U; West, Claire; Leverington-Waite, Michelle; Collier, Sarah; Orford, Simon; Goram, Richard; Yang, Cai-Yun; King, Julie; Allen, Alexandra M; Burridge, Amanda; Edwards, Keith J; Griffiths, Simon

    2017-04-01

    Understanding the genomic complexity of bread wheat (Triticum aestivum L.) is a cornerstone in the quest to unravel the processes of domestication and the following adaptation of domesticated wheat to a wide variety of environments across the globe. Additionally, it is of importance for future improvement of the crop, particularly in the light of climate change. Focusing on the adaptation after domestication, a nested association mapping (NAM) panel of 60 segregating biparental populations was developed, mainly involving landrace accessions from the core set of the Watkins hexaploid wheat collection optimized for genetic diversity. A modern spring elite variety, "Paragon," was used as common reference parent. Genetic maps were constructed following identical rules to make them comparable. In total, 1611 linkage groups were identified, based on recombination from an estimated 126,300 crossover events over the whole NAM panel. A consensus map, named landrace consensus map (LRC), was constructed and contained 2498 genetic loci. These newly developed genetics tools were used to investigate the rules underlying genome fluidity or rigidity, e.g., by comparing marker distances and marker orders. In general, marker order was highly correlated, which provides support for strong synteny between bread wheat accessions. However, many exceptional cases of incongruent linkage groups and increased marker distances were also found. Segregation distortion was detected for many markers, sometimes as hot spots present in different populations. Furthermore, evidence for translocations in at least 36 of the maps was found. These translocations fell, in general, into many different translocation classes, but a few translocation classes were found in several accessions, the most frequent one being the well-known T5B:7B translocation. Loci involved in recombination rate, which is an interesting trait for plant breeding, were identified by QTL analyses using the crossover counts as a trait

  11. Privacy in the Genomic Era

    PubMed Central

    NAVEED, MUHAMMAD; AYDAY, ERMAN; CLAYTON, ELLEN W.; FELLAY, JACQUES; GUNTER, CARL A.; HUBAUX, JEAN-PIERRE; MALIN, BRADLEY A.; WANG, XIAOFENG

    2015-01-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward. PMID:26640318

  12. Recombination Drives Vertebrate Genome Contraction

    PubMed Central

    Nam, Kiwoong; Ellegren, Hans

    2012-01-01

    Selective and/or neutral processes may govern variation in DNA content and, ultimately, genome size. The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes. We used whole-genome data on small insertions and deletions within transposable elements from chicken and zebra finch to demonstrate clear links between recombination rate and a number of attributes of reduced DNA content. Recombination rate was negatively correlated with the length of introns, transposable elements, and intergenic spacer and with the rate of short insertions. Importantly, it was positively correlated with gene density, the rate of short deletions, the deletion bias, and the net change in sequence length. All these observations point at a pattern of more condensed genome structure in regions of high recombination. Based on the observed rates of small insertions and deletions and assuming that these rates are representative for the whole genome, we estimate that the genome of the most recent common ancestor of birds and lizards has lost nearly 20% of its DNA content up until the present. Expansion of transposable elements can counteract the effect of deletions in an equilibrium mutation model; however, since the activity of transposable elements has been low in the avian lineage, the deletion bias is likely to have had a significant effect on genome size evolution in dinosaurs and birds, contributing to the maintenance of a small genome. We also demonstrate that most of the observed correlations between recombination rate and genome contraction parameters are seen in the human genome, including for segregating indel polymorphisms. Our data are compatible with a neutral model in which recombination drives vertebrate genome size evolution and gives no direct support for a role of natural selection in this process. PMID:22570634

  13. Privacy in the Genomic Era.

    PubMed

    Naveed, Muhammad; Ayday, Erman; Clayton, Ellen W; Fellay, Jacques; Gunter, Carl A; Hubaux, Jean-Pierre; Malin, Bradley A; Wang, Xiaofeng

    2015-09-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward.

  14. RECORD: Reference-Assisted Genome Assembly for Closely Related Genomes.

    PubMed

    Buza, Krisztian; Wilczynski, Bartek; Dojer, Norbert

    2015-01-01

    Background. Next-generation sequencing technologies are now producing multiple times the genome size in total reads from a single experiment. This is enough information to reconstruct at least some of the differences between the individual genome studied in the experiment and the reference genome of the species. However, in most typical protocols, this information is disregarded and the reference genome is used. Results. We provide a new approach that allows researchers to reconstruct genomes very closely related to the reference genome (e.g., mutants of the same species) directly from the reads used in the experiment. Our approach applies de novo assembly software to experimental reads and so-called pseudoreads and uses the resulting contigs to generate a modified reference sequence. In this way, it can very quickly, and at no additional sequencing cost, generate new, modified reference sequence that is closer to the actual sequenced genome and has a full coverage. In this paper, we describe our approach and test its implementation called RECORD. We evaluate RECORD on both simulated and real data. We made our software publicly available on sourceforge. Conclusion. Our tests show that on closely related sequences RECORD outperforms more general assisted-assembly software.

  15. Integrated genome browser: visual analytics platform for genomics

    PubMed Central

    Norris, David C.; Loraine, Ann E.

    2016-01-01

    Motivation: Genome browsers that support fast navigation through vast datasets and provide interactive visual analytics functions can help scientists achieve deeper insight into biological systems. Toward this end, we developed Integrated Genome Browser (IGB), a highly configurable, interactive and fast open source desktop genome browser. Results: Here we describe multiple updates to IGB, including all-new capabilities to display and interact with data from high-throughput sequencing experiments. To demonstrate, we describe example visualizations and analyses of datasets from RNA-Seq, ChIP-Seq and bisulfite sequencing experiments. Understanding results from genome-scale experiments requires viewing the data in the context of reference genome annotations and other related datasets. To facilitate this, we enhanced IGB’s ability to consume data from diverse sources, including Galaxy, Distributed Annotation and IGB-specific Quickload servers. To support future visualization needs as new genome-scale assays enter wide use, we transformed the IGB codebase into a modular, extensible platform for developers to create and deploy all-new visualizations of genomic data. Availability and implementation: IGB is open source and is freely available from http://bioviz.org/igb. Contact: aloraine@uncc.edu PMID:27153568

  16. Bovine Genome Database: integrated tools for genome annotation and discovery.

    PubMed

    Childers, Christopher P; Reese, Justin T; Sundaram, Jaideep P; Vile, Donald C; Dickens, C Michael; Childs, Kevin L; Salih, Hanni; Bennett, Anna K; Hagen, Darren E; Adelson, David L; Elsik, Christine G

    2011-01-01

    The Bovine Genome Database (BGD; http://BovineGenome.org) strives to improve annotation of the bovine genome and to integrate the genome sequence with other genomics data. BGD includes GBrowse genome browsers, the Apollo Annotation Editor, a quantitative trait loci (QTL) viewer, BLAST databases and gene pages. Genome browsers, available for both scaffold and chromosome coordinate systems, display the bovine Official Gene Set (OGS), RefSeq and Ensembl gene models, non-coding RNA, repeats, pseudogenes, single-nucleotide polymorphism, markers, QTL and alignments to complementary DNAs, ESTs and protein homologs. The Bovine QTL viewer is connected to the BGD Chromosome GBrowse, allowing for the identification of candidate genes underlying QTL. The Apollo Annotation Editor connects directly to the BGD Chado database to provide researchers with remote access to gene evidence in a graphical interface that allows editing and creating new gene models. Researchers may upload their annotations to the BGD server for review and integration into the subsequent release of the OGS. Gene pages display information for individual OGS gene models, including gene structure, transcript variants, functional descriptions, gene symbols, Gene Ontology terms, annotator comments and links to National Center for Biotechnology Information and Ensembl. Each gene page is linked to a wiki page to allow input from the research community.

  17. Structural Genomics: Correlation Blocks, Population Structure, and Genome Architecture

    PubMed Central

    Hu, Xin-Sheng; Yeh, Francis C.; Wang, Zhiquan

    2011-01-01

    An integration of the pattern of genome-wide inter-site associations with evolutionary forces is important for gaining insights into the genomic evolution in natural or artificial populations. Here, we assess the inter-site correlation blocks and their distributions along chromosomes. A correlation block is broadly termed as the DNA segment within which strong correlations exist between genetic diversities at any two sites. We bring together the population genetic structure and the genomic diversity structure that have been independently built on different scales and synthesize the existing theories and methods for characterizing genomic structure at the population level. We discuss how population structure could shape correlation blocks and their patterns within and between populations. Effects of evolutionary forces (selection, migration, genetic drift, and mutation) on the pattern of genome-wide correlation blocks are discussed. In eukaryote organisms, we briefly discuss the associations between the pattern of correlation blocks and genome assembly features in eukaryote organisms, including the impacts of multigene family, the perturbation of transposable elements, and the repetitive nongenic sequences and GC-rich isochores. Our reviews suggest that the observable pattern of correlation blocks can refine our understanding of the ecological and evolutionary processes underlying the genomic evolution at the population level. PMID:21886455

  18. Integrated genome browser: visual analytics platform for genomics.

    PubMed

    Freese, Nowlan H; Norris, David C; Loraine, Ann E

    2016-07-15

    Genome browsers that support fast navigation through vast datasets and provide interactive visual analytics functions can help scientists achieve deeper insight into biological systems. Toward this end, we developed Integrated Genome Browser (IGB), a highly configurable, interactive and fast open source desktop genome browser. Here we describe multiple updates to IGB, including all-new capabilities to display and interact with data from high-throughput sequencing experiments. To demonstrate, we describe example visualizations and analyses of datasets from RNA-Seq, ChIP-Seq and bisulfite sequencing experiments. Understanding results from genome-scale experiments requires viewing the data in the context of reference genome annotations and other related datasets. To facilitate this, we enhanced IGB's ability to consume data from diverse sources, including Galaxy, Distributed Annotation and IGB-specific Quickload servers. To support future visualization needs as new genome-scale assays enter wide use, we transformed the IGB codebase into a modular, extensible platform for developers to create and deploy all-new visualizations of genomic data. IGB is open source and is freely available from http://bioviz.org/igb aloraine@uncc.edu. © The Author 2016. Published by Oxford University Press.

  19. Aquatic Plant Genomics: Advances, Applications, and Prospects

    PubMed Central

    Li, Gaojie; Yang, Jingjing

    2017-01-01

    Genomics is a discipline in genetics that studies the genome composition of organisms and the precise structure of genes and their expression and regulation. Genomics research has resolved many problems where other biological methods have failed. Here, we summarize advances in aquatic plant genomics with a focus on molecular markers, the genes related to photosynthesis and stress tolerance, comparative study of genomes and genome/transcriptome sequencing technology. PMID:28900619

  20. Evaluating the role of genome downsizing and size thresholds from genome size distributions in angiosperms.

    PubMed

    Zenil-Ferguson, Rosana; Ponciano, José M; Burleigh, J Gordon

    2016-07-01

    Whole-genome duplications (WGDs) can rapidly increase genome size in angiosperms. Yet their mean genome size is not correlated with ploidy. We compared three hypotheses to explain the constancy of genome size means across ploidies. The genome downsizing hypothesis suggests that genome size will decrease by a given percentage after a WGD. The genome size threshold hypothesis assumes that taxa with large genomes or large monoploid numbers will fail to undergo or survive WGDs. Finally, the genome downsizing and threshold hypothesis suggests that both genome downsizing and thresholds affect the relationship between genome size means and ploidy. We performed nonparametric bootstrap simulations to compare observed angiosperm genome size means among species or genera against simulated genome sizes under the three different hypotheses. We evaluated the hypotheses using a decision theory approach and estimated the expected percentage of genome downsizing. The threshold hypothesis improves the approximations between mean genome size and simulated genome size. At the species level, the genome downsizing with thresholds hypothesis best explains the genome size means with a 15% genome downsizing percentage. In the genus level simulations, the monoploid number threshold hypothesis best explains the data. Thresholds of genome size and monoploid number added to genome downsizing at species level simulations explain the observed means of angiosperm genome sizes, and monoploid number is important for determining the genome size mean at the genus level. © 2016 Botanical Society of America.

  1. Microbial Genomics Data from the DOE Joint Genome Institute (JGI)

    DOE Data Explorer

    The JGI makes high-quality genome sequencing data freely available to the greater scientific community through its web portal. Having played a significant role in the federally funded Human Genome Project -- generating the complete sequences of Chromosomes 5, 16, and 19--the JGI has now moved on to contributing in other critical areas of genomics research. While NIH-funded genome sequencing activities continue to emphasize human biomedical targets and applications, the JGI has since shifted its focus to the non-human components of the biosphere, particularly those relevant to the science mission of the Department of Energy. With efficiencies of scale established at the PGF, and capacity now exceeding three billion bases generated on a monthly basis, the JGI has tackled scores of additional genomes. These include more than 60 microbial genomes and many important multicellular organisms and communities of microbes. In partnership with other federal institutions and universities, the JGI is in the process of sequencing a frog (Xenopus tropicalis), a green alga (Chlamydomonas reinhardtii), a diatom (Thalassiosira pseudonana) , the cottonwood tree (Populus trichocarpa), and a host of agriculturally important plants and plant pathogens. Microorganisms, for example those that thrive under extreme conditions such as high acidity, radiation, and metal contamination, are of particular interest to the DOE and JGI. Investigations by JGI and its partners are shedding light on the cellular machinery of microbes and how they can be harnessed to clean up contaminated soil or water, capture carbon from the atmosphere, and produce potentially important sources of energy such as hydrogen and methane. [Excerpt from the JGI page "Who We Are" at http://www.jgi.doe.gov/whoweare/whoweare.html] From the JGI webportal users can view a photo grid of organisims, check assemblies for status, access the Integrated Microbial Genomes (IMG) system to do comparative analysis of publicly available

  2. A universal genomic coordinate translator for comparative genomics.

    PubMed

    Zamani, Neda; Sundström, Görel; Meadows, Jennifer R S; Höppner, Marc P; Dainat, Jacques; Lantz, Henrik; Haas, Brian J; Grabherr, Manfred G

    2014-06-30

    Genomic duplications constitute major events in the evolution of species, allowing paralogous copies of genes to take on fine-tuned biological roles. Unambiguously identifying the orthology relationship between copies across multiple genomes can be resolved by synteny, i.e. the conserved order of genomic sequences. However, a comprehensive analysis of duplication events and their contributions to evolution would require all-to-all genome alignments, which increases at N2 with the number of available genomes, N. Here, we introduce Kraken, software that omits the all-to-all requirement by recursively traversing a graph of pairwise alignments and dynamically re-computing orthology. Kraken scales linearly with the number of targeted genomes, N, which allows for including large numbers of genomes in analyses. We first evaluated the method on the set of 12 Drosophila genomes, finding that orthologous correspondence computed indirectly through a graph of multiple synteny maps comes at minimal cost in terms of sensitivity, but reduces overall computational runtime by an order of magnitude. We then used the method on three well-annotated mammalian genomes, human, mouse, and rat, and show that up to 93% of protein coding transcripts have unambiguous pairwise orthologous relationships across the genomes. On a nucleotide level, 70 to 83% of exons match exactly at both splice junctions, and up to 97% on at least one junction. We last applied Kraken to an RNA-sequencing dataset from multiple vertebrates and diverse tissues, where we confirmed that brain-specific gene family members, i.e. one-to-many or many-to-many homologs, are more highly correlated across species than single-copy (i.e. one-to-one homologous) genes. Not limited to protein coding genes, Kraken also identifies thousands of newly identified transcribed loci, likely non-coding RNAs that are consistently transcribed in human, chimpanzee and gorilla, and maintain significant correlation of expression levels across

  3. Exploring cancer genomic data from the cancer genome atlas project

    PubMed Central

    Lee, Ju-Seog

    2016-01-01

    The Cancer Genome Atlas (TCGA) has compiled genomic, epigenomic, and proteomic data from more than 10,000 samples derived from 33 types of cancer, aiming to improve our understanding of the molecular basis of cancer development. Availability of these genome-wide information provides an unprecedented opportunity for uncovering new key regulators of signaling pathways or new roles of pre-existing members in pathways. To take advantage of the advancement, it will be necessary to learn systematic approaches that can help to uncover novel genes reflecting genetic alterations, prognosis, or response to treatments. This minireview describes the updated status of TCGA project and explains how to use TCGA data. PMID:27530686

  4. Genome Annotation Transfer Utility (GATU): rapid annotation of viral genomes using a closely related reference genome.

