A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens

PubMed Central

Cameron, Andrew; Klima, Cassidy L.; Ha, Reuben; Gruninger, Robert J.; Zaheer, Rahat

2018-01-01

ABSTRACT A novel variant of the AAD(3″) class of aminoglycoside-modifying enzymes was discovered in fatal bovine respiratory disease-associated pathogens Pasteurella multocida and Histophilus somni. The aadA31 gene encodes a spectinomycin/streptomycin adenylyltransferase and was located in a variant of the integrative and conjugative element ICEMh1, a mobile genetic element transmissible among members of the family Pasteurellaceae. The gene was also detected in Mannheimia haemolytica from a case of porcine pneumonia and in Moraxella bovoculi from a case of keratoconjunctivitis. IMPORTANCE Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species. PMID:29507894

Heterogeneity of reward mechanisms.

PubMed

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

Examining Two Sets of Introgression Lines in Rice (Oryza sativa L.) Reveals Favorable Alleles that Improve Grain Zn and Fe Concentrations

PubMed Central

Hu, Xia; Cheng, Li-Rui; Xu, Jian-Long; Shi, Yu-Min; Li, Zhi-Kang

2015-01-01

In the modern world, the grain mineral concentration (GMC) in rice (Oryza sativa L.) not only includes important micronutrient elements such as iron (Fe) and zinc (Zn), but it also includes toxic heavy metal elements, especially cadmium (Cd) and lead (Pb). To date, the genetic mechanisms underlying the regulation of GMC, especially the genetic background and G × E effects of GMC, remain largely unknown. In this study, we adopted two sets of backcross introgression lines (BILs) derived from IR75862 (a Zn-dense rice variety) as the donor parent and two elite indica varieties, Ce258 and Zhongguangxiang1, as recurrent parents to detect QTL affecting GMC traits including Fe, Zn, Cd and Pb concentrations in two environments. We detected a total of 22 loci responsible for GMC traits, which are distributed on all 12 rice chromosomes except 5, 9 and 10. Six genetic overlap (GO) regions affecting multiple elements were found, in which most donor alleles had synergistic effects on GMC. Some toxic heavy metal-independent loci (such as qFe1, qFe2 and qZn12) and some regions that have opposite genetic effects on micronutrient (Fe and Zn) and heavy metal element (Pb) concentrations (such as GO-IV) may be useful for marker-assisted biofortification breeding in rice. We discuss three important points affecting biofortification breeding efforts in rice, including correlations between different GMC traits, the genetic background effect and the G × E effect. PMID:26161553

Genetic Basis of Melanin Pigmentation in Butterfly Wings.

PubMed

Zhang, Linlin; Martin, Arnaud; Perry, Michael W; van der Burg, Karin R L; Matsuoka, Yuji; Monteiro, Antónia; Reed, Robert D

2017-04-01

Despite the variety, prominence, and adaptive significance of butterfly wing patterns, surprisingly little is known about the genetic basis of wing color diversity. Even though there is intense interest in wing pattern evolution and development, the technical challenge of genetically manipulating butterflies has slowed efforts to functionally characterize color pattern development genes. To identify candidate wing pigmentation genes, we used RNA sequencing to characterize transcription across multiple stages of butterfly wing development, and between different color pattern elements, in the painted lady butterfly Vanessa cardui This allowed us to pinpoint genes specifically associated with red and black pigment patterns. To test the functions of a subset of genes associated with presumptive melanin pigmentation, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in four different butterfly genera. pale , Ddc , and yellow knockouts displayed reduction of melanin pigmentation, consistent with previous findings in other insects. Interestingly, however, yellow-d , ebony , and black knockouts revealed that these genes have localized effects on tuning the color of red, brown, and ochre pattern elements. These results point to previously undescribed mechanisms for modulating the color of specific wing pattern elements in butterflies, and provide an expanded portrait of the insect melanin pathway. Copyright © 2017 by the Genetics Society of America.

Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health.

PubMed

Cabello, Felipe C; Godfrey, Henry P; Tomova, Alexandra; Ivanova, Larisa; Dölz, Humberto; Millanao, Ana; Buschmann, Alejandro H

2013-07-01

The worldwide growth of aquaculture has been accompanied by a rapid increase in therapeutic and prophylactic usage of antimicrobials including those important in human therapeutics. Approximately 80% of antimicrobials used in aquaculture enter the environment with their activity intact where they select for bacteria whose resistance arises from mutations or more importantly, from mobile genetic elements containing multiple resistance determinants transmissible to other bacteria. Such selection alters biodiversity in aquatic environments and the normal flora of fish and shellfish. The commonality of the mobilome (the total of all mobile genetic elements in a genome) between aquatic and terrestrial bacteria together with the presence of residual antimicrobials, biofilms, and high concentrations of bacteriophages where the aquatic environment may also be contaminated with pathogens of human and animal origin can stimulate exchange of genetic information between aquatic and terrestrial bacteria. Several recently found genetic elements and resistance determinants for quinolones, tetracyclines, and β-lactamases are shared between aquatic bacteria, fish pathogens, and human pathogens, and appear to have originated in aquatic bacteria. Excessive use of antimicrobials in aquaculture can thus potentially negatively impact animal and human health as well as the aquatic environment and should be better assessed and regulated. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Genetic Basis of Melanin Pigmentation in Butterfly Wings

PubMed Central

Zhang, Linlin; Martin, Arnaud; Perry, Michael W.; van der Burg, Karin R. L.; Matsuoka, Yuji; Monteiro, Antónia; Reed, Robert D.

2017-01-01

Despite the variety, prominence, and adaptive significance of butterfly wing patterns, surprisingly little is known about the genetic basis of wing color diversity. Even though there is intense interest in wing pattern evolution and development, the technical challenge of genetically manipulating butterflies has slowed efforts to functionally characterize color pattern development genes. To identify candidate wing pigmentation genes, we used RNA sequencing to characterize transcription across multiple stages of butterfly wing development, and between different color pattern elements, in the painted lady butterfly Vanessa cardui. This allowed us to pinpoint genes specifically associated with red and black pigment patterns. To test the functions of a subset of genes associated with presumptive melanin pigmentation, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in four different butterfly genera. pale, Ddc, and yellow knockouts displayed reduction of melanin pigmentation, consistent with previous findings in other insects. Interestingly, however, yellow-d, ebony, and black knockouts revealed that these genes have localized effects on tuning the color of red, brown, and ochre pattern elements. These results point to previously undescribed mechanisms for modulating the color of specific wing pattern elements in butterflies, and provide an expanded portrait of the insect melanin pathway. PMID:28193726

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies.

PubMed

Yutin, Natalya; Raoult, Didier; Koonin, Eugene V

2013-05-23

Recent advances of genomics and metagenomics reveal remarkable diversity of viruses and other selfish genetic elements. In particular, giant viruses have been shown to possess their own mobilomes that include virophages, small viruses that parasitize on giant viruses of the Mimiviridae family, and transpovirons, distinct linear plasmids. One of the virophages known as the Mavirus, a parasite of the giant Cafeteria roenbergensis virus, shares several genes with large eukaryotic self-replicating transposon of the Polinton (Maverick) family, and it has been proposed that the polintons evolved from a Mavirus-like ancestor. We performed a comprehensive phylogenomic analysis of the available genomes of virophages and traced the evolutionary connections between the virophages and other selfish genetic elements. The comparison of the gene composition and genome organization of the virophages reveals 6 conserved, core genes that are organized in partially conserved arrays. Phylogenetic analysis of those core virophage genes, for which a sufficient diversity of homologs outside the virophages was detected, including the maturation protease and the packaging ATPase, supports the monophyly of the virophages. The results of this analysis appear incompatible with the origin of polintons from a Mavirus-like agent but rather suggest that Mavirus evolved through recombination between a polinton and an unknown virus. Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements. The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies

PubMed Central

2013-01-01

Background Recent advances of genomics and metagenomics reveal remarkable diversity of viruses and other selfish genetic elements. In particular, giant viruses have been shown to possess their own mobilomes that include virophages, small viruses that parasitize on giant viruses of the Mimiviridae family, and transpovirons, distinct linear plasmids. One of the virophages known as the Mavirus, a parasite of the giant Cafeteria roenbergensis virus, shares several genes with large eukaryotic self-replicating transposon of the Polinton (Maverick) family, and it has been proposed that the polintons evolved from a Mavirus-like ancestor. Results We performed a comprehensive phylogenomic analysis of the available genomes of virophages and traced the evolutionary connections between the virophages and other selfish genetic elements. The comparison of the gene composition and genome organization of the virophages reveals 6 conserved, core genes that are organized in partially conserved arrays. Phylogenetic analysis of those core virophage genes, for which a sufficient diversity of homologs outside the virophages was detected, including the maturation protease and the packaging ATPase, supports the monophyly of the virophages. The results of this analysis appear incompatible with the origin of polintons from a Mavirus-like agent but rather suggest that Mavirus evolved through recombination between a polinton and an unknownvirus. Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements. Conclusions The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements. PMID:23701946

SZDB: A Database for Schizophrenia Genetic Research

PubMed Central

Wu, Yong; Yao, Yong-Gang

2017-01-01

Abstract Schizophrenia (SZ) is a debilitating brain disorder with a complex genetic architecture. Genetic studies, especially recent genome-wide association studies (GWAS), have identified multiple variants (loci) conferring risk to SZ. However, how to efficiently extract meaningful biological information from bulk genetic findings of SZ remains a major challenge. There is a pressing need to integrate multiple layers of data from various sources, eg, genetic findings from GWAS, copy number variations (CNVs), association and linkage studies, gene expression, protein–protein interaction (PPI), co-expression, expression quantitative trait loci (eQTL), and Encyclopedia of DNA Elements (ENCODE) data, to provide a comprehensive resource to facilitate the translation of genetic findings into SZ molecular diagnosis and mechanism study. Here we developed the SZDB database (http://www.szdb.org/), a comprehensive resource for SZ research. SZ genetic data, gene expression data, network-based data, brain eQTL data, and SNP function annotation information were systematically extracted, curated and deposited in SZDB. In-depth analyses and systematic integration were performed to identify top prioritized SZ genes and enriched pathways. Multiple types of data from various layers of SZ research were systematically integrated and deposited in SZDB. In-depth data analyses and integration identified top prioritized SZ genes and enriched pathways. We further showed that genes implicated in SZ are highly co-expressed in human brain and proteins encoded by the prioritized SZ risk genes are significantly interacted. The user-friendly SZDB provides high-confidence candidate variants and genes for further functional characterization. More important, SZDB provides convenient online tools for data search and browse, data integration, and customized data analyses. PMID:27451428

Development and applications of transgenesis in the yellow fever mosquito, Aedes aegypti.

PubMed

Adelman, Zachary N; Jasinskiene, Nijole; James, Anthony A

2002-04-30

Transgenesis technology has been developed for the yellow fever mosquito, Aedes aegypti. Successful integration of exogenous DNA into the germline of this mosquito has been achieved with the class II transposable elements, Hermes, mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of Drosophila melanogaster, and fluorescent protein genes, can be used to monitor the insertion of these elements. The availability of multiple elements and marker genes provides a powerful set of tools to investigate basic biological properties of this vector insect, as well as the materials for developing novel, genetics-based, control strategies for the transmission of disease.

References for Haplotype Imputation in the Big Data Era

PubMed Central

Li, Wenzhi; Xu, Wei; Li, Qiling; Ma, Li; Song, Qing

2016-01-01

Imputation is a powerful in silico approach to fill in those missing values in the big datasets. This process requires a reference panel, which is a collection of big data from which the missing information can be extracted and imputed. Haplotype imputation requires ethnicity-matched references; a mismatched reference panel will significantly reduce the quality of imputation. However, currently existing big datasets cover only a small number of ethnicities, there is a lack of ethnicity-matched references for many ethnic populations in the world, which has hampered the data imputation of haplotypes and its downstream applications. To solve this issue, several approaches have been proposed and explored, including the mixed reference panel, the internal reference panel and genotype-converted reference panel. This review article provides the information and comparison between these approaches. Increasing evidence showed that not just one or two genetic elements dictate the gene activity and functions; instead, cis-interactions of multiple elements dictate gene activity. Cis-interactions require the interacting elements to be on the same chromosome molecule, therefore, haplotype analysis is essential for the investigation of cis-interactions among multiple genetic variants at different loci, and appears to be especially important for studying the common diseases. It will be valuable in a wide spectrum of applications from academic research, to clinical diagnosis, prevention, treatment, and pharmaceutical industry. PMID:27274952

Development and validation of a 48-target analytical method for high-throughput monitoring of genetically modified organisms.

PubMed

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-05

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.

Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms

PubMed Central

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-01

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection. PMID:25556930

Study on validation method for femur finite element model under multiple loading conditions

NASA Astrophysics Data System (ADS)

Guan, Fengjiao; Zhang, Guanjun; Liu, Jie; Wang, Shujing; Luo, Xu

2018-03-01

Acquisition of accurate and reliable constitutive parameters related to bio-tissue materials was beneficial to improve biological fidelity of a Finite Element (FE) model and predict impact damages more effectively. In this paper, a femur FE model was established under multiple loading conditions with diverse impact positions. Then, based on sequential response surface method and genetic algorithms, the material parameters identification was transformed to a multi-response optimization problem. Finally, the simulation results successfully coincided with force-displacement curves obtained by numerous experiments. Thus, computational accuracy and efficiency of the entire inverse calculation process were enhanced. This method was able to effectively reduce the computation time in the inverse process of material parameters. Meanwhile, the material parameters obtained by the proposed method achieved higher accuracy.

Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli

PubMed Central

Samir, Parimal; Rahul; Slaughter, James C.; Link, Andrew J.

2015-01-01

Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well. PMID:26247773

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

PubMed

Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I; Jackson, Anne U; Schmidt, Ellen M; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J; Shungin, Dmitry; Hughes, Maria F; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M; Magnusson, Patrik K; Salfati, Elias L; Rallidis, Loukianos S; Theusch, Elizabeth; Smith, Andrew J P; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H; Joehanes, Roby; Kim, Stuart K; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O; Bochud, Murielle; Absher, Devin; Adair, Linda S; Amin, Najaf; Arking, Dan E; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R; Barroso, Inês; Bevan, Stephen; Bis, Joshua C; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Bornstein, Stefan R; Brown, Morris J; Burnier, Michel; Cabrera, Claudia P; Chambers, John C; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S; Chung, Ren-Hua; Collins, Francis S; Connell, John M; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F; Doney, Alex S F; Drenos, Fotios; Edkins, Sarah; Eicher, John D; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H Franco; Franco-Cereceda, Anders; Fraser, Ross M; Ganesh, Santhi K; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H; Goodarzi, Mark O; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A; Hingorani, Aroon D; Hirschhorn, Joel N; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A; Hunt, Steven C; Ikram, M Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S; Kosova, Gulum; Krauss, Ronald M; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S; Marouli, Eirini; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E; Morris, Andrew D; Morrison, Alanna C; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J; O'Reilly, Paul F; Ong, Ken K; Paccaud, Fred; Palmer, Cameron D; Parsa, Afshin; Pedersen, Nancy L; Penninx, Brenda W; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P; Psaty, Bruce M; Quertermous, Thomas; Rao, Dabeeru C; Rasheed, Asif; Rayner, N William N W R; Renström, Frida; Rettig, Rainer; Rice, Kenneth M; Roberts, Robert; Rose, Lynda M; Rossouw, Jacques; Samani, Nilesh J; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H; Smith, Albert V; Sosa, Maria X; Spector, Tim D; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E; Stringham, Heather M; Sundstrom, Johan; Swift, Amy J; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D; Tremoli, Elena; Uitterlinden, Andre G; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M; van Iperen, Erik P A; Vasan, Ramachandran S; Verwoert, Germaine C; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F; Vollenweider, Peter; Wagner, Aline; Wain, Louise V; Wareham, Nicholas J; Watkins, Hugh; Weder, Alan B; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F; Wong, Tien Y; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S; Mohlke, Karen L; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J; Willer, Cristen J; Franke, Lude; Hovingh, G Kees; Taylor, Kent D; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L; Njølstad, Inger; Schwarz, Peter Eh; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I; Rotter, Jerome I; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G; Kuulasmaa, Kari; Franks, Paul W; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N A; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J F; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P; Newton-Cheh, Christopher; Munroe, Patricia B

2016-10-01

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

PubMed Central

Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A.; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H. Franco; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N William N.W.R.; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.-H.; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter EH.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H.-Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

2016-01-01

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation. PMID:27618452

The [KIL-d] element specifically regulates viral gene expression in yeast.

PubMed Central

Tallóczy, Z; Mazar, R; Georgopoulos, D E; Ramos, F; Leibowitz, M J

2000-01-01

The cytoplasmically inherited [KIL-d] element epigenetically regulates killer virus gene expression in Saccharomyces cerevisiae. [KIL-d] results in variegated defects in expression of the M double-stranded RNA viral segment in haploid cells that are "healed" in diploids. We report that the [KIL-d] element is spontaneously lost with a frequency of 10(-4)-10(-5) and reappears with variegated phenotypic expression with a frequency of > or =10(-3). This high rate of loss and higher rate of reappearance is unlike any known nucleic acid replicon but resembles the behavior of yeast prions. However, [KIL-d] is distinct from the known yeast prions in its relative guanidinium hydrochloride incurability and independence of Hsp104 protein for its maintenance. Despite its transmissibility by successive cytoplasmic transfers, multiple cytoplasmic nucleic acids have been proven not to carry the [KIL-d] trait. [KIL-d] epigenetically regulates the expression of the M double-stranded RNA satellite virus genome, but fails to alter the expression of M cDNA. This specificity remained even after a cycle of mating and meiosis. Due to its unique genetic properties and viral RNA specificity, [KIL-d] represents a new type of genetic element that interacts with a viral RNA genome. PMID:10835384

Deciphering the genomes of 16 Acanthamoeba species does not provide evidence of integration of known giant virus-associated mobile genetic elements.

PubMed

Chelkha, Nisrine; Colson, Philippe; Levasseur, Anthony; La Scola, Bernard

2018-06-02

Giant viruses infect protozoa, especially amoebae of the genus Acanthamoeba. These viruses possess genetic elements named Mobilome. So far, this mobilome comprises provirophages which are integrated into the genome of their hosts, transpovirons, and Maverick/Polintons. Virophages replicate inside virus factories within Acanthamoeba and can decrease the infectivity of giant viruses. The virophage infecting CroV was found to be integrated in the host of CroV, Cafeteria roenbergensis, thus protecting C. roenbergensis by reduction of CroV multiplication. Because of this unique property, assessment of the mechanisms of replication of virophages and their relationship with giant viruses is a key element of this investigation. This work aimed at evaluating the presence and the dynamic of these mobile elements in sixteen Acanthamoeba genomes. No significant traces of the integration of genomes or sequences from known virophages were identified in all the available Acanthamoeba genomes. These results brought us to hypothesize that the interactions between mimiviruses and their virophages might occur through different mechanisms, or at low frequency. An additional explanation could be that our knowledge of the diversity of virophages is still very limited. Copyright © 2018 Elsevier B.V. All rights reserved.

Mobile genetic element proliferation and gene inactivation impact over the genome structure and metabolic capabilities of Sodalis glossinidius, the secondary endosymbiont of tsetse flies

PubMed Central

2010-01-01

Background Genome reduction is a common evolutionary process in symbiotic and pathogenic bacteria. This process has been extensively characterized in bacterial endosymbionts of insects, where primary mutualistic bacteria represent the most extreme cases of genome reduction consequence of a massive process of gene inactivation and loss during their evolution from free-living ancestors. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, contains one of the few complete genomes of bacteria at the very beginning of the symbiotic association, allowing to evaluate the relative impact of mobile genetic element proliferation and gene inactivation over the structure and functional capabilities of this bacterial endosymbiont during the transition to a host dependent lifestyle. Results A detailed characterization of mobile genetic elements and pseudogenes reveals a massive presence of different types of prophage elements together with five different families of IS elements that have proliferated across the genome of Sodalis glossinidius at different levels. In addition, a detailed survey of intergenic regions allowed the characterization of 1501 pseudogenes, a much higher number than the 972 pseudogenes described in the original annotation. Pseudogene structure reveals a minor impact of mobile genetic element proliferation in the process of gene inactivation, with most of pseudogenes originated by multiple frameshift mutations and premature stop codons. The comparison of metabolic profiles of Sodalis glossinidius and tsetse fly primary endosymbiont Wiglesworthia glossinidia based on their whole gene and pseudogene repertoires revealed a novel case of pathway inactivation, the arginine biosynthesis, in Sodalis glossinidius together with a possible case of metabolic complementation with Wigglesworthia glossinidia for thiamine biosynthesis. Conclusions The complete re-analysis of the genome sequence of Sodalis glossinidius reveals novel insights in the evolutionary transition from a free-living ancestor to a host-dependent lifestyle, with a massive proliferation of mobile genetic elements mainly of phage origin although with minor impact in the process of gene inactivation that is taking place in this bacterial genome. The metabolic analysis of the whole endosymbiotic consortia of tsetse flies have revealed a possible phenomenon of metabolic complementation between primary and secondary endosymbionts that can contribute to explain the co-existence of both bacterial endosymbionts in the context of the tsetse host. PMID:20649993

CRISPR-Cas systems target a diverse collection of invasive mobile genetic elements in human microbiomes

PubMed Central

2013-01-01

Background Bacteria and archaea develop immunity against invading genomes by incorporating pieces of the invaders' sequences, called spacers, into a clustered regularly interspaced short palindromic repeats (CRISPR) locus between repeats, forming arrays of repeat-spacer units. When spacers are expressed, they direct CRISPR-associated (Cas) proteins to silence complementary invading DNA. In order to characterize the invaders of human microbiomes, we use spacers from CRISPR arrays that we had previously assembled from shotgun metagenomic datasets, and identify contigs that contain these spacers' targets. Results We discover 95,000 contigs that are putative invasive mobile genetic elements, some targeted by hundreds of CRISPR spacers. We find that oral sites in healthy human populations have a much greater variety of mobile genetic elements than stool samples. Mobile genetic elements carry genes encoding diverse functions: only 7% of the mobile genetic elements are similar to known phages or plasmids, although a much greater proportion contain phage- or plasmid-related genes. A small number of contigs share similarity with known integrative and conjugative elements, providing the first examples of CRISPR defenses against this class of element. We provide detailed analyses of a few large mobile genetic elements of various types, and a relative abundance analysis of mobile genetic elements and putative hosts, exploring the dynamic activities of mobile genetic elements in human microbiomes. A joint analysis of mobile genetic elements and CRISPRs shows that protospacer-adjacent motifs drive their interaction network; however, some CRISPR-Cas systems target mobile genetic elements lacking motifs. Conclusions We identify a large collection of invasive mobile genetic elements in human microbiomes, an important resource for further study of the interaction between the CRISPR-Cas immune system and invaders. PMID:23628424

Population and clinical genetics of human transposable elements in the (post) genomic era

PubMed Central

Rishishwar, Lavanya; Wang, Lu; Clayton, Evan A.; Mariño-Ramírez, Leonardo; McDonald, John F.; Jordan, I. King

2017-01-01

ABSTRACT Recent technological developments—in genomics, bioinformatics and high-throughput experimental techniques—are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health. PMID:28228978

Mycobacterium avium restriction fragment length polymorphism-IS IS1245 and the simple double repetitive element polymerase chain reaction typing method to screen genetic diversity in Brazilian strains.

PubMed

Sequeira, Patrícia Carvalho de; Fonseca, Leila de Souza; Silva, Marlei Gomes da; Saad, Maria Helena Féres

2005-11-01

Simple double repetitive element polymerase chain reaction (MaDRE-PCR) and Pvu II-IS1245 restriction fragment length polymorphism (RFLP) typing methods were used to type 41 Mycobacterium avium isolates obtained from 14 AIDS inpatients and 10 environment and animals specimens identified among 53 mycobacteria isolated from 237 food, chicken, and pig. All environmental and animals strains showed orphan patterns by both methods. By MaDRE-PCR four patients, with multiple isolates, showed different patterns, suggesting polyclonal infection that was confirmed by RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium strains demonstrated that the method seems to be useful as simple and less expensive typing method for screening genetic diversity in M. avium strains on selected epidemiological studies, although with limitation on analysis identical patterns except for one band.

Epigenomics and the concept of degeneracy in biological systems

PubMed Central

Mason, Paul H.; Barron, Andrew B.

2014-01-01

Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

PubMed Central

2016-01-01

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI. PMID:26862400

Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles

PubMed Central

Nandi, Tannistha; Holden, Matthew T.G.; Didelot, Xavier; Mehershahi, Kurosh; Boddey, Justin A.; Beacham, Ifor; Peak, Ian; Harting, John; Baybayan, Primo; Guo, Yan; Wang, Susana; How, Lee Chee; Sim, Bernice; Essex-Lopresti, Angela; Sarkar-Tyson, Mitali; Nelson, Michelle; Smither, Sophie; Ong, Catherine; Aw, Lay Tin; Hoon, Chua Hui; Michell, Stephen; Studholme, David J.; Titball, Richard; Chen, Swaine L.; Parkhill, Julian

2015-01-01

Burkholderia pseudomallei (Bp) is the causative agent of the infectious disease melioidosis. To investigate population diversity, recombination, and horizontal gene transfer in closely related Bp isolates, we performed whole-genome sequencing (WGS) on 106 clinical, animal, and environmental strains from a restricted Asian locale. Whole-genome phylogenies resolved multiple genomic clades of Bp, largely congruent with multilocus sequence typing (MLST). We discovered widespread recombination in the Bp core genome, involving hundreds of regions associated with multiple haplotypes. Highly recombinant regions exhibited functional enrichments that may contribute to virulence. We observed clade-specific patterns of recombination and accessory gene exchange, and provide evidence that this is likely due to ongoing recombination between clade members. Reciprocally, interclade exchanges were rarely observed, suggesting mechanisms restricting gene flow between clades. Interrogation of accessory elements revealed that each clade harbored a distinct complement of restriction-modification (RM) systems, predicted to cause clade-specific patterns of DNA methylation. Using methylome sequencing, we confirmed that representative strains from separate clades indeed exhibit distinct methylation profiles. Finally, using an E. coli system, we demonstrate that Bp RM systems can inhibit uptake of non-self DNA. Our data suggest that RM systems borne on mobile elements, besides preventing foreign DNA invasion, may also contribute to limiting exchanges of genetic material between individuals of the same species. Genomic clades may thus represent functional units of genetic isolation in Bp, modulating intraspecies genetic diversity. PMID:25236617

The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

PubMed Central

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H.; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Barberio, Manuela Terranova; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D.; Nestle, Frank O.

2015-01-01

Summary Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analysing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets, and uncovered insights into genetic control for regulatory T cells. This dataset also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. PMID:25772697

The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

PubMed

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

2015-04-09

Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Ribosomal DNA Organization Before and After Magnification in Drosophila melanogaster

PubMed Central

Bianciardi, Alessio; Boschi, Manuela; Swanson, Ellen E.; Belloni, Massimo; Robbins, Leonard G.

2012-01-01

In all eukaryotes, the ribosomal RNA genes are stably inherited redundant elements. In Drosophila melanogaster, the presence of a Ybb− chromosome in males, or the maternal presence of the Ribosomal exchange (Rex) element, induces magnification: a heritable increase of rDNA copy number. To date, several alternative classes of mechanisms have been proposed for magnification: in situ replication or extra-chromosomal replication, either of which might act on short or extended strings of rDNA units, or unequal sister chromatid exchange. To eliminate some of these hypotheses, none of which has been clearly proven, we examined molecular-variant composition and compared genetic maps of the rDNA in the bb2 mutant and in some magnified bb+ alleles. The genetic markers used are molecular-length variants of IGS sequences and of R1 and R2 mobile elements present in many 28S sequences. Direct comparison of PCR products does not reveal any particularly intensified electrophoretic bands in magnified alleles compared to the nonmagnified bb2 allele. Hence, the increase of rDNA copy number is diluted among multiple variants. We can therefore reject mechanisms of magnification based on multiple rounds of replication of short strings. Moreover, we find no changes of marker order when pre- and postmagnification maps are compared. Thus, we can further restrict the possible mechanisms to two: replication in situ of an extended string of rDNA units or unequal exchange between sister chromatids. PMID:22505623

Function of the CRISPR-Cas System of the Human Pathogen Clostridium difficile

PubMed Central

Boudry, Pierre; Semenova, Ekaterina; Monot, Marc; Datsenko, Kirill A.; Lopatina, Anna; Sekulovic, Ognjen; Ospina-Bedoya, Maicol; Fortier, Louis-Charles; Severinov, Konstantin; Dupuy, Bruno

2015-01-01

ABSTRACT Clostridium difficile is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen, C. difficile must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to foreign genetic invaders. Our recent data revealed active expression and processing of CRISPR RNAs from multiple type I-B CRISPR arrays in C. difficile reference strain 630. Here, we demonstrate active expression of CRISPR arrays in strain R20291, an epidemic C. difficile strain. Through genome sequencing and host range analysis of several new C. difficile phages and plasmid conjugation experiments, we provide evidence of defensive function of the CRISPR-Cas system in both C. difficile strains. We further demonstrate that C. difficile Cas proteins are capable of interference in a heterologous host, Escherichia coli. These data set the stage for mechanistic and physiological analyses of CRISPR-Cas-mediated interactions of important global human pathogen with its genetic parasites. PMID:26330515

Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements

PubMed Central

Dolja, Valerian V.

2014-01-01

SUMMARY Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms. Structurally similar, apparently homologous capsids are present in a huge variety of icosahedral viruses that infect bacteria, archaea, and eukaryotes. These findings prompted the concept of the capsid as the virus “self” that defines the identity of deep, ancient viral lineages. However, several other widespread viral “hallmark genes” encode key components of the viral replication apparatus (such as polymerases and helicases) and combine with different capsid proteins, given the inherently modular character of viral evolution. Furthermore, diverse, widespread, capsidless selfish genetic elements, such as plasmids and various types of transposons, share hallmark genes with viruses. Viruses appear to have evolved from capsidless selfish elements, and vice versa, on multiple occasions during evolution. At the earliest, precellular stage of life's evolution, capsidless genetic parasites most likely emerged first and subsequently gave rise to different classes of viruses. In this review, we develop the concept of a greater virus world which forms an evolutionary network that is held together by shared conserved genes and includes both bona fide capsid-encoding viruses and different classes of capsidless replicons. Theoretical studies indicate that selfish replicons (genetic parasites) inevitably emerge in any sufficiently complex evolving ensemble of replicators. Therefore, the key signature of the greater virus world is not the presence of a capsid but rather genetic, informational parasitism itself, i.e., various degrees of reliance on the information processing systems of the host. PMID:24847023

Inevitability of Genetic Parasites

PubMed Central

Iranzo, Jaime; Puigbò, Pere; Lobkovsky, Alexander E.; Wolf, Yuri I.

2016-01-01

Abstract Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites (cheaters) necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT). We mathematically derive the threshold value of the minimal transfer rate required for selfish element persistence, depending on the element duplication and loss rates as well as the cost to the host. Estimation of the characteristic gene duplication, loss and transfer rates for transposons, plasmids and virus-related elements in multiple groups of diverse bacteria and archaea indicates that most of these rates are compatible with the long term persistence of parasites. Notably, a small but non-zero rate of HGT is also required for the persistence of non-parasitic genes. We hypothesize that cells cannot tune their horizontal transfer rates to be below the threshold required for parasite persistence without experiencing highly detrimental side-effects. As a lower boundary to the minimum DNA transfer rate that a cell can withstand, we consider the process of genome degradation and mutational meltdown of populations through Muller’s ratchet. A numerical assessment of this hypothesis suggests that microbial populations cannot purge parasites while escaping Muller’s ratchet. Thus, genetic parasites appear to be virtually inevitable in cellular organisms. PMID:27503291

Adaptation of genetically monomorphic bacteria: evolution of copper resistance through multiple horizontal gene transfers of complex and versatile mobile genetic elements.

PubMed

Richard, D; Ravigné, V; Rieux, A; Facon, B; Boyer, C; Boyer, K; Grygiel, P; Javegny, S; Terville, M; Canteros, B I; Robène, I; Vernière, C; Chabirand, A; Pruvost, O; Lefeuvre, P

2017-04-01

Copper-based antimicrobial compounds are widely used to control plant bacterial pathogens. Pathogens have adapted in response to this selective pressure. Xanthomonas citri pv. citri, a major citrus pathogen causing Asiatic citrus canker, was first reported to carry plasmid-encoded copper resistance in Argentina. This phenotype was conferred by the copLAB gene system. The emergence of resistant strains has since been reported in Réunion and Martinique. Using microsatellite-based genotyping and copLAB PCR, we demonstrated that the genetic structure of the copper-resistant strains from these three regions was made up of two distant clusters and varied for the detection of copLAB amplicons. In order to investigate this pattern more closely, we sequenced six copper-resistant X. citri pv. citri strains from Argentina, Martinique and Réunion, together with reference copper-resistant Xanthomonas and Stenotrophomonas strains using long-read sequencing technology. Genes involved in copper resistance were found to be strain dependent with the novel identification in X. citri pv. citri of copABCD and a cus heavy metal efflux resistance-nodulation-division system. The genes providing the adaptive trait were part of a mobile genetic element similar to Tn3-like transposons and included in a conjugative plasmid. This indicates the system's great versatility. The mining of all available bacterial genomes suggested that, within the bacterial community, the spread of copper resistance associated with mobile elements and their plasmid environments was primarily restricted to the Xanthomonadaceae family. © 2017 John Wiley & Sons Ltd.

When to suspect a genetic syndrome.

PubMed

Solomon, Benjamin D; Muenke, Maximilian

2012-11-01

Family physicians should be able to recognize findings on physical examination and history that suggest the presence of a genetic syndrome to aid in the diagnosis and treatment of potentially affected patients, as well as subspecialty referral. General themes that can alert family physicians to the presence of genetic conditions include dysmorphic features that are evident on physical examination; multiple anomalies in one patient; unexplained neurocognitive impairment; and a family history that is suggestive of a hereditary disease. The presence of one obvious malformation should not limit the full evaluation, because additional, subtler findings will often be important in the differential diagnosis. Taking an accurate three-generation family history is invaluable when considering a genetic syndrome. Important elements include the age and sex of family members; when family members were affected by disease or when they died; the ethnic background; and if there is consanguinity. Genetic subspecialists can assist family physicians in diagnosis, suggest additional testing and referrals if warranted, help direct medical care, and provide counseling for affected patients and their families.

Genetic Nature of Elemental Contents in Wheat Grains and Its Genomic Prediction: Toward the Effective Use of Wheat Landraces from Afghanistan

PubMed Central

Yamaoka, Shuhei; Yoshimura, Kazusa; Kondou, Youichi; Onogi, Akio; Matsui, Minami; Iwata, Hiroyoshi; Ban, Tomohiro

2017-01-01

Profiling elemental contents in wheat grains and clarifying the underlying genetic systems are important for the breeding of biofortified crops. Our objective was to evaluate the genetic potential of 269 Afghan wheat landraces for increasing elemental contents in wheat cultivars. The contents of three major (Mg, K, and P) and three minor (Mn, Fe, and Zn) elements in wheat grains were measured by energy dispersive X-ray fluorescence spectrometry. Large variations in elemental contents were observed among landraces. Marker-based heritability estimates were low to moderate, suggesting that the elemental contents are complex quantitative traits. Genetic correlations between two locations (Japan and Afghanistan) and among the six elements were estimated using a multi-response Bayesian linear mixed model. Low-to-moderate genetic correlations were observed among major elements and among minor elements respectively, but not between major and minor elements. A single-response genome-wide association study detected only one significant marker, which was associated with Zn, suggesting it will be difficult to increase the elemental contents of wheat by conventional marker-assisted selection. Genomic predictions for major elemental contents were moderately or highly accurate, whereas those for minor elements were mostly low or moderate. Our results indicate genomic selection may be useful for the genetic improvement of elemental contents in wheat. PMID:28072876

Unlocking the genetic diversity of Creole wheats.

PubMed

Vikram, Prashant; Franco, Jorge; Burgueño-Ferreira, Juan; Li, Huihui; Sehgal, Deepmala; Saint Pierre, Carolina; Ortiz, Cynthia; Sneller, Clay; Tattaris, Maria; Guzman, Carlos; Sansaloni, Carolina Paola; Ellis, Mark; Fuentes-Davila, Guillermo; Reynolds, Matthew; Sonders, Kai; Singh, Pawan; Payne, Thomas; Wenzl, Peter; Sharma, Achla; Bains, Navtej Singh; Singh, Gyanendra Pratap; Crossa, José; Singh, Sukhwinder

2016-03-15

Climate change and slow yield gains pose a major threat to global wheat production. Underutilized genetic resources including landraces and wild relatives are key elements for developing high-yielding and climate-resilient wheat varieties. Landraces introduced into Mexico from Europe, also known as Creole wheats, are adapted to a wide range of climatic regimes and represent a unique genetic resource. Eight thousand four hundred and sixteen wheat landraces representing all dimensions of Mexico were characterized through genotyping-by-sequencing technology. Results revealed sub-groups adapted to specific environments of Mexico. Broadly, accessions from north and south of Mexico showed considerable genetic differentiation. However, a large percentage of landrace accessions were genetically very close, although belonged to different regions most likely due to the recent (nearly five centuries before) introduction of wheat in Mexico. Some of the groups adapted to extreme environments and accumulated high number of rare alleles. Core reference sets were assembled simultaneously using multiple variables, capturing 89% of the rare alleles present in the complete set. Genetic information about Mexican wheat landraces and core reference set can be effectively utilized in next generation wheat varietal improvement.

Complete genetic analysis of plasmids carrying mcr-1 and other resistance genes in an Escherichia coli isolate of animal origin.

PubMed

Li, Ruichao; Xie, Miaomiao; Lv, Jingzhang; Wai-Chi Chan, Edward; Chen, Sheng

2017-03-01

To investigate the genetic features of three plasmids recovered from an MCR-1 and ESBL-producing Escherichia coli strain, HYEC7, and characterize the transmission mechanism of mcr-1 . The genetic profiles of three plasmids were determined by PCR, S1-PFGE, Southern hybridization and WGS analysis. The ability of the mcr-1 -bearing plasmid to undergo conjugation was also assessed. The mcr-1 -bearing transposon Tn 6330 was characterized by PCR and DNA sequencing. Complete sequences of three plasmids were obtained. A non-conjugative phage P7-like plasmid, pHYEC7- mcr1 , was found to harbour the mcr-1 -bearing transposon Tn 6330 , which could be excised from the plasmid by generating a circular intermediate harbouring mcr-1 and the IS Apl1 element. The insertion of the circular intermediate into another plasmid, pHYEC7-IncHI2, could form pHNSHP45-2, the original IncHI2-type mcr-1 -carrying plasmid that was reported. The third plasmid, pHYEC7-110, harboured two replicons, IncX1 and IncFIB, and comprised multiple antimicrobial resistance mobile elements, some of which were shared by pHYEC7-IncHI2. The Tn 6330 element located in the phage-like plasmid pHYEC7- mcr1 could be excised from the plasmid and formed a circular intermediate that could be integrated into plasmids containing the IS Apl1 element. This phenomenon indicated that Tn 6330 is a key element responsible for widespread dissemination of mcr-1 among various types of plasmids and bacterial chromosomes. The dissemination rate of such an element may be further enhanced upon translocation into phage-like vectors, which may also be transmitted via transduction events. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Selfish genetic elements and sexual selection: their impact on male fertility.

PubMed

Price, Tom A R; Wedell, Nina

2008-03-01

Females of many species mate with more than one male (polyandry), yet the adaptive significance of polyandry is poorly understood. One hypothesis to explain the widespread occurrence of multiple mating is that it may allow females to utilize post-copulatory mechanisms to reduce the risk of fertilizing their eggs with sperm from incompatible males. Selfish genetic elements (SGEs) are ubiquitous in eukaryotes, frequent sources of reproductive incompatibilities, and associated with fitness costs. However, their impact on sexual selection is largely unexplored. In this review we examine the link between SGEs, male fertility and sperm competitive ability. We show there is widespread evidence that SGEs are associated with reduced fertility in both animals and plants, and present some recent data showing that males carrying SGEs have reduced paternity in sperm competition. We also discuss possible reasons why male gametes are particularly vulnerable to the selfish actions of SGEs. The widespread reduction in male fertility caused by SGEs implies polyandry may be a successful female strategy to bias paternity against SGE-carrying males.

Selfish genetic elements and sexual selection: their impact on male fertility.

PubMed

Price, Tom A R; Wedell, Nina

2008-09-01

Females of many species mate with more than one male (polyandry), yet the adaptive significance of polyandry is poorly understood. One hypothesis to explain the widespread occurrence of multiple mating is that it may allow females to utilize post-copulatory mechanisms to reduce the risk of fertilizing their eggs with sperm from incompatible males. Selfish genetic elements (SGEs) are ubiquitous in eukaryotes, frequent sources of reproductive incompatibilities, and associated with fitness costs. However, their impact on sexual selection is largely unexplored. In this review we examine the link between SGEs, male fertility and sperm competitive ability. We show there is widespread evidence that SGEs are associated with reduced fertility in both animals and plants, and present some recent data showing that males carrying SGEs have reduced paternity in sperm competition. We also discuss possible reasons why male gametes are particularly vulnerable to the selfish actions of SGEs. The widespread reduction in male fertility caused by SGEs implies polyandry may be a successful female strategy to bias paternity against SGE-carrying males.

Genetic variation affecting exon skipping contributes to brain structural atrophy in Alzheimer's disease.

PubMed

Lee, Younghee; Han, Seonggyun; Kim, Dongwook; Kim, Dokyoon; Horgousluoglu, Emrin; Risacher, Shannon L; Saykin, Andrew J; Nho, Kwangsik

2018-01-01

Genetic variation in cis-regulatory elements related to splicing machinery and splicing regulatory elements (SREs) results in exon skipping and undesired protein products. We developed a splicing decision model to identify actionable loci among common SNPs for gene regulation. The splicing decision model identified SNPs affecting exon skipping by analyzing sequence-driven alternative splicing (AS) models and by scanning the genome for the regions with putative SRE motifs. We used non-Hispanic Caucasians with neuroimaging, and fluid biomarkers for Alzheimer's disease (AD) and identified 17,088 common exonic SNPs affecting exon skipping. GWAS identified one SNP (rs1140317) in HLA-DQB1 as significantly associated with entorhinal cortical thickness, AD neuroimaging biomarker, after controlling for multiple testing. Further analysis revealed that rs1140317 was significantly associated with brain amyloid-f deposition (PET and CSF). HLA-DQB1 is an essential immune gene and may regulate AS, thereby contributing to AD pathology. SRE may hold potential as novel therapeutic targets for AD.

Comparative genome analysis and characterization of the Salmonella Typhimurium strain CCRJ_26 isolated from swine carcasses using whole-genome sequencing approach.

PubMed

Panzenhagen, P H N; Cabral, C C; Suffys, P N; Franco, R M; Rodrigues, D P; Conte-Junior, C A

2018-04-01

Salmonella pathogenicity relies on virulence factors many of which are clustered within the Salmonella pathogenicity islands. Salmonella also harbours mobile genetic elements such as virulence plasmids, prophage-like elements and antimicrobial resistance genes which can contribute to increase its pathogenicity. Here, we have genetically characterized a selected S. Typhimurium strain (CCRJ_26) from our previous study with Multiple Drugs Resistant profile and high-frequency PFGE clonal profile which apparently persists in the pork production centre of Rio de Janeiro State, Brazil. By whole-genome sequencing, we described the strain's genome virulent content and characterized the repertoire of bacterial plasmids, antibiotic resistance genes and prophage-like elements. Here, we have shown evidence that strain CCRJ_26 genome possible represent a virulence-associated phenotype which may be potentially virulent in human infection. Whole-genome sequencing technologies are still costly and remain underexplored for applied microbiology in Brazil. Hence, this genomic description of S. Typhimurium strain CCRJ_26 will provide help in future molecular epidemiological studies. The analysis described here reveals a quick and useful pipeline for bacterial virulence characterization using whole-genome sequencing approach. © 2018 The Society for Applied Microbiology.

Successful Gene Tagging in Lettuce Using the Tnt1 Retrotransposon from Tobacco

PubMed Central

Mazier, Marianne; Botton, Emmanuel; Flamain, Fabrice; Bouchet, Jean-Paul; Courtial, Béatrice; Chupeau, Marie-Christine; Chupeau, Yves; Maisonneuve, Brigitte; Lucas, Hélène

2007-01-01

The tobacco (Nicotiana tabacum) element Tnt1 is one of the few identified active retrotransposons in plants. These elements possess unique properties that make them ideal genetic tools for gene tagging. Here, we demonstrate the feasibility of gene tagging using the retrotransposon Tnt1 in lettuce (Lactuca sativa), which is the largest genome tested for retrotransposon mutagenesis so far. Of 10 different transgenic bushes carrying a complete Tnt1 containing T-DNA, eight contained multiple transposed copies of Tnt1. The number of transposed copies of the element per plant was particularly high, the smallest number being 28. Tnt1 transposition in lettuce can be induced by a very simple in vitro culture protocol. Tnt1 insertions were stable in the progeny of the primary transformants and could be segregated genetically. Characterization of the sequences flanking some insertion sites revealed that Tnt1 often inserted into genes. The progeny of some primary transformants showed phenotypic alterations due to recessive mutations. One of these mutations was due to Tnt1 insertion in the gibberellin 3β-hydroxylase gene. Taken together, these results indicate that Tnt1 is a powerful tool for insertion mutagenesis especially in plants with a large genome. PMID:17351058

Conditions for success of engineered underdominance gene drive systems.

PubMed

Edgington, Matthew P; Alphey, Luke S

2017-10-07

Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genetic conflicts: the usual suspects and beyond

PubMed Central

McLaughlin, Richard N.

2017-01-01

ABSTRACT Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements. PMID:28057823

Discovering functional DNA elements using population genomic information: a proof of concept using human mtDNA.

PubMed

Schrider, Daniel R; Kern, Andrew D

2014-06-09

Identifying the complete set of functional elements within the human genome would be a windfall for multiple areas of biological research including medicine, molecular biology, and evolution. Complete knowledge of function would aid in the prioritization of loci when searching for the genetic bases of disease or adaptive phenotypes. Because mutations that disrupt function are disfavored by natural selection, purifying selection leaves a detectable signature within functional elements; accordingly, this signal has been exploited for over a decade through the use of genomic comparisons of distantly related species. While this is so, the functional complement of the genome changes extensively across time and between lineages; therefore, evidence of the current action of purifying selection in humans is essential. Because the removal of deleterious mutations by natural selection also reduces within-species genetic diversity within functional loci, dense population genetic data have the potential to reveal genomic elements that are currently functional. Here, we assess the potential of this approach by examining an ultradeep sample of human mitochondrial genomes (n = 16,411). We show that the high density of polymorphism in this data set precisely delineates regions experiencing purifying selection. Furthermore, we show that the number of segregating alleles at a site is strongly correlated with its divergence across species after accounting for known mutational biases in human mitochondrial DNA (ρ = 0.51; P < 2.2 × 10(-16)). These two measures track one another at a remarkably fine scale across many loci-a correlation that is purely the result of natural selection. Our results demonstrate that genetic variation has the potential to reveal with surprising precision which regions in the genome are currently performing important functions and likely to have deleterious fitness effects when mutated. As more complete human genomes are sequenced, similar power to reveal purifying selection may be achievable in the human nuclear genome. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Selfish genetic elements and the gene’s-eye view of evolution

PubMed Central

2016-01-01

During the last few decades, we have seen an explosion in the influx of details about the biology of selfish genetic elements. Ever since the early days of the field, the gene’s-eye view of Richard Dawkins, George Williams, and others, has been instrumental to make sense of new empirical observations and to the generation of new hypotheses. However, the close association between selfish genetic elements and the gene’s-eye view has not been without critics and several other conceptual frameworks have been suggested. In particular, proponents of multilevel selection models have used selfish genetic elements to criticize the gene’s-eye view. In this paper, I first trace the intertwined histories of the study of selfish genetic elements and the gene’s-eye view and then discuss how their association holds up when compared with other proposed frameworks. Next, using examples from transposable elements and the major transitions, I argue that different models highlight separate aspects of the evolution of selfish genetic elements and that the productive way forward is to maintain a plurality of perspectives. Finally, I discuss how the empirical study of selfish genetic elements has implications for other conceptual issues associated with the gene’s-eye view, such as agential thinking, adaptationism, and the role of fitness maximizing models in evolution. PMID:29491953

The cost of copy number in a selfish genetic element: the 2-μm plasmid of Saccharomyces cerevisiae.

PubMed

Harrison, Ellie; Koufopanou, V; Burt, A; MacLean, R C

2012-11-01

Many autonomously replicating genetic elements exist as multiple copies within the cell. The copy number of these elements is often assumed to have important fitness consequences for both element and host, yet the forces shaping its evolution are not well understood. The 2 μm is a multicopy plasmid of Saccharomyces yeasts, encoding just four genes that are solely involved in plasmid replication. One simple model for the fitness relationship between yeasts and 2 μm is that plasmid copy number evolves as a trade-off between selection for increased vertical transmission, favouring high copy number, and selection for decreased virulence, favouring low copy number. To test this model, we experimentally manipulated the copy number of the plasmid and directly measured the fitness cost, in terms of growth rate reduction, associated with high plasmid copy number. We find that the fitness burden imposed by the 2 μm increases with plasmid copy number, such that each copy imposes a fitness burden of 0.17% (± 0.008%), greatly exceeding the cost expected for it to be stably maintained in yeast populations. Our results demonstrate the crucial importance of copy number in the evolution of yeast per 2 μm associations and pave the way for future studies examining how selection can shape the cost of multicopy elements. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Virus world as an evolutionary network of viruses and capsidless selfish elements.

PubMed

Koonin, Eugene V; Dolja, Valerian V

2014-06-01

Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms. Structurally similar, apparently homologous capsids are present in a huge variety of icosahedral viruses that infect bacteria, archaea, and eukaryotes. These findings prompted the concept of the capsid as the virus "self" that defines the identity of deep, ancient viral lineages. However, several other widespread viral "hallmark genes" encode key components of the viral replication apparatus (such as polymerases and helicases) and combine with different capsid proteins, given the inherently modular character of viral evolution. Furthermore, diverse, widespread, capsidless selfish genetic elements, such as plasmids and various types of transposons, share hallmark genes with viruses. Viruses appear to have evolved from capsidless selfish elements, and vice versa, on multiple occasions during evolution. At the earliest, precellular stage of life's evolution, capsidless genetic parasites most likely emerged first and subsequently gave rise to different classes of viruses. In this review, we develop the concept of a greater virus world which forms an evolutionary network that is held together by shared conserved genes and includes both bona fide capsid-encoding viruses and different classes of capsidless replicons. Theoretical studies indicate that selfish replicons (genetic parasites) inevitably emerge in any sufficiently complex evolving ensemble of replicators. Therefore, the key signature of the greater virus world is not the presence of a capsid but rather genetic, informational parasitism itself, i.e., various degrees of reliance on the information processing systems of the host. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Three in One—Multiple Faunal Elements within an Endangered European Butterfly Species

PubMed Central

Junker, Marius; Zimmermann, Marie; Ramos, Ana A.; Gros, Patrick; Konvička, Martin; Nève, Gabriel; Rákosy, László; Tammaru, Toomas

2015-01-01

Ice ages within Europe forced many species to retreat to refugia, of which three major biogeographic basic types can be distinguished: "Mediterranean", "Continental" and "Alpine / Arctic" species. However, this classification often fails to explain the complex phylogeography of European species with a wide range of latitudinal and altitudinal distribution. Hence, we tested for the possibility that all three mentioned faunal elements are represented within one species. Our data was obtained by scoring 1,307 Euphydryas aurinia individuals (46 European locations) for 17 allozyme loci, and sequencing a subset of 492 individuals (21 sites) for a 626 base pairs COI fragment. Genetic diversity indices, F statistics, hierarchical analyses of molecular variance, individual-based clustering, and networks were used to explore the phylogeographic patterns. The COI fragment represented 18 haplotypes showing a strong geographic structure. All but one allozyme loci analysed were polymorphic with a mean F ST of 0.20, supporting a pronounced among population structure. Interpretation of both genetic marker systems, using several analytical tools, calls for the recognition of twelve genetic groups. These analyses consistently distinguished different groups in Iberia (2), Italy, Provence, Alps (3), Slovenia, Carpathian Basin, the lowlands of West and Central Europe as well as Estonia, often with considerable additional substructures. The genetic data strongly support the hypothesis that E. aurinia survived the last glaciation in Mediterranean, extra-Mediterranean and perialpine refugia. It is thus a rare example of a model organism that combines attributes of faunal elements from all three of these sources. The observed differences between allozymes and mtDNA most likely result from recent introgression of mtDNA into nuclear allozyme groups. Our results indicate discrepancies with the morphologically-based subspecies models, underlining the need to revise the current taxonomy. PMID:26566029

Next-Generation Sequence Analysis Reveals Transfer of Methicillin Resistance to a Methicillin-Susceptible Staphylococcus aureus Strain That Subsequently Caused a Methicillin-Resistant Staphylococcus aureus Outbreak: a Descriptive Study.