    PubMed

    Tcherepanov, Vasily; Ehlers, Angelika; Upton, Chris

    2006-06-13

    Since DNA sequencing has become easier and cheaper, an increasing number of closely related viral genomes have been sequenced. However, many of these have been deposited in GenBank without annotations, severely limiting their value to researchers. While maintaining comprehensive genomic databases for a set of virus families at the Viral Bioinformatics Resource Center http://www.biovirus.org and Viral Bioinformatics - Canada http://www.virology.ca, we found that researchers were unnecessarily spending time annotating viral genomes that were close relatives of already annotated viruses. We have therefore designed and implemented a novel tool, Genome Annotation Transfer Utility (GATU), to transfer annotations from a previously annotated reference genome to a new target genome, thereby greatly reducing this laborious task. GATU transfers annotations from a reference genome to a closely related target genome, while still giving the user final control over which annotations should be included. GATU also detects open reading frames present in the target but not the reference genome and provides the user with a variety of bioinformatics tools to quickly determine if these ORFs should also be included in the annotation. After this process is complete, GATU saves the newly annotated genome as a GenBank, EMBL or XML-format file. The software is coded in Java and runs on a variety of computer platforms. Its user-friendly Graphical User Interface is specifically designed for users trained in the biological sciences. GATU greatly simplifies the initial stages of genome annotation by using a closely related genome as a reference. It is not intended to be a gene prediction tool or a "complete" annotation system, but we have found that it significantly reduces the time required for annotation of genes and mature peptides as well as helping to standardize gene names between related organisms by transferring reference genome annotations to the target genome. The program is freely

  5. The genome of Eucalyptus grandis

    SciTech Connect

    Myburg, Alexander A.; Grattapaglia, Dario; Tuskan, Gerald A.; Hellsten, Uffe; Hayes, Richard D.; Grimwood, Jane; Jenkins, Jerry; Lindquist, Erika; Tice, Hope; Bauer, Diane; Goodstein, David M.; Dubchak, Inna; Poliakov, Alexandre; Mizrachi, Eshchar; Kullan, Anand R. K.; Hussey, Steven G.; Pinard, Desre; van der Merwe, Karen; Singh, Pooja; van Jaarsveld, Ida; Silva-Junior, Orzenil B.; Togawa, Roberto C.; Pappas, Marilia R.; Faria, Danielle A.; Sansaloni, Carolina P.; Petroli, Cesar D.; Yang, Xiaohan; Ranjan, Priya; Tschaplinski, Timothy J.; Ye, Chu-Yu; Li, Ting; Sterck, Lieven; Vanneste, Kevin; Murat, Florent; Soler, Marçal; Clemente, Hélène San; Saidi, Naijib; Cassan-Wang, Hua; Dunand, Christophe; Hefer, Charles A.; Bornberg-Bauer, Erich; Kersting, Anna R.; Vining, Kelly; Amarasinghe, Vindhya; Ranik, Martin; Naithani, Sushma; Elser, Justin; Boyd, Alexander E.; Liston, Aaron; Spatafora, Joseph W.; Dharmwardhana, Palitha; Raja, Rajani; Sullivan, Christopher; Romanel, Elisson; Alves-Ferreira, Marcio; Külheim, Carsten; Foley, William; Carocha, Victor; Paiva, Jorge; Kudrna, David; Brommonschenkel, Sergio H.; Pasquali, Giancarlo; Byrne, Margaret; Rigault, Philippe; Tibbits, Josquin; Spokevicius, Antanas; Jones, Rebecca C.; Steane, Dorothy A.; Vaillancourt, René E.; Potts, Brad M.; Joubert, Fourie; Barry, Kerrie; Pappas, Georgios J.; Strauss, Steven H.; Jaiswal, Pankaj; Grima-Pettenati, Jacqueline; Salse, Jérôme; Van de Peer, Yves; Rokhsar, Daniel S.; Schmutz, Jeremy

    2014-06-11

    Eucalypts are the world s most widely planted hardwood trees. Their broad adaptability, rich species diversity, fast growth and superior multipurpose wood, have made them a global renewable resource of fiber and energy that mitigates human pressures on natural forests. We sequenced and assembled >94% of the 640 Mbp genome of Eucalyptus grandis into its 11 chromosomes. A set of 36,376 protein coding genes were predicted revealing that 34% occur in tandem duplications, the largest proportion found thus far in any plant genome. Eucalypts also show the highest diversity of genes for plant specialized metabolism that act as chemical defence against biotic agents and provide unique pharmaceutical oils. Resequencing of a set of inbred tree genomes revealed regions of strongly conserved heterozygosity, likely hotspots of inbreeding depression. The resequenced genome of the sister species E. globulus underscored the high inter-specific genome colinearity despite substantial genome size variation in the genus. The genome of E. grandis is the first reference for the early diverging Rosid order Myrtales and is placed here basal to the Eurosids. This resource expands knowledge on the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.

  6. [Genome editing of industrial microorganism].

    PubMed

    Zhu, Linjiang; Li, Qi

    2015-03-01

    Genome editing is defined as highly-effective and precise modification of cellular genome in a large scale. In recent years, such genome-editing methods have been rapidly developed in the field of industrial strain improvement. The quickly-updating methods thoroughly change the old mode of inefficient genetic modification, which is "one modification, one selection marker, and one target site". Highly-effective modification mode in genome editing have been developed including simultaneous modification of multiplex genes, highly-effective insertion, replacement, and deletion of target genes in the genome scale, cut-paste of a large DNA fragment. These new tools for microbial genome editing will certainly be applied widely, and increase the efficiency of industrial strain improvement, and promote the revolution of traditional fermentation industry and rapid development of novel industrial biotechnology like production of biofuel and biomaterial. The technological principle of these genome-editing methods and their applications were summarized in this review, which can benefit engineering and construction of industrial microorganism.

  7. Comparative Genome Mapping in Brassica

    PubMed Central

    Lagercrantz, U.; Lydiate, D. J.

    1996-01-01

    A Brassica nigra genetic linkage map was developed from a highly polymorphic cross analyzed with a set of low copy number Brassica RFLP probes. The Brassica genome is extensively duplicated with eight distinct sets of chromosomal segments, each present in three copies, covering virtually the whole genome. Thus, B. nigra could be descended from a hexaploid ancestor. A comparative analysis of B. nigra, B. oleracea and B. rapa genomes, based on maps developed using a common set of RFLP probes, was also performed. The three genomes have distinct chromosomal structures differentiated by a large number of rearrangements, but collinear regions involving virtually the whole of each the three genomes were identified. The genic contents of B. nigra, B. oleracea and B. rapa were basically equivalent and differences in chromosome number (8, 9 and 10, respectively) are probably the result of chromsome fusions and/or fissions. The strong conservation of overall genic content across the three Brassica genomes mirrors the conservation of genic content observed over a much longer evolutionary span in cereals. However, the rate of chromosomal rearrangement in crucifers is much higher than that observed in cereal genomes. PMID:8978073

  8. Components of Adenovirus Genome Packaging

    PubMed Central

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  9. Jumbled Genomes: Missing Apicomplexan Synteny

    PubMed Central

    DeBarry, Jeremy D.; Kissinger, Jessica C.

    2011-01-01

    Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses, and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multicellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g., malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from six genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species, and within these conserved regions, there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes. PMID:21504890

  10. Functional genomics of intracellular bacteria.

    PubMed

    de Barsy, Marie; Greub, Gilbert

    2013-07-01

    During the genomic era, a large amount of whole-genome sequences accumulated, which identified many hypothetical proteins of unknown function. Rapidly, functional genomics, which is the research domain that assign a function to a given gene product, has thus been developed. Functional genomics of intracellular pathogenic bacteria exhibit specific peculiarities due to the fastidious growth of most of these intracellular micro-organisms, due to the close interaction with the host cell, due to the risk of contamination of experiments with host cell proteins and, for some strict intracellular bacteria such as Chlamydia, due to the absence of simple genetic system to manipulate the bacterial genome. To identify virulence factors of intracellular pathogenic bacteria, functional genomics often rely on bioinformatic analyses compared with model organisms such as Escherichia coli and Bacillus subtilis. The use of heterologous expression is another common approach. Given the intracellular lifestyle and the many effectors that are used by the intracellular bacteria to corrupt host cell functions, functional genomics is also often targeting the identification of new effectors such as those of the T4SS of Brucella and Legionella.

  11. Radiation Induced Genomic Instability

    SciTech Connect

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  12. Comparative genomics reveals insights into avian genome evolution and adaptation.

    PubMed

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M; Lee, Chul; Storz, Jay F; Antunes, Agostinho; Greenwold, Matthew J; Meredith, Robert W; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S; Gatesy, John; Hoffmann, Federico G; Opazo, Juan C; Håstad, Olle; Sawyer, Roger H; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A; Green, Richard E; O'Brien, Stephen J; Griffin, Darren; Johnson, Warren E; Haussler, David; Ryder, Oliver A; Willerslev, Eske; Graves, Gary R; Alström, Per; Fjeldså, Jon; Mindell, David P; Edwards, Scott V; Braun, Edward L; Rahbek, Carsten; Burt, David W; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D; Gilbert, M Thomas P; Wang, Jun

    2014-12-12

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits. Copyright © 2014, American Association for the Advancement of Science.

  13. Comparative genomics reveals insights into avian genome evolution and adaptation

    PubMed Central

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M.; Lee, Chul; Storz, Jay F.; Antunes, Agostinho; Greenwold, Matthew J.; Meredith, Robert W.; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R.; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T.; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V.; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S.; Gatesy, John; Hoffmann, Federico G.; Opazo, Juan C.; Håstad, Olle; Sawyer, Roger H.; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W.; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F.; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A.; Green, Richard E.; O’Brien, Stephen J.; Griffin, Darren; Johnson, Warren E.; Haussler, David; Ryder, Oliver A.; Willerslev, Eske; Graves, Gary R.; Alström, Per; Fjeldså, Jon; Mindell, David P.; Edwards, Scott V.; Braun, Edward L.; Rahbek, Carsten; Burt, David W.; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D.; Gilbert, M. Thomas P.; Wang, Jun

    2015-01-01

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits. PMID:25504712

  14. Behavior, Brain, and Genome in Genomic Disorders: Finding the Correspondences

    PubMed Central

    Grigorenko, Elena L.; Urban, Alexander E.; Mencl, Einar

    2014-01-01

    Objective Within the last decade or so, there has been an acceleration of research attempting to connect specific genetic lesions to patterns of brain structure and activation. This article comments on observations that have been made based on these recent data and discusses their importance for the field of investigations into developmental disorders. Method In making these observations, we focus on one specific genomic lesion, the well-studied, yet still incompletely understood, 22q11.2 deletion syndrome (22q11.2DS). Results We demonstrate the degree of variability in the phenotype that occurs at both the brain and behavioral levels of genomic disorders, and describe how this variability is, upon close inspection, represented at the genomic level. Conclusion We emphasize the importance of combining genetic/genomic analyses and neuroimaging for research and for future clinical diagnostic purposes, and for the purposes of developing individualized, patient-tailored treatment and remediation approaches. PMID:20814258

  15. Genome Modeling System: A Knowledge Management Platform for Genomics

    PubMed Central

    Griffith, Malachi; Griffith, Obi L.; Smith, Scott M.; Ramu, Avinash; Callaway, Matthew B.; Brummett, Anthony M.; Kiwala, Michael J.; Coffman, Adam C.; Regier, Allison A.; Oberkfell, Ben J.; Sanderson, Gabriel E.; Mooney, Thomas P.; Nutter, Nathaniel G.; Belter, Edward A.; Du, Feiyu; Long, Robert L.; Abbott, Travis E.; Ferguson, Ian T.; Morton, David L.; Burnett, Mark M.; Weible, James V.; Peck, Joshua B.; Dukes, Adam; McMichael, Joshua F.; Lolofie, Justin T.; Derickson, Brian R.; Hundal, Jasreet; Skidmore, Zachary L.; Ainscough, Benjamin J.; Dees, Nathan D.; Schierding, William S.; Kandoth, Cyriac; Kim, Kyung H.; Lu, Charles; Harris, Christopher C.; Maher, Nicole; Maher, Christopher A.; Magrini, Vincent J.; Abbott, Benjamin S.; Chen, Ken; Clark, Eric; Das, Indraniel; Fan, Xian; Hawkins, Amy E.; Hepler, Todd G.; Wylie, Todd N.; Leonard, Shawn M.; Schroeder, William E.; Shi, Xiaoqi; Carmichael, Lynn K.; Weil, Matthew R.; Wohlstadter, Richard W.; Stiehr, Gary; McLellan, Michael D.; Pohl, Craig S.; Miller, Christopher A.; Koboldt, Daniel C.; Walker, Jason R.; Eldred, James M.; Larson, David E.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.

    2015-01-01

    In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms. PMID:26158448

  16. The bonobo genome compared with the chimpanzee and human genomes

    PubMed Central

    Prüfer, Kay; Munch, Kasper; Hellmann, Ines; Akagi, Keiko; Miller, Jason R.; Walenz, Brian; Koren, Sergey; Sutton, Granger; Kodira, Chinnappa; Winer, Roger; Knight, James R.; Mullikin, James C.; Meader, Stephen J.; Ponting, Chris P.; Lunter, Gerton; Higashino, Saneyuki; Hobolth, Asger; Dutheil, Julien; Karakoç, Emre; Alkan, Can; Sajjadian, Saba; Catacchio, Claudia Rita; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Junhold, Jörg; Patterson, Nick; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Symer, David E.; Mailund, Thomas; Schierup, Mikkel H.; Andrés, Aida M.; Kelso, Janet; Pääbo, Svante

    2012-01-01

    Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours1–4, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. PMID:22722832

  17. Plant genomics: homoplasy heaven in a lycophyte genome.

    PubMed

    Friedman, William E

    2011-07-26

    The recent genomic sequencing of Selaginella, a member of the lycophyte lineage of vascular plants, opens up all kinds of new opportunities to examine the patterns of evolutionary innovation and the creation of the basic bauplan of plants.

  18. The bonobo genome compared with the chimpanzee and human genomes.

    PubMed

    Prüfer, Kay; Munch, Kasper; Hellmann, Ines; Akagi, Keiko; Miller, Jason R; Walenz, Brian; Koren, Sergey; Sutton, Granger; Kodira, Chinnappa; Winer, Roger; Knight, James R; Mullikin, James C; Meader, Stephen J; Ponting, Chris P; Lunter, Gerton; Higashino, Saneyuki; Hobolth, Asger; Dutheil, Julien; Karakoç, Emre; Alkan, Can; Sajjadian, Saba; Catacchio, Claudia Rita; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Junhold, Jörg; Patterson, Nick; Siebauer, Michael; Good, Jeffrey M; Fischer, Anne; Ptak, Susan E; Lachmann, Michael; Symer, David E; Mailund, Thomas; Schierup, Mikkel H; Andrés, Aida M; Kelso, Janet; Pääbo, Svante

    2012-06-28

    Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.

  19. Genome Modeling System: A Knowledge Management Platform for Genomics.

    PubMed

    Griffith, Malachi; Griffith, Obi L; Smith, Scott M; Ramu, Avinash; Callaway, Matthew B; Brummett, Anthony M; Kiwala, Michael J; Coffman, Adam C; Regier, Allison A; Oberkfell, Ben J; Sanderson, Gabriel E; Mooney, Thomas P; Nutter, Nathaniel G; Belter, Edward A; Du, Feiyu; Long, Robert L; Abbott, Travis E; Ferguson, Ian T; Morton, David L; Burnett, Mark M; Weible, James V; Peck, Joshua B; Dukes, Adam; McMichael, Joshua F; Lolofie, Justin T; Derickson, Brian R; Hundal, Jasreet; Skidmore, Zachary L; Ainscough, Benjamin J; Dees, Nathan D; Schierding, William S; Kandoth, Cyriac; Kim, Kyung H; Lu, Charles; Harris, Christopher C; Maher, Nicole; Maher, Christopher A; Magrini, Vincent J; Abbott, Benjamin S; Chen, Ken; Clark, Eric; Das, Indraniel; Fan, Xian; Hawkins, Amy E; Hepler, Todd G; Wylie, Todd N; Leonard, Shawn M; Schroeder, William E; Shi, Xiaoqi; Carmichael, Lynn K; Weil, Matthew R; Wohlstadter, Richard W; Stiehr, Gary; McLellan, Michael D; Pohl, Craig S; Miller, Christopher A; Koboldt, Daniel C; Walker, Jason R; Eldred, James M; Larson, David E; Dooling, David J; Ding, Li; Mardis, Elaine R; Wilson, Richard K

    2015-07-01

    In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

  20. Orthology for comparative genomics in the mouse genome database.

    PubMed

    Dolan, Mary E; Baldarelli, Richard M; Bello, Susan M; Ni, Li; McAndrews, Monica S; Bult, Carol J; Kadin, James A; Richardson, Joel E; Ringwald, Martin; Eppig, Janan T; Blake, Judith A

    2015-08-01

    The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

  1. [Human genome project: a federator program of genomic medicine].

    PubMed

    Sfar, S; Chouchane, L

    2008-05-01

    The Human Genome Project improves our understanding of the molecular genetics basis of the inherited and complex diseases such as diabetes, schizophrenia, and cancer. Information from the human genome sequence is essential for several antenatal and neonatal screening programmes. The new genomic tools emerging from this project have revolutionized biology and medicine and have transformed our understanding of health and the provision of healthcare. Its implications pervade all areas of medicine, from disease prediction and prevention to the diagnosis and treatment of all forms of disease. Increasingly, it will be possible to drive predisposition testing into clinical practice, to develop new treatments or to adapt available treatments more specifically to an individual's genetic make-up. This genomic information should transform the traditional medications that are effective for every members of the population to personalized medicine and personalized therapy. The pharmacogenomics could give rise to a new generation of highly effective drugs that treat causes, not just symptoms.

  2. Capturing prokaryotic dark matter genomes.

    PubMed

    Gasc, Cyrielle; Ribière, Céline; Parisot, Nicolas; Beugnot, Réjane; Defois, Clémence; Petit-Biderre, Corinne; Boucher, Delphine; Peyretaillade, Eric; Peyret, Pierre

    2015-12-01

    Prokaryotes are the most diverse and abundant cellular life forms on Earth. Most of them, identified by indirect molecular approaches, belong to microbial dark matter. The advent of metagenomic and single-cell genomic approaches has highlighted the metabolic capabilities of numerous members of this dark matter through genome reconstruction. Thus, linking functions back to the species has revolutionized our understanding of how ecosystem function is sustained by the microbial world. This review will present discoveries acquired through the illumination of prokaryotic dark matter genomes by these innovative approaches. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. HUGO: The Human Genome Organization

    SciTech Connect

    Bodmer, W.F. )

    1991-01-01

    The Human Genome Organization (HUGO) was established to provide an international coordinating scientific body with the following purposes: to assist with the coordination of scientific research on the human genome and to foster collaboration between scientists; to coordinate and to facilitate the exchange of data and biomaterials relevant to this research; to encourage public debate and provide information and advice on the scientific, ethical, social, legal, and commercial implications of the human genome project. Six advisory committees have been created to assist with the planning and implementation of HUGO's tasks.

  4. Functional genomics in reproductive medicine.

    PubMed

    Barratt, Christopher L R; Hughes, David C; Afnan, Masoud; Brewis, Ian A

    2002-02-01

    The British Fertility Society organised a workshop on Functional Genomics in Reproductive Medicine at the University of Birmingham on 13-14 September 2001. The primary aim was to inform delegates about the power of the technology that has been made available after completion of the sequencing of the human genome, and to stimulate debate about using functional genomics to address both clinical and scientific questions in reproductive medicine. Three specific areas were addressed: proteomics, gene expression and bioinformatics. Although the sophistication and plethora of techniques available were obvious, major limitations in the technology were also discussed. The future promises to be very challenging indeed.

  5. Crop genomics: advances and applications.

    PubMed

    Morrell, Peter L; Buckler, Edward S; Ross-Ibarra, Jeffrey

    2011-12-29

    The completion of reference genome sequences for many important crops and the ability to perform high-throughput resequencing are providing opportunities for improving our understanding of the history of plant domestication and to accelerate crop improvement. Crop plant comparative genomics is being transformed by these data and a new generation of experimental and computational approaches. The future of crop improvement will be centred on comparisons of individual plant genomes, and some of the best opportunities may lie in using combinations of new genetic mapping strategies and evolutionary analyses to direct and optimize the discovery and use of genetic variation. Here we review such strategies and insights that are emerging.