PubMed

Weterings, Veronica; Bosch, Thijs; Witteveen, Sandra; Landman, Fabian; Schouls, Leo; Kluytmans, Jan

2017-09-01

Resistance to methicillin in Staphylococcus aureus is caused primarily by the mecA gene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCC mec ). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant Staphylococcus aureus (MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible S. aureus (MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCC mec and subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCC mec and that the resulting MRSA strain caused an outbreak. Copyright © 2017 American Society for Microbiology.

Chinese children with autism: A multiple chemical elements profile in erythrocytes.

PubMed

Wu, Jing; Liu, Duo-Jian; Shou, Xiao-Jing; Zhang, Ji-Shui; Meng, Fan-Chao; Liu, Ya-Qiong; Han, Song-Ping; Zhang, Rong; Jia, Jin-Zhu; Wang, Jing-Yu; Han, Ji-Sheng

2018-06-01

Several lines of evidence suggested that abnormal levels of certain chemical elements may contribute to the development of autism spectrum disorders (ASD). The present work aimed to investigate the multiple chemical elements profile in the erythrocytes of autistic versus typically developing children (TDC) of China. Analyses were carried out to explore the possible association between levels of elements and the risk as well as the severity of ASD. Erythrocyte levels of 11 elements (32%) among 34 detected elements in autistic group were significantly different from those in the TDC group. To our knowledge, this is the first study which compared the levels of rare earth elements in erythrocytes between children with or without ASD. Five elements including Pb, Na, Ca, Sb, and La are associated with the Childhood Autism Rating Scale (CARS) total score. Also, a series of tendencies were found in this research which was believed to affect auditory response, taste, smell, and touch, as well as fear or nervousness. It can be concluded that Chinese autistic children suffer from multi-chemical element imbalances which involves a complex combination of genetic and environmental factors. The results showed a significant correlation between abnormal levels of several chemical elements and the severity of the autistic syndrome. It is suggested that abnormal levels of some chemical elements may contribute to the development of autism spectrum disorders (ASD). In this work, the impact of element imbalances on the risk and severity of ASD was investigated, focusing on the analysis of abnormal levels of the multi-chemical elements profile in erythrocytes compared with typically developing children. Furthermore, the results showed a significant correlation between abnormal levels of several chemical elements and the severity of the autistic syndrome. Autism Res 2018, 11: 834-845. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Structural characterization of a novel full-length transcript promoter from Horseradish Latent Virus (HRLV) and its transcriptional regulation by multiple stress responsive transcription factors.

PubMed

Khan, Ahamed; Shrestha, Ankita; Bhuyan, Kashyap; Maiti, Indu B; Dey, Nrisingha

2018-01-01

The promoter fragment described in this study can be employed for strong transgene expression under both biotic and abiotic stress conditions. Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to address various environmental stimuli during the course of evolution. One such mechanism involves the retention of discrete stress responsive cis-elements which are required for their survival and host-specificity. Here we describe the characterization of a novel Caulimoviral promoter isolated from Horseradish Latent Virus (HRLV) and its regulation by multiple stress responsive Transcription factors (TFs) namely DREB1, AREB1 and TGA1a. The activity of full length transcript (Flt-) promoter from HRLV (- 677 to + 283) was investigated in both transient and transgenic assays where we identified H12 (- 427 to + 73) as the highest expressing fragment having ~ 2.5-fold stronger activity than the CaMV35S promoter. The H12 promoter was highly active and near-constitutive in the vegetative and reproductive parts of both Tobacco and Arabidopsis transgenic plants. Interestingly, H12 contains a distinct cluster of cis-elements like dehydration-responsive element (DRE-core; GCCGAC), an ABA-responsive element (ABRE; ACGTGTC) and as-1 element (TGACG) which are known to be induced by cold, drought and pathogen/SA respectively. The specific binding of DREB1, AREB1 and TGA1a to DRE, ABRE and as-1 elements respectively were confirmed by the gel-binding assays using H12 promoter-specific probes. Detailed mutational analysis of the H12 promoter suggested that the presence of DRE-core and as-1 element was indispensable for its activity which was further confirmed by the transactivation assays. Our studies imply that H12 could be a valuable genetic tool for regulated transgene expression under diverse environmental conditions.

MIDAS: A Modular DNA Assembly System for Synthetic Biology.

PubMed

van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

2018-04-20

A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

Genetic conflicts: the usual suspects and beyond.

PubMed

McLaughlin, Richard N; Malik, Harmit S

2017-01-01

Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements. © 2017. Published by The Company of Biologists Ltd.

An In-Depth Characterization of the Major Psoriasis Susceptibility Locus Identifies Candidate Susceptibility Alleles within an HLA-C Enhancer Element

PubMed Central

Clop, Alex; Bertoni, Anna; Spain, Sarah L.; Simpson, Michael A.; Pullabhatla, Venu; Tonda, Raul; Hundhausen, Christian; Di Meglio, Paola; De Jong, Pieter; Hayday, Adrian C.; Nestle, Frank O.; Barker, Jonathan N.; Bell, Robert J. A.; Capon, Francesca; Trembath, Richard C.

2013-01-01

Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC) locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC. PMID:23990973

Selfish genetic elements, genetic conflict, and evolutionary innovation.

PubMed

Werren, John H

2011-06-28

Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible "evolutionary functions" of SGEs.

Selfish genetic elements, genetic conflict, and evolutionary innovation

PubMed Central

Werren, John H.

2011-01-01

Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible “evolutionary functions” of SGEs. PMID:21690392

Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

PubMed

Guthrie, O'neil W

2017-10-01

In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

An Exploration of Gardens in Maycoba, Mexico: Change in the Environment of a Population Genetically Prone to Diabetes

PubMed Central

Begay, R. Cruz; Chaudhari, Lisa S.; Esparza-Romero, Julian; Romero, Rene Urquidez; Schulz, Leslie O.

2013-01-01

Gardens are an important part of the environment as they play multiple roles and are central to the lifestyle and economy of many communities. The investigators use qualitative methods to explore patterns and perceptions about changes in gardening and cultivation in the community of Maycoba, Mexico. Maycoba is home to a large community of Pima Indians, an Indigenous population genetically prone to diabetes. Pima Indians living in the United States have been shown to have an extremely high prevalence of diabetes, but the genetically comparable Pimas in Maycoba, Mexico, were found to have little diabetes in the early 1990s. The authors examine home gardens and other cultivation in the area as an element of a changing environment and lifestyle during the past 15 years. Methods include interviews and focus groups. Preliminary findings are presented in this paper. PMID:25364623

Novel Tn916-like elements confer aminoglycoside/macrolide co-resistance in clinical isolates of Streptococcus gallolyticus ssp. gallolyticus.

PubMed

Kambarev, Stanimir; Pecorari, Frédéric; Corvec, Stéphane

2018-02-09

Streptococcus gallolyticus ssp. gallolyticus (Sgg) is a commensal bacterium and an opportunistic pathogen. In humans it has been clinically associated with the incidence of colorectal cancer (CRC) and epidemiologically recognized as an emerging cause of infective endocarditis (IE). The standard therapy of Sgg includes the administration of a penicillin in combination with an aminoglycoside. Even though penicillin-resistant isolates have still not been reported, epidemiological studies have shown that this microbe is a reservoir of multiple acquired genes, conferring resistance to tetracyclines, aminoglycosides, macrolides and glycopeptides. However, the underlying antibiotic resistance mobilome of Sgg remains poorly understood. To investigate the mobile genetic basis of antibiotic resistance in multiresistant clinical Sgg. Isolate NTS31106099 was recovered from a patient with IE and CRC at Nantes University Hospital, France and studied by Illumina WGS and comparative genomics. Molecular epidemiology of the identified mobile element(s) was performed using antibiotic susceptibility testing (AST), PCR, PFGE and WGS. Mobility was investigated by PCR and filter mating. Two novel conjugative transposons, Tn6263 and Tn6331, confer aminoglycoside/macrolide co-resistance in clinical Sgg. They display classical family Tn916/Tn1545 modular architecture and harbour an aph(3')-III→sat4→ant(6)-Ia→erm(B) multiresistance gene cluster, related to pRE25 of Enterococcus faecium. These and/or closely related elements are highly prevalent among genetically heterogeneous clinical isolates of Sgg. Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Developmental Patterning as a Quantitative Trait: Genetic Modulation of the Hoxb6 Mutant Skeletal Phenotype

PubMed Central

Kappen, Claudia

2016-01-01

The process of patterning along the anterior-posterior axis in vertebrates is highly conserved. The function of Hox genes in the axis patterning process is particularly well documented for bone development in the vertebral column and the limbs. We here show that Hoxb6, in skeletal elements at the cervico-thoracic junction, controls multiple independent aspects of skeletal pattern, implicating discrete developmental pathways as substrates for this transcription factor. In addition, we demonstrate that Hoxb6 function is subject to modulation by genetic factors. These results establish Hox-controlled skeletal pattern as a quantitative trait modulated by gene-gene interactions, and provide evidence that distinct modifiers influence the function of conserved developmental genes in fundamental patterning processes. PMID:26800342

A fitness cost associated with the antibiotic resistance enzyme SME-1 beta-lactamase.

PubMed

Marciano, David C; Karkouti, Omid Y; Palzkill, Timothy

2007-08-01

The bla(TEM-1) beta-lactamase gene has become widespread due to the selective pressure of beta-lactam use and its stable maintenance on transferable DNA elements. In contrast, bla(SME-1) is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of bla(SME-1) via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, bla(SME-1) was determined to impart a fitness cost upon Escherichia coli in multiple genetic contexts and assays. Genetic screens and designed SME-1 mutants were utilized to identify the source of this fitness cost. These experiments established that the SME-1 protein was required for the fitness cost but also that the enzyme activity of SME-1 was not associated with the fitness cost. The genetic screens suggested that the SME-1 signal sequence was involved in the fitness cost. Consistent with these findings, exchange of the SME-1 signal sequence for the TEM-1 signal sequence alleviated the fitness cost while replacing the TEM-1 signal sequence with the SME-1 signal sequence imparted a fitness cost to TEM-1 beta-lactamase. Taken together, these results suggest that fitness costs associated with some beta-lactamases may limit their dissemination.

A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 β-Lactamase

PubMed Central

Marciano, David C.; Karkouti, Omid Y.; Palzkill, Timothy

2007-01-01

The blaTEM-1 β-lactamase gene has become widespread due to the selective pressure of β-lactam use and its stable maintenance on transferable DNA elements. In contrast, blaSME-1 is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of blaSME-1 via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, blaSME-1 was determined to impart a fitness cost upon Escherichia coli in multiple genetic contexts and assays. Genetic screens and designed SME-1 mutants were utilized to identify the source of this fitness cost. These experiments established that the SME-1 protein was required for the fitness cost but also that the enzyme activity of SME-1 was not associated with the fitness cost. The genetic screens suggested that the SME-1 signal sequence was involved in the fitness cost. Consistent with these findings, exchange of the SME-1 signal sequence for the TEM-1 signal sequence alleviated the fitness cost while replacing the TEM-1 signal sequence with the SME-1 signal sequence imparted a fitness cost to TEM-1 β-lactamase. Taken together, these results suggest that fitness costs associated with some β-lactamases may limit their dissemination. PMID:17565956

HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers

PubMed Central

Stadhouders, Ralph; Aktuna, Suleyman; Thongjuea, Supat; Aghajanirefah, Ali; Pourfarzad, Farzin; van IJcken, Wilfred; Lenhard, Boris; Rooks, Helen; Best, Steve; Menzel, Stephan; Grosveld, Frank; Thein, Swee Lay; Soler, Eric

2014-01-01

Genetic studies have identified common variants within the intergenic region (HBS1L-MYB) between GTP-binding elongation factor HBS1L and myeloblastosis oncogene MYB on chromosome 6q that are associated with elevated fetal hemoglobin (HbF) levels and alterations of other clinically important human erythroid traits. It is unclear how these noncoding sequence variants affect multiple erythrocyte characteristics. Here, we determined that several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We found that several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels. These data provide a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a target for therapeutic induction of HbF to ameliorate sickle cell and β-thalassemia disease severity. PMID:24614105

Genealogical evidence for epidemics of selfish genes.

PubMed

Ingvarsson, Par K; Taylor, Douglas R

2002-08-20

Some genetic elements spread infectiously in populations by increasing their rate of genetic transmission at the expense of other genes in the genome. These so-called selfish genetic elements comprise a substantial portion of eukaryotic genomes and have long been viewed as a potent evolutionary force. Despite this view, little is known about the evolutionary history of selfish genetic elements in natural populations, or their genetic effects on other portions of the genome. Here we use nuclear and chloroplast gene genealogies in two species of Silene to show the historical pattern of selection on a well known selfish genetic element, cytoplasmic male sterility. We provide evidence that evolution of cytoplasmic male sterility has been characterized by frequent turnovers of mutations in natural populations, thus supporting an epidemic model for the evolution of selfish genes, where new mutations repeatedly arise and rapidly sweep through populations.

Hormonal, behavioral, and life-history traits exhibit correlated shifts in relation to population establishment in a novel environment.

PubMed

Atwell, Jonathan W; Cardoso, Gonçalo C; Whittaker, Danielle J; Price, Trevor D; Ketterson, Ellen D

2014-12-01

Climate change, habitat alteration, range expansions, and biological invasions are all predicted to require rapid shifts in multiple traits including behavior and life history, both for initial population establishment and subsequent adaptation. Hormonal mechanisms likely play a key role in facilitating or constraining plastic and genetic responses for suites of traits, but few studies have evaluated their role in shaping contemporary adaptation or diversification. We examined multiple phenotypic adjustments and associated hormonal changes following a recent (early 1980s) colonization event, in which a temperate-breeding songbird, the dark-eyed junco (Junco hyemalis), became established in the Mediterranean climate of San Diego, California. The milder climate has led to an extended breeding season and year-round residency, and we document shifts in multiple sexually selected behaviors and plumage traits. Testosterone titers in San Diego were elevated for longer but with a lower peak value compared to a nearby native-range population, and correlations between testosterone and related traits were similar within and among populations. A common garden study indicated that changes in testosterone likely represent plastic responses to the less seasonal environment of the city, providing the context against which subsequent genetic changes in morphology likely occurred. We argue that correlated shifts in multiple traits, organized by underlying physiology, may be a generally important element of many successful adjustments to changing environments.

Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Guillou, F.

2005-04-01

In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

Modularization of genetic elements promotes synthetic metabolic engineering.

PubMed

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular manipulations for enhancing luminescent bioreporters performance in the detection of toxic chemicals.

PubMed

Yagur-Kroll, Sharon; Belkin, Shimshon

2014-01-01

Microbial whole-cell bioreporters are genetically modified microorganisms that produce a quantifiable output in response to the presence of toxic chemicals or other stress factors. These bioreporters harbor a genetic fusion between a sensing element (usually a gene regulatory element responsive to the target) and a reporter element, the product of which may be quantitatively monitored either by its presence or by its activity. In this chapter we review genetic manipulations undertaken in order to improve bioluminescent bioreporter performance by increasing luminescent output, lowering the limit of detection, and shortening the response time. We describe molecular manipulations applied to all aspects of whole-cell bioreporters: the host strain, the expression system, the sensing element, and the reporter element. The molecular construction of whole-cell luminescent bioreporters, harboring fusions of gene promoter elements to reporter genes, has been around for over three decades; in most cases, these two genetic elements are combined "as is." This chapter outlines diverse molecular manipulations for enhancing the performance of such sensors.

Hybrid antenna arrays with non-uniform Electromagnetic Band Gap lattices for wireless communication networks

NASA Astrophysics Data System (ADS)

Mourtzios, Ch.; Siakavara, K.

2015-08-01

A method to design hybrid antenna configurations with very low profile, suitable for smart and Multiple Input-Multiple Output antenna systems is proposed. The antennas are incorporated with novel Electromagnetic Band Gap (EBG) surfaces with non-similar cells. These non-uniform EBG surfaces have been properly designed to cause focusing, of the incident waves, thus enhancing the characteristics of operation of antenna elements positioned in close proximity to the surface and also to increase the isolation between them. Theoretical analysis of the reflection mechanism of this type of lattices as well as the prediction of the resulting performance of the antenna is presented. All these considerations are validated with implementation and simulation of the hybrid structures inside the Universal Mobile Telecommunications System frequency band. The results show that increment of the gain and isolation between the antenna elements can be obtained. Moreover, results for the correlation coefficient between the elements, for Gaussian distribution of the incoming waves have been received and the tolerance of the antennas to the variation of the polarization characteristics of the incoming waves has been investigated. A Genetic Algorithm has been constructed and applied to find the proper geometry of the hybrid antennas in order the correlation coefficient to be minimized and get almost independent from the polarization of incident waves.

Heavy Metals Toxicity and the Environment

PubMed Central

Tchounwou, Paul B; Yedjou, Clement G; Patlolla, Anita K; Sutton, Dwayne J

2013-01-01

Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity. PMID:22945569

ISOLATED FROM CLINICAL AND ENVIRONMENTAL SOURCES IN NORTHEAST THAILAND.

PubMed

Mala, Wanida; Kaewkes, Wanlop; Tattawasart, Unchalee; Wongwajana, Suwin; Faksri, Kiatichai; Chomvarin, Chariya

2016-09-01

Emergence of multiple drug resistance in Vibrio cholerae has been increasing around the world including Northeast Thailand. In this study, 92 isolates of V. cholerae (50 O1 and 42 non-O1/non-O139 isolates) from clinical and environmental sources in Northeast Thailand were randomly selected and investigated for the presence of SXT element, class 1 integron and antimicrobial resistance genes. Genotypic-phenotypic concordance of antimicrobial resistance was also determined. Using PCR-based assays, 79% of V. cholerae isolates were positive for SXT element, whereas only 1% was positive for class 1 integron. SXT element harbored antimicrobial resistance genes, dfrA1 or dfr18, floR, strB, sul2, and tetA. Overall phenotypic-genotypic concordance of antimicrobial resistance was 78%, with highest and lowest value being for trimethoprim (83%) and chloramphenicol (70%), respectively. Ninety-two percent of V. cholerae O1 strains isolated from clinical sources harbored both dfrA1 (O1-specific trimethoprim resistance gene) and dfr18 (non-O1-specific trimethoprim resistance gene), whereas only 5% of V. cholerae non-O1/non-O139 strains harbored both genes. All V. cholerae O1 isolated from environmental source harbored dfr18 but 48% of V. cholerae non-O1/non-O139 harbored dfrA1. This study indicates that SXT element was the main contributor to the circulation of multiple-drug resistance determinants in V. cholerae strains in Northeast Thailand and that genetic exchange of SXT element can occur in both V. cholerae O1 and non-O1/non-O139 strains from clinical and environmental sources.

Genetic architecture and balancing selection: the life and death of differentiated variants.

PubMed

Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

2017-05-01

Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

Establishing a Twin Register: An Invaluable Resource for (Behavior) Genetic, Epidemiological, Biomarker, and 'Omics' Studies.

PubMed

Odintsova, Veronika V; Willemsen, Gonneke; Dolan, Conor V; Hottenga, Jouke-Jan; Martin, Nicholas G; Slagboom, P Eline; Ordoñana, Juan R; Boomsma, Dorret I

2018-06-01

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register.

Review of Amyotrophic Lateral Sclerosis, Parkinson's and Alzheimer's diseases helps further define pathology of the novel paradigm for Alzheimer's with heavy metals as primary disease cause.

PubMed

Cavaleri, Franco

2015-12-01

Pathologies of neurological diseases are increasingly recognized to have common structural and molecular events that can fit, sometimes loosely, into a central pathological theme. A better understanding of the genetic, proteomic and metabolic similarities between three common neurodegenerative diseases - Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) - and how these similarities relate to their unique pathological features may shed more light on the underlying pathology of each. These are complex multigenic neuroinflammatory diseases caused by a combined action by multiple genetic mutations, lifestyle factors and environmental elements including a proposed contribution by transition metals. This comprehensive dynamic makes disease decoding and treatment difficult. One case of ALS, for example, can manifest from a very different pool of genetic mutations than another. In the case of ALS multiple genes in addition to SOD1 are implicated in the pathogenesis of both sporadic and familial variants of the disease. These genes play different roles in the processing and trafficking of signalling, metabolic and structural proteins. However, many of these genetic mutations or the cellular machinery they regulate can play a role in one form or another in PD and AD as well. In addition, the more recent understanding of how TREM-2 mutations factor into inflammatory response has shed new light on how chronic inflammatory activity can escalate to uncontrolled systemic levels in a variety of inflammatory diseases from neurodegenerative, auto-inflammatory and autoimmune diseases. TREM-2 mutations represent yet another complicating element in these multigenic disease pathologies. This review takes us one step back to discuss basic pathological features of these neurodegenerative diseases known to us for some time. However, the objective is to discuss the possibility of related or linked mechanisms that may exist through these basic disease hallmarks that we often classify as absolute signatures of one disease. These new perspectives will be discussed in the context of a new paradigm for Alzheimer's disease that implicates heavy metals as a primary cause. Plausible links between these distinctly different pathologies are presented showing intersections of their distinct pathologies that hinge on metal interactions.

Resveratrol stimulates c-Fos gene transcription via activation of ERK1/2 involving multiple genetic elements.

PubMed

Thiel, Gerald; Rössler, Oliver G

2018-06-05

The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules. We analyzed chromatin-integrated c-Fos promoter-luciferase reporter genes where transcription factor binding sites were destroyed by point mutations or deletion mutagenesis. The results show that mutation of the binding sites for serum response factor (SRF), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) significantly reduced reporter gene transcription following stimulation of the cells with resveratrol. Inactivation of the binding sites for signal transducer and activator of transcription (STAT) or ternary complex factors did not influence resveratrol-regulated c-Fos promoter activity. Thus, the c-Fos promoter contains three resveratrol-responsive elements, the cAMP response element (CRE), and the binding sites for SRF and AP-1. Moreover, we show that the transcriptional activation potential of the c-Fos protein is increased in resveratrol-stimulated cells, indicating that the biological activity of c-Fos is elevated by resveratrol stimulation. Pharmacological and genetic experiments revealed that the protein kinase ERK1/2 is the signal transducer that connects resveratrol treatment with the c-Fos gene. Copyright © 2018 Elsevier B.V. All rights reserved.

Origin and evolution of SINEs in eukaryotic genomes.

PubMed

Kramerov, D A; Vassetzky, N S

2011-12-01

Short interspersed elements (SINEs) are one of the two most prolific mobile genomic elements in most of the higher eukaryotes. Although their biology is still not thoroughly understood, unusual life cycle of these simple elements amplified as genomic parasites makes their evolution unique in many ways. In contrast to most genetic elements including other transposons, SINEs emerged de novo many times in evolution from available molecules (for example, tRNA). The involvement of reverse transcription in their amplification cycle, huge number of genomic copies and modular structure allow variation mechanisms in SINEs uncommon or rare in other genetic elements (module exchange between SINE families, dimerization, and so on.). Overall, SINE evolution includes their emergence, progressive optimization and counteraction to the cell's defense against mobile genetic elements.

Molecular characterization of the 2011 Hong Kong scarlet fever outbreak.

PubMed

Tse, Herman; Bao, Jessie Y J; Davies, Mark R; Maamary, Peter; Tsoi, Hoi-Wah; Tong, Amy H Y; Ho, Tom C C; Lin, Chi-Ho; Gillen, Christine M; Barnett, Timothy C; Chen, Jonathan H K; Lee, Mianne; Yam, Wing-Cheong; Wong, Chi-Kin; Ong, Cheryl-Lynn Y; Chan, Yee-Wai; Wu, Cheng-Wei; Ng, Tony; Lim, Wilina W L; Tsang, Thomas H F; Tse, Cindy W S; Dougan, Gordon; Walker, Mark J; Lok, Si; Yuen, Kwok-Yung

2012-08-01

A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases resulted in the isolation of Streptococcus pyogenes emm12 with multiple antibiotic resistances. Phylogenetic analysis of 22 emm12 scarlet fever outbreak isolates, 7 temporally and geographically matched emm12 non-scarlet fever isolates, and 18 emm12 strains isolated during 2005-2010 indicated the outbreak was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16 and HKU30), coupled with diagnostic polymerase chain reaction assays, identified 2 mobile genetic elements distributed across the major lineages: a 64.9-kb integrative and conjugative element encoding tetracycline and macrolide resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1 strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to neutrophils and virulence in a humanized plasminogen murine model. However, in contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests that factors such as mobile genetic elements, environmental factors, and host immune status may have contributed to the 2011 scarlet fever outbreak.