  6. Genomic imprinting syndromes and cancer.

    PubMed

    Lim, Derek Hock Kiat; Maher, Eamonn Richard

    2010-01-01

    Genomic imprinting represents a form of epigenetic control of gene expression in which one allele of a gene is preferentially expressed according to the parent-of-origin of the allele. Genomic imprinting plays an important role in normal growth and development. Disruption of imprinting can result in a number of human imprinting syndromes and predispose to cancer. In this chapter, we describe a number of human imprinting syndromes to illustrate the concepts of genomic imprinting and how loss of imprinting of imprinted genes their relationship to human neoplasia.

  7. Chemical genomics in plant biology.

    PubMed

    Sadhukhan, Ayan; Sahoo, Lingaraj; Panda, Sanjib Kumar

    2012-06-01

    Chemical genomics is a newly emerged and rapidly progressing field in biology, where small chemical molecules bind specifically and reversibly to protein(s) to modulate their function(s), leading to the delineation and subsequent unravelling of biological processes. This approach overcomes problems like lethality and redundancy of classical genetics. Armed with the powerful techniques of combinatorial synthesis, high-throughput screening and target discovery chemical genomics expands its scope to diverse areas in biology. The well-established genetic system of Arabidopsis model allows chemical genomics to enter into the realm of plant biology exploring signaling pathways of growth regulators, endomembrane signaling cascades, plant defense mechanisms and many more events.

  8. Genome dynamics during experimental evolution

    PubMed Central

    Barrick, Jeffrey E.; Lenski, Richard E.

    2014-01-01

    Evolutionary changes in organismal traits may occur gradually or suddenly. Until recently, however, there has been little direct information about how phenotypic changes are related to the rate and nature of underlying changes in genotype. Technological advances enabling whole-genome and whole-population sequencing coupled with experiments that watch evolution in action have brought new precision and insights to studies of mutation rates and genome evolution. Here, we discuss the evolutionary forces and ecological processes that govern genome dynamics in various laboratory systems in the context of relevant population genetic theory, and we relate these findings to evolution in natural populations. PMID:24166031

  9. Processing massive datasets in genomics

    NASA Astrophysics Data System (ADS)

    Artiguenave, F.

    2011-02-01

    Life science researches have been profoundly impacted by technological advances allowing faster and cheaper DNA sequencing. Opening a wide range of applications in medical and biology, the last generation sequencing platforms raised new challenges, in particular in processing, analysing and interpreting massive data. In this talk, the growing role of bioinformatics will be illustrated by providing some figures about genome sequencing and others applications aimed at unravelling biological mechanisms. Methods to gather insights from massive amount of data will be illustrated by the genome annotation process, by which genes are identified in the genome sequence.

  10. Human genome. 1993 Program report

    SciTech Connect

    Not Available

    1994-03-01

    The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

  11. Computational Challenges of Personal Genomics

    PubMed Central

    Bolouri, Hamid

    2008-01-01

    It is widely predicted that cost and efficiency gains in sequencing will usher in an era of personal genomics and personalized, predictive, preventive, and participatory medicine within a decade. I review the computational challenges ahead and propose general and specific directions for research and development. There is an urgent need to develop semantic ontologies that span genomics, molecular systems biology, and medical data. Although the development of such ontologies would be costly and difficult, the benefits will far outweigh the costs. I argue that availability of such ontologies would allow a revolution in web-services for personal genomics and medicine. PMID:19440448

  12. Deep whole-genome sequencing of 90 Han Chinese genomes.

    PubMed

    Lan, Tianming; Lin, Haoxiang; Zhu, Wenjuan; Laurent, Tellier Christian Asker Melchior; Yang, Mengcheng; Liu, Xin; Wang, Jun; Wang, Jian; Yang, Huanming; Xu, Xun; Guo, Xiaosen

    2017-09-01

    Next-generation sequencing provides a high-resolution insight into human genetic information. However, the focus of previous studies has primarily been on low-coverage data due to the high cost of sequencing. Although the 1000 Genomes Project and the Haplotype Reference Consortium have both provided powerful reference panels for imputation, low-frequency and novel variants remain difficult to discover and call with accuracy on the basis of low-coverage data. Deep sequencing provides an optimal solution for the problem of these low-frequency and novel variants. Although whole-exome sequencing is also a viable choice for exome regions, it cannot account for noncoding regions, sometimes resulting in the absence of important, causal variants. For Han Chinese populations, the majority of variants have been discovered based upon low-coverage data from the 1000 Genomes Project. However, high-coverage, whole-genome sequencing data are limited for any population, and a large amount of low-frequency, population-specific variants remain uncharacterized. We have performed whole-genome sequencing at a high depth (∼×80) of 90 unrelated individuals of Chinese ancestry, collected from the 1000 Genomes Project samples, including 45 Northern Han Chinese and 45 Southern Han Chinese samples. Eighty-three of these 90 have been sequenced by the 1000 Genomes Project. We have identified 12 568 804 single nucleotide polymorphisms, 2 074 210 short InDels, and 26 142 structural variations from these 90 samples. Compared to the Han Chinese data from the 1000 Genomes Project, we have found 7 000 629 novel variants with low frequency (defined as minor allele frequency < 5%), including 5 813 503 single nucleotide polymorphisms, 1 169 199 InDels, and 17 927 structural variants. Using deep sequencing data, we have built a greatly expanded spectrum of genetic variation for the Han Chinese genome. Compared to the 1000 Genomes Project, these Han Chinese deep sequencing data enhance the

  13. The Materials Genome Project

    NASA Astrophysics Data System (ADS)

    Aourag, H.

    2008-09-01

    In the past, the search for new and improved materials was characterized mostly by the use of empirical, trial- and-error methods. This picture of materials science has been changing as the knowledge and understanding of fundamental processes governing a material's properties and performance (namely, composition, structure, history, and environment) have increased. In a number of cases, it is now possible to predict a material's properties before it has even been manufactured thus greatly reducing the time spent on testing and development. The objective of modern materials science is to tailor a material (starting with its chemical composition, constituent phases, and microstructure) in order to obtain a desired set of properties suitable for a given application. In the short term, the traditional "empirical" methods for developing new materials will be complemented to a greater degree by theoretical predictions. In some areas, computer simulation is already used by industry to weed out costly or improbable synthesis routes. Can novel materials with optimized properties be designed by computers? Advances in modelling methods at the atomic level coupled with rapid increases in computer capabilities over the last decade have led scientists to answer this question with a resounding "yes'. The ability to design new materials from quantum mechanical principles with computers is currently one of the fastest growing and most exciting areas of theoretical research in the world. The methods allow scientists to evaluate and prescreen new materials "in silico" (in vitro), rather than through time consuming experimentation. The Materials Genome Project is to pursue the theory of large scale modeling as well as powerful methods to construct new materials, with optimized properties. Indeed, it is the intimate synergy between our ability to predict accurately from quantum theory how atoms can be assembled to form new materials and our capacity to synthesize novel materials atom

  14. Genomics, environmental genomics and the issue of microbial species.

    PubMed

    Ward, D M; Cohan, F M; Bhaya, D; Heidelberg, J F; Kühl, M; Grossman, A

    2008-02-01

    A microbial species concept is crucial for interpreting the variation detected by genomics and environmental genomics among cultivated microorganisms and within natural microbial populations. Comparative genomic analyses of prokaryotic species as they are presently described and named have led to the provocative idea that prokaryotes may not form species as we think about them for plants and animals. There are good reasons to doubt whether presently recognized prokaryotic species are truly species. To achieve a better understanding of microbial species, we believe it is necessary to (i) re-evaluate traditional approaches in light of evolutionary and ecological theory, (ii) consider that different microbial species may have evolved in different ways and (iii) integrate genomic, metagenomic and genome-wide expression approaches with ecological and evolutionary theory. Here, we outline how we are using genomic methods to (i) identify ecologically distinct populations (ecotypes) predicted by theory to be species-like fundamental units of microbial communities, and (ii) test their species-like character through in situ distribution and gene expression studies. By comparing metagenomic sequences obtained from well-studied hot spring cyanobacterial mats with genomic sequences of two cultivated cyanobacterial ecotypes, closely related to predominant native populations, we can conduct in situ population genetics studies that identify putative ecotypes and functional genes that determine the ecotypes' ecological distinctness. If individuals within microbial communities are found to be grouped into ecologically distinct, species-like populations, knowing about such populations should guide us to a better understanding of how genomic variation is linked to community function.

  15. Genome Update. Let the consumer beware: Streptomyces genome sequence quality.

    PubMed

    Studholme, David J

    2016-01-01

    A genome sequence assembly represents a model of a genome. This article explores some tools and methods for assessing the quality of an assembly, using publicly available data for Streptomyces species as the example. There is great variability in quality of assemblies deposited in GenBank. Only in a small minority of these assemblies are the raw data available, enabling full appraisal of the assembly quality.

  16. Challenges in Whole-Genome Annotation of Pyrosequenced Eukaryotic Genomes

    SciTech Connect

    Kuo, Alan; Grigoriev, Igor

    2009-04-17

    Pyrosequencing technologies such as 454/Roche and Solexa/Illumina vastly lower the cost of nucleotide sequencing compared to the traditional Sanger method, and thus promise to greatly expand the number of sequenced eukaryotic genomes. However, the new technologies also bring new challenges such as shorter reads and new kinds and higher rates of sequencing errors, which complicate genome assembly and gene prediction. At JGI we are deploying 454 technology for the sequencing and assembly of ever-larger eukaryotic genomes. Here we describe our first whole-genome annotation of a purely 454-sequenced fungal genome that is larger than a yeast (>30 Mbp). The pezizomycotine (filamentous ascomycote) Aspergillus carbonarius belongs to the Aspergillus section Nigri species complex, members of which are significant as platforms for bioenergy and bioindustrial technology, as members of soil microbial communities and players in the global carbon cycle, and as agricultural toxigens. Application of a modified version of the standard JGI Annotation Pipeline has so far predicted ~;;10k genes. ~;;12percent of these preliminary annotations suffer a potential frameshift error, which is somewhat higher than the ~;;9percent rate in the Sanger-sequenced and conventionally assembled and annotated genome of fellow Aspergillus section Nigri member A. niger. Also,>90percent of A. niger genes have potential homologs in the A. carbonarius preliminary annotation. Weconclude, and with further annotation and comparative analysis expect to confirm, that 454 sequencing strategies provide a promising substrate for annotation of modestly sized eukaryotic genomes. We will also present results of annotation of a number of other pyrosequenced fungal genomes of bioenergy interest.

  17. Identification of genomic sites for CRISPR/Cas9-based genome editing in the Vitis vinifera genome

    USDA-ARS?s Scientific Manuscript database

    CRISPR/Cas9 has been recently demonstrated as an effective and popular genome editing tool for modifying genomes of human, animals, microorganisms, and plants. Success of such genome editing is highly dependent on the availability of suitable target sites in the genomes to be edited. Many specific t...

  18. Natural Genomic Design in Sinorhizobium meliloti: Novel Genomic Architectures

    PubMed Central

    Guo, Xianwu; Flores, Margarita; Mavingui, Patrick; Fuentes, Sara Isabel; Hernández, Georgina; Dávila, Guillermo; Palacios, Rafael

    2003-01-01

    The complete nucleotide sequence of the genome of Sinorhizobium meliloti, the symbiont of alfalfa, was reported in 2001 by an international consortium of laboratories. The genome comprises a chromosome of 3.65 megabases (Mb) and two megaplasmids, pSymA and pSymB, of 1.35 Mb and 1.68 Mb, respectively. Based on the nucleotide sequence of the whole genome, we designed a pathway of consecutive rearrangements leading to novel genomic architectures. In a first step we obtained derivative strains containing two replicons; in a second step we obtained a strain containing the genetic information in one single replicon of 6.68 MB. From this last architecture we isolated revertants containing two replicons, and from these we could return to the original architecture showing the three replicons. We found that the relative frequency of excision of cointegrated replicons is higher at the site used for the cointegration than at other sites. This might conciliate two apparently opposed facts: the highly dynamic state of genomic architecture in S. meliloti and the common observation that different isolates and derived cellular clones of S. meliloti usually present the architecture of one chromosome and two distinct megaplasmids. Different aspects that must be considered to obtain full advantage of the strategy of natural genomic design are discussed. PMID:12902376

  19. Natural genomic design in Sinorhizobium meliloti: novel genomic architectures.

    PubMed

    Guo, Xianwu; Flores, Margarita; Mavingui, Patrick; Fuentes, Sara Isabel; Hernández, Georgina; Dávila, Guillermo; Palacios, Rafael

    2003-08-01

    The complete nucleotide sequence of the genome of Sinorhizobium meliloti, the symbiont of alfalfa, was reported in 2001 by an international consortium of laboratories. The genome comprises a chromosome of 3.65 megabases (Mb) and two megaplasmids, pSymA and pSymB, of 1.35 Mb and 1.68 Mb, respectively. Based on the nucleotide sequence of the whole genome, we designed a pathway of consecutive rearrangements leading to novel genomic architectures. In a first step we obtained derivative strains containing two replicons; in a second step we obtained a strain containing the genetic information in one single replicon of 6.68 MB. From this last architecture we isolated revertants containing two replicons, and from these we could return to the original architecture showing the three replicons. We found that the relative frequency of excision of cointegrated replicons is higher at the site used for the cointegration than at other sites. This might conciliate two apparently opposed facts: the highly dynamic state of genomic architecture in S. meliloti and the common observation that different isolates and derived cellular clones of S. meliloti usually present the architecture of one chromosome and two distinct megaplasmids. Different aspects that must be considered to obtain full advantage of the strategy of natural genomic design are discussed.

  20. Computational Genomics: From Genome Sequence To Global Gene Regulation

    NASA Astrophysics Data System (ADS)

    Li, Hao

    2000-03-01

    As various genome projects are shifting to the post-sequencing phase, it becomes a big challenge to analyze the sequence data and extract biological information using computational tools. In the past, computational genomics has mainly focused on finding new genes and mapping out their biological functions. With the rapid accumulation of experimental data on genome-wide gene activities, it is now possible to understand how genes are regulated on a genomic scale. A major mechanism for gene regulation is to control the level of transcription, which is achieved by regulatory proteins that bind to short DNA sequences - the regulatory elements. We have developed a new approach to identifying regulatory elements in genomes. The approach formalizes how one would proceed to decipher a ``text'' consisting of a long string of letters written in an unknown language that did not delineate words. The algorithm is based on a statistical mechanics model in which the sequence is segmented probabilistically into ``words'' and a ``dictionary'' of ``words'' is built concurrently. For the control regions in the yeast genome, we built a ``dictionary'' of about one thousand words which includes many known as well as putative regulatory elements. I will discuss how we can use this dictionary to search for genes that are likely to be regulated in a similar fashion and to analyze gene expression data generated from DNA micro-array experiments.

  1. Invisible genomes: the genomics revolution and patenting practice.

    PubMed

    Bostanci, Adam; Calvert, Jane

    2008-03-01

    In the mid-1990s, the company Human Genome Sciences submitted three potentially revolutionary patent applications to the US Patent and Trademark Office, each of which claimed the entire genome sequence of a microorganism. The patent examiners, however, objected to these applications, and after negotiation they were eventually re-written to resemble more traditional gene patents. In this paper, which is based on a study of the patent examination files, we examine the reasons why these patent applications were unsuccessful in their original form. We show that with respect to utility and novelty, the patent attorney's case built on an understanding of the genome as a computer-related invention. The patent examiners did not object to the patenting of complete genome sequences as computer-related inventions on moral grounds or in terms of the distinction between a discovery and an invention. Instead, their objections were based on classification, rules and procedure. Rather than patent examiners having a notion of a genome that should not be patented, the notion of a 'genome', and the ways in which it may be different from a 'gene', played no role in these debates. We discuss the consequences of our findings for patenting in the biosciences.

  2. The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine.

    PubMed

    2012-08-01

    The Global Cancer Genomics Consortium (GCGC) is an international collaborative platform that amalgamates cancer biologists, cutting-edge genomics, and high-throughput expertise with medical oncologists and surgical oncologists; they address the most important translational questions that are central to cancer research and treatment. The annual GCGC symposium was held at the Advanced Centre for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to 11, 2011. The symposium showcased international next-generation sequencing efforts that explore cancer-specific transcriptomic changes, single-nucleotide polymorphism, and copy number variations in various types of cancers, as well as the structural genomics approach to develop new therapeutic targets and chemical probes. From the spectrum of studies presented at the symposium, it is evident that the translation of emerging cancer genomics knowledge into clinical applications can only be achieved through the integration of multidisciplinary expertise. In summary, the GCGC symposium provided practical knowledge on structural and cancer genomics approaches, as well as an exclusive platform for focused cancer genomics endeavors. ©2012 AACR.

  3. SMART on FHIR Genomics: facilitating standardized clinico-genomic apps.

    PubMed

    Alterovitz, Gil; Warner, Jeremy; Zhang, Peijin; Chen, Yishen; Ullman-Cullere, Mollie; Kreda, David; Kohane, Isaac S

    2015-11-01

    Supporting clinical decision support for personalized medicine will require linking genome and phenome variants to a patient's electronic health record (EHR), at times on a vast scale. Clinico-genomic data standards will be needed to unify how genomic variant data are accessed from different sequencing systems. A specification for the basis of a clinic-genomic standard, building upon the current Health Level Seven International Fast Healthcare Interoperability Resources (FHIR®) standard, was developed. An FHIR application protocol interface (API) layer was attached to proprietary sequencing platforms and EHRs in order to expose gene variant data for presentation to the end-user. Three representative apps based on the SMART platform were built to test end-to-end feasibility, including integration of genomic and clinical data. Successful design, deployment, and use of the API was demonstrated and adopted by HL7 Clinical Genomics Workgroup. Feasibility was shown through development of three apps by various types of users with background levels and locations. This prototyping work suggests that an entirely data (and web) standards-based approach could prove both effective and efficient for advancing personalized medicine. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Valorization of lubricant-based wastewater for bacterial neutral lipids production: Growth-linked biosynthesis.