Molecular Characterization of the 2011 Hong Kong Scarlet Fever Outbreak

PubMed Central

Tse, Herman; Bao, Jessie Y. J.; Davies, Mark R.; Maamary, Peter; Tsoi, Hoi-Wah; Tong, Amy H. Y.; Ho, Tom C. C.; Lin, Chi-Ho; Gillen, Christine M.; Barnett, Timothy C.; Chen, Jonathan H. K.; Lee, Mianne; Yam, Wing-Cheong; Wong, Chi-Kin; Ong, Cheryl-lynn Y.; Chan, Yee-Wai; Wu, Cheng-Wei; Ng, Tony; Lim, Wilina W. L.; Tsang, Thomas H. F.; Tse, Cindy W. S.; Dougan, Gordon; Walker, Mark J.; Lok, Si; Yuen, Kwok-Yung

2012-01-01

A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases resulted in the isolation of Streptococcus pyogenes emm12 with multiple antibiotic resistances. Phylogenetic analysis of 22 emm12 scarlet fever outbreak isolates, 7 temporally and geographically matched emm12 non–scarlet fever isolates, and 18 emm12 strains isolated during 2005–2010 indicated the outbreak was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16 and HKU30), coupled with diagnostic polymerase chain reaction assays, identified 2 mobile genetic elements distributed across the major lineages: a 64.9-kb integrative and conjugative element encoding tetracycline and macrolide resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1 strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to neutrophils and virulence in a humanized plasminogen murine model. However, in contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests that factors such as mobile genetic elements, environmental factors, and host immune status may have contributed to the 2011 scarlet fever outbreak. PMID:22615319

Genomic epidemiology of global Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli.

PubMed

Stoesser, N; Sheppard, A E; Peirano, G; Anson, L W; Pankhurst, L; Sebra, R; Phan, H T T; Kasarskis, A; Mathers, A J; Peto, T E A; Bradford, P; Motyl, M R; Walker, A S; Crook, D W; Pitout, J D

2017-07-19

The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common infections. bla KPC , encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10 kb). Here we characterize the genetic features of bla KPC emergence in global E. coli, 2008-2013, using both long- and short-read whole-genome sequencing. Amongst 43/45 successfully sequenced bla KPC -E. coli strains, we identified substantial strain diversity (n = 21 sequence types, 18% of annotated genes in the core genome); substantial plasmid diversity (≥9 replicon types); and substantial bla KPC -associated, mobile genetic element (MGE) diversity (50% not within complete Tn4401 elements). We also found evidence of inter-species, regional and international plasmid spread. In several cases bla KPC was found on high copy number, small Col-like plasmids, previously associated with horizontal transmission of resistance genes in the absence of antimicrobial selection pressures. E. coli is a common human pathogen, but also a commensal in multiple environmental and animal reservoirs, and easily transmissible. The association of bla KPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. bla TEM , bla CTX-M ) suggests that it may become similarly prevalent.

Whole-Genome Comparison Reveals Novel Genetic Elements That Characterize the Genome of Industrial Strains of Saccharomyces cerevisiae

PubMed Central

Borneman, Anthony R.; Desany, Brian A.; Riches, David; Affourtit, Jason P.; Forgan, Angus H.; Pretorius, Isak S.; Egholm, Michael; Chambers, Paul J.

2011-01-01

Human intervention has subjected the yeast Saccharomyces cerevisiae to multiple rounds of independent domestication and thousands of generations of artificial selection. As a result, this species comprises a genetically diverse collection of natural isolates as well as domesticated strains that are used in specific industrial applications. However the scope of genetic diversity that was captured during the domesticated evolution of the industrial representatives of this important organism remains to be determined. To begin to address this, we have produced whole-genome assemblies of six commercial strains of S. cerevisiae (four wine and two brewing strains). These represent the first genome assemblies produced from S. cerevisiae strains in their industrially-used forms and the first high-quality assemblies for S. cerevisiae strains used in brewing. By comparing these sequences to six existing high-coverage S. cerevisiae genome assemblies, clear signatures were found that defined each industrial class of yeast. This genetic variation was comprised of both single nucleotide polymorphisms and large-scale insertions and deletions, with the latter often being associated with ORF heterogeneity between strains. This included the discovery of more than twenty probable genes that had not been identified previously in the S. cerevisiae genome. Comparison of this large number of S. cerevisiae strains also enabled the characterization of a cluster of five ORFs that have integrated into the genomes of the wine and bioethanol strains on multiple occasions and at diverse genomic locations via what appears to involve the resolution of a circular DNA intermediate. This work suggests that, despite the scrutiny that has been directed at the yeast genome, there remains a significant reservoir of ORFs and novel modes of genetic transmission that may have significant phenotypic impact in this important model and industrial species. PMID:21304888

Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by Targeted Sequencing.

PubMed

Carlson, Jenna C; Taub, Margaret A; Feingold, Eleanor; Beaty, Terri H; Murray, Jeffrey C; Marazita, Mary L; Leslie, Elizabeth J

2017-07-17

Orofacial clefts (OFCs), including nonsyndromic cleft lip with or without cleft palate (NSCL/P), are common birth defects. NSCL/P is highly heterogeneous with multiple phenotypic presentations. Two common subtypes of NSCL/P are cleft lip (CL) and cleft lip with cleft palate (CLP) which have different population prevalence. Similarly, NSCL/P can be divided into bilateral and unilateral clefts, with unilateral being the most common. Individuals with unilateral NSCL/P are more likely to be affected on the left side of the upper lip, but right side affection also occurs. Moreover, NSCL/P is twice as common in males as in females. The goal of this study is to discover genetic variants that have different effects in case subgroups. We conducted both common variant and rare variant analyses in 1034 individuals of Asian ancestry with NSCL/P, examining four sources of heterogeneity within CL/P: cleft type, sex, laterality, and side. We identified several regions associated with subtype differentiation: cleft type differences in 8q24 (p = 1.00 × 10 -4 ), laterality differences in IRF6, a gene previously implicated with wound healing (p = 2.166 × 10 -4 ), sex differences and side of unilateral CL differences in FGFR2 (p = 3.00 × 10 -4 ; p = 6.00 × 10 -4 ), and sex differences in VAX1 (p < 1.00 × 10 -4 ) among others. Many of the regions associated with phenotypic modification were either adjacent to or overlapping functional elements based on ENCODE chromatin marks and published craniofacial enhancers. We have identified multiple common and rare variants as potential phenotypic modifiers of NSCL/P, and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs. Birth Defects Research 109:1030-1038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

NASA Astrophysics Data System (ADS)

Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

2017-06-01

Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

MS in self-identified Hispanic/Latino individuals living in the US

PubMed Central

Amezcua, Lilyana; Oksenberg, Jorge R; McCauley, Jacob L

2017-01-01

Self-identified Hispanic/Latino individuals living with multiple sclerosis (MS) in the continental United States (US) are a diverse group that represents different cultural and ancestral backgrounds. A marked variability in the way MS affects various subgroups of Hispanics in the US has been observed. We reviewed and synthesized available data about MS in Hispanics in the US. There are likely a host of multifactorial elements contributing to these observations that could be explained by genetic, environmental, and social underpinnings. Barriers to adequate MS care in Hispanics are likely to include delivery of culturally competent care and social and economic disadvantages. Considerable efforts, including the formation of a national consortium known as the Alliance for Research in Hispanic Multiple Sclerosis (ARHMS), are underway to help further explore these various factors. PMID:28979795

A ganglioneuroma of the sigmoid colon presenting as leading point of intussusception in a child: a case report.

PubMed

Soccorso, Giampiero; Puls, Florian; Richards, Cathy; Pringle, Howard; Nour, Shawqui

2009-01-01

We present a case of intestinal ganglioneuroma (GN) of the sigmoid colon in a 5-year-old girl, which caused intermittent colocolic intussusception. Ganglioneuromas are rare benign tumors of the autonomic nervous system composed of mature ganglion cells and satellite cells. Colonic GNs are uncommon. The unusual intramural proliferation of neural elements in this case resembled the diffuse intestinal ganglioneuromatosis, which is known to be associated with multiple endocrine neoplasia type 2B. However, the specific mutations of multiple endocrine neoplasia type 2B were not found by genetic sequencing. This is the first pediatric case described in the literature of a solitary polypoid GN presenting as a colocolic intussusception. We present a brief overview of intestinal ganglioneuromatous lesions and associated conditions.

Origin and evolution of SINEs in eukaryotic genomes

PubMed Central

Kramerov, D A; Vassetzky, N S

2011-01-01

Short interspersed elements (SINEs) are one of the two most prolific mobile genomic elements in most of the higher eukaryotes. Although their biology is still not thoroughly understood, unusual life cycle of these simple elements amplified as genomic parasites makes their evolution unique in many ways. In contrast to most genetic elements including other transposons, SINEs emerged de novo many times in evolution from available molecules (for example, tRNA). The involvement of reverse transcription in their amplification cycle, huge number of genomic copies and modular structure allow variation mechanisms in SINEs uncommon or rare in other genetic elements (module exchange between SINE families, dimerization, and so on.). Overall, SINE evolution includes their emergence, progressive optimization and counteraction to the cell's defense against mobile genetic elements. PMID:21673742

Scientific reporting is suboptimal for aspects that characterize genetic risk prediction studies: a review of published articles based on the Genetic RIsk Prediction Studies statement.

PubMed

Iglesias, Adriana I; Mihaescu, Raluca; Ioannidis, John P A; Khoury, Muin J; Little, Julian; van Duijn, Cornelia M; Janssens, A Cecile J W

2014-05-01

Our main objective was to raise awareness of the areas that need improvements in the reporting of genetic risk prediction articles for future publications, based on the Genetic RIsk Prediction Studies (GRIPS) statement. We evaluated studies that developed or validated a prediction model based on multiple DNA variants, using empirical data, and were published in 2010. A data extraction form based on the 25 items of the GRIPS statement was created and piloted. Forty-two studies met our inclusion criteria. Overall, more than half of the evaluated items (34 of 62) were reported in at least 85% of included articles. Seventy-seven percentage of the articles were identified as genetic risk prediction studies through title assessment, but only 31% used the keywords recommended by GRIPS in the title or abstract. Seventy-four percentage mentioned which allele was the risk variant. Overall, only 10% of the articles reported all essential items needed to perform external validation of the risk model. Completeness of reporting in genetic risk prediction studies is adequate for general elements of study design but is suboptimal for several aspects that characterize genetic risk prediction studies such as description of the model construction. Improvements in the transparency of reporting of these aspects would facilitate the identification, replication, and application of genetic risk prediction models. Copyright © 2014 Elsevier Inc. All rights reserved.

Transposable genetic elements in Spirulina and potential applications for genetic engineering

NASA Astrophysics Data System (ADS)

Hiroyuki, Kojima; Qin, Song; Thankappan, Ajith Kumar; Yoshikazu, Kawata; Shin-Ichi, Yano

1998-03-01

Transposable elements in cyanobacteria are briefly reviewed. Evidence is presented to show that transposable elements in Spirulina platensis is actually reflected on the phenotype change, i e., helical to straight filaments. Transposition intermediates of DNA were isolated from the extrachromosome and the transposition was related to helical variations in Spirulina. Uses of transposable elements for microalgal recombination are discussed based on the transposition mechanism.

A maternal-effect selfish genetic element in Caenorhabditis elegans.

PubMed

Ben-David, Eyal; Burga, Alejandro; Kruglyak, Leonid

2017-06-09

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans The element is made up of sup-35 , a maternal-effect toxin that kills developing embryos, and pha-1 , its zygotically expressed antidote. pha-1 has long been considered essential for pharynx development on the basis of its mutant phenotype, but this phenotype arises from a loss of suppression of sup-35 toxicity. Inactive copies of the sup-35/pha-1 element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements. Copyright © 2017, American Association for the Advancement of Science.

A Locus Encoding Variable Defense Systems against Invading DNA Identified in Streptococcus suis

PubMed Central

Okura, Masatoshi; Nozawa, Takashi; Watanabe, Takayasu; Murase, Kazunori; Nakagawa, Ichiro; Takamatsu, Daisuke; Osaki, Makoto; Sekizaki, Tsutomu; Gottschalk, Marcelo; Hamada, Shigeyuki

2017-01-01

Streptococcus suis, an important zoonotic pathogen, is known to have an open pan-genome and to develop a competent state. In S. suis, limited genetic lineages are suggested to be associated with zoonosis. However, little is known about the evolution of diversified lineages and their respective phenotypic or ecological characteristics. In this study, we performed comparative genome analyses of S. suis, with a focus on the competence genes, mobile genetic elements, and genetic elements related to various defense systems against exogenous DNAs (defense elements) that are associated with gene gain/loss/exchange mediated by horizontal DNA movements and their restrictions. Our genome analyses revealed a conserved competence-inducing peptide type (pherotype) of the competence system and large-scale genome rearrangements in certain clusters based on the genome phylogeny of 58 S. suis strains. Moreover, the profiles of the defense elements were similar or identical to each other among the strains belonging to the same genomic clusters. Our findings suggest that these genetic characteristics of each cluster might exert specific effects on the phenotypic or ecological differences between the clusters. We also found certain loci that shift several types of defense elements in S. suis. Of note, one of these loci is a previously unrecognized variable region in bacteria, at which strains of distinct clusters code for different and various defense elements. This locus might represent a novel defense mechanism that has evolved through an arms race between bacteria and invading DNAs, mediated by mobile genetic elements and genetic competence. PMID:28379509

Genetic algorithm with maximum-minimum crossover (GA-MMC) applied in optimization of radiation pattern control of phased-array radars for rocket tracking systems.

PubMed

Silva, Leonardo W T; Barros, Vitor F; Silva, Sandro G

2014-08-18

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence.

Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) Applied in Optimization of Radiation Pattern Control of Phased-Array Radars for Rocket Tracking Systems

PubMed Central

Silva, Leonardo W. T.; Barros, Vitor F.; Silva, Sandro G.

2014-01-01

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence. PMID:25196013

Multiple Query Evaluation Based on an Enhanced Genetic Algorithm.

ERIC Educational Resources Information Center

Tamine, Lynda; Chrisment, Claude; Boughanem, Mohand

2003-01-01

Explains the use of genetic algorithms to combine results from multiple query evaluations to improve relevance in information retrieval. Discusses niching techniques, relevance feedback techniques, and evolution heuristics, and compares retrieval results obtained by both genetic multiple query evaluation and classical single query evaluation…

Enamel formation and amelogenesis imperfecta.

PubMed

Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

2007-01-01

Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel. Copyright 2007 S. Karger AG, Basel.

Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion

PubMed Central

Kleinfelter, Lara M.; Jangra, Rohit K.; Jae, Lucas T.; Herbert, Andrew S.; Mittler, Eva; Stiles, Katie M.; Wirchnianski, Ariel S.; Kielian, Margaret; Brummelkamp, Thijn R.

2015-01-01

ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the New World. No vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. We performed a haploid genetic screen in human cells to identify host factors required for entry by Andes virus, a highly virulent New World hantavirus. We found that multiple genes involved in cholesterol sensing, regulation, and biosynthesis, including key components of the sterol response element-binding protein (SREBP) pathway, are critical for Andes virus entry. Genetic or pharmacological disruption of the membrane-bound transcription factor peptidase/site-1 protease (MBTPS1/S1P), an SREBP control element, dramatically reduced infection by virulent hantaviruses of both the Old World and New World clades but not by rhabdoviruses or alphaviruses, indicating that this pathway is broadly, but selectively, required by hantaviruses. These results could be fully explained as arising from the modest depletion of cellular membrane cholesterol that accompanied S1P disruption. Mechanistic studies of cells and with protein-free liposomes suggested that high levels of cholesterol are specifically needed for hantavirus membrane fusion. Taken together, our results indicate that the profound dependence on target membrane cholesterol is a fundamental, and unusual, biophysical property of hantavirus glycoprotein-membrane interactions during entry. PMID:26126854

Preferential inclusion of extrachromosomal genetic elements in yeast meiotic spores.

PubMed

Brewer, B J; Fangman, W L

1980-09-01

During meiosis and sporulation in the yeast Saccharomyces cerevisiae, extrachromosomal traits are efficiently transmitted to haploid spores. Although the pattern of inheritance of chromosomal traits reflects the mechanism of regular chromosomal segregation in meiosis, it is not known what processes are reflected by the efficient inheritance of extrachromosomal traits. Because extrachromosomal genetic elements in yeast are present in multiple copies, perpetuation of an extrachromosomal trait could occur by the passive envelopment of a subset of copies or by an active sequestering of all or a subset of copies within the four spores. We show that only subsets of the four extrachromosomal nucleic acids commonly found in yeast are transmitted through meiosis--55% of mitochondrial DNA copies, 82% of the 2-micron DNA plasmids, and about 70% of the L and M double-stranded RNAs. However, electron micrographs of serial sections through yeast asci indicate that the four spore enclose only 30% of the total ascus material. Thus these extrachromosomal elements are preferentially included within the spores, indicating that their inheritance is not a random process. Transmission of mitochondrial DNA can be accounted for by the observed enclosure of 52% of the mitochondrial volume within the spores. The high transmission frequencies of the double-stranded RNAs (which exist as virus-like particles in the cytoplasm) and 2-micron DNA must indicate that either these nucleic acids are actively recruited from the cytoplasm by some mechanism or they are associated in some way with the nucleus during meiosis.

Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in Clostridium difficile Strains and Prophages Target Multiple Phage Types within This Pathogen

PubMed Central

Hargreaves, Katherine R.; Flores, Cesar O.; Lawley, Trevor D.

2014-01-01

ABSTRACT Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. PMID:25161187

An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees.

PubMed

Liang, Ying; Liao, Bo; Zhu, Wen

2017-01-01

Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.

Mobile Genetic Elements: In Silico, In Vitro, In Vivo

PubMed Central

Arkhipova, Irina R.; Rice, Phoebe A.

2016-01-01

Mobile genetic elements (MGEs), also called transposable elements (TEs), represent universal components of most genomes and are intimately involved in nearly all aspects of genome organization, function, and evolution. However, there is currently a gap between fast-paced TE discovery in silico, stimulated by exponential growth of comparative genomic studies, and a limited number of experimental models amenable to more traditional in vitro and in vivo studies of structural, mechanistic, and regulatory properties of diverse MGEs. Experimental and computational scientists came together to bridge this gap at a recent conference, “Mobile Genetic Elements: in silico, in vitro, in vivo,” held at the Marine Biological Laboratory (MBL) in Woods Hole, MA, USA. PMID:26822117

Ribo-attenuators: novel elements for reliable and modular riboswitch engineering.

PubMed

Folliard, Thomas; Mertins, Barbara; Steel, Harrison; Prescott, Thomas P; Newport, Thomas; Jones, Christopher W; Wadhams, George; Bayer, Travis; Armitage, Judith P; Papachristodoulou, Antonis; Rothschild, Lynn J

2017-07-04

Riboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, thus increasing their reliability for a wide range of applications.

New approaches in GMO detection.

PubMed

Querci, Maddalena; Van den Bulcke, Marc; Zel, Jana; Van den Eede, Guy; Broll, Hermann

2010-03-01

The steady rate of development and diffusion of genetically modified plants and their increasing diversification of characteristics, genes and genetic control elements poses a challenge in analysis of genetically modified organisms (GMOs). It is expected that in the near future the picture will be even more complex. Traditional approaches, mostly based on the sequential detection of one target at a time, or on a limited multiplexing, allowing only a few targets to be analysed at once, no longer meet the testing requirements. Along with new analytical technologies, new approaches for the detection of GMOs authorized for commercial purposes in various countries have been developed that rely on (1) a smart and accurate strategy for target selection, (2) the use of high-throughput systems or platforms for the detection of multiple targets and (3) algorithms that allow the conversion of analytical results into an indication of the presence of individual GMOs potentially present in an unknown sample. This paper reviews the latest progress made in GMO analysis, taking examples from the most recently developed strategies and tools, and addresses some of the critical aspects related to these approaches.

Lack of robustness of life extension associated with several single-gene P element mutations in Drosophila melanogaster.

PubMed

Mockett, Robin J; Nobles, Amber C

2013-10-01

The hypothesis tested in this study was that single-gene mutations found previously to extend the life span of Drosophila melanogaster could do so consistently in both long-lived y w and standard w (1118) genetic backgrounds. GAL4 drivers were used to express upstream activation sequence (UAS)-responder transgenes globally or in the nervous system. Transgenes associated with oxidative damage prevention (UAS-hSOD1 and UAS-GCLc) or removal (EP-UAS-Atg8a and UAS-dTOR (FRB) ) failed to increase mean life spans in any expression pattern in either genetic background. Flies containing a UAS-EGFP-bMSRA (C) transgene associated with protein repair were found not to exhibit life extension or detectable enhanced green fluorescent protein (EGFP) activity. The presence of UAS-responder transgenes was confirmed by PCR amplification and sequencing at the 5' and 3' end of each insertion. These results cast doubt on the robustness of life extension in flies carrying single-gene mutations and suggest that the effects of all such mutations should be tested independently in multiple genetic backgrounds and laboratory environments.

Identification and applications of the Petunia class II Act1/dTph1 transposable element system.

PubMed

Gerats, Tom; Zethof, Jan; Vandenbussche, Michiel

2013-01-01

Transposable genetic elements are considered to be ubiquitous. Despite this, their mutagenic capacity has been exploited in only a few species. The main plant species are maize, Antirrhinum, and Petunia. Representatives of all three major groups of class II elements, viz., hAT-, CACTA- and Mutator-like elements, have been identified in Petunia. Here we focus on the research "history" of the Petunia two-element Act1-dTph1 system and the development of its application in forward- and reverse-genetics studies.

ICE Afe 1, an actively excising genetic element from the biomining bacterium Acidithiobacillus ferrooxidans.

PubMed

Bustamante, Paula; Covarrubias, Paulo C; Levicán, Gloria; Katz, Assaf; Tapia, Pablo; Holmes, David; Quatrini, Raquel; Orellana, Omar

2012-01-01

Integrative conjugative elements (ICEs) are self-transferred mobile genetic elements that contribute to horizontal gene transfer. An ICE (ICEAfe1) was identified in the genome of Acidithiobacillus ferrooxidans ATCC 23270. Excision of the element and expression of relevant genes under normal and DNA-damaging growth conditions was analyzed. Bioinformatic tools and DNA amplification methods were used to identify and to assess the excision and expression of genes related to the mobility of the element. Both basal and mitomycin C-inducible excision as well as expression and induction of the genes for integration/excision are demonstrated, suggesting that ICEAfe1 is an actively excising SOS-regulated mobile genetic element. The presence of a complete set of genes encoding self-transfer functions that are induced in response to DNA damage caused by mitomycin C additionally suggests that this element is capable of conjugative transfer to suitable recipient strains. Transfer of ICEAfe1 may provide selective advantages to other acidophiles in this ecological niche through dissemination of gene clusters expressing transfer RNAs, CRISPRs, and exopolysaccharide biosynthesis enzymes, probably by modification of translation efficiency, resistance to bacteriophage infection and biofilm formation, respectively. These data open novel avenues of research on conjugative transformation of biotechnologically relevant microorganisms recalcitrant to genetic manipulation. Copyright © 2013 S. Karger AG, Basel.

Targeted Capture Sequencing in Whitebark Pine Reveals Range-Wide Demographic and Adaptive Patterns Despite Challenges of a Large, Repetitive Genome.

PubMed

Syring, John V; Tennessen, Jacob A; Jennings, Tara N; Wegrzyn, Jill; Scelfo-Dalbey, Camille; Cronn, Richard

2016-01-01

Whitebark pine (Pinus albicaulis) inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats - climate change, white pine blister rust, mountain pine beetle, and fire exclusion - and it is suffering significant mortality range-wide, prompting the tree to be listed as 'globally endangered' by the International Union for Conservation of Nature and 'endangered' by the Canadian government. Conservation collections (in situ and ex situ) are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 27 GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp), and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits), targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect. Quinquefolia) due to their limited genetic divergence.

Multiple cis-acting elements involved in up-regulation of a cytochrome P450 gene conferring resistance to deltamethrin in smal brown planthopper, Laodelphax striatellus (Fallén).

PubMed

Pu, Jian; Sun, Haina; Wang, Jinda; Wu, Min; Wang, Kangxu; Denholm, Ian; Han, Zhaojun

2016-11-01

As well as arising from single point mutations in binding sites or detoxifying enzymes, it is likely that insecticide resistance mechanisms are frequently controlled by multiple genetic factors, resulting in resistance being inherited as a quantitative trait. However, empirical evidence for this is still rare. Here we analyse the causes of up-regulation of CYP6FU1, a monoxygenase implicated in resistance to deltamethrin in the rice pest Laodelphax striatellus. The 5'-flanking region of this gene was cloned and sequenced from individuals of a susceptible and a resistant strain. A luminescent reporter assay was used to evaluate different 5'-flanking regions and their fragments for promoter activity. Mutations enhancing promoter activity in various fragments were characterized, singly and in combination, by site mutation recovery. Nucleotide diversity in flanking sequences was greatly reduced in deltamethrin-resistant insects compared to susceptible ones. Phylogenetic sequence analysis found that CYP6FU1 had five different types of 5'-flanking region. All five types were present in a susceptible strain but only a single type showing the highest promoter activity was present in a resistant strain. Four cis-acting elements were identified whose influence on up-regulation was much more pronounced in combination than when present singly. Of these, two were new transcription factor (TF) binding sites produced by mutations, another one was also a new TF binding site alternated from an existing one, and the fourth was a unique transcription start site. These results demonstrate that multiple cis-acting elements are involved in up-regulating CYP6FU1 to generate a resistance phenotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

PubMed

Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

2016-04-01

To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes.

Spread of ISCR1 elements containing blaDHA-₁ and multiple antimicrobial resistance genes leading to increase of flomoxef resistance in extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae.

PubMed

Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

2011-09-01

Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6')-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6')-Ib-cr, armA, and bla(DHA-1) were all identified on these self-transferable bla(CTX-M)-carrying plasmids. The genetic environments of ISCR1 associated with armA, bla(DHA-1), and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study.

Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression.

PubMed

Akbari, Omar S; Chen, Chun-Hong; Marshall, John M; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A

2014-12-19

Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology.

PubMed

Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko; Gerdes, Kenn

2018-06-07

Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules. Copyright © 2018 Elsevier Inc. All rights reserved.