    PubMed

    Da Silva, Pedro D M P; Lima, Filipa; Alves, Maria Madalena; Bijmans, Martijn F M; Pereira, Maria Alcina

    2016-09-15

    Lipids produced by microorganisms are currently of great interest as raw material for either biofuels or oleochemicals production. Significant biosynthesis of neutral lipids, such as triacylglycerol (TAG) and wax esters (WE) are thought to be limited to a few strains. Hydrocarbonoclastic bacteria (HCB), key players in bioremediation of hydrocarbon contaminated ecosystems, are among this group of strains. Hydrocarbon rich wastewaters have been overlooked concerning their potential as raw material for microbial lipids production. In this study, lubricant-based wastewater was fed, as sole carbon source, to two HCB representative wild strains: Alcanivorax borkumensis SK2, and Rhodococcus opacus PD630. Neutral lipid production was observed with both strains cultivated under uncontrolled conditions of pH and dissolved oxygen. A. borkumensis SK2 was further investigated in a pH- and OD-controlled fermenter. Different phases were assessed separately in terms of lipids production and alkanes removal. The maximum TAG production rate occurred during stationary phase (4 mg-TAG/L h). The maximum production rate of WE-like compounds was 15 mg/L h, and was observed during exponential growth phase. Hydrocarbons removal was 97% of the gas chromatography (GC) resolved straight-chain alkanes. The maximum removal rate was observed during exponential growth phase (6 mg-alkanes/L h). This investigation proposes a novel approach for the management of lubricant waste oil, aiming at its conversion into valuable lipids. The feasibility of the concept is demonstrated under low salt (0.3%) and saline (3.3%) conditions, and presents clues for its technological development, since growth associated oil production opens the possibility for establishing continuous fermentation processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Comparative genomic analysis of sixty mycobacteriophage genomes: Genome clustering, gene acquisition and gene size

    PubMed Central

    Hatfull, Graham F.; Jacobs-Sera, Deborah; Lawrence, Jeffrey G.; Pope, Welkin H.; Russell, Daniel A.; Ko, Ching-Chung; Weber, Rebecca J.; Patel, Manisha C.; Germane, Katherine L.; Edgar, Robert H.; Hoyte, Natasha N.; Bowman, Charles A.; Tantoco, Anthony T.; Paladin, Elizabeth C.; Myers, Marlana S.; Smith, Alexis L.; Grace, Molly S.; Pham, Thuy T.; O'Brien, Matthew B.; Vogelsberger, Amy M.; Hryckowian, Andrew J.; Wynalek, Jessica L.; Donis-Keller, Helen; Bogel, Matt W.; Peebles, Craig L.; Cresawn, Steve G.; Hendrix, Roger W.

    2010-01-01

    Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of sixty – all infecting a common bacterial host – provides further insight into their diversity and evolution. Of the sixty phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, five of which can be further divided into subclusters; five genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the six genomes in cluster D share more than 97.5% average nucleotide similarity with each other. In contrast, similarity between the two genomes in Cluster I is barely detectable by diagonal plot analysis. The total of 6,858 predicted ORFs have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit smaller average size than genes of their host (205 residues compared to 315), phage genes in higher flux average only ∼100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains. PMID:20064525

  6. The soft genome

    PubMed Central

    Anava, Sarit; Posner, Rachel; Rechavi, Oded

    2014-01-01

    Caenorhabditis elegans (C. elegans) nematodes transmit small RNAs across generations, a process that enables transgenerational regulation of genes. In contrast to changes to the DNA sequence, transgenerational transmission of small RNA-mediated responses is reversible, and thus enables “soft” or “flexible” inheritance of acquired characteristics. Until very recently only introduction of foreign genetic material (viruses, transposons, transgenes) was shown to directly lead to inheritance of small RNAs. New discoveries however, demonstrate that starvation also triggers inheritance of endogenous small RNAs in C.elegans. Multiple generations of worms inherit starvation-responsive endogenous small RNAs, and starvation also results in heritable extension of the progeny's lifespan. In this Commentary paper we explore the intriguing possibility that large parts of the genome and many additional traits are similarly subjected to heritable small RNA-mediated regulation, and focus on the potential influence of transgenerational RNAi on the worm's physiology. While the universal relevance of this mechanism remains to be discovered, we will examine how the discoveries made in worms already challenge long held dogmas in genetics and evolution. PMID:26430554

  7. inGeno – an integrated genome and ortholog viewer for improved genome to genome comparisons

    PubMed Central

    Liang, Chunguang; Dandekar, Thomas

    2006-01-01

    Background Systematic genome comparisons are an important tool to reveal gene functions, pathogenic features, metabolic pathways and genome evolution in the era of post-genomics. Furthermore, such comparisons provide important clues for vaccines and drug development. Existing genome comparison software often lacks accurate information on orthologs, the function of similar genes identified and genome-wide reports and lists on specific functions. All these features and further analyses are provided here in the context of a modular software tool "inGeno" written in Java with Biojava subroutines. Results InGeno provides a user-friendly interactive visualization platform for sequence comparisons (comprehensive reciprocal protein – protein comparisons) between complete genome sequences and all associated annotations and features. The comparison data can be acquired from several different sequence analysis programs in flexible formats. Automatic dot-plot analysis includes output reduction, filtering, ortholog testing and linear regression, followed by smart clustering (local collinear blocks; LCBs) to reveal similar genome regions. Further, the system provides genome alignment and visualization editor, collinear relationships and strain-specific islands. Specific annotations and functions are parsed, recognized, clustered, logically concatenated and visualized and summarized in reports. Conclusion As shown in this study, inGeno can be applied to study and compare in particular prokaryotic genomes against each other (gram positive and negative as well as close and more distantly related species) and has been proven to be sensitive and accurate. This modular software is user-friendly and easily accommodates new routines to meet specific user-defined requirements. PMID:17054788

  8. [Plant rhabdoviruses with bipartite genomes].

    PubMed

    Kondo, Hideki

    2013-01-01

    Members of the family Rhabdoviridae (order Mononegavirales) have a broad range of hosts, including humans, livestock, fish, plants, and invertebrates. They have a nonsegmented negative-sense RNA as the genome. Orchid fleck virus (OFV) is distributed world-wide on several orchid plants and transmitted by the false spider mite, Brevipalpus californicus. Based on its virions morphology and cytopathic effects in the infected cells, OFV was tentatively placed as unassigned plant rhabdoviruses in the sixth ICTV Report. However, the molecular studies reveled that OFV has a unique two-segmented negative-sense RNA genome that resembles monopartite genomes of plant nucleorhabdoviruses. In this review, we describe the current knowledge on the genome structure and gene expression strategy of OFV, the possible mechanism of nuclear viroplasm formation, and the taxonomical consideration of the virus as well.

  9. Genomic Contraindications for Heart Transplantation.

    PubMed

    Char, Danton S; Lázaro-Muñoz, Gabriel; Barnes, Aliessa; Magnus, David; Deem, Michael J; Lantos, John D

    2017-03-02

    Genome sequencing raises new ethical challenges. Decoding the genome produces new forms of diagnostic and prognostic information; however, the information is often difficult to interpret. The connection between most genetic variants and their phenotypic manifestations is not understood. This scenario is particularly true for disorders that are not associated with an autosomal genetic variant. The analytic uncertainty is compounded by moral uncertainty about how, exactly, the results of genomic testing should influence clinical decisions. In this Ethics Rounds, we present a case in which genomic findings seemed to play a role in deciding whether a patient was to be listed as a transplant candidate. We then asked experts in bioethics and cardiology to discuss the implications of such decisions.

  10. Genome engineering in human cells.

    PubMed

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  11. Genomics and Health Impact Update

    MedlinePlus

    ... Publications Birth Defects/ Child Health Cancer Cardiovascular Diseases Chronic Disease Ethics, Policy and Law Genomics in Practice Newborn Screening Pharmacogenomics Reproductive Health Tools/ Databases AMD Clips News Concepts/ Comments Pathogenicity/ Antimicrobial Resistance Epidemiology/ ...

  12. Collaborators | Office of Cancer Genomics

    Cancer.gov

    The TARGET initiative is jointly managed within the National Cancer Institute (NCI) by the Office of Cancer Genomics (OCG)Opens in a New Tab and the Cancer Therapy Evaluation Program (CTEP)Opens in a New Tab.

  13. Evolutionary genomics: transdomain gene transfers.

    PubMed

    Bordenstein, Seth R

    2007-11-06

    Biologists have until now conceded that bacterial gene transfer to multicellular animals is relatively uncommon in Nature. A new study showing promiscuous insertions of bacterial endosymbiont genes into invertebrate genomes ushers in a shift in this paradigm.

  14. Genomic Resources for Cancer Epidemiology

    Cancer.gov

    This page provides links to research resources, complied by the Epidemiology and Genomics Research Program, that may be of interest to genetic epidemiologists conducting cancer research, but is not exhaustive.

  15. Genomics and equal opportunity ethics.

    PubMed

    Cappelen, A W; Norheim, O F; Tungodden, B

    2008-05-01

    Genomics provides information on genetic susceptibility to diseases and new possibilities for interventions which can fundamentally alter the design of fair health policies. The aim of this paper is to explore implications of genomics from the perspective of equal opportunity ethics. The ideal of equal opportunity requires that individuals are held responsible for some, but not all, factors that affect their health. Informational problems, however, often make it difficult to implement the ideal of equal opportunity in the context of healthcare. In this paper, examples are considered of how new genetic information may affect the way individual responsibility for choice is assigned. It is also argued that genomics may result in relocation of the responsibility cut by providing both new information and new technology. Finally, how genomics may affect healthcare policies and the market for health insurance is discussed.

  16. Recent advances in crustacean genomics.

    PubMed

    Stillman, Jonathon H; Colbourne, John K; Lee, Carol E; Patel, Nipam H; Phillips, Michelle R; Towle, David W; Eads, Brian D; Gelembuik, Greg W; Henry, Raymond P; Johnson, Eric A; Pfrender, Michael E; Terwilliger, Nora B

    2008-12-01

    Crustaceans are a diverse and ancient group of arthropods that have long been studied as interesting model systems in biology, especially for understanding animal evolution and physiology and for environmentally relevant studies. Like many model systems, advances in DNA-sequencing methodologies have led to a large amount of genomics-related projects. The purpose of this article is to highlight the genome projects and functional genomics (transcriptomics) projects that are currently underway in crustacean biology. Specifically, we have surveyed the amount of publicly available DNA sequence data (both genomic and EST data) across all crustacean taxa for which a significant number of DNA sequences have been generated. Several ongoing projects are presented including the ecology of invasive species, thermal physiology, ion and water balance, ecology and evolutionary biology, and developmental biology.

  17. Genomic characterization of Nontuberculous Mycobacteria

    PubMed Central

    Fedrizzi, Tarcisio; Meehan, Conor J.; Grottola, Antonella; Giacobazzi, Elisabetta; Fregni Serpini, Giulia; Tagliazucchi, Sara; Fabio, Anna; Bettua, Clotilde; Bertorelli, Roberto; De Sanctis, Veronica; Rumpianesi, Fabio; Pecorari, Monica; Jousson, Olivier; Tortoli, Enrico; Segata, Nicola

    2017-01-01

    Mycobacterium tuberculosis and Mycobacterium leprae have remained, for many years, the primary species of the genus Mycobacterium of clinical and microbiological interest. The other members of the genus, referred to as nontuberculous mycobacteria (NTM), have long been underinvestigated. In the last decades, however, the number of reports linking various NTM species with human diseases has steadily increased and treatment difficulties have emerged. Despite the availability of whole genome sequencing technologies, limited effort has been devoted to the genetic characterization of NTM species. As a consequence, the taxonomic and phylogenetic structure of the genus remains unsettled and genomic information is lacking to support the identification of these organisms in a clinical setting. In this work, we widen the knowledge of NTMs by reconstructing and analyzing the genomes of 41 previously uncharacterized NTM species. We provide the first comprehensive characterization of the genomic diversity of NTMs and open new venues for the clinical identification of opportunistic pathogens from this genus. PMID:28345639

  18. Genomic Datasets for Cancer Research

    Cancer.gov

    A variety of datasets from genome-wide association studies of cancer and other genotype-phenotype studies, including sequencing and molecular diagnostic assays, are available to approved investigators through the Extramural National Cancer Institute Data Access Committee.

  19. Genomic medicine and data sharing.

    PubMed

    Raza, Sobia; Hall, Alison

    2017-09-01

    Effective data sharing does not occur in the UK despite being essential for the delivery of high-quality genomic services to patients across clinical specialities and to optimize advances in genomic medicine. Original papers, reviews, guidelines, policy papers and web-resources. Data sharing for genomic medicine requires appropriate infrastructure and policies, together with acceptance by health professionals and the public of the necessity of data sharing for clinical care. There is ongoing debate around the different technical approaches and safeguards that could be used to facilitate data sharing while minimizing the risks to individuals of identification. Lack of consensus undermines trust and confidence. Ongoing policy developments around genomics and health data create opportunities to ensure systems and policies are in place to support proportionate, effective and safeguarded data sharing. Mechanisms to improve public trust.

  20. Genomic understanding of glioblastoma expanded

    Cancer.gov

    Glioblastoma multiforme (GBM) was the first cancer type to be systematically studied by TCGA in 2008. In a new, complementary report, TCGA experts examined more than 590 GBM samples--the largest to date utilizing genomic characterization techniques and ne

  1. Do Echinoderm Genomes Measure Up?

    PubMed Central

    Cameron, R. Andrew; Kudtarkar, Parul; Gordon, Susan M.; Worley, Kim C.; Gibbs, Richard A.

    2015-01-01

    Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org. PMID:25701080

  2. The circadian clock goes genomic.

    PubMed

    Staiger, Dorothee; Shin, Jieun; Johansson, Mikael; Davis, Seth J

    2013-06-24

    Large-scale biology among plant species, as well as comparative genomics of circadian clock architecture and clock-regulated output processes, have greatly advanced our understanding of the endogenous timing system in plants.

  3. Collaborators | Office of Cancer Genomics

    Cancer.gov

    The TARGET initiative is jointly managed within the National Cancer Institute (NCI) by the Office of Cancer Genomics (OCG)Opens in a New Tab and the Cancer Therapy Evaluation Program (CTEP)Opens in a New Tab.

  4. Eukaryotic Genomics Data from the DOE Joint Genome Institute (JGI)

    DOE Data Explorer

    The JGI makes high-quality genome sequencing data freely available to the greater scientific community through its web portal. Having played a significant role in the federally funded Human Genome Project -- generating the complete sequences of Chromosomes 5, 16, and 19--the JGI has now moved on to contributing in other critical areas of genomics research. While NIH-funded genome sequencing activities continue to emphasize human biomedical targets and applications, the JGI has since shifted its focus to the non-human components of the biosphere, particularly those relevant to the science mission of the Department of Energy. With efficiencies of scale established at the PGF, and capacity now exceeding three billion bases generated on a monthly basis, the JGI has tackled scores of additional genomes. These include more than 60 microbial genomes and many important multicellular organisms and communities of microbes. In partnership with other federal institutions and universities, the JGI is in the process of sequencing a frog (Xenopus tropicalis), a green alga (Chlamydomonas reinhardtii), a diatom (Thalassiosira pseudonana) , the cottonwood tree (Populus trichocarpa), and a host of agriculturally important plants and plant pathogens. Microorganisms, for example those that thrive under extreme conditions such as high acidity, radiation, and metal contamination, are of particular interest to the DOE and JGI. Investigations by JGI and its partners are shedding light on the cellular machinery of microbes and how they can be harnessed to clean up contaminated soil or water, capture carbon from the atmosphere, and produce potentially important sources of energy such as hydrogen and methane. [Excerpt from the JGI page "Who We Are" at http://www.jgi.doe.gov/whoweare/whoweare.html] From the JGI webportal users can choose Eukaryotic genomes from a photo list, access the JGI FTP directories to download data files, use the Tree of Life navigation tool, or choose a genome and go

  5. Genome sequences and great expectations

    PubMed Central

    Iliopoulos, Ioannis; Tsoka, Sophia; Andrade, Miguel A; Janssen, Paul; Audit, Benjamin; Tramontano, Anna; Valencia, Alfonso; Leroy, Christophe; Sander, Chris; Ouzounis, Christos A

    2001-01-01

    To assess how automatic function assignment will contribute to genome annotation in the next five years, we have performed an analysis of 31 available genome sequences. An emerging pattern is that function can be predicted for almost two-thirds of the 73,500 genes that were analyzed. Despite progress in computational biology, there will always be a great need for large-scale experimental determination of protein function. PMID:11178275

  6. Plague in the genomic area.

    PubMed

    Drancourt, M

    2012-03-01

    With plague being not only a subject of interest for historians, but still a disease of public health concern in several countries, mainly in Africa, there were hopes that analyses of the Yersinia pestis genomes would put an end to this deadly epidemic pathogen. Genomics revealed that Y. pestis isolates evolved from Yersinia pseudotuberculosis in Central Asia some millennia ago, after the acquisition of two Y. pestis-specific plasmids balanced genomic reduction parallel with the expansion of insertion sequences, illustrating the modern concept that, except for the acquisition of plasmid-borne toxin-encoding genes, the increased virulence of Y. pestis resulted from gene loss rather than gene acquisition. The telluric persistence of Y. pestis reminds us of this close relationship, and matters in terms of plague epidemiology. Whereas biotype Orientalis isolates spread worldwide, the Antiqua and Medievalis isolates showed more limited expansion. In addition to animal ectoparasites, human ectoparasites such as the body louse may have participated in this expansion and in devastating historical epidemics. The recent analysis of a Black Death genome indicated that it was more closely related to the Orientalis branch than to the Medievalis branch. Modern Y. pestis isolates grossly exhibit the same gene content, but still undergo micro-evolution in geographically limited areas by differing in the genome architecture, owing to inversions near insertion sequences and the stabilization of the YpfPhi prophage in Orientalis biotype isolates. Genomics have provided several new molecular tools for the genotyping and phylogeographical tracing of isolates and description of plague foci. However, genomics and post-genomics approaches have not yet provided new tools for the prevention, diagnosis and management of plague patients and the plague epidemics still raging in some sub-Saharan countries. © 2012 The Author. Clinical Microbiology and Infection © 2012 European Society of

  7. Genome Exploitation and Bioinformatics Tools

    NASA Astrophysics Data System (ADS)

    de Jong, Anne; van Heel, Auke J.; Kuipers, Oscar P.

    Bioinformatic tools can greatly improve the efficiency of bacteriocin screening efforts by limiting the amount of strains. Different classes of bacteriocins can be detected in genomes by looking at different features. Finding small bacteriocins can be especially challenging due to low homology and because small open reading frames (ORFs) are often omitted from annotations. In this chapter, several bioinformatic tools/strategies to identify bacteriocins in genomes are discussed.