An innovative artificial bee colony algorithm and its application to a practical intercell scheduling problem

NASA Astrophysics Data System (ADS)

Li, Dongni; Guo, Rongtao; Zhan, Rongxin; Yin, Yong

2018-06-01

In this article, an innovative artificial bee colony (IABC) algorithm is proposed, which incorporates two mechanisms. On the one hand, to provide the evolutionary process with a higher starting level, genetic programming (GP) is used to generate heuristic rules by exploiting the elements that constitute the problem. On the other hand, to achieve a better balance between exploration and exploitation, a leading mechanism is proposed to attract individuals towards a promising region. To evaluate the performance of IABC in solving practical and complex problems, it is applied to the intercell scheduling problem with limited transportation capacity. It is observed that the GP-generated rules incorporate the elements of the most competing human-designed rules, and they are more effective than the human-designed ones. Regarding the leading mechanism, the strategies of the ageing leader and multiple challengers make the algorithm less likely to be trapped in local optima.

An analysis of mobile genetic elements in three Plasmodium species and their potential impact on the nucleotide composition of the P. falciparum genome.

PubMed

Durand, Pierre M; Oelofse, Andries J; Coetzer, Theresa L

2006-11-04

The completed genome sequences of the malaria parasites P. falciparum, P. y. yoelii and P. vivax have revealed some unusual features. P. falciparum contains the most AT rich genome sequenced so far--over 90% in some regions. In comparison, P. y. yoelii is approximately 77% and P. vivax is approximately 55% AT rich. The evolutionary reasons for these findings are unknown. Mobile genetic elements have a considerable impact on genome evolution but a thorough investigation of these elements in Plasmodium has not been undertaken. We therefore performed a comprehensive genome analysis of these elements and their derivatives in the three Plasmodium species. Whole genome analysis was performed using bioinformatic methods. Forty potential protein encoding sequences with features of transposable elements were identified in P. vivax, eight in P. y. yoelii and only six in P. falciparum. Further investigation of the six open reading frames in P. falciparum revealed that only one is potentially an active mobile genetic element. Most of the open reading frames identified in all three species are hypothetical proteins. Some represent annotated host proteins such as the putative telomerase reverse transcriptase genes in P. y. yoelii and P. falciparum. One of the P. vivax open reading frames identified in this study demonstrates similarity to telomerase reverse transcriptase and we conclude it to be the orthologue of this gene. There is a divergence in the frequencies of mobile genetic elements in the three Plasmodium species investigated. Despite the limitations of whole genome analytical methods, it is tempting to speculate that mobile genetic elements might have been a driving force behind the compositional bias of the P. falciparum genome.

Are electronic health records ready for genomic medicine?

PubMed

Scheuner, Maren T; de Vries, Han; Kim, Benjamin; Meili, Robin C; Olmstead, Sarah H; Teleki, Stephanie

2009-07-01

The goal of this project was to assess genetic/genomic content in electronic health records. Semistructured interviews were conducted with key informants. Questions addressed documentation, organization, display, decision support and security of family history and genetic test information, and challenges and opportunities relating to integrating genetic/genomics content in electronic health records. There were 56 participants: 10 electronic health record specialists, 18 primary care clinicians, 16 medical geneticists, and 12 genetic counselors. Few clinicians felt their electronic record met their current genetic/genomic medicine needs. Barriers to integration were mostly related to problems with family history data collection, documentation, and organization. Lack of demand for genetics content and privacy concerns were also mentioned as challenges. Data elements and functionality requirements that clinicians see include: pedigree drawing; clinical decision support for familial risk assessment and genetic testing indications; a patient portal for patient-entered data; and standards for data elements, terminology, structure, interoperability, and clinical decision support rules. Although most said that there is little impact of genetics/genomics on electronic records today, many stated genetics/genomics would be a driver of content in the next 5-10 years. Electronic health records have the potential to enable clinical integration of genetic/genomic medicine and improve delivery of personalized health care; however, structured and standardized data elements and functionality requirements are needed.

[Molecular-genetic analysis of wheat (T. aestivum L.) genome with introgression of Ae. cylindrica Host genetic elements].

PubMed

Galaev, A V; Sivolap, Iu M

2005-01-01

Wheat-aegilops hybrid plants Triticum aestivum L. (2n = 42) x Aegilops cylindrica Host (2n = 28) were investigated with using microsatellite markers. In two BC1F9 lines some genome modifications connected with losing DNA fragments of initial variety or appearing of Aegilops genome elements were detected. In some investigated hybrids new amplicons lacking in parental plants were found. Substitution of wheat chromosomes for aegilops chromosomes was not revealed. Analysis of microsatellite loci in BC2F5 plants showed stable introgression of aegilops genetic elements into wheat; elimination of some transferred aegilops DNA fragments in the course of backcrossing; decreasing size of introgressive elements after backcrossing. Introgressive lines were classified according to genome changes.

IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic lupus erythematosus

PubMed Central

Niewold, Timothy B; Kelly, Jennifer A; Kariuki, Silvia N; Franek, Beverly S; Kumar, Akaash A; Kaufman, Kenneth M; Thomas, Kenaz; Walker, Daniel; Kamp, Stan; Frost, Jacqueline M; Wong, Andrew K; Merrill, Joan T; Alarcón-Riquelme, Marta E; Tikly, Mohammed; Ramsey-Goldman, Rosalind; Reveille, John D; Petri, Michelle A; Edberg, Jeffrey C; Kimberly, Robert P; Alarcón, Graciela S; Kamen, Diane L; Gilkeson, Gary S; Vyse, Timothy J; James, Judith A; Gaffney, Patrick M; Moser, Kathy L; Crow, Mary K; Harley, John B

2012-01-01

Objective High serum interferon α (IFNα) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNα production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variation in IRF5 is associated with SLE susceptibility; however, it is unclear how IRF5 functional genetic elements contribute to human disease. Methods 1034 patients with SLE and 989 controls of European ancestry, 555 patients with SLE and 679 controls of African–American ancestry, and 73 patients with SLE of South African ancestry were genotyped at IRF5 polymorphisms, which define major haplotypes. Serum IFNα activity was measured using a functional assay. Results In European ancestry subjects, anti-double-stranded DNA (dsDNA) and anti-Ro antibodies were each associated with different haplotypes characterised by a different combination of functional genetic elements (OR > 2.56, p >003C; 1.9×10−14 for both). These IRF5 haplotype-auto-antibody associations strongly predicted higher serum IFNα in patients with SLE and explained > 70% of the genetic risk of SLE due to IRF5. In African–American patients with SLE a similar relationship between serology and IFNα was observed, although the previously described European ancestry-risk haplotype was present at admixture proportions in African–American subjects and absent in African patients with SLE. Conclusions The authors define a novel risk haplotype of IRF5 that is associated with anti-dsDNA antibodies and show that risk of SLE due to IRF5 genotype is largely dependent upon particular auto-antibodies. This suggests that auto-antibodies are directly pathogenic in human SLE, resulting in increased IFNα in cooperation with particular combinations of IRF5 functional genetic elements. SLE is a systemic autoimmune disorder affecting multiple organ systems including the skin, musculoskeletal, renal and haematopoietic systems. Humoral autoimmunity is a hallmark of SLE, and patients frequently have circulating auto-antibodies directed against dsDNA, as well as RNA binding proteins (RBP). Anti-RBP autoantibodies include antibodies which recognize Ro, La, Smith (anti-Sm), and ribonucleoprotein (anti-nRNP), collectively referred to as anti-retinol-binding protein). Anti-retinol-binding protein and anti-dsDNA auto-antibodies are rare in the healthy population.1 These auto-antibodies can be present in sera for years preceding the onset of clinical SLE illness2 and are likely pathogenic in SLE.34 PMID:22088620

The effectiveness of argumentation in tutorial dialogues with an Intelligent Tutoring System for genetic risk of breast cancer.

PubMed

Cedillos-Whynott, Elizabeth M; Wolfe, Christopher R; Widmer, Colin L; Brust-Renck, Priscila G; Weil, Audrey; Reyna, Valerie F

2016-09-01

BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings.

The effectiveness of argumentation in tutorial dialogues with an Intelligent Tutoring System for genetic risk of breast cancer

PubMed Central

Cedillos-Whynott, Elizabeth M.; Wolfe, Christopher R.; Widmer, Colin L.; Brust-Renck, Priscila G.; Weil, Audrey; Reyna, Valerie F.

2017-01-01

BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings. PMID:26511370

A shift in anterior–posterior positional information underlies the fin-to-limb evolution

PubMed Central

Onimaru, Koh; Kuraku, Shigehiro; Takagi, Wataru; Hyodo, Susumu; Sharpe, James; Tanaka, Mikiko

2015-01-01

The pectoral fins of ancestral fishes had multiple proximal elements connected to their pectoral girdles. During the fin-to-limb transition, anterior proximal elements were lost and only the most posterior one remained as the humerus. Thus, we hypothesised that an evolutionary alteration occurred in the anterior–posterior (AP) patterning system of limb buds. In this study, we examined the pectoral fin development of catshark (Scyliorhinus canicula) and revealed that the AP positional values in fin buds are shifted more posteriorly than mouse limb buds. Furthermore, examination of Gli3 function and regulation shows that catshark fins lack a specific AP patterning mechanism, which restricts its expression to an anterior domain in tetrapods. Finally, experimental perturbation of AP patterning in catshark fin buds results in an expansion of posterior values and loss of anterior skeletal elements. Together, these results suggest that a key genetic event of the fin-to-limb transformation was alteration of the AP patterning network. DOI: http://dx.doi.org/10.7554/eLife.07048.001 PMID:26283004

Development of Multiple-Element Flame Emission Spectrometer Using CCD Detection

ERIC Educational Resources Information Center

Seney, Caryn S.; Sinclair, Karen V.; Bright, Robin M.; Momoh, Paul O.; Bozeman, Amelia D.

2005-01-01

The full wavelength coverage of charge coupled device (CCD) detector when coupled with an echelle spectrography, the system allows for simultaneously multiple element spectroscopy to be performed. The multiple-element flame spectrometer was built and characterized through the analysis of environmentally significant elements such as Ca, K, Na, Cu,…

Low-pass sequencing for microbial comparative genomics

PubMed Central

Goo, Young Ah; Roach, Jared; Glusman, Gustavo; Baliga, Nitin S; Deutsch, Kerry; Pan, Min; Kennedy, Sean; DasSarma, Shiladitya; Victor Ng, Wailap; Hood, Leroy

2004-01-01

Background We studied four extremely halophilic archaea by low-pass shotgun sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non-pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand single pass genomic sequences per genome were obtained. The data were analyzed by comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid approach that can readily be performed on any cultured microbe. Results As expected, the four archaeal halophiles analyzed exhibit both bacterial and eukaryotic characteristics as well as uniquely archaeal traits. All five halophiles exhibit greater than sixty percent GC content and low isoelectric points (pI) for their predicted proteins. Multiple insertion sequence (IS) elements, often involved in genome rearrangements, were identified in H. lacusprofundi and H. marismortui. The core biological functions that govern cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these four other halophiles. Multiple TATA box binding protein (TBP) and transcription factor IIB (TFB) homologs were identified from most of the four shotgunned halophiles. The reconstructed molecular tree of all five halophiles shows a large divergence between these species, but with the closest relationship being between H. sp. NRC-1 and H. lacusprofundi. Conclusion Despite the diverse habitats of these species, all five halophiles share (1) high GC content and (2) low protein isoelectric points, which are characteristics associated with environmental exposure to UV radiation and hypersalinity, respectively. Identification of multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest that genome structure and dynamic genome reorganization might be similar to that previously observed in the IS-element rich genome of H. sp. NRC-1. Identification of multiple TBP and TFB homologs in these four halophiles are consistent with the hypothesis that different types of complex transcriptional regulation may occur through multiple TBP-TFB combinations in response to rapidly changing environmental conditions. Low-pass shotgun sequence analyses of genomes permit extensive and diverse analyses, and should be generally useful for comparative microbial genomics. PMID:14718067

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing.

PubMed

Balci, T B; Hartley, T; Xi, Y; Dyment, D A; Beaulieu, C L; Bernier, F P; Dupuis, L; Horvath, G A; Mendoza-Londono, R; Prasad, C; Richer, J; Yang, X-R; Armour, C M; Bareke, E; Fernandez, B A; McMillan, H J; Lamont, R E; Majewski, J; Parboosingh, J S; Prasad, A N; Rupar, C A; Schwartzentruber, J; Smith, A C; Tétreault, M; Innes, A M; Boycott, K M

2017-09-01

Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Meeting report for mobile DNA 2010.

PubMed

Chaconas, George; Craig, Nancy; Curcio, M Joan; Deininger, Prescott; Feschotte, Cedric; Levin, Henry; Rice, Phoebe A; Voytas, Daniel F

2010-08-24

An international conference on mobile DNA was held 24-28 April 2010 in Montreal, Canada. Sponsored by the American Society for Microbiology, the conference's goal was to bring together researchers from around the world who study transposition in diverse organisms using multiple experimental approaches. The meeting drew over 190 attendees and most contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into eight scientific sessions, which ranged in topic from the evolutionary dynamics of mobile genetic elements to transposition reaction mechanisms. Here we present highlights from the platform sessions with a focus on talks presented by the invited speakers.

Theories that narrate the world: Ronald A. Fisher's mass selection and Sewall Wright's shifting balance.

PubMed

Rosales, Alirio

2017-04-01

Theories are composed of multiple interacting components. I argue that some theories have narratives as essential components, and that narratives function as integrative devices of the mathematical components of theories. Narratives represent complex processes unfolding in time as a sequence of stages, and hold the mathematical elements together as pieces in the investigation of a given process. I present two case studies from population genetics: R. A. Fisher's "mas selection" theory, and Sewall Wright's shifting balance theory. I apply my analysis to an early episode of the "R. A. Fisher - Sewall Wright controversy." Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Synthetic Medea selfish genetic elements drive population replacement in Drosophila, and a theoretical exploration of Medea-dependent population suppression

PubMed Central

Akbari, Omar S.; Chen, Chun-Hong; Marshall, John M.; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A.

2013-01-01

Insects act as vectors for diseases of plants, animals and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression. PMID:23654248

Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres.

PubMed

Gent, Jonathan I; Wang, Kai; Jiang, Jiming; Dawe, R Kelly

2015-08-01

While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift. Copyright © 2015 by the Genetics Society of America.

Genetic exchange between endogenous and exogenous LINE-1 repetitive elements in mouse cells.

PubMed Central

Belmaaza, A; Wallenburg, J C; Brouillette, S; Gusew, N; Chartrand, P

1990-01-01

The repetitive LINE (L1) elements of the mouse, which are present at about 10(5) copies per genome and share over 80% of sequence homology, were examined for their ability to undergo genetic exchange with exogenous L1 sequences. The exogenous L1 sequences, carried by a shuttle vector, consisted of an internal fragment from L1Md-A2, a previously described member of the L1 family of the mouse. Using an assay that does not require the reconstitution of a selectable marker we found that this vector, in either circular or linear form, acquired DNA sequences from endogenous L1 elements at a frequency of 10(-3) to 10(-4) per rescued vector. Physical analysis of the acquired L1 sequences revealed that distinct endogenous L1 elements acted as donors and that different subfamilies participated. These results demonstrate that L1 elements are readily capable of genetic exchange. Apart from gene conversion events, the acquisition of L1 sequences outside the region of homology suggested that a second mechanism was also involved in the genetic exchange. A model which accounts for this mechanism is presented and its potential implication on the rearrangement of L1 elements is discussed. Images PMID:1978749

Multiple testing and power calculations in genetic association studies.

PubMed

So, Hon-Cheong; Sham, Pak C

2011-01-01

Modern genetic association studies typically involve multiple single-nucleotide polymorphisms (SNPs) and/or multiple genes. With the development of high-throughput genotyping technologies and the reduction in genotyping cost, investigators can now assay up to a million SNPs for direct or indirect association with disease phenotypes. In addition, some studies involve multiple disease or related phenotypes and use multiple methods of statistical analysis. The combination of multiple genetic loci, multiple phenotypes, and multiple methods of evaluating associations between genotype and phenotype means that modern genetic studies often involve the testing of an enormous number of hypotheses. When multiple hypothesis tests are performed in a study, there is a risk of inflation of the type I error rate (i.e., the chance of falsely claiming an association when there is none). Several methods for multiple-testing correction are in popular use, and they all have strengths and weaknesses. Because no single method is universally adopted or always appropriate, it is important to understand the principles, strengths, and weaknesses of the methods so that they can be applied appropriately in practice. In this article, we review the three principle methods for multiple-testing correction and provide guidance for calculating statistical power.

Matrix multiplication operations with data pre-conditioning in a high performance computing architecture

DOEpatents

Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

2013-11-05

Mechanisms for performing matrix multiplication operations with data pre-conditioning in a high performance computing architecture are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A load and splat operation is performed to load an element of a second vector operand and replicating the element to each of a plurality of elements of a second target vector register. A multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product of the matrix multiplication operation is accumulated with other partial products of the matrix multiplication operation.

Increasing persistency in lay and stabilising egg quality in longer laying cycles. What are the challenges?

PubMed Central

Bain, M. M.; Nys, Y.; Dunn, I.C.

2016-01-01

Abstract In the past 50 years, selection starting initially at the breed level and then using quantitative genetics coupled with a sophisticated breeding pyramid, has resulted in a very productive hybrid for a variety of traits associated with egg production.One major trait currently being developed further is persistency of lay and the concept of the “long life” layer. Persistency in lay however cannot be achieved without due consideration of how to sustain egg quality and the health and welfare of the birds in longer laying cycles. These multiple goals require knowledge and consideration of the bird’s physiology, nutritional requirements, which vary depending on age and management system, reproductive status and choice of the selection criteria applied.The recent advent of molecular genetics offers considerable hope that these multiple elements can be balanced for the good of all in the industry including the hens.The “long life” layer, which will be capable of producing 500 eggs in a laying cycle of 100 weeks, is therefore on the horizon, bringing with it the benefits of a more efficient utilisation of diminishing resources, including land, water, raw materials for feed as well as a reduction in waste, and an overall reduced carbon footprint. PMID:26982003

Visual detection of multiple genetically modified organisms in a capillary array.

PubMed

Shao, Ning; Chen, Jianwei; Hu, Jiaying; Li, Rong; Zhang, Dabing; Guo, Shujuan; Hui, Junhou; Liu, Peng; Yang, Litao; Tao, Sheng-Ce

2017-01-31

There is an urgent need for rapid, low-cost multiplex methodologies for the monitoring of genetically modified organisms (GMOs). Here, we report a C[combining low line]apillary A[combining low line]rray-based L[combining low line]oop-mediated isothermal amplification for M[combining low line]ultiplex visual detection of nucleic acids (CALM) platform for the simple and rapid monitoring of GMOs. In CALM, loop-mediated isothermal amplification (LAMP) primer sets are pre-fixed to the inner surface of capillaries. The surface of the capillary array is hydrophobic while the capillaries are hydrophilic, enabling the simultaneous loading and separation of the LAMP reaction mixtures into each capillary by capillary forces. LAMP reactions in the capillaries are then performed in parallel, and the results are visually detected by illumination with a hand-held UV device. Using CALM, we successfully detected seven frequently used transgenic genes/elements and five plant endogenous reference genes with high specificity and sensitivity. Moreover, we found that measurements of real-world blind samples by CALM are consistent with results obtained by independent real-time PCRs. Thus, with an ability to detect multiple nucleic acids in a single easy-to-operate test, we believe that CALM will become a widely applied technology in GMO monitoring.

Increasing persistency in lay and stabilising egg quality in longer laying cycles. What are the challenges?

PubMed

Bain, M M; Nys, Y; Dunn, I C

2016-06-01

In the past 50 years, selection starting initially at the breed level and then using quantitative genetics coupled with a sophisticated breeding pyramid, has resulted in a very productive hybrid for a variety of traits associated with egg production. One major trait currently being developed further is persistency of lay and the concept of the "long life" layer. Persistency in lay however cannot be achieved without due consideration of how to sustain egg quality and the health and welfare of the birds in longer laying cycles. These multiple goals require knowledge and consideration of the bird's physiology, nutritional requirements, which vary depending on age and management system, reproductive status and choice of the selection criteria applied. The recent advent of molecular genetics offers considerable hope that these multiple elements can be balanced for the good of all in the industry including the hens. The "long life" layer, which will be capable of producing 500 eggs in a laying cycle of 100 weeks, is therefore on the horizon, bringing with it the benefits of a more efficient utilisation of diminishing resources, including land, water, raw materials for feed as well as a reduction in waste, and an overall reduced carbon footprint.

Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma

PubMed Central

2012-01-01

Background The aim of this study was to clarify the role of global hypomethylation of repetitive elements in determining the genetic and clinical features of multiple myeloma (MM). Methods We assessed global methylation levels using four repetitive elements (long interspersed nuclear element-1 (LINE-1), Alu Ya5, Alu Yb8, and Satellite-α) in clinical samples comprising 74 MM samples and 11 benign control samples (7 cases of monoclonal gammopathy of undetermined significance (MGUS) and 4 samples of normal plasma cells (NPC)). We also evaluated copy-number alterations using array-based comparative genomic hybridization, and performed methyl-CpG binding domain sequencing (MBD-seq). Results Global levels of the repetitive-element methylation declined with the degree of malignancy of plasma cells (NPC>MGUS>MM), and there was a significant inverse correlation between the degree of genomic loss and the LINE-1 methylation levels. We identified 80 genomic loci as common breakpoints (CBPs) around commonly lost regions, which were significantly associated with increased LINE-1 densities. MBD-seq analysis revealed that average DNA-methylation levels at the CBP loci and relative methylation levels in regions with higher LINE-1 densities also declined during the development of MM. We confirmed that levels of methylation of the 5' untranslated region of respective LINE-1 loci correlated strongly with global LINE-1 methylation levels. Finally, there was a significant association between LINE-1 hypomethylation and poorer overall survival (hazard ratio 2.8, P = 0.015). Conclusion Global hypomethylation of LINE-1 is associated with the progression of and poorer prognosis for MM, possibly due to frequent copy-number loss. PMID:23259664

Human genetics of infectious diseases: a unified theory

PubMed Central

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

NASA Astrophysics Data System (ADS)

Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-06-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

DNA transposon-based gene vehicles - scenes from an evolutionary drive

PubMed Central

2013-01-01

DNA transposons are primitive genetic elements which have colonized living organisms from plants to bacteria and mammals. Through evolution such parasitic elements have shaped their host genomes by replicating and relocating between chromosomal loci in processes catalyzed by the transposase proteins encoded by the elements themselves. DNA transposable elements are constantly adapting to life in the genome, and self-suppressive regulation as well as defensive host mechanisms may assist in buffering ‘cut-and-paste’ DNA mobilization until accumulating mutations will eventually restrict events of transposition. With the reconstructed Sleeping Beauty DNA transposon as a powerful engine, a growing list of transposable elements with activity in human cells have moved into biomedical experimentation and preclinical therapy as versatile vehicles for delivery and genomic insertion of transgenes. In this review, we aim to link the mechanisms that drive transposon evolution with the realities and potential challenges we are facing when adapting DNA transposons for gene transfer. We argue that DNA transposon-derived vectors may carry inherent, and potentially limiting, traits of their mother elements. By understanding in detail the evolutionary journey of transposons, from host colonization to element multiplication and inactivation, we may better exploit the potential of distinct transposable elements. Hence, parallel efforts to investigate and develop distinct, but potent, transposon-based vector systems will benefit the broad applications of gene transfer. Insight and clever optimization have shaped new DNA transposon vectors, which recently debuted in the first DNA transposon-based clinical trial. Learning from an evolutionary drive may help us create gene vehicles that are safer, more efficient, and less prone for suppression and inactivation. PMID:24320156

Worldwide genetic diversity for mineral element concentrations in rice grain

USDA-ARS?s Scientific Manuscript database

With the aim of identifying rice (Oryza spp.) germplasm having enhanced grain nutritional value, the mineral nutrient and trace element content (a.k.a. ionome) of whole (unmilled) grains from a set of 1763 rice accessions of diverse geographic and genetic origin were evaluated. Seed for analysis o...

Interaction-based evolution: how natural selection and nonrandom mutation work together.

PubMed

Livnat, Adi

2013-10-18

The modern evolutionary synthesis leaves unresolved some of the most fundamental, long-standing questions in evolutionary biology: What is the role of sex in evolution? How does complex adaptation evolve? How can selection operate effectively on genetic interactions? More recently, the molecular biology and genomics revolutions have raised a host of critical new questions, through empirical findings that the modern synthesis fails to explain: for example, the discovery of de novo genes; the immense constructive role of transposable elements in evolution; genetic variance and biochemical activity that go far beyond what traditional natural selection can maintain; perplexing cases of molecular parallelism; and more. Here I address these questions from a unified perspective, by means of a new mechanistic view of evolution that offers a novel connection between selection on the phenotype and genetic evolutionary change (while relying, like the traditional theory, on natural selection as the only source of feedback on the fit between an organism and its environment). I hypothesize that the mutation that is of relevance for the evolution of complex adaptation-while not Lamarckian, or "directed" to increase fitness-is not random, but is instead the outcome of a complex and continually evolving biological process that combines information from multiple loci into one. This allows selection on a fleeting combination of interacting alleles at different loci to have a hereditary effect according to the combination's fitness. This proposed mechanism addresses the problem of how beneficial genetic interactions can evolve under selection, and also offers an intuitive explanation for the role of sex in evolution, which focuses on sex as the generator of genetic combinations. Importantly, it also implies that genetic variation that has appeared neutral through the lens of traditional theory can actually experience selection on interactions and thus has a much greater adaptive potential than previously considered. Empirical evidence for the proposed mechanism from both molecular evolution and evolution at the organismal level is discussed, and multiple predictions are offered by which it may be tested. This article was reviewed by Nigel Goldenfeld (nominated by Eugene V. Koonin), Jürgen Brosius and W. Ford Doolittle.

Macrolide resistance gene erm(TR) and erm(TR)-carrying genetic elements in Streptococcus agalactiae: characterization of ICESagTR7, a new composite element containing IMESp2907.

PubMed

Mingoia, Marina; Morici, Eleonora; Marini, Emanuela; Brenciani, Andrea; Giovanetti, Eleonora; Varaldo, Pietro E

2016-03-01

The objective of this study was to investigate macrolide-resistant Streptococcus agalactiae isolates harbouring erm(TR), an erm(A) gene subclass, with emphasis on their erm(TR)-carrying genetic elements. Four erm(TR)-carrying elements have been described to date: three closely related (ICE10750-RD.2, Tn1806 and ICESp1108) in Streptococcus pyogenes, Streptococcus pneumoniae and S. pyogenes, respectively; and one completely different (IMESp2907, embedded in ICESp2906 to form ICESp2905) in S. pyogenes. Seventeen macrolide-resistant erm(TR)-positive S. agalactiae isolates were phenotypically and genotypically characterized. Their erm(TR)-carrying elements were explored by analysing the distinctive recombination genes of known erm(TR)-carrying integrative and conjugative elements (ICEs) and by PCR mapping. The new genetic context and organization of IMESp2907 in S. agalactiae were explored using several experimental procedures and in silico analyses. Five isolates harboured ICE10750-RD.2/Tn1806, five isolates harboured ICESp1108 and five isolates bore unknown erm(TR)-carrying elements. The remaining two isolates, exhibiting identical serotypes and pulsotypes, harboured IMESp2907 in a new genetic environment, which was further investigated in one of the two isolates, SagTR7. IMESp2907 was circularizable in S. agalactiae, as described in S. pyogenes. The new IMESp2907 junctions were identified based on its site-specific integration; the att sites were almost identical to those in S. pyogenes. In strain SagTR7, erm(TR)-carrying IMESp2907 was embedded in an erm(TR)-less internal element related to ICE10750-RD.2/Tn1806, which, in turn, was embedded in an ICESde3396-like element. The resulting whole ICE, ICESagTR7 (∼129 kb), was integrated into the chromosome downstream of the rplL gene, and was excisable in circular form and transferable by conjugation. This is the first study exploring erm(TR)-carrying genetic elements in S. agalactiae. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A selfish genetic element confers non-Mendelian inheritance in rice.

PubMed

Yu, Xiaowen; Zhao, Zhigang; Zheng, Xiaoming; Zhou, Jiawu; Kong, Weiyi; Wang, Peiran; Bai, Wenting; Zheng, Hai; Zhang, Huan; Li, Jing; Liu, Jiafan; Wang, Qiming; Zhang, Long; Liu, Kai; Yu, Yang; Guo, Xiuping; Wang, Jiulin; Lin, Qibing; Wu, Fuqing; Ren, Yulong; Zhu, Shanshan; Zhang, Xin; Cheng, Zhijun; Lei, Cailin; Liu, Shijia; Liu, Xi; Tian, Yunlu; Jiang, Ling; Ge, Song; Wu, Chuanyin; Tao, Dayun; Wang, Haiyang; Wan, Jianmin

2018-06-08

Selfish genetic elements are pervasive in eukaryote genomes, but their role remains controversial. We show that qHMS7 , a major quantitative genetic locus for hybrid male sterility between wild rice ( Oryza meridionalis ) and Asian cultivated rice ( O. sativa ), contains two tightly linked genes [ Open Reading Frame 2 ( ORF2 ) and ORF3 ]. ORF2 encodes a toxic genetic element that aborts pollen in a sporophytic manner, whereas ORF3 encodes an antidote that protects pollen in a gametophytic manner. Pollens lacking ORF3 are selectively eliminated, leading to segregation distortion in the progeny. Analysis of the genetic sequence suggests that ORF3 arose first, followed by gradual functionalization of ORF2 Furthermore, this toxin-antidote system may have promoted the differentiation and/or maintained the genome stability of wild and cultivated rice. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Comparative Genomics of the Listeria monocytogenes ST204 Subgroup

PubMed Central

Fox, Edward M.; Allnutt, Theodore; Bradbury, Mark I.; Fanning, Séamus; Chandry, P. Scott

2016-01-01

The ST204 subgroup of Listeria monocytogenes is among the most frequently isolated in Australia from a range of environmental niches. In this study we provide a comparative genomics analysis of food and food environment isolates from geographically diverse sources. Analysis of the ST204 genomes showed a highly conserved core genome with the majority of variation seen in mobile genetic elements such as plasmids, transposons and phage insertions. Most strains (13/15) harbored plasmids, which although varying in size contained highly conserved sequences. Interestingly 4 isolates contained a conserved plasmid of 91,396 bp. The strains examined were isolated over a period of 12 years and from different geographic locations suggesting plasmids are an important component of the genetic repertoire of this subgroup and may provide a range of stress tolerance mechanisms. In addition to this 4 phage insertion sites and 2 transposons were identified among isolates, including a novel transposon. These genetic elements were highly conserved across isolates that harbored them, and also contained a range of genetic markers linked to stress tolerance and virulence. The maintenance of conserved mobile genetic elements in the ST204 population suggests these elements may contribute to the diverse range of niches colonized by ST204 isolates. Environmental stress selection may contribute to maintaining these genetic features, which in turn may be co-selecting for virulence markers relevant to clinical infection with ST204 isolates. PMID:28066377

Comparative Genomics of the Listeria monocytogenes ST204 Subgroup.

PubMed

Fox, Edward M; Allnutt, Theodore; Bradbury, Mark I; Fanning, Séamus; Chandry, P Scott

2016-01-01

The ST204 subgroup of Listeria monocytogenes is among the most frequently isolated in Australia from a range of environmental niches. In this study we provide a comparative genomics analysis of food and food environment isolates from geographically diverse sources. Analysis of the ST204 genomes showed a highly conserved core genome with the majority of variation seen in mobile genetic elements such as plasmids, transposons and phage insertions. Most strains (13/15) harbored plasmids, which although varying in size contained highly conserved sequences. Interestingly 4 isolates contained a conserved plasmid of 91,396 bp. The strains examined were isolated over a period of 12 years and from different geographic locations suggesting plasmids are an important component of the genetic repertoire of this subgroup and may provide a range of stress tolerance mechanisms. In addition to this 4 phage insertion sites and 2 transposons were identified among isolates, including a novel transposon. These genetic elements were highly conserved across isolates that harbored them, and also contained a range of genetic markers linked to stress tolerance and virulence. The maintenance of conserved mobile genetic elements in the ST204 population suggests these elements may contribute to the diverse range of niches colonized by ST204 isolates. Environmental stress selection may contribute to maintaining these genetic features, which in turn may be co-selecting for virulence markers relevant to clinical infection with ST204 isolates.

Genetic therapy for the nervous system.

PubMed

Bowers, William J; Breakefield, Xandra O; Sena-Esteves, Miguel

2011-04-15

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state.

Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

NASA Technical Reports Server (NTRS)

Norga, Koenraad K.; Gurganus, Marjorie C.; Dilda, Christy L.; Yamamoto, Akihiko; Lyman, Richard F.; Patel, Prajal H.; Rubin, Gerald M.; Hoskins, Roger A.; Mackay, Trudy F.; Bellen, Hugo J.

2003-01-01

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases.

PubMed

Narayanasamy, Ganesh; Stathakis, Sotirios; Gutierrez, Alonso N; Pappas, Evangelos; Crownover, Richard; Floyd, John R; Papanikolaou, Niko

2017-10-01

In this treatment planning study, we compare the plan quality and delivery parameters for the treatment of multiple brain metastases using 2 monoisocentric techniques: the Multiple Metastases Element from Brainlab and the RapidArc volumetric-modulated arc therapy from Varian Medical Systems. Eight patients who were treated in our institution for multiple metastases (3-7 lesions) were replanned with Multiple Metastases Element using noncoplanar dynamic conformal arcs. The same patients were replanned with the RapidArc technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed using a single isocenter. Plan quality metrics (conformity index, homogeneity index, gradient index, and R 50% ), monitor unit, and the planning time were recorded. Comparison of the Multiple Metastases Element and RapidArc plans was performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed rank test. A paired Wilcoxon signed rank test between Multiple Metastases Element and RapidArc showed comparable plan quality metrics and dose to brain. Mean ± standard deviation values of conformity index were 1.8 ± 0.7 and 1.7 ± 0.6, homogeneity index were 1.3 ± 0.1 and 1.3 ± 0.1, gradient index were 5.0 ± 1.8 and 5.1 ± 1.9, and R 50% were 4.9 ± 1.8 and 5.0 ± 1.9 for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans, respectively. The mean value of monitor units in Multiple Metastases Element plan was 7286 ± 1065, which is significantly lower than the RapidArc monitor units of 9966 ± 1533 ( P < .05). For the planning of multiple brain lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element planning software produced equivalent conformity, homogeneity, dose falloff, and brain V 12 Gy but required significantly lower monitor units, when compared to RapidArc plans.

A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases

PubMed Central

Stathakis, Sotirios; Gutierrez, Alonso N.; Pappas, Evangelos; Crownover, Richard; Floyd, John R.; Papanikolaou, Niko

2016-01-01

Background: In this treatment planning study, we compare the plan quality and delivery parameters for the treatment of multiple brain metastases using 2 monoisocentric techniques: the Multiple Metastases Element from Brainlab and the RapidArc volumetric-modulated arc therapy from Varian Medical Systems. Methods: Eight patients who were treated in our institution for multiple metastases (3-7 lesions) were replanned with Multiple Metastases Element using noncoplanar dynamic conformal arcs. The same patients were replanned with the RapidArc technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed using a single isocenter. Plan quality metrics (conformity index, homogeneity index, gradient index, and R50%), monitor unit, and the planning time were recorded. Comparison of the Multiple Metastases Element and RapidArc plans was performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed rank test. Results: A paired Wilcoxon signed rank test between Multiple Metastases Element and RapidArc showed comparable plan quality metrics and dose to brain. Mean ± standard deviation values of conformity index were 1.8 ± 0.7 and 1.7 ± 0.6, homogeneity index were 1.3 ± 0.1 and 1.3 ± 0.1, gradient index were 5.0 ± 1.8 and 5.1 ± 1.9, and R50% were 4.9 ± 1.8 and 5.0 ± 1.9 for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans, respectively. The mean value of monitor units in Multiple Metastases Element plan was 7286 ± 1065, which is significantly lower than the RapidArc monitor units of 9966 ± 1533 (P < .05). Conclusion: For the planning of multiple brain lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element planning software produced equivalent conformity, homogeneity, dose falloff, and brain V12 Gy but required significantly lower monitor units, when compared to RapidArc plans. PMID:27612917

Mobile genetic elements and cancer. From mutations to gene therapy.

PubMed

Kozeretska, I A; Demydov, S V; Ostapchenko, L I

2011-12-01

In the present review, an association between cancer and the activity of the non-LTR retroelements L1, Alu, and SVA, as well as endogenous retroviruses, in the human genome, is analyzed. Data suggesting that transposons have been involved in embryogenesis and malignization processes, are presented. Events that lead to the activation of mobile elements in mammalian somatic cells, as well as the use of mobile elements in genetic screening and cancer gene therapy, are reviewed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortiz, Rosario, E-mail: r_oh@ciencias.unam.mx; Kouznetsova, Anna, E-mail: Anna.Kouznetsova@ki.se; Echeverría-Martínez, Olga M., E-mail: omem@ciencias.unam.mx

The synaptonemal complex (SC) is a proteinaceous structure that holds the homologous chromosomes in close proximity while they exchange genetic material in a process known as meiotic recombination. This meiotic recombination leads to genetic variability in sexually reproducing organisms. The ultrastructure of the SC is studied by electron microscopy and it is observed as a tripartite structure. Two lateral elements (LE) separated by a central region (CR) confer its classical tripartite organization. The LEs are the anchoring platform for the replicated homologous chromosomes to properly exchange genetic material with one another. An accurate assembly of the LE is indispensable formore » the proper completion of meiosis. Ultrastructural studies suggested that the LE is organized as a multilayered unit. However, no validation of this model has been previously provided. In this ultrastructural study, by using mice with different genetic backgrounds that affect the LE width, we provide further evidence that support a multilayered organization of the LE. Additionally, we provide data suggesting additional roles of the different cohesin complex components in the structure of the LEs of the SC. - Highlights: • The lateral element of the synaptonemal complex is a multilayered structure. • The width of the lateral element in synaptonemal complex-null mice is different. • Two cohesin complex cores plus one axial element form a wild-type lateral element. • The layers of the lateral element can be analyzed in different null mice models.« less

[Application of Multiple Genetic Markers in a Case of Determination of Half Sibling].

PubMed

Yang, Xue; Shi, Mei-sen; Yuan, Li; Lu, Di

2016-02-01

A case of half sibling was determined with multiple genetic markers, which could be potentially applied for determination of half sibling relationship from same father. Half sibling relationship was detected by 39 autosomal STR genetic markers, 23 Y-chromosomal STR genetic markers and 12 X -chromosomal STR genetic markers among ZHAO -1, ZHAO -2, ZHAO -3, ZHAO -4, and ZHAO-5. According to autosomal STR, Y-STR and X-STR genotyping results, it was determined that ZHAO-4 (alleged half sibling) was unrelated with ZHAO-1 and ZHAO-2; however, ZHAO-3 (alleged half sibling), ZHAO-5 (alleged half sibling) shared same genetic profile with ZHAO-1, and ZHAO-2 from same father. It is reliable to use multiple genetic markers and family gene reconstruction to determine half sibling relationship from same father, but it is difficult to determination by calculating half sibling index with ITO and discriminant functions.

Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torella, JP; Boehm, CR; Lienert, F

2013-12-28

In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminatormore » parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.« less

Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres

PubMed Central

Gent, Jonathan I.; Wang, Kai; Jiang, Jiming; Dawe, R. Kelly

2015-01-01

While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift. PMID:26063660

Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis

PubMed Central

Wang, Yanqun; Liu, Di; Shi, Weifeng; Lu, Roujian; Wang, Wenling; Zhao, Yanjie; Deng, Yao; Zhou, Weimin; Ren, Hongguang; Wu, Jun; Wang, Yu; Wu, Guizhen

2015-01-01

ABSTRACT The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus. PMID:26350969

Genome-Wide Comparison of Magnaporthe Species Reveals a Host-Specific Pattern of Secretory Proteins and Transposable Elements

PubMed Central

Gowda, Malali

2016-01-01

Blast disease caused by the Magnaporthe species is a major factor affecting the productivity of rice, wheat and millets. This study was aimed at generating genomic information for rice and non-rice Magnaporthe isolates to understand the extent of genetic variation. We have sequenced the whole genome of the Magnaporthe isolates, infecting rice (leaf and neck), finger millet (leaf and neck), foxtail millet (leaf) and buffel grass (leaf). Rice and finger millet isolates infecting both leaf and neck tissues were sequenced, since the damage and yield loss caused due to neck blast is much higher as compared to leaf blast. The genome-wide comparison was carried out to study the variability in gene content, candidate effectors, repeat element distribution, genes involved in carbohydrate metabolism and SNPs. The analysis of repeat element footprints revealed some genes such as naringenin, 2-oxoglutarate 3-dioxygenase being targeted by Pot2 and Occan, in isolates from different host species. Some repeat insertions were host-specific while other insertions were randomly shared between isolates. The distributions of repeat elements, secretory proteins, CAZymes and SNPs showed significant variation across host-specific lineages of Magnaporthe indicating an independent genome evolution orchestrated by multiple genomic factors. PMID:27658241

Grasshopper, a long terminal repeat (LTR) retroelement in the phytopathogenic fungus Magnaporthe grisea.

PubMed

Dobinson, K F; Harris, R E; Hamer, J E

1993-01-01

The fungal phytopathogen Magnaporthe grisea parasitizes a wide variety of gramineous hosts. In the course of investigating the genetic relationship between pathogen genotype and host specificity we identified a retroelement that is present in some strains of M. grisea that infect finger millet and goosegrass (members of the plant genus Eleusine). The element, designated grasshopper (grh), is present in multiple copies and dispersed throughout the genome. DNA sequence analysis showed that grasshopper contains 198 base pair direct, long terminal repeats (LTRs) with features characteristic of retroviral and retrotransposon LTRs. Within the element we identified an open reading frame with sequences homologous to the reverse transcriptase, RNaseH, and integrase domains of retroelement pol genes. Comparison of the open reading frame with sequences from other retroelements showed that grh is related to the gypsy family of retrotransposons. Comparisons of the distribution of the grasshopper element with other dispersed repeated DNA sequences in M. grisea indicated that grasshopper was present in a broadly dispersed subgroup of Eleusine pathogens, suggesting that the element was acquired subsequent to the evolution of this host-specific form. We present arguments that the amplification of different retroelements within populations of M. grisea is a consequence of the clonal organization of the fungal populations.

Characterization of mobile genetic elements in antibiotic resistant Salmonella enterica isolates from food animals

USDA-ARS?s Scientific Manuscript database

Antibiotic resistance (AR) is a major concern for the agricultural industry in the U.S. and globally. The problem of AR is further complicated by AR genes often being located on mobile genetic elements (MGEs) resulting in their spread among bacteria. In order to investigate the relationship between ...

[Plant transposable elements and their application in genetics and biotechnology].

PubMed

Ovcharenko, O O; Rudas, V A; Kuchuk, M V

2006-01-01

Data concerning plant transposable elements and their contribution to plant genome evolution are reviewed. Much attention is focused on utilization of transgenic plants as heterologous hosts of transposons for investigation of transposition mechanisms and gene cloning. Probable ways of the use of plant transposons as genetic tools in biotechnology are discussed.

The chromosomal organization of horizontal gene transfer in bacteria.

PubMed

Oliveira, Pedro H; Touchon, Marie; Cury, Jean; Rocha, Eduardo P C

2017-10-10

Bacterial adaptation is accelerated by the acquisition of novel traits through horizontal gene transfer, but the integration of these genes affects genome organization. We found that transferred genes are concentrated in only ~1% of the chromosomal regions (hotspots) in 80 bacterial species. This concentration increases with genome size and with the rate of transfer. Hotspots diversify by rapid gene turnover; their chromosomal distribution depends on local contexts (neighboring core genes), and content in mobile genetic elements. Hotspots concentrate most changes in gene repertoires, reduce the trade-off between genome diversification and organization, and should be treasure troves of strain-specific adaptive genes. Most mobile genetic elements and antibiotic resistance genes are in hotspots, but many hotspots lack recognizable mobile genetic elements and exhibit frequent homologous recombination at flanking core genes. Overrepresentation of hotspots with fewer mobile genetic elements in naturally transformable bacteria suggests that homologous recombination and horizontal gene transfer are tightly linked in genome evolution.Horizontal gene transfer (HGT) is an important mechanism for genome evolution and adaptation in bacteria. Here, Oliveira and colleagues find HGT hotspots comprising  ~ 1% of the chromosomal regions in 80 bacterial species.

Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales

NASA Astrophysics Data System (ADS)

Bhérer, Claude; Campbell, Christopher L.; Auton, Adam

2017-04-01

In humans, males have lower recombination rates than females over the majority of the genome, but the opposite is usually true near the telomeres. These broad-scale differences have been known for decades, yet little is known about differences at the fine scale. By combining data sets, we have collected recombination events from over 100,000 meioses and have constructed sex-specific genetic maps at a previously unachievable resolution. Here we show that, although a substantial fraction of the genome shows some degree of sexually dimorphic recombination, the vast majority of hotspots are shared between the sexes, with only a small number of putative sex-specific hotspots. Wavelet analysis indicates that most of the differences can be attributed to the fine scale, and that variation in rate between the sexes can mostly be explained by differences in hotspot magnitude, rather than location. Nonetheless, known recombination-associated genomic features, such as THE1B repeat elements, show systematic differences between the sexes.

Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

PubMed Central

Gilbert, James; Man, Heng-Ye

2017-01-01

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.ASDs are highly heterogeneous in their genetic basis.ASDs share common features at the cellular and molecular levels in the brain.Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function. PMID:29209173

Fuzzy-logic based strategy for validation of multiplex methods: example with qualitative GMO assays.

PubMed

Bellocchi, Gianni; Bertholet, Vincent; Hamels, Sandrine; Moens, W; Remacle, José; Van den Eede, Guy

2010-02-01

This paper illustrates the advantages that a fuzzy-based aggregation method could bring into the validation of a multiplex method for GMO detection (DualChip GMO kit, Eppendorf). Guidelines for validation of chemical, bio-chemical, pharmaceutical and genetic methods have been developed and ad hoc validation statistics are available and routinely used, for in-house and inter-laboratory testing, and decision-making. Fuzzy logic allows summarising the information obtained by independent validation statistics into one synthetic indicator of overall method performance. The microarray technology, introduced for simultaneous identification of multiple GMOs, poses specific validation issues (patterns of performance for a variety of GMOs at different concentrations). A fuzzy-based indicator for overall evaluation is illustrated in this paper, and applied to validation data for different genetically modified elements. Remarks were drawn on the analytical results. The fuzzy-logic based rules were shown to be applicable to improve interpretation of results and facilitate overall evaluation of the multiplex method.

How Genetics Has Helped Piece Together the MAPK Signaling Pathway.

PubMed

Ashton-Beaucage, Dariel; Therrien, Marc

2017-01-01

Cells respond to changes in their environment, to developmental cues, and to pathogen aggression through the action of a complex network of proteins. These networks can be decomposed into a multitude of signaling pathways that relay signals from the microenvironment to the cellular components involved in eliciting a specific response. Perturbations in these signaling processes are at the root of multiple pathologies, the most notable of these being cancer. The study of receptor tyrosine kinase (RTK) signaling led to the first description of a mechanism whereby an extracellular signal is transmitted to the nucleus to induce a transcriptional response. Genetic studies conducted in drosophila and nematodes have provided key elements to this puzzle. Here, we briefly discuss the somewhat lesser known contribution of these multicellular organisms to our understanding of what has come to be known as the prototype of signaling pathways. We also discuss the ostensibly much larger network of regulators that has emerged from recent functional genomic investigations of RTK/RAS/ERK signaling.

Genetics Reasoning with Multiple External Representations.

ERIC Educational Resources Information Center

Tsui, Chi-Yan; Treagust, David F.

2003-01-01

Explores a case study of a class of 10th grade students whose learning of genetics involved activities using BioLogica, a computer program that features multiple external representations (MERs). Findings indicate that the MERs in BioLogica contributed to students' development of genetics reasoning by engendering their motivation and interest but…

Genetic and epigenetic variation in the lineage specification of regulatory T cells

PubMed Central

Arvey, Aaron; van der Veeken, Joris; Plitas, George; Rich, Stephen S; Concannon, Patrick; Rudensky, Alexander Y

2015-01-01

Regulatory T (Treg) cells, which suppress autoimmunity and other inflammatory states, are characterized by a distinct set of genetic elements controlling their gene expression. However, the extent of genetic and associated epigenetic variation in the Treg cell lineage and its possible relation to disease states in humans remain unknown. We explored evolutionary conservation of regulatory elements and natural human inter-individual epigenetic variation in Treg cells to identify the core transcriptional control program of lineage specification. Analysis of single nucleotide polymorphisms in core lineage-specific enhancers revealed disease associations, which were further corroborated by high-resolution genotyping to fine map causal polymorphisms in lineage-specific enhancers. Our findings suggest that a small set of regulatory elements specify the Treg lineage and that genetic variation in Treg cell-specific enhancers may alter Treg cell function contributing to polygenic disease. DOI: http://dx.doi.org/10.7554/eLife.07571.001 PMID:26510014

A Simple Test of Class-Level Genetic Association Can Reveal Novel Cardiometabolic Trait Loci.

PubMed

Qian, Jing; Nunez, Sara; Reed, Eric; Reilly, Muredach P; Foulkes, Andrea S

2016-01-01

Characterizing the genetic determinants of complex diseases can be further augmented by incorporating knowledge of underlying structure or classifications of the genome, such as newly developed mappings of protein-coding genes, epigenetic marks, enhancer elements and non-coding RNAs. We apply a simple class-level testing framework, termed Genetic Class Association Testing (GenCAT), to identify protein-coding gene association with 14 cardiometabolic (CMD) related traits across 6 publicly available genome wide association (GWA) meta-analysis data resources. GenCAT uses SNP-level meta-analysis test statistics across all SNPs within a class of elements, as well as the size of the class and its unique correlation structure, to determine if the class is statistically meaningful. The novelty of findings is evaluated through investigation of regional signals. A subset of findings are validated using recently updated, larger meta-analysis resources. A simulation study is presented to characterize overall performance with respect to power, control of family-wise error and computational efficiency. All analysis is performed using the GenCAT package, R version 3.2.1. We demonstrate that class-level testing complements the common first stage minP approach that involves individual SNP-level testing followed by post-hoc ascribing of statistically significant SNPs to genes and loci. GenCAT suggests 54 protein-coding genes at 41 distinct loci for the 13 CMD traits investigated in the discovery analysis, that are beyond the discoveries of minP alone. An additional application to biological pathways demonstrates flexibility in defining genetic classes. We conclude that it would be prudent to include class-level testing as standard practice in GWA analysis. GenCAT, for example, can be used as a simple, complementary and efficient strategy for class-level testing that leverages existing data resources, requires only summary level data in the form of test statistics, and adds significant value with respect to its potential for identifying multiple novel and clinically relevant trait associations.

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

PubMed Central

Supple, Megan A.; Hines, Heather M.; Dasmahapatra, Kanchon K.; Lewis, James J.; Nielsen, Dahlia M.; Lavoie, Christine; Ray, David A.; Salazar, Camilo; McMillan, W. Owen; Counterman, Brian A.

2013-01-01

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations. PMID:23674305

[Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

PubMed

Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

2010-12-01

In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

Transposable Elements and Genetic Instabilities in Crop Plants

DOE R&D Accomplishments Database

Burr, B.; Burr, F.

1981-04-10

Transposable elements have long been associated with certain unstable loci in maize and have been intensively studied by McClintock and others. It is known that a transposable element can control the expression of the structural genes at the locus where it resides. These controlling elements in maize are now beginning to be studied at the molecular level. Using recombinant molecular probes we have been able to describe the changes induced by the controlling element Ds at the shrunken locus. Ds elements appear to be large and dissimilar insertions into the wild-type locus - two elements actually map within the transcribed region of the gene. Genetic instabilities have been described in other economically important plants but the bases for these phenomena have not been understood. We believe that it is likely that some of these instabilities are the result of transposable element activity much as in the case of maize.