  8. Population Genomics of Paramecium Species.

    PubMed

    Johri, Parul; Krenek, Sascha; Marinov, Georgi K; Doak, Thomas G; Berendonk, Thomas U; Lynch, Michael

    2017-05-01

    Population-genomic analyses are essential to understanding factors shaping genomic variation and lineage-specific sequence constraints. The dearth of such analyses for unicellular eukaryotes prompted us to assess genomic variation in Paramecium, one of the most well-studied ciliate genera. The Paramecium aurelia complex consists of ∼15 morphologically indistinguishable species that diverged subsequent to two rounds of whole-genome duplications (WGDs, as long as 320 MYA) and possess extremely streamlined genomes. We examine patterns of both nuclear and mitochondrial polymorphism, by sequencing whole genomes of 10-13 worldwide isolates of each of three species belonging to the P. aurelia complex: P. tetraurelia, P. biaurelia, P. sexaurelia, as well as two outgroup species that do not share the WGDs: P. caudatum and P. multimicronucleatum. An apparent absence of global geographic population structure suggests continuous or recent dispersal of Paramecium over long distances. Intergenic regions are highly constrained relative to coding sequences, especially in P. caudatum and P. multimicronucleatum that have shorter intergenic distances. Sequence diversity and divergence are reduced up to ∼100-150 bp both upstream and downstream of genes, suggesting strong constraints imposed by the presence of densely packed regulatory modules. In addition, comparison of sequence variation at non-synonymous and synonymous sites suggests similar recent selective pressures on paralogs within and orthologs across the deeply diverging species. This study presents the first genome-wide population-genomic analysis in ciliates and provides a valuable resource for future studies in evolutionary and functional genetics in Paramecium. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Contact | Office of Cancer Genomics

    Cancer.gov

    For more information about the Office of Cancer Genomics, please contact: Office of Cancer Genomics National Cancer Institute 31 Center Drive, 10A07 Bethesda, Maryland 20892-2580 Phone: (240) 781-3280 Fax: (240) 541-4510 Email: ocg@mail.nih.gov *Please note that this site will not function properly in Internet Explorer unless you completely turn off the Compatibility View*

  10. Upstream—News in Genomics

    PubMed Central

    2002-01-01

    This report on the literature spans from May to July, highlighting breakthroughs on several important genomes, including mouse, zebrafish, Fugu and Plasmodium. Recent papers have reported on a mechanism for genome size reduction in Arabidopsis, comparisons and verifications of large-scale protein–protein interaction datasets, developments in RNA interference approaches for mammalian systems and a solidphase peptide tagging method for proteomics. PMID:18629049

  11. Genome shortcut leads to problems

    SciTech Connect

    Anderson, C.

    1993-03-19

    Mega YACs (yeast artificial chromosomes), which can carry DNA sequences up to 1.4 million bases long, were anticipated as a major for mapping the human genome. They have been found to have as much as 80% chimerism, however, and contain many deletions and rearrangements. This makes them useless for high-resolution mapping, but they are effective for connecting points over long distances. Mega YACs are still useful for mapping 95% of the human genome.

  12. A Million Cancer Genome Warehouse

    DTIC Science & Technology

    2012-11-20

    Cibulskis, K., Fennell , T. J., et al. (2010). A map of human genome variation from population scale sequencing. Nature, 467(7319), 1061-1073. 42 Li, H...Handsaker, B., Wysoker, A., Fennell , T., Ruan, J., Homer, N., et al. (2009). The sequence alignment/map format and SAMtools. Bioinformatics, 25(16...Cibulskis, K., Fennell , T. J., et al. (2010). A map of human genome variation from population scale sequencing. Nature, 467(7319), 1061-1073. 93 Lee

  13. Zebrafish genomics comes of age.

    PubMed

    Tan, Haihan; Zsigmond, Aron

    2013-09-01

    The ZF-HEALTH/EuFishBiomed workshop on "Genomics and High-throughput Sequencing Technologies with the Zebrafish Model" took place in December 2012 in Cambridge, United Kingdom. The organisers, Fiona Wardle and Ferenc Müller, brought together developmental biologists, geneticists, and bioinformaticians from Europe and the rest of the world to share findings and insights about the latest genomic capabilities and applications in this popular model organism.

  14. Genomic Landscapes of Pancreatic Neoplasia

    PubMed Central

    Wood, Laura D.; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a deadly disease with a dismal prognosis. However, recent advances in sequencing and bioinformatic technology have led to the systematic characterization of the genomes of all major tumor types in the pancreas. This characterization has revealed the unique genomic landscape of each tumor type. This knowledge will pave the way for improved diagnostic and therapeutic approaches to pancreatic tumors that take advantage of the genetic alterations in these neoplasms. PMID:25812653

  15. Genomic Aspects of Research Involving Polyploid Plants

    SciTech Connect

    Yang, Xiaohan; Ye, Chuyu; Tschaplinski, Timothy J; Wullschleger, Stan D; Tuskan, Gerald A

    2011-01-01

    Almost all extant plant species have spontaneously doubled their genomes at least once in their evolutionary histories, resulting in polyploidy which provided a rich genomic resource for evolutionary processes. Moreover, superior polyploid clones have been created during the process of crop domestication. Polyploid plants generated by evolutionary processes and/or crop domestication have been the intentional or serendipitous focus of research dealing with the dynamics and consequences of genome evolution. One of the new trends in genomics research is to create synthetic polyploid plants which provide materials for studying the initial genomic changes/responses immediately after polyploid formation. Polyploid plants are also used in functional genomics research to study gene expression in a complex genomic background. In this review, we summarize the recent progress in genomics research involving ancient, young, and synthetic polyploid plants, with a focus on genome size evolution, genomics diversity, genomic rearrangement, genetic and epigenetic changes in duplicated genes, gene discovery, and comparative genomics. Implications on plant sciences including evolution, functional genomics, and plant breeding are presented. It is anticipated that polyploids will be a regular subject of genomics research in the foreseeable future as the rapid advances in DNA sequencing technology create unprecedented opportunities for discovering and monitoring genomic and transcriptomic changes in polyploid plants. The fast accumulation of knowledge on polyploid formation, maintenance, and divergence at whole-genome and subgenome levels will not only help plant biologists understand how plants have evolved and diversified, but also assist plant breeders in designing new strategies for crop improvement.

  16. Draft Genome Sequence of Lactobacillus rhamnosus 2166

    PubMed Central

    Melnikov, Vyacheslav G.; Kosarev, Igor V.; Abramov, Vyacheslav M.

    2014-01-01

    In this report, we present a draft sequence of the genome of Lactobacillus rhamnosus strain 2166, a potential novel probiotic. Genome annotation and read mapping onto a reference genome of L. rhamnosus strain GG allowed for the identification of the differences and similarities in the genomic contents and gene arrangements of these strains. PMID:24558254

  17. 2004 Structural, Function and Evolutionary Genomics

    SciTech Connect

    Douglas L. Brutlag Nancy Ryan Gray

    2005-03-23

    This Gordon conference will cover the areas of structural, functional and evolutionary genomics. It will take a systematic approach to genomics, examining the evolution of proteins, protein functional sites, protein-protein interactions, regulatory networks, and metabolic networks. Emphasis will be placed on what we can learn from comparative genomics and entire genomes and proteomes.

  18. The dynamic genome of Hydra

    PubMed Central

    Chapman, Jarrod A.; Kirkness, Ewen F.; Simakov, Oleg; Hampson, Steven E.; Mitros, Therese; Weinmaier, Therese; Rattei, Thomas; Balasubramanian, Prakash G.; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G.; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M.; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E.; Putnam, Nicholas H.; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E.; Gee, Lydia; Kibler, Dennis F.; Law, Lee; Lindgens, Dirk; Martinez, Daniel E.; Peng, Jisong; Wigge, Philip A.; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R. H.; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M.; Wheeler, Benjamin M.; Peterson, Kevin J.; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A.; Strausberg, Robert L.; Venter, J. Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C. G.; Holstein, Thomas W.; Fujisawa, Toshitaka; Bode, Hans R.; David, Charles N.; Rokhsar, Daniel S.; Steele, Robert E.

    2015-01-01

    The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction. PMID:20228792

  19. The dynamic genome of Hydra.

    PubMed

    Chapman, Jarrod A; Kirkness, Ewen F; Simakov, Oleg; Hampson, Steven E; Mitros, Therese; Weinmaier, Thomas; Rattei, Thomas; Balasubramanian, Prakash G; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E; Putnam, Nicholas H; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E; Gee, Lydia; Kibler, Dennis F; Law, Lee; Lindgens, Dirk; Martinez, Daniel E; Peng, Jisong; Wigge, Philip A; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R H; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M; Wheeler, Benjamin M; Peterson, Kevin J; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C G; Holstein, Thomas W; Fujisawa, Toshitaka; Bode, Hans R; David, Charles N; Rokhsar, Daniel S; Steele, Robert E

    2010-03-25

    The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.

  20. Shannon Information in Complete Genomes

    NASA Astrophysics Data System (ADS)

    Hsieh, Li-Ching; Chang, Chang-Heng; Lee, Hoong-Chien

    2004-03-01

    Genomes are books of life and necessarily carry a huge amount of information. This study was first motivated by the question: "How much information do complete genomes have?" As an answer we measured a particular type of Shannon information in all prokaryotes and eukaryotes whose complete genomes have been sequenced and are available in publically assessible database. The Shannon information in complete genome sequences follow an extremely simple pattern. With the exception of one eukaryote the Shannon information in all (more than 200) complete sequences belong to a single universality class given by a simple geometric recursion formula. The data are interpreted in terms of models for genome growth and inferred to suggest that the ancestors of present day genomes began to grow, mainly by stochastic, selectively neutral, duplications and short mutations, most likely when they were not more than 300 nt long. This notion of selective neutralism independently corroborates Kimura's neutral theory of evolution which was based on the investigation of polymorphisms of genes.

  1. Integrating genomics into Eucalyptus breeding.

    PubMed

    Grattapaglia, Dario

    2004-09-30

    The advent of high throughput genomic technologies has opened new perspectives in the speed, scale and detail with which one can investigate genes, genomes and complex traits in Eucalyptus species. A genomic approach to a more detailed understanding of important metabolic and physiological processes, which affect tree growth and stress resistance, and the identification of genes and their allelic variants, which determine the major chemical and physical features of wood properties, should eventually lead to new opportunities for directed genetic modifications of far-reaching economic impact in forest industry. It should be kept in mind, however, that basic breeding strategies, coupled with sophisticated quantitative methods, breeder's experience and breeder's intuition, will continue to generate significant genetic gains and have a clear measurable impact on production forestry. Even with a much more global view of genetic processes, genomics will only succeed in contributing to the development of improved industrial forests if it is strongly interconnected with intensive fieldwork and creative breeding. Integrated genomic projects involving multi-species expressed sequence tag sequencing and quantitative trait locus detection, single nucleotide polymorphism discovery for association mapping, and the development of a gene-rich physical map for the Eucalyptus genome will quickly move toward linking phenotypes to genes that control the wood formation processes that define industrial-level traits. Exploiting the full power of the superior natural phenotypic variation in wood properties found in Eucalyptus genetic resources will undoubtedly be a key factor to reach this goal.

  2. Genome position and gene amplification.

    PubMed

    Gajduskova, Pavla; Snijders, Antoine M; Kwek, Serena; Roydasgupta, Ritu; Fridlyand, Jane; Tokuyasu, Taku; Pinkel, Daniel; Albertson, Donna G

    2007-01-01

    Amplifications, regions of focal high-level copy number change, lead to overexpression of oncogenes or drug resistance genes in tumors. Their presence is often associated with poor prognosis; however, the use of amplification as a mechanism for overexpression of a particular gene in tumors varies. To investigate the influence of genome position on propensity to amplify, we integrated a mutant form of the gene encoding dihydrofolate reductase into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells. We observed site-specific differences in methotrexate sensitivity, amplicon organization and amplification frequency. One site was uniquely associated with a significantly enhanced propensity to amplify and recurrent amplicon boundaries, possibly implicating a rare folate-sensitive fragile site in initiating amplification. Hierarchical clustering of gene expression patterns and subsequent gene enrichment analysis revealed two clusters differing significantly in expression of MYC target genes independent of integration site. These studies suggest that genome context together with the particular challenges to genome stability experienced during the progression to cancer contribute to the propensity to amplify a specific oncogene or drug resistance gene, whereas the overall functional response to drug (or other) challenge may be independent of the genomic location of an oncogene.

  3. Genomics and marine microbial ecology.

    PubMed

    Pedrós-Alió, Carlos

    2006-09-01

    Genomics has brought about a revolution in all fields of biology. Before the development of microbial ecology in the 1970s, microbes were not even considered in marine ecological studies. Today we know that half of the total primary production of the planet must be credited to microorganisms. This and other discoveries have changed dramatically the perspective and the focus of marine microbial ecology. The application of genomics-based approaches has provided new challenges and has allowed the discovery of novel functions, an appreciation of the great diversity of microorganisms, and the introduction of controversial ideas regarding the concepts of species, genome, and niche. Nevertheless, thorough knowledge of the traditional disciplines of biology is necessary to explore the possibilities arising from these new insights. This work reviews the different genomic techniques that can be applied to marine microbial ecology, including both sequencing of the complete genomes of microorganisms and metagenomics, which, in turn, can be complemented with the study of mRNAs (transcriptomics) and proteins (proteomics). The example of proteorhodopsin illustrates the type of information that can be gained from these approaches. A genomics perspective constitutes a map that will allow microbiologists to focus their research on potentially more productive aspects.

  4. Implementing genomic medicine in pathology.

    PubMed

    Williams, Eli S; Hegde, Madhuri

    2013-07-01

    The finished sequence of the Human Genome Project, published 50 years after Watson and Crick's seminal paper on the structure of DNA, pushed human genetics into the public eye and ushered in the genomic era. A significant, if overlooked, aspect of the race to complete the genome was the technology that propelled scientists to the finish line. DNA sequencing technologies have become more standardized, automated, and capable of higher throughput. This technology has continued to grow at an astounding rate in the decade since the Human Genome Project was completed. Today, massively parallel sequencing, or next-generation sequencing (NGS), allows the detection of genetic variants across the entire genome. This ability has led to the identification of new causes of disease and is changing the way we categorize, treat, and manage disease. NGS approaches such as whole-exome sequencing and whole-genome sequencing are rapidly becoming an affordable genetic testing strategy for the clinical laboratory. One test can now provide vast amounts of health information pertaining not only to the disease of interest, but information that may also predict adult-onset disease, reveal carrier status for a rare disease and predict drug responsiveness. The issue of what to do with these incidental findings, along with questions pertaining to NGS testing strategies, data interpretation and storage, and applying genetic testing results into patient care, remains without a clear answer. This review will explore these issues and others relevant to the implementation of NGS in the clinical laboratory.

  5. Rat Genome and Model Resources.

    PubMed

    Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

    2017-07-01

    Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

  6. Comparative genomic analyses in Asparagus.

    PubMed

    Kuhl, Joseph C; Havey, Michael J; Martin, William J; Cheung, Foo; Yuan, Qiaoping; Landherr, Lena; Hu, Yi; Leebens-Mack, James; Town, Christopher D; Sink, Kenneth C

    2005-12-01

    Garden asparagus (Asparagus officinalis L.) belongs to the monocot family Asparagaceae in the order Asparagales. Onion (Allium cepa L.) and Asparagus officinalis are 2 of the most economically important plants of the core Asparagales, a well supported monophyletic group within the Asparagales. Coding regions in onion have lower GC contents than the grasses. We compared the GC content of 3374 unique expressed sequence tags (ESTs) from A. officinalis with Lycoris longituba and onion (both members of the core Asparagales), Acorus americanus (sister to all other monocots), the grasses, and Arabidopsis. Although ESTs in A. officinalis and Acorus had a higher average GC content than Arabidopsis, Lycoris, and onion, all were clearly lower than the grasses. The Asparagaceae have the smallest nuclear genomes among all plants in the core Asparagales, which typically have huge genomes. Within the Asparagaceae, European Asparagus species have approximately twice the nuclear DNA of that of southern African Asparagus species. We cloned and sequenced 20 genomic amplicons from European A. officinalis and the southern African species Asparagus plumosus and observed no clear evidence for a recent genome doubling in A. officinalis relative to A. plumosus. These results indicate that members of the genus Asparagus with smaller genomes may be useful genomic models for plants in the core Asparagales.

  7. Mutational Dynamics of Aroid Chloroplast Genomes

    PubMed Central

    Ahmed, Ibrar; Biggs, Patrick J.; Matthews, Peter J.; Collins, Lesley J.; Hendy, Michael D.; Lockhart, Peter J.

    2012-01-01

    A characteristic feature of eukaryote and prokaryote genomes is the co-occurrence of nucleotide substitution and insertion/deletion (indel) mutations. Although similar observations have also been made for chloroplast DNA, genome-wide associations have not been reported. We determined the chloroplast genome sequences for two morphotypes of taro (Colocasia esculenta; family Araceae) and compared these with four publicly available aroid chloroplast genomes. Here, we report the extent of genome-wide association between direct and inverted repeats, indels, and substitutions in these aroid chloroplast genomes. We suggest that alternative but not mutually exclusive hypotheses explain the mutational dynamics of chloroplast genome evolution. PMID:23204304

  8. Comparative genomic hybridization with single cells after whole genome amplification

    SciTech Connect

    Haddad, B.R.; Baldini, A.; Hughes, M.R.

    1994-09-01

    Conventional karyotype analysis is the ideal way to diagnose chromosomal imbalances. However it requires cell culture and chromosome preparation. There are instances where a very small number of cells are available for cytogenetic evaluation and chromosomes cannot be obtained. Comparative genomic hybridization (CGH) is a novel molecular cytogenetic technique that provides information about genetic imbalances affecting the genome. The power of this technique lies in its ability to detect genetic imbalances using total genomic DNA. We have previously demonstrated the feasibility of whole genome amplification from single cells for subsequent analysis of multiple genetic loci by PCR. In this present work, we combine whole genome amplification with CGH to detect chromosomal imbalances from small numbers of cells. Both cytogenetically normal and abnormal cells were individually picked by micromanipulation and subjected to whole genome amplification using random oligonucleotide primers. Amplified test and control DNA were differentially labeled by incorporation of digoxigenin or biotin, mixed together and hybridized to normal male metaphase spreads. Hybridization was detected with two fluorochromes, rhodamine-anti-digoxigenin and FITC -Avidin. Ratio of intensities of the two fluorochromes along the target chromosomes was analyzed using locally developed computer imaging software. Using the combination of whole genome amplification and CGH, we were able to detect different chromosomal aneuploidies from 30, 20, and 10 cells. It can also be applied to the analysis of fetal cells sorted from maternal circulation, or to tumor cells obtained from needle biopsies or from different body fluids and effusions. Finally, its successful application to single cells will have a great impact on preimplantation diagnosis.

  9. Widespread Recurrent Evolution of Genomic Features

    PubMed Central

    Maeso, Ignacio; Roy, Scott William; Irimia, Manuel

    2012-01-01

    The recent explosion of genome sequences from all major phylogenetic groups has unveiled an unexpected wealth of cases of recurrent evolution of strikingly similar genomic features in different lineages. Here, we review the diverse known types of recurrent evolution in eukaryotic genomes, with a special focus on metazoans, ranging from reductive genome evolution to origins of splice-leader trans-splicing, from tandem exon duplications to gene family expansions. We first propose a general classification scheme for evolutionary recurrence at the genomic level, based on the type of driving force—mutation or selection—and the environmental and genomic circumstances underlying these forces. We then discuss various cases of recurrent genomic evolution under this scheme. Finally, we provide a broader context for repeated genomic evolution, including the unique relationship of genomic recurrence with the genotype–phenotype map, and the ways in which the study of recurrent genomic evolution can be used to understand fundamental evolutionary processes. PMID:22417916

  10. Correlation between genome reduction and bacterial growth.

    PubMed

    Kurokawa, Masaomi; Seno, Shigeto; Matsuda, Hideo; Ying, Bei-Wen

    2016-12-01

    Genome reduction by removing dispensable genomic sequences in bacteria is commonly used in both fundamental and applied studies to determine the minimal genetic requirements for a living system or to develop highly efficient bioreactors. Nevertheless, whether and how the accumulative loss of dispensable genomic sequences disturbs bacterial growth remains unclear. To investigate the relationship between genome reduction and growth, a series of Escherichia coli strains carrying genomes reduced in a stepwise manner were used. Intensive growth analyses revealed that the accumulation of multiple genomic deletions caused decreases in the exponential growth rate and the saturated cell density in a deletion-length-dependent manner as well as gradual changes in the patterns of growth dynamics, regardless of the growth media. Accordingly, a perspective growth model linking genome evolution to genome engineering was proposed. This study provides the first demonstration of a quantitative connection between genomic sequence and bacterial growth, indicating that growth rate is potentially associated with dispensable genomic sequences.

  11. Correlation between genome reduction and bacterial growth

    PubMed Central

    Kurokawa, Masaomi; Seno, Shigeto; Matsuda, Hideo; Ying, Bei-Wen

    2016-01-01

    Genome reduction by removing dispensable genomic sequences in bacteria is commonly used in both fundamental and applied studies to determine the minimal genetic requirements for a living system or to develop highly efficient bioreactors. Nevertheless, whether and how the accumulative loss of dispensable genomic sequences disturbs bacterial growth remains unclear. To investigate the relationship between genome reduction and growth, a series of Escherichia coli strains carrying genomes reduced in a stepwise manner were used. Intensive growth analyses revealed that the accumulation of multiple genomic deletions caused decreases in the exponential growth rate and the saturated cell density in a deletion-length-dependent manner as well as gradual changes in the patterns of growth dynamics, regardless of the growth media. Accordingly, a perspective growth model linking genome evolution to genome engineering was proposed. This study provides the first demonstration of a quantitative connection between genomic sequence and bacterial growth, indicating that growth rate is potentially associated with dispensable genomic sequences. PMID:27374613

  12. The snail (Biomphalaria glabrata) genome project.

    PubMed

    Raghavan, Nithya; Knight, Matty

    2006-04-01

    In 2001, ideas for a snail genome project were discussed at the American Society of Parasitologists meeting (New Mexico) and a snail genome consortium was subsequently established (the first consortium meeting was held in 2005). A proposal for sequencing the snail genome was submitted to the National Human Genome Research Institute, and Biomphalaria glabrata was prioritized as a non-mammalian sequencing target in 2004. The sequencing of the genome of this medically important snail is now underway.

  13. Genomic repeats, genome plasticity and the dynamics of Mycoplasma evolution

    PubMed Central

    Rocha, Eduardo P. C.; Blanchard, Alain

    2002-01-01

    Mycoplasmas evolved by a drastic reduction in genome size, but their genomes contain numerous repeated sequences with important roles in their evolution. We have established a bioinformatic strategy to detect the major recombination hot-spots in the genomes of Mycoplasma pneumoniae, Mycoplasma genitalium, Ureaplasma urealyticum and Mycoplasma pulmonis. This allowed the identification of large numbers of potentially variable regions, as well as a comparison of the relative recombination potentials of different genomic regions. Different trends are perceptible among mycoplasmas, probably due to different functional and structural constraints. The largest potential for illegitimate recombination in M.pulmonis is found at the vsa locus and its comparison in two different strains reveals numerous changes since divergence. On the other hand, the main M.pneumoniae and M.genitalium adhesins rely on large distant repeats and, hence, homologous recombination for variation. However, the relation between the existence of repeats and antigenic variation is not necessarily straightforward, since repeats of P1 adhesin were found to be anti-correlated with epitopes recognized by patient antibodies. These different strategies have important consequences for the structures of genomes, since large distant repeats correlate well with the major chromosomal rearrangements. Probably to avoid such events, mycoplasmas strongly avoid inverse repeats, in comparison to co-oriented repeats. PMID:11972343

  14. Genomic disorders: A window into human gene and genome evolution

    PubMed Central

    Carvalho, Claudia M. B.; Zhang, Feng; Lupski, James R.

    2010-01-01

    Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events. PMID:20080665

  15. A dictionary based informational genome analysis

    PubMed Central

    2012-01-01

    Background In the post-genomic era several methods of computational genomics are emerging to understand how the whole information is structured within genomes. Literature of last five years accounts for several alignment-free methods, arisen as alternative metrics for dissimilarity of biological sequences. Among the others, recent approaches are based on empirical frequencies of DNA k-mers in whole genomes. Results Any set of words (factors) occurring in a genome provides a genomic dictionary. About sixty genomes were analyzed by means of informational indexes based on genomic dictionaries, where a systemic view replaces a local sequence analysis. A software prototype applying a methodology here outlined carried out some computations on genomic data. We computed informational indexes, built the genomic dictionaries with different sizes, along with frequency distributions. The software performed three main tasks: computation of informational indexes, storage of these in a database, index analysis and visualization. The validation was done by investigating genomes of various organisms. A systematic analysis of genomic repeats of several lengths, which is of vivid interest in biology (for example to compute excessively represented functional sequences, such as promoters), was discussed, and suggested a method to define synthetic genetic networks. Conclusions We introduced a methodology based on dictionaries, and an efficient motif-finding software application for comparative genomics. This approach could be extended along many investigation lines, namely exported in other contexts of computational genomics, as a basis for discrimination of genomic pathologies. PMID:22985068

  16. GIPSy: Genomic island prediction software.

    PubMed

    Soares, Siomar C; Geyik, Hakan; Ramos, Rommel T J; de Sá, Pablo H C G; Barbosa, Eudes G V; Baumbach, Jan; Figueiredo, Henrique C P; Miyoshi, Anderson; Tauch, Andreas; Silva, Artur; Azevedo, Vasco

    2016-08-20

    Bacteria are highly diverse organisms that are able to adapt to a broad range of environments and hosts due to their high genomic plasticity. Horizontal gene transfer plays a pivotal role in this genome plasticity and in evolution by leaps through the incorporation of large blocks of genome sequences, ordinarily known as genomic islands (GEIs). GEIs may harbor genes encoding virulence, metabolism, antibiotic resistance and symbiosis-related functions, namely pathogenicity islands (PAIs), metabolic islands (MIs), resistance islands (RIs) and symbiotic islands (SIs). Although many software for the prediction of GEIs exist, they only focus on PAI prediction and present other limitations, such as complicated installation and inconvenient user interfaces. Here, we present GIPSy, the genomic island prediction software, a standalone and user-friendly software for the prediction of GEIs, built on our previously developed pathogenicity island prediction software (PIPS). We also present four application cases in which we crosslink data from literature to PAIs, MIs, RIs and SIs predicted by GIPSy. Briefly, GIPSy correctly predicted the following previously described GEIs: 13 PAIs larger than 30kb in Escherichia coli CFT073; 1 MI for Burkholderia pseudomallei K96243, which seems to be a miscellaneous island; 1 RI of Acinetobacter baumannii AYE, named AbaR1; and, 1 SI of Mesorhizobium loti MAFF303099 presenting a mosaic structure. GIPSy is the first life-style-specific genomic island prediction software to perform analyses of PAIs, MIs, RIs and SIs, opening a door for a better understanding of bacterial genome plasticity and the adaptation to new traits.

  17. GOLD: The Genomes Online Database

    DOE Data Explorer

    Kyrpides, Nikos; Liolios, Dinos; Chen, Amy; Tavernarakis, Nektarios; Hugenholtz, Philip; Markowitz, Victor; Bernal, Alex

    Since its inception in 1997, GOLD has continuously monitored genome sequencing projects worldwide and has provided the community with a unique centralized resource that integrates diverse information related to Archaea, Bacteria, Eukaryotic and more recently Metagenomic sequencing projects. As of September 2007, GOLD recorded 639 completed genome projects. These projects have their complete sequence deposited into the public archival sequence databases such as GenBank EMBL,and DDBJ. From the total of 639 complete and published genome projects as of 9/2007, 527 were bacterial, 47 were archaeal and 65 were eukaryotic. In addition to the complete projects, there were 2158 ongoing sequencing projects. 1328 of those were bacterial, 59 archaeal and 771 eukaryotic projects. Two types of metadata are provided by GOLD: (i) project metadata and (ii) organism/environment metadata. GOLD CARD pages for every project are available from the link of every GOLD_STAMP ID. The information in every one of these pages is organized into three tables: (a) Organism information, (b) Genome project information and (c) External links. [The Genomes On Line Database (GOLD) in 2007: Status of genomic and metagenomic projects and their associated metadata, Konstantinos Liolios, Konstantinos Mavromatis, Nektarios Tavernarakis and Nikos C. Kyrpides, Nucleic Acids Research Advance Access published online on November 2, 2007, Nucleic Acids Research, doi:10.1093/nar/gkm884]

    The basic tables in the GOLD database that can be browsed or searched include the following information:

    • Gold Stamp ID
    • Organism name
    • Domain
    • Links to information sources
    • Size and link to a map, when available
    • Chromosome number, Plas number, and GC content
    • A link for downloading the actual genome data
    • Institution that did the sequencing
    • Funding source
    • Database where information resides
    • Publication status and information

    • Human Genome Education Program

      SciTech Connect

      Richard Myers; Lane Conn

      2000-05-01

      The funds from the DOE Human Genome Program, for the project period 2/1/96 through 1/31/98, have provided major support for the curriculum development and field testing efforts for two high school level instructional units: Unit 1, ''Exploring Genetic Conditions: Genes, Culture and Choices''; and Unit 2, ''DNA Snapshots: Peaking at Your DNA''. In the original proposal, they requested DOE support for the partial salary and benefits of a Field Test Coordinator position to: (1) complete the field testing and revision of two high school curriculum units, and (2) initiate the education of teachers using these units. During the project period of this two-year DOE grant, a part-time Field-Test Coordinator was hired (Ms. Geraldine Horsma) and significant progress has been made in both of the original proposal objectives. Field testing for Unit 1 has occurred in over 12 schools (local and non-local sites with diverse student populations). Field testing for Unit 2 has occurred in over 15 schools (local and non-local sites) and will continue in 12-15 schools during the 96-97 school year. For both curricula, field-test sites and site teachers were selected for their interest in genetics education and in hands-on science education. Many of the site teachers had no previous experience with HGEP or the unit under development. Both of these first-year biology curriculum units, which contain genetics, biotechnology, societal, ethical and cultural issues related to HGP, are being implemented in many local and non-local schools (SF Bay Area, Southern California, Nebraska, Hawaii, and Texas) and in programs for teachers. These units will reach over 10,000 students in the SF Bay Area and continues to receive support from local corporate and private philanthropic organizations. Although HGEP unit development is nearing completion for both units, data is still being gathered and analyzed on unit effectiveness and student learning. The final field testing result from this analysis will

    • Saccharomyces Genome Database: the genomics resource of budding yeast

      PubMed Central

      Cherry, J. Michael; Hong, Eurie L.; Amundsen, Craig; Balakrishnan, Rama; Binkley, Gail; Chan, Esther T.; Christie, Karen R.; Costanzo, Maria C.; Dwight, Selina S.; Engel, Stacia R.; Fisk, Dianna G.; Hirschman, Jodi E.; Hitz, Benjamin C.; Karra, Kalpana; Krieger, Cynthia J.; Miyasato, Stuart R.; Nash, Rob S.; Park, Julie; Skrzypek, Marek S.; Simison, Matt; Weng, Shuai; Wong, Edith D.

      2012-01-01

      The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use. PMID:22110037

    • [The National Genome Research Network. Genome research in Germany].

      PubMed

      Bickeböller, Heike

      2007-02-01

      In 2001 Germany's Federal Ministry of Education and Research (BMFM) initiated the National Genome Research Network (NGFN). The goals of the NGFN are the investigation of the molecular basis of common diseases to improve new methods for prevention, diagnosis and therapy. The disease-oriented genome networks investigate cardiovascular diseases, cancer, diseases of the nervous system, diseases due to environmental factors and infection, and inflammation. They are supported by technological platforms and a component for technology transfer. The explicit aims include better integration of public health research and economy in order to gain an efficient economical and technological utilisation and application in community health. This article describes the creation of the NGFN in the context of international and national genome research, shows the structure and content of the NGFN and gives examples for NGFN research in networks on a highly, internationally recognised level.

  1. Genomics made easier: an introductory tutorial to genome datamining.

    PubMed

    Schattner, Peter

    2009-03-01

    Integrated genome databases--such as the UCSC, Ensembl and NCBI MapViewer databases--and their associated data querying and visualization interfaces (e.g. the genome browsers) have transformed the way that molecular biologists, geneticists and bioinformaticists analyze genomic data. Nevertheless, because of the complexity of these tools, many researchers take advantage of only a fraction of their capabilities. In this tutorial, using examples from medical genetics and alternative splicing, I describe some of the biological questions that can be addressed with these techniques. I also show why doing so typically is more effective than using alternative methods and indicate some of the resources available for learning more about the advanced capabilities of these powerful tools.

  2. Genome size: a novel genomic signature in support of Afrotheria.

    PubMed

    Redi, Carlo Alberto; Garagna, Silvia; Zuccotti, Maurizio; Capanna, Ernesto

    2007-04-01

    Molecular phylogenetic analyses suggest an emerging phylogeny for the extant Placentalia (eutherian) that radically departs from morphologically based constructions of the past. Placental mammals are partitioned into four supraordinal clades: Afrotheria, Xenarthra, Laurasiatheria, and Euarchontoglires. Afrotheria form an endemic African clade that includes elephant shrews, golden moles, tenrecs, aardvarks, hyraxes, elephants, dugongs, and manatees. Datamining databases of genome size (GS) shows that till today just one afrotherian GS has been evaluated, that of the aardvark Orycteropus afer. We show that the GSs of six selected representatives across the Afrotheria supraordinal group are among the highest for the extant Placentalia, providing a novel genomic signature of this enigmatic group. The mean GS value of Afrotheria, 5.3 +/- 0.7 pg, is the highest reported for the extant Placentalia. This should assist in planning new genome sequencing initiatives.

  3. Exploring cancer genomic data from the cancer genome atlas project.

    PubMed

    Lee, Ju-Seog

    2016-11-01

    The Cancer Genome Atlas (TCGA) has compiled genomic, epigenomic, and proteomic data from more than 10,000 samples derived from 33 types of cancer, aiming to improve our understanding of the molecular basis of cancer development. Availability of these genome-wide information provides an unprecedented opportunity for uncovering new key regulators of signaling pathways or new roles of pre-existing members in pathways. To take advantage of the advancement, it will be necessary to learn systematic approaches that can help to uncover novel genes reflecting genetic alterations, prognosis, or response to treatments. This minireview describes the updated status of TCGA project and explains how to use TCGA data. [BMB Reports 2016; 49(11): 607-611].

  4. Mapping whole genome shotgun sequence and variant calling in mammalian species without their reference genomes

    USDA-ARS?s Scientific Manuscript database

    Genomics research in mammals has produced reference genome sequences that are essential for identifying variation associated with disease. High quality reference genome sequences are now available for humans, model species, and economically important agricultural animals. Comparisons between these s...

  5. Accelerated Genome Engineering through Multiplexing

    PubMed Central

    Zhao, Huimin

    2015-01-01

    Throughout the biological sciences, the past fifteen years have seen a push towards the analysis and engineering of biological systems at the organism level. Given the complexity of even the simplest organisms, though, to elicit a phenotype of interest often requires genotypic manipulation of several loci. By traditional means, sequential editing of genomic targets requires a significant investment of time and labor, as the desired editing event typically occurs at a very low frequency against an overwhelming unedited background. In recent years, the development of a suite of new techniques has greatly increased editing efficiency, opening up the possibility for multiple editing events to occur in parallel. Termed as multiplexed genome engineering, this approach to genome editing has greatly expanded the scope of possible genome manipulations in diverse hosts, ranging from bacteria to human cells. The enabling technologies for multiplexed genome engineering include oligonucleotide-based and nuclease-based methodologies, and their application has led to the great breadth of successful examples described in this review. While many technical challenges remain, there also exists a multiplicity of opportunities in this rapidly expanding field. PMID:26394307

  6. Comparative genomics for biodiversity conservation

    PubMed Central

    Grueber, Catherine E.