Domestication of Plants in the Americas: Insights from Mendelian and Molecular Genetics

PubMed Central

Pickersgill, Barbara

2007-01-01

Background Plant domestication occurred independently in four different regions of the Americas. In general, different species were domesticated in each area, though a few species were domesticated independently in more than one area. The changes resulting from human selection conform to the familiar domestication syndrome, though different traits making up this syndrome, for example loss of dispersal, are achieved by different routes in crops belonging to different families. Genetic and Molecular Analyses of Domestication Understanding of the genetic control of elements of the domestication syndrome is improving as a result of the development of saturated linkage maps for major crops, identification and mapping of quantitative trait loci, cloning and sequencing of genes or parts of genes, and discoveries of widespread orthologies in genes and linkage groups within and between families. As the modes of action of the genes involved in domestication and the metabolic pathways leading to particular phenotypes become better understood, it should be possible to determine whether similar phenotypes have similar underlying genetic controls, or whether human selection in genetically related but independently domesticated taxa has fixed different mutants with similar phenotypic effects. Conclusions Such studies will permit more critical analysis of possible examples of multiple domestications and of the origin(s) and spread of distinctive variants within crops. They also offer the possibility of improving existing crops, not only major food staples but also minor crops that are potential export crops for developing countries or alternative crops for marginal areas. PMID:17766847

Incompatibility and competitive exclusion of genomic segments between sibling Drosophila species.

PubMed

Fang, Shu; Yukilevich, Roman; Chen, Ying; Turissini, David A; Zeng, Kai; Boussy, Ian A; Wu, Chung-I

2012-06-01

The extent and nature of genetic incompatibilities between incipient races and sibling species is of fundamental importance to our view of speciation. However, with the exception of hybrid inviability and sterility factors, little is known about the extent of other, more subtle genetic incompatibilities between incipient species. Here we experimentally demonstrate the prevalence of such genetic incompatibilities between two young allopatric sibling species, Drosophila simulans and D. sechellia. Our experiments took advantage of 12 introgression lines that carried random introgressed D. sechellia segments in different parts of the D. simulans genome. First, we found that these introgression lines did not show any measurable sterility or inviability effects. To study if these sechellia introgressions in a simulans background contained other fitness consequences, we competed and genetically tracked the marked alleles within each introgression against the wild-type alleles for 20 generations. Strikingly, all marked D. sechellia introgression alleles rapidly decreased in frequency in only 6 to 7 generations. We then developed computer simulations to model our competition results. These simulations indicated that selection against D. sechellia introgression alleles was high (average s = 0.43) and that the marker alleles and the incompatible alleles did not separate in 78% of the introgressions. The latter result likely implies that most introgressions contain multiple genetic incompatibilities. Thus, this study reveals that, even at early stages of speciation, many parts of the genome diverge to a point where introducing foreign elements has detrimental fitness consequences, but which cannot be seen using standard sterility and inviability assays.

Genetic therapy for the nervous system

PubMed Central

Bowers, William J.; Breakefield, Xandra O.; Sena-Esteves, Miguel

2011-01-01

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state. PMID:21429918

Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone.

PubMed

Ben Zakour, Nouri L; Davies, Mark R; You, Yuanhai; Chen, Jonathan H K; Forde, Brian M; Stanton-Cook, Mitchell; Yang, Ruifu; Cui, Yujun; Barnett, Timothy C; Venturini, Carola; Ong, Cheryl-lynn Y; Tse, Herman; Dougan, Gordon; Zhang, Jianzhong; Yuen, Kwok-Yung; Beatson, Scott A; Walker, Mark J

2015-11-02

The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of scarlet fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of scarlet fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 scarlet fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone

PubMed Central

Ben Zakour, Nouri L.; Davies, Mark R.; You, Yuanhai; Chen, Jonathan H. K.; Forde, Brian M.; Stanton-Cook, Mitchell; Yang, Ruifu; Cui, Yujun; Barnett, Timothy C.; Venturini, Carola; Ong, Cheryl-lynn Y.; Tse, Herman; Dougan, Gordon; Zhang, Jianzhong; Yuen, Kwok-Yung; Beatson, Scott A.; Walker, Mark J.

2015-01-01

The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome123. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone45, with bacteriophage-encoded determinants DNase Sda16 and superantigen SpeA27 contributing to enhanced virulence and colonization respectively. Outbreaks of scarlet fever in Hong Kong and China in 2011, caused primarily by emm12 GAS8910, led to our investigation of the next most common cause of scarlet fever, emm1 GAS89. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 scarlet fever clones1011 in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements. PMID:26522788

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology.

PubMed

Hernanz-Koers, Miguel; Gandía, Mónica; Garrigues, Sandra; Manzanares, Paloma; Yenush, Lynne; Orzaez, Diego; Marcos, Jose F

2018-07-01

Current challenges in the study and biotechnological exploitation of filamentous fungi are the optimization of DNA cloning and fungal genetic transformation beyond model fungi, the open exchange of ready-to-use and standardized genetic elements among the research community, and the availability of universal synthetic biology tools and rules. The GoldenBraid (GB) cloning framework is a Golden Gate-based DNA cloning system developed for plant synthetic biology through Agrobacterium tumefaciens-mediated genetic transformation (ATMT). In this study, we develop reagents for the adaptation of GB version 3.0 from plants to filamentous fungi through: (i) the expansion of the GB toolbox with the domestication of fungal-specific genetic elements; (ii) the design of fungal-specific GB structures; and (iii) the ATMT and gene disruption of the plant pathogen Penicillium digitatum as a proof of concept. Genetic elements domesticated into the GB entry vector pUPD2 include promoters, positive and negative selection markers and terminators. Interestingly, some GB elements can be directly exchanged between plants and fungi, as demonstrated with the marker hph for Hyg R or the fluorescent protein reporter YFP. The iterative modular assembly of elements generates an endless number of diverse transcriptional units and other higher order combinations in the pDGB3α/pDGB3Ω destination vectors. Furthermore, the original plant GB syntax was adapted here to incorporate specific GB structures for gene disruption through homologous recombination and dual selection. We therefore have successfully adapted the GB technology for the ATMT of fungi. We propose the name of FungalBraid (FB) for this new branch of the GB technology that provides open, exchangeable and collaborative resources to the fungal research community. Copyright © 2018 Elsevier Inc. All rights reserved.

Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

DOE PAGES

Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong; ...

2016-04-12

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundancemore » of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. In addition, as governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.« less

Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundancemore » of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. In addition, as governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.« less

Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture.

PubMed

Johnson, Timothy A; Stedtfeld, Robert D; Wang, Qiong; Cole, James R; Hashsham, Syed A; Looft, Torey; Zhu, Yong-Guan; Tiedje, James M

2016-04-12

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk. Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. As governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically. Copyright © 2016 Johnson et al.

Transposable elements as agents of rapid adaptation may explain the genetic paradox of invasive species.

PubMed

Stapley, Jessica; Santure, Anna W; Dennis, Stuart R

2015-05-01

Rapid adaptation of invasive species to novel habitats has puzzled evolutionary biologists for decades, especially as this often occurs in the face of limited genetic variability. Although some ecological traits common to invasive species have been identified, little is known about the possible genomic/genetic mechanisms that may underlie their success. A common scenario in many introductions is that small founder population sizes will often lead to reduced genetic diversity, but that invading populations experience large environmental perturbations, such as changes in habitat and environmental stress. Although sudden and intense stress is usually considered in a negative context, these perturbations may actually facilitate rapid adaptation by affecting genome structure, organization and function via interactions with transposable elements (TEs), especially in populations with low genetic diversity. Stress-induced changes in TE activity can alter gene action and can promote structural variation that may facilitate the rapid adaptation observed in new environments. We focus here on the adaptive potential of TEs in relation to invasive species and highlight their role as powerful mutational forces that can rapidly create genetic diversity. We hypothesize that activity of transposable elements can explain rapid adaptation despite low genetic variation (the genetic paradox of invasive species), and provide a framework under which this hypothesis can be tested using recently developed and emerging genomic technologies. © 2015 John Wiley & Sons Ltd.

Genetic variation and biological activity of isolates of lymantria dispar multiple nucleopolyhedrovirus from north america, europe, and asia

USDA-ARS?s Scientific Manuscript database

Little is known about genetic variation of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV; Baculoviridae: Alphabaculovirus) at the nucleotide sequence level. To obtain a more comprehensive view of genetic diversity among isolates of LdMNPV, partial sequences of the lef-8 gene were generated...

Novel Applications of Multi-task Learning and Multiple Output Regression to Multiple Genetic Trait Prediction

USDA-ARS?s Scientific Manuscript database

Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait predicti...

Functional and mechanistic diversity of distal transcription enhancers

PubMed Central

Bulger, Michael; Groudine, Mark

2013-01-01

Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

p53 regulates the mevalonate pathway in human glioblastoma multiforme

PubMed Central

Laezza, C; D'Alessandro, A; Di Croce, L; Picardi, P; Ciaglia, E; Pisanti, S; Malfitano, A M; Comegna, M; Faraonio, R; Gazzerro, P; Bifulco, M

2015-01-01

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3′-hydroxy-3′-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression. PMID:26469958

Can you hear me now? Understanding vertebrate middle ear development

PubMed Central

Chapman, Susan Caroline

2010-01-01

The middle ear is a composite organ formed from all three germ layers and the neural crest. It provides the link between the outside world and the inner ear, where sound is transduced and routed to the brain for processing. Extensive classical and modern studies have described the complex morphology and origin of the middle ear. Non-mammalian vertebrates have a single ossicle, the columella. Mammals have three functionally equivalent ossicles, designated the malleus, incus and stapes. In this review, I focus on the role of genes known to function in the middle ear. Genetic studies are beginning to unravel the induction and patterning of the multiple middle ear elements including the tympanum, skeletal elements, the air-filled cavity, and the insertion point into the inner ear oval window. Future studies that elucidate the integrated spatio-temporal signaling mechanisms required to pattern the middle ear organ system are needed. The longer-term translational benefits of understanding normal and abnormal ear development will have a direct impact on human health outcomes. PMID:21196256

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Structured populations of Sulfolobus acidocaldarius with susceptibility to mobile genetic elements

USGS Publications Warehouse

Anderson, Rika E.; Kouris, Angela; Seward, Christopher H.; Campbell, Kate M.; Whitaker, Rachel J.

2017-01-01

The impact of a structured environment on genome evolution can be determined through comparative population genomics of species that live in the same habitat. Recent work comparing three genome sequences of Sulfolobus acidocaldarius suggested that highly structured, extreme, hot spring environments do not limit dispersal of this thermoacidophile, in contrast to other co-occurring Sulfolobus species. Instead, a high level of conservation among these three S. acidocaldarius genomes was hypothesized to result from rapid, global-scale dispersal promoted by low susceptibility to viruses that sets S. acidocaldarius apart from its sister Sulfolobus species. To test this hypothesis, we conducted a comparative analysis of 47 genomes of S. acidocaldarius from spatial and temporal sampling of two hot springs in Yellowstone National Park. While we confirm the low diversity in the core genome, we observe differentiation among S. acidocaldarius populations, likely resulting from low migration among hot spring “islands” in Yellowstone National Park. Patterns of genomic variation indicate that differing geological contexts result in the elimination or preservation of diversity among differentiated populations. We observe multiple deletions associated with a large genomic island rich in glycosyltransferases, differential integrations of the Sulfolobus turreted icosahedral virus, as well as two different plasmid elements. These data demonstrate that neither rapid dispersal nor lack of mobile genetic elements result in low diversity in the S. acidocaldariusgenomes. We suggest instead that significant differences in the recent evolutionary history, or the intrinsic evolutionary rates, of sister Sulfolobusspecies result in the relatively low diversity of the S. acidocaldarius genome.

A Linear Electromagnetic Piston Pump

NASA Astrophysics Data System (ADS)

Hogan, Paul H.

Advancements in mobile hydraulics for human-scale applications have increased demand for a compact hydraulic power supply. Conventional designs couple a rotating electric motor to a hydraulic pump, which increases the package volume and requires several energy conversions. This thesis investigates the use of a free piston as the moving element in a linear motor to eliminate multiple energy conversions and decrease the overall package volume. A coupled model used a quasi-static magnetic equivalent circuit to calculate the motor inductance and the electromagnetic force acting on the piston. The force was an input to a time domain model to evaluate the mechanical and pressure dynamics. The magnetic circuit model was validated with finite element analysis and an experimental prototype linear motor. The coupled model was optimized using a multi-objective genetic algorithm to explore the parameter space and maximize power density and efficiency. An experimental prototype linear pump coupled pistons to an off-the-shelf linear motor to validate the mechanical and pressure dynamics models. The magnetic circuit force calculation agreed within 3% of finite element analysis, and within 8% of experimental data from the unoptimized prototype linear motor. The optimized motor geometry also had good agreement with FEA; at zero piston displacement, the magnetic circuit calculates optimized motor force within 10% of FEA in less than 1/1000 the computational time. This makes it well suited to genetic optimization algorithms. The mechanical model agrees very well with the experimental piston pump position data when tuned for additional unmodeled mechanical friction. Optimized results suggest that an improvement of 400% of the state of the art power density is attainable with as high as 85% net efficiency. This demonstrates that a linear electromagnetic piston pump has potential to serve as a more compact and efficient supply of fluid power for the human scale.

Reexamining the P-Element Invasion of Drosophila melanogaster Through the Lens of piRNA Silencing

PubMed Central

Kelleher, Erin S.

2016-01-01

Transposable elements (TEs) are both important drivers of genome evolution and genetic parasites with potentially dramatic consequences for host fitness. The recent explosion of research on regulatory RNAs reveals that small RNA-mediated silencing is a conserved genetic mechanism through which hosts repress TE activity. The invasion of the Drosophila melanogaster genome by P elements, which happened on a historical timescale, represents an incomparable opportunity to understand how small RNA-mediated silencing of TEs evolves. Repression of P-element transposition emerged almost concurrently with its invasion. Recent studies suggest that this repression is implemented in part, and perhaps predominantly, by the Piwi-interacting RNA (piRNA) pathway, a small RNA-mediated silencing pathway that regulates TE activity in many metazoan germlines. In this review, I consider the P-element invasion from both a molecular and evolutionary genetic perspective, reconciling classic studies of P-element regulation with the new mechanistic framework provided by the piRNA pathway. I further explore the utility of the P-element invasion as an exemplar of the evolution of piRNA-mediated silencing. In light of the highly-conserved role for piRNAs in regulating TEs, discoveries from this system have taxonomically broad implications for the evolution of repression. PMID:27516614

Selfish genetic elements favor the evolution of a distinction between soma and germline.

PubMed

Johnson, Louise J

2008-08-01

Many multicellular organisms have evolved a dedicated germline. This can benefit the whole organism, but its advantages to genetic parasites have not been explored. Here I model the evolutionary success of a selfish element, such as a transposable element or endosymbiont, which is capable of creating or strengthening a germline-soma distinction in a primitively multicellular host, and find that it will always benefit the element to do so. Genes causing germline sequestration can therefore spread in a population even if germline sequestration is maladaptive for the host organism. Costly selfish elements are expected to survive only in sexual populations, so sexual species may experience an additional push toward germline-soma distinction, and hence toward cell differentiation and multicellularity.

Genetics Home Reference: Peters anomaly

MedlinePlus

... eye (cornea). During development of the eye, the elements of the anterior segment form separate structures. However, ... are some genetic conditions more common in particular ethnic groups? Genetic Changes Mutations in the FOXC1 , PAX6 , PITX2 , ...

Natural Hot Spots for Gain of Multiple Resistances: Arsenic and Antibiotic Resistances in Heterotrophic, Aerobic Bacteria from Marine Hydrothermal Vent Fields

PubMed Central

Farias, Pedro; Espírito Santo, Christophe; Branco, Rita; Francisco, Romeu; Santos, Susana; Hansen, Lars; Sorensen, Soren

2015-01-01

Microorganisms are responsible for multiple antibiotic resistances that have been associated with resistance/tolerance to heavy metals, with consequences to public health. Many genes conferring these resistances are located on mobile genetic elements, easily exchanged among phylogenetically distant bacteria. The objective of the present work was to isolate arsenic-, antimonite-, and antibiotic-resistant strains and to determine the existence of plasmids harboring antibiotic/arsenic/antimonite resistance traits in phenotypically resistant strains, in a nonanthropogenically impacted environment. The hydrothermal Lucky Strike field in the Azores archipelago (North Atlantic, between 11°N and 38°N), at the Mid-Atlantic Ridge, protected under the OSPAR Convention, was sampled as a metal-rich pristine environment. A total of 35 strains from 8 different species were isolated in the presence of arsenate, arsenite, and antimonite. ACR3 and arsB genes were amplified from the sediment's total DNA, and 4 isolates also carried ACR3 genes. Phenotypic multiple resistances were found in all strains, and 7 strains had recoverable plasmids. Purified plasmids were sequenced by Illumina and assembled by EDENA V3, and contig annotation was performed using the “Rapid Annotation using the Subsystems Technology” server. Determinants of resistance to copper, zinc, cadmium, cobalt, and chromium as well as to the antibiotics β-lactams and fluoroquinolones were found in the 3 sequenced plasmids. Genes coding for heavy metal resistance and antibiotic resistance in the same mobile element were found, suggesting the possibility of horizontal gene transfer and distribution of theses resistances in the bacterial population. PMID:25636836

Phase discriminating capacitive array sensor system

NASA Technical Reports Server (NTRS)

Vranish, John M. (Inventor); Rahim, Wadi (Inventor)

1993-01-01

A phase discriminating capacitive sensor array system which provides multiple sensor elements which are maintained at a phase and amplitude based on a frequency reference provided by a single frequency stabilized oscillator. Sensor signals provided by the multiple sensor elements are controlled by multiple phase control units, which correspond to the multiple sensor elements, to adjust the sensor signals from the multiple sensor elements based on the frequency reference. The adjustment made to the sensor signals is indicated by output signals which indicate the proximity of the object. The output signals may also indicate the closing speed of the object based on the rate of change of the adjustment made, and the edges of the object based on a sudden decrease in the adjustment made.

Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen Erwinia Tracheiphila

PubMed Central

Shapiro, Lori R.; Scully, Erin D.; Straub, Timothy J.; Park, Jihye; Stephenson, Andrew G.; Beattie, Gwyn A.; Gleason, Mark L.; Kolter, Roberto; Coelho, Miguel C.; De Moraes, Consuelo M.; Mescher, Mark C.; Zhaxybayeva, Olga

2016-01-01

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, Kentucky, and Michigan. These genomes exhibit a high proportion of recent horizontal gene acquisitions, invasion and remarkable amplification of mobile genetic elements, and pseudogenization of approximately 20% of the coding sequences. These genome attributes indicate that E. tracheiphila recently emerged as a host-restricted pathogen. Furthermore, chromosomal rearrangements associated with phage and transposable element proliferation contribute to substantial differences in gene content and genetic architecture between the six E. tracheiphila strains and other Erwinia species. Together, these data lead us to hypothesize that E. tracheiphila has undergone recent evolution through both genome decay (pseudogenization) and genome expansion (horizontal gene transfer and mobile element amplification). Despite evidence of dramatic genomic changes, the six strains are genetically monomorphic, suggesting a recent population bottleneck and emergence into E. tracheiphila’s current ecological niche. PMID:26992913

Current strategies for mobilome research.

PubMed

Jørgensen, Tue S; Kiil, Anne S; Hansen, Martin A; Sørensen, Søren J; Hansen, Lars H

2014-01-01

Mobile genetic elements (MGEs) are pivotal for bacterial evolution and adaptation, allowing shuffling of genes even between distantly related bacterial species. The study of these elements is biologically interesting as the mode of genetic propagation is kaleidoscopic and important, as MGEs are the main vehicles of the increasing bacterial antibiotic resistance that causes thousands of human deaths each year. The study of MGEs has previously focused on plasmids from individual isolates, but the revolution in sequencing technology has allowed the study of mobile genomic elements of entire communities using metagenomic approaches. The problem in using metagenomic sequencing for the study of MGEs is that plasmids and other mobile elements only comprise a small fraction of the total genetic content that are difficult to separate from chromosomal DNA based on sequence alone. The distinction between plasmid and chromosome is important as the mobility and regulation of genes largely depend on their genetic context. Several different approaches have been proposed that specifically enrich plasmid DNA from community samples. Here, we review recent approaches used to study entire plasmid pools from complex environments, and point out possible future developments for and pitfalls of these approaches. Further, we discuss the use of the PacBio long-read sequencing technology for MGE discovery.

Enhanced production of recombinant proteins with Corynebacterium glutamicum by deletion of insertion sequences (IS elements).

PubMed

Choi, Jae Woong; Yim, Sung Sun; Kim, Min Jeong; Jeong, Ki Jun

2015-12-29

In most bacteria, various jumping genetic elements including insertion sequences elements (IS elements) cause a variety of genetic rearrangements resulting in harmful effects such as genome and recombinant plasmid instability. The genetic stability of a plasmid in a host is critical for high-level production of recombinant proteins, and in this regard, the development of an IS element-free strain could be a useful strategy for the enhanced production of recombinant proteins. Corynebacterium glutamicum, which is a workhorse in the industrial-scale production of various biomolecules including recombinant proteins, also has several IS elements, and it is necessary to identify the critical IS elements and to develop IS element deleted strain. From the cultivation of C. glutamicum harboring a plasmid for green fluorescent protein (GFP) gene expression, non-fluorescent clones were isolated by FACS (fluorescent activated cell sorting). All the isolated clones had insertions of IS elements in the GFP coding region, and two major IS elements (ISCg1 and ISCg2 families) were identified. By co-cultivating cells harboring either the isolated IS element-inserted plasmid or intact plasmid, it was clearly confirmed that cells harboring the IS element-inserted plasmids became dominant during the cultivation due to their growth advantage over cells containing intact plasmids, which can cause a significant reduction in recombinant protein production during cultivation. To minimize the harmful effects of IS elements on the expression of heterologous genes in C. glutamicum, two IS element free C. glutamicum strains were developed in which each major IS element was deleted, and enhanced productivity in the engineered C. glutamicum strain was successfully demonstrated with three models: GFP, poly(3-hydroxybutyrate) [P(3HB)] and γ-aminobutyrate (GABA). Our findings clearly indicate that the hopping of IS elements could be detrimental to the production of recombinant proteins in C. glutamicum, emphasizing the importance of developing IS element free host strains.

Emerging Importance of Helicases in Plant Stress Tolerance: Characterization of Oryza sativa Repair Helicase XPB2 Promoter and Its Functional Validation in Tobacco under Multiple Stresses

PubMed Central

Raikwar, Shailendra; Srivastava, Vineet K.; Gill, Sarvajeet S.; Tuteja, Renu; Tuteja, Narendra

2015-01-01

Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. Helicases, the unique molecular motors, are emerged as prospective molecules to engineer stress tolerance in plants and are involved in nucleic acid metabolism including DNA repair. The repair helicase, XPB is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress conditions. Here, we report the in silico analysis of novel stress inducible promoter of Oryza sativa XPB2 (OsXPB2). The in vivo validation of functionality/activity of OsXPB2 promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. The present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration, or cold) and hormone (Auxin, ABA, or MeJA) induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA, or ABA responsive, respectively. Functional analysis was done by Agrobacterium-mediated transient assay using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present findings suggest that OsXPB2 promoter is a multi-stress inducible promoter and has potential applications in sustainable crop production under abiotic stresses by regulating desirable pattern of gene expression. PMID:26734018

Complete Sequencing of pNDM-HK Encoding NDM-1 Carbapenemase from a Multidrug-Resistant Escherichia coli Strain Isolated in Hong Kong

PubMed Central

Ho, Pak Leung; Lo, Wai U.; Yeung, Man Kiu; Lin, Chi Ho; Chow, Kin Hung; Ang, Irene; Tong, Amy Hin Yan; Bao, Jessie Yun-Juan; Lok, Si; Lo, Janice Yee Chi

2011-01-01

Background The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited. Methodology We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced. Principal Findings The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla TEM-1, bla NDM-1, Δbla DHA-1), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively. Significance The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa. PMID:21445317

Spread of ISCR1 Elements Containing blaDHA-1 and Multiple Antimicrobial Resistance Genes Leading to Increase of Flomoxef Resistance in Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae▿

PubMed Central

Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

2011-01-01

Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6′)-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6′)-Ib-cr, armA, and blaDHA-1 were all identified on these self-transferable blaCTX-M-carrying plasmids. The genetic environments of ISCR1 associated with armA, blaDHA-1, and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study. PMID:21746945

Emerging Importance of Helicases in Plant Stress Tolerance: Characterization of Oryza sativa Repair Helicase XPB2 Promoter and Its Functional Validation in Tobacco under Multiple Stresses.

PubMed

Raikwar, Shailendra; Srivastava, Vineet K; Gill, Sarvajeet S; Tuteja, Renu; Tuteja, Narendra

2015-01-01

Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. Helicases, the unique molecular motors, are emerged as prospective molecules to engineer stress tolerance in plants and are involved in nucleic acid metabolism including DNA repair. The repair helicase, XPB is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress conditions. Here, we report the in silico analysis of novel stress inducible promoter of Oryza sativa XPB2 (OsXPB2). The in vivo validation of functionality/activity of OsXPB2 promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. The present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration, or cold) and hormone (Auxin, ABA, or MeJA) induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA, or ABA responsive, respectively. Functional analysis was done by Agrobacterium-mediated transient assay using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present findings suggest that OsXPB2 promoter is a multi-stress inducible promoter and has potential applications in sustainable crop production under abiotic stresses by regulating desirable pattern of gene expression.

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila.

PubMed

Chen, Chun-Hong; Huang, Haixia; Ward, Catherine M; Su, Jessica T; Schaeffer, Lorian V; Guo, Ming; Hay, Bruce A

2007-04-27

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies

PubMed Central

Liu, Zhonghua; Lin, Xihong

2017-01-01

Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391

Multiple phenotype association tests using summary statistics in genome-wide association studies.

PubMed

Liu, Zhonghua; Lin, Xihong

2018-03-01

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.

Genetics Home Reference: multiple epiphyseal dysplasia

MedlinePlus

... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study. BMC Musculoskelet ...

Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants.