    2015-01-01

    Genomic approaches are gathering momentum in biology and emerging opportunities lie in the creative use of comparative molecular methods for revealing the processes that influence diversity of wildlife. However, few comparative genomic studies are performed with explicit and specific objectives to aid conservation of wild populations. Here I provide a brief overview of comparative genomic approaches that offer specific benefits to biodiversity conservation. Because conservation examples are few, I draw on research from other areas to demonstrate how comparing genomic data across taxa may be used to inform the characterisation of conservation units and studies of hybridisation, as well as studies that provide conservation outcomes from a better understanding of the drivers of divergence. A comparative approach can also provide valuable insight into the threatening processes that impact rare species, such as emerging diseases and their management in conservation. In addition to these opportunities, I note areas where additional research is warranted. Overall, comparing and contrasting the genomic composition of threatened and other species provide several useful tools for helping to preserve the molecular biodiversity of the global ecosystem. PMID:26106461

  7. Expanding genomics of mycorrhizal symbiosis

    SciTech Connect

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; Grigoriev, Igor V.

    2014-11-04

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolve through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism.

  8. Expanding genomics of mycorrhizal symbiosis

    DOE PAGES

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; ...

    2014-11-04

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolvemore » through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism.« less

  9. The genome of Chenopodium quinoa.

    PubMed

    Jarvis, David E; Ho, Yung Shwen; Lightfoot, Damien J; Schmöckel, Sandra M; Li, Bo; Borm, Theo J A; Ohyanagi, Hajime; Mineta, Katsuhiko; Michell, Craig T; Saber, Noha; Kharbatia, Najeh M; Rupper, Ryan R; Sharp, Aaron R; Dally, Nadine; Boughton, Berin A; Woo, Yong H; Gao, Ge; Schijlen, Elio G W M; Guo, Xiujie; Momin, Afaque A; Negrão, Sónia; Al-Babili, Salim; Gehring, Christoph; Roessner, Ute; Jung, Christian; Murphy, Kevin; Arold, Stefan T; Gojobori, Takashi; Linden, C Gerard van der; van Loo, Eibertus N; Jellen, Eric N; Maughan, Peter J; Tester, Mark

    2017-02-16

    Chenopodium quinoa (quinoa) is a highly nutritious grain identified as an important crop to improve world food security. Unfortunately, few resources are available to facilitate its genetic improvement. Here we report the assembly of a high-quality, chromosome-scale reference genome sequence for quinoa, which was produced using single-molecule real-time sequencing in combination with optical, chromosome-contact and genetic maps. We also report the sequencing of two diploids from the ancestral gene pools of quinoa, which enables the identification of sub-genomes in quinoa, and reduced-coverage genome sequences for 22 other samples of the allotetraploid goosefoot complex. The genome sequence facilitated the identification of the transcription factor likely to control the production of anti-nutritional triterpenoid saponins found in quinoa seeds, including a mutation that appears to cause alternative splicing and a premature stop codon in sweet quinoa strains. These genomic resources are an important first step towards the genetic improvement of quinoa.

  10. Genomic profiling of breast cancers.

    PubMed

    Curtis, Christina

    2015-02-01

    To describe recent advances in the application of advanced genomic technologies towards the identification of biomarkers of prognosis and treatment response in breast cancer. Advances in high-throughput genomic profiling such as massively parallel sequencing have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. These tools also hold promise for precision medicine through accurate patient prognostication, stratification, and the dynamic monitoring of treatment response. For example, recent efforts have defined robust molecular subgroups of breast cancer and novel subtype-specific oncogenes. In addition, previously unappreciated activating mutations in human epidermal growth factor receptor 2 have been reported, suggesting new therapeutic opportunities. Genomic profiling of cell-free tumor DNA and circulating tumor cells has been used to monitor disease burden and the emergence of resistance, and such 'liquid biopsy' approaches may facilitate the early, noninvasive detection of aggressive disease. Finally, single-cell genomics is coming of age and will contribute to an understanding of breast cancer evolutionary dynamics. Here, we highlight recent studies that employ high-throughput genomic technologies in an effort to elucidate breast cancer biology, discover new therapeutic targets, improve prognostication and stratification, and discuss the implications for precision cancer medicine.

  11. NCBI prokaryotic genome annotation pipeline.

    PubMed

    Tatusova, Tatiana; DiCuccio, Michael; Badretdin, Azat; Chetvernin, Vyacheslav; Nawrocki, Eric P; Zaslavsky, Leonid; Lomsadze, Alexandre; Pruitt, Kim D; Borodovsky, Mark; Ostell, James

    2016-08-19

    Recent technological advances have opened unprecedented opportunities for large-scale sequencing and analysis of populations of pathogenic species in disease outbreaks, as well as for large-scale diversity studies aimed at expanding our knowledge across the whole domain of prokaryotes. To meet the challenge of timely interpretation of structure, function and meaning of this vast genetic information, a comprehensive approach to automatic genome annotation is critically needed. In collaboration with Georgia Tech, NCBI has developed a new approach to genome annotation that combines alignment based methods with methods of predicting protein-coding and RNA genes and other functional elements directly from sequence. A new gene finding tool, GeneMarkS+, uses the combined evidence of protein and RNA placement by homology as an initial map of annotation to generate and modify ab initio gene predictions across the whole genome. Thus, the new NCBI's Prokaryotic Genome Annotation Pipeline (PGAP) relies more on sequence similarity when confident comparative data are available, while it relies more on statistical predictions in the absence of external evidence. The pipeline provides a framework for generation and analysis of annotation on the full breadth of prokaryotic taxonomy. For additional information on PGAP see https://www.ncbi.nlm.nih.gov/genome/annotation_prok/ and the NCBI Handbook, https://www.ncbi.nlm.nih.gov/books/NBK174280/. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Advances in Genome Biology & Technology

    SciTech Connect

    Thomas J. Albert, Jon R. Armstrong, Raymond K. Auerback, W. Brad Barbazuk, et al.

    2007-12-01

    This year's meeting focused on the latest advances in new DNA sequencing technologies and the applications of genomics to disease areas in biology and biomedicine. Daytime plenary sessions highlighted cutting-edge research in areas such as complex genetic diseases, comparative genomics, medical sequencing, massively parallel DNA sequencing, and synthetic biology. Technical approaches being developed and utilized in contemporary genomics research were presented during evening concurrent sessions. Also, as in previous years, poster sessions bridged the morning and afternoon plenary sessions. In addition, for the third year in a row, the Advances in Genome Biology and Technology (AGBT) meeting was preceded by a pre-meeting workshop that aimed to provide an introductory overview for trainees and other meeting attendees. This year, speakers at the workshop focused on next-generation sequencing technologies, including their experiences, findings, and helpful advise for others contemplating using these platforms in their research. Speakers from genome centers and core sequencing facilities were featured and the workshop ended with a roundtable discussion, during which speakers fielded questions from the audience.

  13. Genomic signals for whole chromosomes

    NASA Astrophysics Data System (ADS)

    Cristea, Paul D.

    2003-06-01

    The paper presents some new results in the analysis of genomic information at the scale of whole chromosomes or whole genomes based on the conversion into genomic signals. Mainly, the phase analysis -- phase, cumulated phase and unwrapped phase, and the sequence path analysis are presented. The unwrapped phase displays an almost linear variation along whole chromosomes. The property holds for all the investigated genomes, being shared by both prokaryotes and eukaryotes, while the magnitude and sign of the unwrapped phase slope is specific for each taxon and chromosome. Such a behavior proves a rule similar to Chargaff's rule, but reveals a statistical regularity of the succession of the nucleotides -- a second order statistics, not only of the distribution of nucleotides -- a first order statistics. The cumulated phase of the genomic signal of certain prokaryotes also shows interesting specific behavior. The comparison between the behavior of the cumulated phase and of the unwrapped phae across the putative origins and termini of the replichores suggests an interesting model for the structure of chromosomes.

  14. Genome edited sheep and cattle.

    PubMed

    Proudfoot, Chris; Carlson, Daniel F; Huddart, Rachel; Long, Charles R; Pryor, Jane H; King, Tim J; Lillico, Simon G; Mileham, Alan J; McLaren, David G; Whitelaw, C Bruce A; Fahrenkrug, Scott C

    2015-02-01

    Genome editing tools enable efficient and accurate genome manipulation. An enhanced ability to modify the genomes of livestock species could be utilized to improve disease resistance, productivity or breeding capability as well as the generation of new biomedical models. To date, with respect to the direct injection of genome editor mRNA into livestock zygotes, this technology has been limited to the generation of pigs with edited genomes. To capture the far-reaching applications of gene-editing, from disease modelling to agricultural improvement, the technology must be easily applied to a number of species using a variety of approaches. In this study, we demonstrate zygote injection of TALEN mRNA can also produce gene-edited cattle and sheep. In both species we have targeted the myostatin (MSTN) gene. In addition, we report a critical innovation for application of gene-editing to the cattle industry whereby gene-edited calves can be produced with specified genetics by ovum pickup, in vitro fertilization and zygote microinjection (OPU-IVF-ZM). This provides a practical alternative to somatic cell nuclear transfer for gene knockout or introgression of desirable alleles into a target breed/genetic line.

  15. [Gel immobilization of human genome].

    PubMed

    Pan, Yingqiu; Zhang, Wei; Chen, Shuqing

    2013-01-01

    To develop a solid phase PCR method by covalent single point immobilization for recycle utilization of human genome. Polymethacrylamide gel was selected as a solid PCR carrier based on DNA-hydrogel copolymer chemistry presented by Mirzabekov. (CH2)6NH2 amino-modified PCR product and randomly fractured formic acid-modified plasmid pGEM-T-HLA-G were used as templates. The specificity of the attachment chemistry was characterized by acrylamide gel electrophoresis, and the thermal stability of method was demonstrated by PCR. This method was applied for the recycle utilization of human genome. Sequencing was used to exclude the possibility of introduced mutations during modification and immobilization procedures. The PCR detections of plasmid DNA and human genome DNA immobilized by polymethacrylamide gel was successful. The thermal stability of method was successfully demonstrated by performing PCR after 16 rounds of standard 36 PCR cycles. And the sequencing was found no mutation. The DNA immobilization method with polymethacrylamide gel as a solid phase carrier is stable and specific, which can be a possible approach for realizing recycle utilization of human genome for whole-genome sequencing and SNP detection.

  16. The Fitness of Genomic Order

    NASA Astrophysics Data System (ADS)

    Zhang, Qiucen; Vyawahare, Saurabh; Austin, Robert

    2012-02-01

    Most bacteria have a single circular chromosome that can range in size from 160,000 to 12,200,000 base pairs. Considering the typical gene density, i.e. 1 gene per 1,000 base pairs, both the number of genes and the ways to arrange are huge. Intuitively, the arrangement of genes on the circle is not important if all of them can be replicated. However, there is typically one origin of replication, and when bacteria is attacked by genotoxic stress during replication, the whole replication process can not be finished. As a result, which gene is replicated first, which is second, ..., becomes very important. Experimentally, we found a broad increase of DNA copy number near the origin of replication (OriC) of bacteria E.coli (˜3200 genes) under genotoxic stress. Since the genes near OriC are mostly efflux pump genes, we propose that there is fitness advantage for those rapid stress response genes got replicated first, because they can facilitate the replication of the rest of genome. Similar to bacterial evolution to present genomic order, in the somatic evolution of cancer, genomic shuffling was also frequently observed, especially under genotoxic chemotherapy. Such re-arrangement of genome can be viewed as a journey to optimal point in the rugged fitness landscape of genomic order.

  17. Genomic dissection of the seed

    PubMed Central

    Becker, Michael G.; Hsu, Ssu-Wei; Harada, John J.; Belmonte, Mark F.

    2014-01-01

    Seeds play an integral role in the global food supply and account for more than 70% of the calories that we consume on a daily basis. To meet the demands of an increasing population, scientists are turning to seed genomics research to find new and innovative ways to increase food production. Seed genomics is evolving rapidly, and the information produced from seed genomics research has exploded over the past two decades. Advances in modern sequencing strategies that profile every molecule in every cell, tissue, and organ and the emergence of new model systems have provided the tools necessary to unravel many of the biological processes underlying seed development. Despite these advances, the analyses and mining of existing seed genomics data remain a monumental task for plant biologists. This review summarizes seed region and subregion genomic data that are currently available for existing and emerging oilseed models. We provide insight into the development of tools on how to analyze large-scale datasets. PMID:25309563

  18. The genome of Prunus mume

    PubMed Central

    Zhang, Qixiang; Chen, Wenbin; Sun, Lidan; Zhao, Fangying; Huang, Bangqing; Yang, Weiru; Tao, Ye; Wang, Jia; Yuan, Zhiqiong; Fan, Guangyi; Xing, Zhen; Han, Changlei; Pan, Huitang; Zhong, Xiao; Shi, Wenfang; Liang, Xinming; Du, Dongliang; Sun, Fengming; Xu, Zongda; Hao, Ruijie; Lv, Tian; Lv, Yingmin; Zheng, Zequn; Sun, Ming; Luo, Le; Cai, Ming; Gao, Yike; Wang, Junyi; Yin, Ye; Xu, Xun; Cheng, Tangren; Wang, Jun

    2012-01-01

    Prunus mume (mei), which was domesticated in China more than 3,000 years ago as ornamental plant and fruit, is one of the first genomes among Prunus subfamilies of Rosaceae been sequenced. Here, we assemble a 280M genome by combining 101-fold next-generation sequencing and optical mapping data. We further anchor 83.9% of scaffolds to eight chromosomes with genetic map constructed by restriction-site-associated DNA sequencing. Combining P. mume genome with available data, we succeed in reconstructing nine ancestral chromosomes of Rosaceae family, as well as depicting chromosome fusion, fission and duplication history in three major subfamilies. We sequence the transcriptome of various tissues and perform genome-wide analysis to reveal the characteristics of P. mume, including its regulation of early blooming in endodormancy, immune response against bacterial infection and biosynthesis of flower scent. The P. mume genome sequence adds to our understanding of Rosaceae evolution and provides important data for improvement of fruit trees. PMID:23271652

  19. Comparative genomics of protoploid Saccharomycetaceae

    PubMed Central

    Souciet, Jean-Luc; Dujon, Bernard; Gaillardin, Claude; Johnston, Mark; Baret, Philippe V.; Cliften, Paul; Sherman, David J.; Weissenbach, Jean; Westhof, Eric; Wincker, Patrick; Jubin, Claire; Poulain, Julie; Barbe, Valérie; Ségurens, Béatrice; Artiguenave, François; Anthouard, Véronique; Vacherie, Benoit; Val, Marie-Eve; Fulton, Robert S.; Minx, Patrick; Wilson, Richard; Durrens, Pascal; Jean, Géraldine; Marck, Christian; Martin, Tiphaine; Nikolski, Macha; Rolland, Thomas; Seret, Marie-Line; Casarégola, Serge; Despons, Laurence; Fairhead, Cécile; Fischer, Gilles; Lafontaine, Ingrid; Leh, Véronique; Lemaire, Marc; de Montigny, Jacky; Neuvéglise, Cécile; Thierry, Agnès; Blanc-Lenfle, Isabelle; Bleykasten, Claudine; Diffels, Julie; Fritsch, Emilie; Frangeul, Lionel; Goëffon, Adrien; Jauniaux, Nicolas; Kachouri-Lafond, Rym; Payen, Célia; Potier, Serge; Pribylova, Lenka; Ozanne, Christophe; Richard, Guy-Franck; Sacerdot, Christine; Straub, Marie-Laure; Talla, Emmanuel

    2009-01-01

    Our knowledge of yeast genomes remains largely dominated by the extensive studies on Saccharomyces cerevisiae and the consequences of its ancestral duplication, leaving the evolution of the entire class of hemiascomycetes only partly explored. We concentrate here on five species of Saccharomycetaceae, a large subdivision of hemiascomycetes, that we call “protoploid” because they diverged from the S. cerevisiae lineage prior to its genome duplication. We determined the complete genome sequences of three of these species: Kluyveromyces (Lachancea) thermotolerans and Saccharomyces (Lachancea) kluyveri (two members of the newly described Lachancea clade), and Zygosaccharomyces rouxii. We included in our comparisons the previously available sequences of Kluyveromyces lactis and Ashbya (Eremothecium) gossypii. Despite their broad evolutionary range and significant individual variations in each lineage, the five protoploid Saccharomycetaceae share a core repertoire of approximately 3300 protein families and a high degree of conserved synteny. Synteny blocks were used to define gene orthology and to infer ancestors. Far from representing minimal genomes without redundancy, the five protoploid yeasts contain numerous copies of paralogous genes, either dispersed or in tandem arrays, that, altogether, constitute a third of each genome. Ancient, conserved paralogs as well as novel, lineage-specific paralogs were identified. PMID:19525356

  20. Expanding genomics of mycorrhizal symbiosis

    PubMed Central

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; Grigoriev, Igor V.

    2014-01-01

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolve through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism. PMID:25408690

  1. AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks.

    PubMed

    Lanza, Val F; Baquero, Fernando; de la Cruz, Fernando; Coque, Teresa M

    2017-01-15

    AcCNET (Accessory genome Constellation Network) is a Perl application that aims to compare accessory genomes of a large number of genomic units, both at qualitative and quantitative levels. Using the proteomes extracted from the analysed genomes, AcCNET creates a bipartite network compatible with standard network analysis platforms. AcCNET allows merging phylogenetic and functional information about the concerned genomes, thus improving the capability of current methods of network analysis. The AcCNET bipartite network opens a new perspective to explore the pangenome of bacterial species, focusing on the accessory genome behind the idiosyncrasy of a particular strain and/or population.

  2. The UCSC Genome Browser database: 2015 update.

    PubMed

    Rosenbloom, Kate R; Armstrong, Joel; Barber, Galt P; Casper, Jonathan; Clawson, Hiram; Diekhans, Mark; Dreszer, Timothy R; Fujita, Pauline A; Guruvadoo, Luvina; Haeussler, Maximilian; Harte, Rachel A; Heitner, Steve; Hickey, Glenn; Hinrichs, Angie S; Hubley, Robert; Karolchik, Donna; Learned, Katrina; Lee, Brian T; Li, Chin H; Miga, Karen H; Nguyen, Ngan; Paten, Benedict; Raney, Brian J; Smit, Arian F A; Speir, Matthew L; Zweig, Ann S; Haussler, David; Kuhn, Robert M; Kent, W James

    2015-01-01

    Launched in 2001 to showcase the draft human genome assembly, the UCSC Genome Browser database (http://genome.ucsc.edu) and associated tools continue to grow, providing a comprehensive resource of genome assemblies and annotations to scientists and students worldwide. Highlights of the past year include the release of a browser for the first new human genome reference assembly in 4 years in December 2013 (GRCh38, UCSC hg38), a watershed comparative genomics annotation (100-species multiple alignment and conservation) and a novel distribution mechanism for the browser (GBiB: Genome Browser in a Box). We created browsers for new species (Chinese hamster, elephant shark, minke whale), 'mined the web' for DNA sequences and expanded the browser display with stacked color graphs and region highlighting. As our user community increasingly adopts the UCSC track hub and assembly hub representations for sharing large-scale genomic annotation data sets and genome sequencing projects, our menu of public data hubs has tripled.

  3. Freshwater bacterial lifestyles inferred from comparative genomics.

    PubMed

    Livermore, Joshua A; Emrich, Scott J; Tan, John; Jones, Stuart E

    2014-03-01

    While micro-organisms actively mediate and participate in freshwater ecosystem services, we know little about freshwater microbial genetic diversity. Genome sequences are available for many bacteria from the human microbiome and the ocean (over 800 and 200, respectively), but only two freshwater genomes are currently available: the streamlined genomes of Polynucleobacter necessarius ssp. asymbioticus and the Actinobacterium AcI-B1. Here, we sequenced and analysed draft genomes of eight phylogentically diverse freshwater bacteria exhibiting a range of lifestyle characteristics. Comparative genomics of these bacteria reveals putative freshwater bacterial lifestyles based on differences in predicted growth rate, capability to respond to environmental stimuli and diversity of useable carbon substrates. Our conceptual model based on these genomic characteristics provides a foundation on which further ecophysiological and genomic studies can be built. In addition, these genomes greatly expand the diversity of existing genomic context for future studies on the ecology and genetics of freshwater bacteria.

  4. Polyploidy and genome evolution in plants.

    PubMed

    Soltis, Pamela S; Marchant, D Blaine; Van de Peer, Yves; Soltis, Douglas E

    2015-12-01

    Plant genomes vary in size and complexity, fueled in part by processes of whole-genome duplication (WGD; polyploidy) and subsequent genome evolution. Despite repeated episodes of WGD throughout the evolutionary history of angiosperms in particular, the genomes are not uniformly large, and even plants with very small genomes carry the signatures of ancient duplication events. The processes governing the evolution of plant genomes following these ancient events are largely unknown. Here, we consider mechanisms of diploidization, evidence of genome reorganization in recently formed polyploid species, and macroevolutionary patterns of WGD in plant genomes and propose that the ongoing genomic changes observed in recent polyploids may illustrate the diploidization processes that result in ancient signatures of WGD over geological timescales. Copyright © 2015. Published by Elsevier Ltd.

  5. Intrapopulation Genome Size Dynamics in Festuca pallens

    PubMed Central

    Šmarda, Petr; Bureš, Petr; Horová, Lucie; Rotreklová, Olga

    2008-01-01

    Background and Aims It is well known that genome size differs among species. However, information on the variation and dynamics of genome size in wild populations and on the early phase of genome size divergence between taxa is currently lacking. Genome size dynamics, heritability and phenotype effects are analysed here in a wild population of Festuca pallens (Poaceae). Methods Genome size was measured using flow cytometry with DAPI dye in 562 seedlings from 17 maternal plants varying in genome size. The repeatability of genome size measurements was verified at different seasons through the use of different standards and with propidium iodide dye; the range of variation observed was tested via analysis of double-peaks. Additionally, chromosome counts were made in selected seedlings. Key Results and Conclusions Analysis of double-peaks showed that genome size varied up to 1·188-fold within all 562 seedlings, 1·119-fold within the progeny of a single maternal plant and 1·117-fold in seedlings from grains of a single inflorescence. Generally, genome sizes of seedlings and their mothers were highly correlated. However, in maternal plants with both larger and smaller genomes, genome sizes of seedlings were shifted towards the population median. This was probably due to the frequency of available paternal genomes (pollen grains) in the population. There was a stabilizing selection on genome size during the development of seedlings into adults, which may be important for stabilizing genome size within species. Furthermore, a positive correlation was found between genome size and the development rate of seedlings. A larger genome may therefore provide a competitive advantage, perhaps explaining the higher proportion of plants with larger genomes in the population studied. The reason for the observed variation may be the recent induction of genome size variation, e.g. by activity of retrotransposons, which may be preserved in the long term by the segregation of

  6. Enhancer Identification through Comparative Genomics

    SciTech Connect

    Visel, Axel; Bristow, James; Pennacchio, Len A.

    2006-10-01

    With the availability of genomic sequence from numerousvertebrates, a paradigm shift has occurred in the identification ofdistant-acting gene regulatory elements. In contrast to traditionalgene-centric studies in which investigators randomly scanned genomicfragments that flank genes of interest in functional assays, the modernapproach begins electronically with publicly available comparativesequence datasets that provide investigators with prioritized lists ofputative functional sequences based on their evolutionary conservation.However, although a large number of tools and resources are nowavailable, application of comparative genomic approaches remains far fromtrivial. In particular, it requires users to dynamically consider thespecies and methods for comparison depending on the specific biologicalquestion under investigation. While there is currently no single generalrule to this end, it is clear that when applied appropriately,comparative genomic approaches exponentially increase our power ingenerating biological hypotheses for subsequent experimentaltesting.

  7. Genome-enabled plant metabolomics.

    PubMed

    Tohge, Takayuki; de Souza, Leonardo Perez; Fernie, Alisdair R

    2014-09-01

    The grand challenge currently facing metabolomics is that of comprehensitivity whilst next generation sequencing and advanced proteomics methods now allow almost complete and at least 50% coverage of their respective target molecules, metabolomics platforms at best offer coverage of just 10% of the small molecule complement of the cell. Here we discuss the use of genome sequence information as an enabling tool for peak identity and for translational metabolomics. Whilst we argue that genome information is not sufficient to compute the size of a species metabolome it is highly useful in predicting the occurrence of a wide range of common metabolites. Furthermore, we describe how via gene functional analysis in model species the identity of unknown metabolite peaks can be resolved. Taken together these examples suggest that genome sequence information is current (and likely will remain), a highly effective tool in peak elucidation in mass spectral metabolomics strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Genome: twisting stories with DNA.

    PubMed

    Noguera-Solano, Ricardo; Ruiz-Gutierrez, Rosaura; Rodriguez-Caso, Juan Manuel

    2013-12-01

    In 1920, the German botanist Hans Winkler coined the concept of the 'genome'. This paper explores the history of a concept that has developed in parallel with advances in biology and supports novel and powerful heuristic biological research in the 21st century. From a structural interpretation (the genome as the haploid number of chromosomes), it has changed to keep pace with technological progress and new interpretations of the material of heredity. In the first place, the 'genome' was extended to include all the material in the nucleus, then the sum of all genes, and (with the discovery of the structure of DNA) the sum of the nucleotide base sequences. In the early 21st century, it has become a much more complex and central concept that has spawned the growing field of studies referred to as the 'omics'.

  9. Multiscale Representation of Genomic Signals

    PubMed Central

    Knijnenburg, Theo A.; Ramsey, Stephen A.; Berman, Benjamin P.; Kennedy, Kathleen A.; Smit, Arian F.A.; Wessels, Lodewyk F.A.; Laird, Peter W.; Aderem, Alan; Shmulevich, Ilya

    2014-01-01

    Genomic information is encoded on a wide range of distance scales, ranging from tens of base pairs to megabases. We developed a multiscale framework to analyze and visualize the information content of genomic signals. Different types of signals, such as GC content or DNA methylation, are characterized by distinct patterns of signal enrichment or depletion across scales spanning several orders of magnitude. These patterns are associated with a variety of genomic annotations, including genes, nuclear lamina associated domains, and repeat elements. By integrating the information across all scales, as compared to using any single scale, we demonstrate improved prediction of gene expression from Polymerase II chromatin immunoprecipitation sequencing (ChIP-seq) measurements and we observed that gene expression differences in colorectal cancer are not most strongly related to gene body methylation, but rather to methylation patterns that extend beyond the single-gene scale. PMID:24727652

  10. Clinical Genomics: Challenges and Opportunities

    PubMed Central

    Vijay, Priyanka; McIntyre, Alexa B.R.; Mason, Christopher E.; Greenfield, Jeffrey P.; Li, Sheng

    2017-01-01

    Next-generation sequencing (NGS) approaches are highly applicable to clinical studies. We review recent advances in sequencing technologies, as well as their benefits and tradeoffs, to provide an overview of clinical genomics from study design to computational analysis. Sequencing technologies enable genomic, transcriptomic, and epigenomic evaluations. Studies that use a combination of whole genome, exome, mRNA, and bisulfite sequencing are now feasible due to decreasing sequencing costs. Single-molecule sequencing increases read length, with the MinION™ nanopore sequencer, which offers a uniquely portable option at a lower cost. Many of the published comparisons we review here address the challenges associated with different sequencing methods. Overall, NGS techniques, coupled with continually improving analysis algorithms, are useful for clinical studies in many realms, including cancer, chronic illness, and neurobiology. We, and others in the field, anticipate the clinical use of NGS approaches will continue to grow, especially as we shift into an era of precision medicine. PMID:27480773

  11. Bioprospecting in the genomic age.

    PubMed

    Hicks, Michael A; Prather, Kristala L J

    2014-01-01

    The genomic revolution promises great advances in the search for useful biocatalysts. Function-based metagenomic approaches have identified several enzymes with properties that make them useful candidates for a variety of bioprocesses. As DNA sequencing costs continue to decline, the volume of genomic data, along with their corresponding predicted protein sequences, will continue to increase dramatically, necessitating new approaches to leverage this information for gene-based bioprospecting efforts. Additionally, as new functions are discovered and correlated with this sequence information, the knowledge of the often complex relationship between a protein's sequence and function will improve. This in turn will lead to better gene-based bioprospecting approaches and facilitate the tailoring of desired properties through protein engineering projects. In this chapter, we discuss a number of recent advances in bioprospecting within the context of the genomic age.

  12. Support Values for Genome Phylogenies

    PubMed Central

    Klötzl, Fabian; Haubold, Bernhard

    2016-01-01

    We have recently developed a distance metric for efficiently estimating the number of substitutions per site between unaligned genome sequences. These substitution rates are called “anchor distances” and can be used for phylogeny reconstruction. Most phylogenies come with bootstrap support values, which are computed by resampling with replacement columns of homologous residues from the original alignment. Unfortunately, this method cannot be applied to anchor distances, as they are based on approximate pairwise local alignments rather than the full multiple sequence alignment necessary for the classical bootstrap. We explore two alternatives: pairwise bootstrap and quartet analysis, which we compare to classical bootstrap. With simulated sequences and 53 human primate mitochondrial genomes, pairwise bootstrap gives better results than quartet analysis. However, when applied to 29 E. coli genomes, quartet analysis comes closer to the classical bootstrap. PMID:26959064

  13. Allerton III. Beyond livestock genomics.

    PubMed

    Hamernik, Debora L; Lewin, Harris A; Schook, Lawrence B

    2003-05-01

    Throughout the Allerton III Conference, several consistent research needs were identified across scientific disciplines. First, additional basic research is needed to identify genomic mechanisms and novel genes/proteins in a variety of tissues under different conditions. Second, expansion of the infrastructure of the scientific community is needed. This can best be accomplished by additional competitive grants programs for training grants, program project grants, and multidisciplinary research projects. Third, the need for improved tools for animal bioinformatics was emphasized. Fourth, competitive grants programs for extension/outreach efforts and application of genomic technologies to production systems are needed. Finally, efforts to publicize and document the benefits of animal genomics for improved human health and animal production systems to members of Congress and the general public should be enhanced.

  14. The genome of Theobroma cacao.

    PubMed

    Argout, Xavier; Salse, Jerome; Aury, Jean-Marc; Guiltinan, Mark J; Droc, Gaetan; Gouzy, Jerome; Allegre, Mathilde; Chaparro, Cristian; Legavre, Thierry; Maximova, Siela N; Abrouk, Michael; Murat, Florent; Fouet, Olivier; Poulain, Julie; Ruiz, Manuel; Roguet, Yolande; Rodier-Goud, Maguy; Barbosa-Neto, Jose Fernandes; Sabot, Francois; Kudrna, Dave; Ammiraju, Jetty Siva S; Schuster, Stephan C; Carlson, John E; Sallet, Erika; Schiex, Thomas; Dievart, Anne; Kramer, Melissa; Gelley, Laura; Shi, Zi; Bérard, Aurélie; Viot, Christopher; Boccara, Michel; Risterucci, Ange Marie; Guignon, Valentin; Sabau, Xavier; Axtell, Michael J; Ma, Zhaorong; Zhang, Yufan; Brown, Spencer; Bourge, Mickael; Golser, Wolfgang; Song, Xiang; Clement, Didier; Rivallan, Ronan; Tahi, Mathias; Akaza, Joseph Moroh; Pitollat, Bertrand; Gramacho, Karina; D'Hont, Angélique; Brunel, Dominique; Infante, Diogenes; Kebe, Ismael; Costet, Pierre; Wing, Rod; McCombie, W Richard; Guiderdoni, Emmanuel; Quetier, Francis; Panaud, Olivier; Wincker, Patrick; Bocs, Stephanie; Lanaud, Claire

    2011-02-01

    We sequenced and assembled the draft genome of Theobroma cacao, an economically important tropical-fruit tree crop that is the source of chocolate. This assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of these genes anchored on the 10 T. cacao chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example, flavonoid-related genes. It also provides a major source of candidate genes for T. cacao improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten T. cacao chromosomes were shaped from an ancestor through eleven chromosome fusions.

  15. Genome inside genome: NGS based identification and assembly of endophytic Sphingopyxis granuli and Pseudomonas aeruginosa genomes from rice genomic reads.

    PubMed

    Battu, Latha; Reddy, Mettu Madhavi; Goud, Burragoni Sravanthi; Ulaganathan, Kayalvili; Kandasamy, Ulaganathan

    2017-02-10

    The interactions between crop plants and the endophytic bacteria colonizing them are poorly understood and experimental methods were found to be inadequate to meet the complexities associated with the interaction. Moreover, research on endophytic bacteria was focused at host plant species level and not at cultivar level which is essential for understanding the role played by them on the productivity of specific crop genotype. High throughput genomics offers valuable tools for identification, characterization of endophytic bacteria and understand their interaction with host plants. In this paper we report the use of high throughput plant genomic data for identification of endophytic bacteria colonizing rice plants. Using this novel next generation sequencing based computational method Sphingopyxis granuli and Pseudomonas aeruginosa were identified as endophytes colonizing the elite indica rice cultivar RP Bio-226 and their draft genome sequences were assembled.

  16. Genomic instability in Rhizobium phaseoli.

    PubMed Central

    Flores, M; González, V; Pardo, M A; Leija, A; Martínez, E; Romero, D; Piñero, D; Dávila, G; Palacios, R

    1988-01-01

    Experience from different laboratories indicates that Rhizobium strains can generate variability in regard to some phenotypic characteristics such as colony morphology or symbiotic properties. On the other hand, several reports suggest that under certain stress conditions or genetic manipulations Rhizobium cells can present genomic rearrangements. In search of frequent genomic rearrangements, we analyzed three Rhizobium strains under laboratory conditions that are not considered to cause stress in bacterial populations. DNAs from direct descendants of a single cell were analyzed in regard to the hybridization patterns obtained, using as probes different recombinant plasmids or cosmids; while most of the probes utilized did not show differences in the hybridization patterns, some of them revealed the occurrence of frequent genomic rearrangements. The implications and possible biological significance of these observations are discussed. Images PMID:3343217

  17. Genomics of Escherichia and Shigella

    NASA Astrophysics Data System (ADS)

    Perna, Nicole T.

    The laboratory workhorse Escherichia coli K-12 is among the most intensively studied living organisms on earth, and this single strain serves as the model system behind much of our understanding of prokaryotic molecular biology. Dense genome sequencing and recent insightful comparative analyses are making the species E. coli, as a whole, an emerging system for studying prokaryotic population genetics and the relationship between system-scale, or genome-scale, molecular evolution and complex traits like host range and pathogenic potential. Genomic perspective has revealed a coherent but dynamic species united by intraspecific gene flow via homologous lateral or horizontal transfer and differentiated by content flux mediated by acquisition of DNA segments from interspecies transfers.

  18. Staphylococcus aureus: superbug, super genome?

    PubMed

    Lindsay, Jodi A; Holden, Matthew T G

    2004-08-01

    Staphylococcus aureus is a common cause of infection in both hospitals and the community, and it is becoming increasingly virulent and resistant to antibiotics. The recent sequencing of seven strains of S. aureus provides unprecedented information about its genome diversity. Subtle differences in core (stable) regions of the genome have been exploited by multi-locus sequence typing (MLST) to understand S. aureus population structure. Dramatic differences in the carriage and spread of accessory genes, including those involved in virulence and resistance, contribute to the emergence of new strains with healthcare implications. Understanding the differences between S. aureus genomes and the controls that govern these changes is helping to improve our knowledge of S. aureus pathogenicity and to predict the evolution of super-superbugs.

  19. How good is our genome?

    PubMed

    Weill, Jean-Claude; Radman, Miroslav

    2004-01-29

    Our genome has evolved to perpetuate itself through the maintenance of the species via an uninterrupted chain of reproductive somas. Accordingly, evolution is not concerned with diseases occurring after the soma's reproductive stage. Following Richard Dawkins, we would like to reassert that we indeed live as disposable somas, slaves of our germline genome, but could soon start rebelling against such slavery. Cancer and its relation to the TP53 gene may offer a paradigmatic example. The observation that the latency period in cancer can be prolonged in mice by increasing the number of TP53 genes in their genome, suggests that sooner or later we will have to address the question of heritable disease avoidance via the manipulation of the human germline.

  20. Mitochondrial genomes of parasitic flatworms.

    PubMed

    Le, Thanh H; Blair, David; McManus, Donald P

    2002-05-01

    Complete or near-complete mitochondrial genomes are now available for 11 species or strains of parasitic flatworms belonging to the Trematoda and the Cestoda. The organization of these genomes is not strikingly different from those of other eumetazoans, although one gene (atp8) commonly found in other phyla is absent from flatworms. The gene order in most flatworms has similarities to those seen in higher protostomes such as annelids. However, the gene order has been drastically altered in Schistosoma mansoni, which obscures this possible relationship. Among the sequenced taxa, base composition varies considerably, creating potential difficulties for phylogeny reconstruction. Long non-coding regions are present in all taxa, but these vary in length from only a few hundred to approximately 10000 nucleotides. Among Schistosoma spp., the long non-coding regions are rich in repeats and length variation among individuals is known. Data from mitochondrial genomes are valuable for studies on species identification, phylogenies and biogeography.