PubMed

Pierce, Brandon L; Ahsan, Habibul; Vanderweele, Tyler J

2011-06-01

Mendelian Randomization (MR) studies assess the causality of an exposure-disease association using genetic determinants [i.e. instrumental variables (IVs)] of the exposure. Power and IV strength requirements for MR studies using multiple genetic variants have not been explored. We simulated cohort data sets consisting of a normally distributed disease trait, a normally distributed exposure, which affects this trait and a biallelic genetic variant that affects the exposure. We estimated power to detect an effect of exposure on disease for varying allele frequencies, effect sizes and samples sizes (using two-stage least squares regression on 10,000 data sets-Stage 1 is a regression of exposure on the variant. Stage 2 is a regression of disease on the fitted exposure). Similar analyses were conducted using multiple genetic variants (5, 10, 20) as independent or combined IVs. We assessed IV strength using the first-stage F statistic. Simulations of realistic scenarios indicate that MR studies will require large (n > 1000), often very large (n > 10,000), sample sizes. In many cases, so-called 'weak IV' problems arise when using multiple variants as independent IVs (even with as few as five), resulting in biased effect estimates. Combining genetic factors into fewer IVs results in modest power decreases, but alleviates weak IV problems. Ideal methods for combining genetic factors depend upon knowledge of the genetic architecture underlying the exposure. The feasibility of well-powered, unbiased MR studies will depend upon the amount of variance in the exposure that can be explained by known genetic factors and the 'strength' of the IV set derived from these genetic factors.

Multiple intensity distributions from a single optical element

NASA Astrophysics Data System (ADS)

Berens, Michael; Bruneton, Adrien; Bäuerle, Axel; Traub, Martin; Wester, Rolf; Stollenwerk, Jochen; Loosen, Peter

2013-09-01

We report on an extension of the previously published two-step freeform optics tailoring algorithm using a Monge-Kantorovich mass transportation framework. The algorithm's ability to design multiple freeform surfaces allows for the inclusion of multiple distinct light paths and hence the implementation of multiple lighting functions in a single optical element. We demonstrate the procedure in the context of automotive lighting, in which a fog lamp and a daytime running lamp are integrated in a single optical element illuminated by two distinct groups of LEDs.

Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

PubMed

Segal, N L; Feng, R; McGuire, S A; Allison, D B; Miller, S

2009-01-01

Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. Both non-additive genetic and common environmental contributions were significant in our model (P-values<0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8-75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8-37.5%) by a common environmental component and the remaining 10.7% by an unshared component. Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

ABI-like transcription factor gene TaABL1 from wheat improves multiple abiotic stress tolerances in transgenic plants.

PubMed

Xu, Dong-Bei; Gao, Shi-Qing; Ma, You-Zhi; Xu, Zhao-Shi; Zhao, Chang-Ping; Tang, Yi-Miao; Li, Xue-Yin; Li, Lian-Cheng; Chen, Yao-Feng; Chen, Ming

2014-12-01

The phytohormone abscisic acid (ABA) plays crucial roles in adaptive responses of plants to abiotic stresses. ABA-responsive element binding proteins (AREBs) are basic leucine zipper transcription factors that regulate the expression of downstream genes containing ABA-responsive elements (ABREs) in promoter regions. A novel ABI-like (ABA-insensitive) transcription factor gene, named TaABL1, containing a conserved basic leucine zipper (bZIP) domain was cloned from wheat. Southern blotting showed that three copies were present in the wheat genome. Phylogenetic analyses indicated that TaABL1 belonged to the AREB subfamily of the bZIP transcription factor family and was most closely related to ZmABI5 in maize and OsAREB2 in rice. Expression of TaABL1 was highly induced in wheat roots, stems, and leaves by ABA, drought, high salt, and low temperature stresses. TaABL1 was localized inside the nuclei of transformed wheat mesophyll protoplast. Overexpression of TaABL1 enhanced responses of transgenic plants to ABA and hastened stomatal closure under stress, thereby improving tolerance to multiple abiotic stresses. Furthermore, overexpression of TaABL1 upregulated or downregulated the expression of some stress-related genes controlling stomatal closure in transgenic plants under ABA and drought stress conditions, suggesting that TaABL1 might be a valuable genetic resource for transgenic molecular breeding.

Genetic programming applied to RFI mitigation in radio astronomy

NASA Astrophysics Data System (ADS)

Staats, K.

2016-12-01

Genetic Programming is a type of machine learning that employs a stochastic search of a solutions space, genetic operators, a fitness function, and multiple generations of evolved programs to resolve a user-defined task, such as the classification of data. At the time of this research, the application of machine learning to radio astronomy was relatively new, with a limited number of publications on the subject. Genetic Programming had never been applied, and as such, was a novel approach to this challenging arena. Foundational to this body of research, the application Karoo GP was developed in the programming language Python following the fundamentals of tree-based Genetic Programming described in "A Field Guide to Genetic Programming" by Poli, et al. Karoo GP was tasked with the classification of data points as signal or radio frequency interference (RFI) generated by instruments and machinery which makes challenging astronomers' ability to discern the desired targets. The training data was derived from the output of an observation run of the KAT-7 radio telescope array built by the South African Square Kilometre Array (SKA-SA). Karoo GP, kNN, and SVM were comparatively employed, the outcome of which provided noteworthy correlations between input parameters, the complexity of the evolved hypotheses, and performance of raw data versus engineered features. This dissertation includes description of novel approaches to GP, such as upper and lower limits to the size of syntax trees, an auto-scaling multiclass classifier, and a Numpy array element manager. In addition to the research conducted at the SKA-SA, it is described how Karoo GP was applied to fine-tuning parameters of a weather prediction model at the South African Astronomical Observatory (SAAO), to glitch classification at the Laser Interferometer Gravitational-wave Observatory (LIGO), and to astro-particle physics at The Ohio State University.

Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis.

PubMed

van der Els, Simon; James, Jennelle K; Kleerebezem, Michiel; Bron, Peter A

2018-04-15

CRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy species Lactococcus lactis The Cas9 expression vector pLABTarget, encoding the Streptocccus pyogenes Cas9 under the control of a constitutive promoter, was constructed, allowing plug and play introduction of short guide RNA (sgRNA) sequences to target specific genetic loci. Introduction of a pepN -targeting derivative of pLABTarget into L. lactis strain MG1363 led to a strong reduction in the number of transformants obtained, which did not occur in a pepN deletion derivative of the same strain, demonstrating the specificity and lethality of the Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the same pLABTarget derivative allowed the selection of a pepN deletion subpopulation from its corresponding single-crossover plasmid integrant precursor, accelerating the construction and selection of gene-specific deletion derivatives in L. lactis Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic elements, allowed the effective curing of plasmids, prophages, and integrative conjugative elements (ICEs). These results establish that pLABTarget enables the effective exploitation of Cas9 targeting in L. lactis , while the broad-host-range vector used suggests that this toolbox could readily be expanded to other Gram-positive bacteria. IMPORTANCE Mobile genetic elements in Lactococcus lactis and other lactic acid bacteria (LAB) play an important role in dairy fermentation, having both positive and detrimental effects during the production of fermented dairy products. The pLABTarget vector offers an efficient cloning platform for Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic elements enabled their effective curing, which is of particular interest in the context of potentially problematic prophages present in a strain. Moreover, Cas9 targeting of other mobile genetic elements enables the deciphering of their contribution to dairy fermentation processes and further establishment of their importance for product characteristics. Copyright © 2018 American Society for Microbiology.

Genetic diversity promotes homeostasis in insect colonies.

PubMed

Oldroyd, Benjamin P; Fewell, Jennifer H

2007-08-01

Although most insect colonies are headed by a singly mated queen, some ant, wasp and bee taxa have evolved high levels of multiple mating or 'polyandry'. We argue here that a contributing factor towards the evolution of polyandry is that the resulting genetic diversity within colonies provides them with a system of genetically based task specialization, enabling them to respond resiliently to environmental perturbation. An alternate view is that genetic contributions to task specialization are a side effect of multiple mating, which evolved through other causes, and that genetically based task specialization now makes little or no contribution to colony fitness.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

PubMed Central

Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

2016-01-01

Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

Macro-environment of breast carcinoma: frequent genetic alterations in the normal appearing skins of patients with breast cancer.

PubMed

Moinfar, Farid; Beham, Alfred; Friedrich, Gerhard; Deutsch, Alexander; Hrzenjak, Andelko; Luschin, Gero; Tavassoli, Fattaneh A

2008-05-01

Genetic abnormalities in microenvironmental tissues with subsequent alterations of reciprocal interactions between epithelial and mesenchymal cells play a key role in the breast carcinogenesis. Although a few reports have demonstrated abnormal fibroblastic functions in normal-appearing fibroblasts taken from the skins of breast cancer patients, the genetic basis of this phenomenon and its implication for carcinogenesis are unexplored. We analyzed 12 mastectomy specimens showing invasive ductal carcinomas. In each case, morphologically normal epidermis and dermis, carcinoma, normal stroma close to carcinoma, and stroma at a distant from carcinoma were microdissected. Metastatic-free lymphatic tissues from lymph nodes served as a control. Using PCR, DNA extracts were examined with 11 microsatellite markers known for a high frequency of allelic imbalances in breast cancer. Losses of heterozygosity and/or microsatellite instability were detected in 83% of the skin samples occurring either concurrently with or independently from the cancerous tissues. In 80% of these cases at least one microsatellite marker displayed loss of heterozygosity or microsatellite instability in the skin, which was absent in carcinoma. A total of 41% of samples showed alterations of certain loci observed exclusively in the carcinoma but not in the skin compartments. Our study suggests that breast cancer is not just a localized genetic disorder, but rather part of a larger field of genetic alterations/instabilities affecting multiple cell populations in the organ with various cellular elements, ultimately contributing to the manifestation of the more 'localized' carcinoma. These data indicate that more global assessment of tumor micro- and macro-environment is crucial for our understanding of breast carcinogenesis.

Identification of rare and novel deletions that cause (δβ)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population.

PubMed

Mayuranathan, Thiyagaraj; Rayabaram, Janakiram; Das, Reena; Arora, Neeraj; Edison, Eunice S; Chandy, Mammen; Srivastava, Alok; Velayudhan, Shaji R

2014-06-01

Hereditary persistence of foetal haemoglobin (HPFH) and (δβ)(0) -thalassaemia are conditions caused by large deletions that involve δ- and β-globin genes in the β-globin cluster, and they are characterized by increased haemoglobin (HbF) levels in adults. Significant phenotypic diversity is observed between the different mutations that cause these conditions. Molecular characterization of these deletions is important for accurate molecular diagnosis, and they will also provide the information on the cis-acting genetic regulatory elements present in the β-globin cluster. We performed gap-PCR, multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescent multiplex PCR (QF-MPCR) and DNA sequencing to detect and characterize the deletions in the β-globin cluster. We characterized six different deletions resulting in (δβ)(0) -thalassaemia or HPFH in 51 unrelated families. With the help of multiple genetic tools, we performed comprehensive genetic analysis of HPFH and (δβ)(0) -thalassaemia in Indian population and could define the molecular basis of these conditions in this population. We also identified two novel HPFH mutations, 49.98 kb (HPFH-9) and 86.7 kb (HPFH-10) deletions, in this population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interaction-based evolution: how natural selection and nonrandom mutation work together

PubMed Central

2013-01-01

Background The modern evolutionary synthesis leaves unresolved some of the most fundamental, long-standing questions in evolutionary biology: What is the role of sex in evolution? How does complex adaptation evolve? How can selection operate effectively on genetic interactions? More recently, the molecular biology and genomics revolutions have raised a host of critical new questions, through empirical findings that the modern synthesis fails to explain: for example, the discovery of de novo genes; the immense constructive role of transposable elements in evolution; genetic variance and biochemical activity that go far beyond what traditional natural selection can maintain; perplexing cases of molecular parallelism; and more. Presentation of the hypothesis Here I address these questions from a unified perspective, by means of a new mechanistic view of evolution that offers a novel connection between selection on the phenotype and genetic evolutionary change (while relying, like the traditional theory, on natural selection as the only source of feedback on the fit between an organism and its environment). I hypothesize that the mutation that is of relevance for the evolution of complex adaptation—while not Lamarckian, or “directed” to increase fitness—is not random, but is instead the outcome of a complex and continually evolving biological process that combines information from multiple loci into one. This allows selection on a fleeting combination of interacting alleles at different loci to have a hereditary effect according to the combination’s fitness. Testing and implications of the hypothesis This proposed mechanism addresses the problem of how beneficial genetic interactions can evolve under selection, and also offers an intuitive explanation for the role of sex in evolution, which focuses on sex as the generator of genetic combinations. Importantly, it also implies that genetic variation that has appeared neutral through the lens of traditional theory can actually experience selection on interactions and thus has a much greater adaptive potential than previously considered. Empirical evidence for the proposed mechanism from both molecular evolution and evolution at the organismal level is discussed, and multiple predictions are offered by which it may be tested. Reviewers This article was reviewed by Nigel Goldenfeld (nominated by Eugene V. Koonin), Jürgen Brosius and W. Ford Doolittle. PMID:24139515

Multiple introductions boosted genetic diversity in the invasive range of black cherry (Prunus serotina; Rosaceae)

PubMed Central

Pairon, Marie; Petitpierre, Blaise; Campbell, Michael; Guisan, Antoine; Broennimann, Olivier; Baret, Philippe V.; Jacquemart, Anne-Laure; Besnard, Guillaume

2010-01-01

Background and Aims Black cherry (Prunus serotina) is a North American tree that is rapidly invading European forests. This species was introduced first as an ornamental plant then it was massively planted by foresters in many countries but its origins and the process of invasion remain poorly documented. Based on a genetic survey of both native and invasive ranges, the invasion history of black cherry was investigated by identifying putative source populations and then assessing the importance of multiple introductions on the maintenance of gene diversity. Methods Genetic variability and structure of 23 populations from the invasive range and 22 populations from the native range were analysed using eight nuclear microsatellite loci and five chloroplast DNA regions. Key Results Chloroplast DNA diversity suggests there were multiple introductions from a single geographic region (the north-eastern United States). A low reduction of genetic diversity was observed in the invasive range for both nuclear and plastid genomes. High propagule pressure including both the size and number of introductions shaped the genetic structure in Europe and boosted genetic diversity. Populations from Denmark, The Netherlands, Belgium and Germany showed high genetic diversity and low differentiation among populations, supporting the hypothesis that numerous introduction events, including multiple individuals and exchanges between sites, have taken place during two centuries of plantation. Conclusions This study postulates that the invasive black cherry has originated from east of the Appalachian Mountains (mainly the Allegheny plateau) and its invasiveness in north-western Europe is mainly due to multiple introductions containing high numbers of individuals. PMID:20400456

[Application of genetic algorithm in blending technology for extractions of Cortex Fraxini].

PubMed

Yang, Ming; Zhou, Yinmin; Chen, Jialei; Yu, Minying; Shi, Xiufeng; Gu, Xijun

2009-10-01

To explore the feasibility of genetic algorithm (GA) on multiple objective blending technology for extractions of Cortex Fraxini. According to that the optimization objective was the combination of fingerprint similarity and the root-mean-square error of multiple key constituents, a new multiple objective optimization model of 10 batches extractions of Cortex Fraxini was built. The blending coefficient was obtained by genetic algorithm. The quality of 10 batches extractions of Cortex Fraxini that after blending was evaluated with the finger print similarity and root-mean-square error as indexes. The quality of 10 batches extractions of Cortex Fraxini that after blending was well improved. Comparing with the fingerprint of the control sample, the similarity was up, but the degree of variation is down. The relative deviation of the key constituents was less than 10%. It is proved that genetic algorithm works well on multiple objective blending technology for extractions of Cortex Fraxini. This method can be a reference to control the quality of extractions of Cortex Fraxini. Genetic algorithm in blending technology for extractions of Chinese medicines is advisable.

Achondroplasia and multiple-suture craniosynostosis.

PubMed

Albino, Frank P; Wood, Benjamin C; Oluigbo, Chima O; Lee, Angela C; Oh, Albert K; Rogers, Gary F

2015-01-01

Genetic mutations in the fibroblast growth factor receptor 3 gene may lead to achondroplasia or syndromic forms of craniosynostosis. Despite sharing a common genetic basis, craniosynostosis has rarely been described in cases of confirmed achondroplasia. We report an infant with achondroplasia who developed progressive multiple-suture craniosynostosis to discuss the genetic link between these clinical entities and to describe the technical challenges associated with the operative management.

Multi-physics optimization of three-dimensional microvascular polymeric components

NASA Astrophysics Data System (ADS)

Aragón, Alejandro M.; Saksena, Rajat; Kozola, Brian D.; Geubelle, Philippe H.; Christensen, Kenneth T.; White, Scott R.

2013-01-01

This work discusses the computational design of microvascular polymeric materials, which aim at mimicking the behavior found in some living organisms that contain a vascular system. The optimization of the topology of the embedded three-dimensional microvascular network is carried out by coupling a multi-objective constrained genetic algorithm with a finite-element based physics solver, the latter validated through experiments. The optimization is carried out on multiple conflicting objective functions, namely the void volume fraction left by the network, the energy required to drive the fluid through the network and the maximum temperature when the material is subjected to thermal loads. The methodology presented in this work results in a viable alternative for the multi-physics optimization of these materials for active-cooling applications.

Evaluating the mush extraction + multiple magma batch model for the Lake City magmatic system (Colorado, USA) using zircon U/Pb TIMS-TEA

NASA Astrophysics Data System (ADS)

Pamukcu, A. S.; Schoene, B.; Deering, C. D.

2016-12-01

Volcanic eruptions that involve a wide range of magma types highlight questions on genetic and geometric relationships between magmas in the crust prior to eruption. The Lake City magmatic system (Colorado, USA) is one such example: exposed in the caldera are ignimbrites from the 23 Ma Sunshine Peak Tuff, which range in composition and crystallinity with time (crystal-poor rhyolite to crystal-rich trachyte), and resurgent intrusions of porphyritic syenite, monzonite, and dacite (Hon 1987). Field relations and bulk rock geochemistry suggest the Lake City magmatic system was complex, with magmas of these various types existing concurrently as multiple magma batches, though not necessarily always in contact (Kennedy et al. 2015). Geochemical modeling further suggests that the crystal-poor rhyolites were liquids extracted from a syenitic mush and that the crystal-rich trachytes are remobilized portions of this cumulate. To address the genetic and geometric links between these magmas in more detail, we utilize TIMS-TEA to assess U/Pb zircon geochronology and trace element geochemistry in concert. For each eruptive unit/magma type, zircons were roughly separated into size groupings (small, medium, large), imaged by cathodoluminescence (CL), and analyzed individually by CA-ID-TIMS. Preliminary results indicate that zircons crystallized over a period of 177±31 ky, which is within the range suggested by Ar/Ar geochronology (80-300 ky, Bove et al. 2001). Consistent with the current model for the Lake City system, zircons from the rhyolites and trachytes overlap in age, while those of the dacites are younger. There is no clear relationship between age and CL zoning pattern or crystal size (e.g., small crystals are not always the youngest). We can further address relationships between the rhyolite, trachyte, and syenite using TEA to assess trace elements of the dated zircons. Rhyolite-MELTS models suggest that zircons crystallized in a rhyolitic melt derived from the trachyte/syenite will have similar LREEs and MREEs but higher HREEs than those that crystallized in the mush. In addition, if the trachytes are remobilized cumulates that are represented by the post-caldera syenites, we expect that trace element contents of zircon from these units will be largely similar.

The impact of transposable elements on mammalian development

PubMed Central

Garcia-Perez, Jose L.; Widmann, Thomas J.; Adams, Ian R.

2018-01-01

Summary Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that significantly impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and how the somatic activity of TEs can influence gene regulatory networks. PMID:27875251

A genomic island integrated into recA of Vibrio cholerae contains a divergent recA and provides multi-pathway protection from DNA damage.

PubMed

Rapa, Rita A; Islam, Atiqul; Monahan, Leigh G; Mutreja, Ankur; Thomson, Nicholas; Charles, Ian G; Stokes, Harold W; Labbate, Maurizio

2015-04-01

Lateral gene transfer (LGT) has been crucial in the evolution of the cholera pathogen, Vibrio cholerae. The two major virulence factors are present on two different mobile genetic elements, a bacteriophage containing the cholera toxin genes and a genomic island (GI) containing the intestinal adhesin genes. Non-toxigenic V. cholerae in the aquatic environment are a major source of novel DNA that allows the pathogen to morph via LGT. In this study, we report a novel GI from a non-toxigenic V. cholerae strain containing multiple genes involved in DNA repair including the recombination repair gene recA that is 23% divergent from the indigenous recA and genes involved in the translesion synthesis pathway. This is the first report of a GI containing the critical gene recA and the first report of a GI that targets insertion into a specific site within recA. We show that possession of the island in Escherichia coli is protective against DNA damage induced by UV-irradiation and DNA targeting antibiotics. This study highlights the importance of genetic elements such as GIs in the evolution of V. cholerae and emphasizes the importance of environmental strains as a source of novel DNA that can influence the pathogenicity of toxigenic strains. © 2014 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Extensive epistasis for olfactory behaviour, sleep and waking activity in Drosophila melanogaster.

PubMed

Swarup, Shilpa; Harbison, Susan T; Hahn, Lauren E; Morozova, Tatiana V; Yamamoto, Akihiko; Mackay, Trudy F C; Anholt, Robert R H

2012-02-01

Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insertions in Semaphorin-5C (Sema-5c) and Calreticulin (Crc), pleiotropic genes that affect olfactory behaviour and startle behaviour and, in the case of Crc, sleep phenotypes. We introduced Canton-S B (CSB) third chromosomes with or without a P-element insertion at the Crc or Sema-5c locus in multiple wild-derived inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and assessed the effects of epistasis on the olfactory response to benzaldehyde and, for Crc, also on sleep. In each case, we found substantial epistasis and significant variation in the magnitude of epistasis. The predominant direction of epistatic effects was to suppress the mutant phenotype. These observations support a previous study on startle behaviour using the same D. melanogaster chromosome substitution lines, which concluded that suppressing epistasis may buffer the effects of new mutations. However, epistatic effects are not correlated among the different phenotypes. Thus, suppressing epistasis appears to be a pervasive general feature of natural populations to protect against the effects of new mutations, but different epistatic interactions modulate different phenotypes affected by mutations at the same pleiotropic gene.

System and method for image registration of multiple video streams

DOEpatents

Dillavou, Marcus W.; Shum, Phillip Corey; Guthrie, Baron L.; Shenai, Mahesh B.; Deaton, Drew Steven; May, Matthew Benton

2018-02-06

Provided herein are methods and systems for image registration from multiple sources. A method for image registration includes rendering a common field of interest that reflects a presence of a plurality of elements, wherein at least one of the elements is a remote element located remotely from another of the elements and updating the common field of interest such that the presence of the at least one of the elements is registered relative to another of the elements.

The MAX Statistic is Less Powerful for Genome Wide Association Studies Under Most Alternative Hypotheses.

PubMed

Shifflett, Benjamin; Huang, Rong; Edland, Steven D

2017-01-01

Genotypic association studies are prone to inflated type I error rates if multiple hypothesis testing is performed, e.g., sequentially testing for recessive, multiplicative, and dominant risk. Alternatives to multiple hypothesis testing include the model independent genotypic χ 2 test, the efficiency robust MAX statistic, which corrects for multiple comparisons but with some loss of power, or a single Armitage test for multiplicative trend, which has optimal power when the multiplicative model holds but with some loss of power when dominant or recessive models underlie the genetic association. We used Monte Carlo simulations to describe the relative performance of these three approaches under a range of scenarios. All three approaches maintained their nominal type I error rates. The genotypic χ 2 and MAX statistics were more powerful when testing a strictly recessive genetic effect or when testing a dominant effect when the allele frequency was high. The Armitage test for multiplicative trend was most powerful for the broad range of scenarios where heterozygote risk is intermediate between recessive and dominant risk. Moreover, all tests had limited power to detect recessive genetic risk unless the sample size was large, and conversely all tests were relatively well powered to detect dominant risk. Taken together, these results suggest the general utility of the multiplicative trend test when the underlying genetic model is unknown.

Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence

PubMed Central

Bao, Yun-Juan; Liang, Zhong; Mayfield, Jeffrey A.; McShan, William M.; Lee, Shaun W.; Ploplis, Victoria A.; Castellino, Francis J.

2016-01-01

Symmetric genomic rearrangements around replication axes in genomes are commonly observed in prokaryotic genomes, including Group A Streptococcus (GAS). However, asymmetric rearrangements are rare. Our previous studies showed that the hypervirulent invasive GAS strain, M23ND, containing an inactivated transcriptional regulator system, covRS, exhibits unique extensive asymmetric rearrangements, which reconstructed a genomic structure distinct from other GAS genomes. In the current investigation, we identified the rearrangement events and examined the genetic consequences and evolutionary implications underlying the rearrangements. By comparison with a close phylogenetic relative, M18-MGAS8232, we propose a molecular model wherein a series of asymmetric rearrangements have occurred in M23ND, involving translocations, inversions and integrations mediated by multiple factors, viz., rRNA-comX (factor for late competence), transposons and phage-encoded gene segments. Assessments of the cumulative gene orientations and GC skews reveal that the asymmetric genomic rearrangements did not affect the general genomic integrity of the organism. However, functional distributions reveal re-clustering of a broad set of CovRS-regulated actively transcribed genes, including virulence factors and metabolic genes, to the same leading strand, with high confidence (p-value ~10−10). The re-clustering of the genes suggests a potential selection advantage for the spatial proximity to the transcription complexes, which may contain the global transcriptional regulator, CovRS, and other RNA polymerases. Their proximities allow for efficient transcription of the genes required for growth, virulence and persistence. A new paradigm of survival strategies of GAS strains is provided through multiple genomic rearrangements, while, at the same time, maintaining genomic integrity. PMID:27329479

Detecting disease-predisposing variants: the haplotype method.

PubMed Central

Valdes, A M; Thomson, G

1997-01-01

For many HLA-associated diseases, multiple alleles-- and, in some cases, multiple loci--have been suggested as the causative agents. The haplotype method for identifying disease-predisposing amino acids in a genetic region is a stratification analysis. We show that, for each haplotype combination containing all the amino acid sites involved in the disease process, the relative frequencies of amino acid variants at sites not involved in disease but in linkage disequilibrium with the disease-predisposing sites are expected to be the same in patients and controls. The haplotype method is robust to mode of inheritance and penetrance of the disease and can be used to determine unequivocally whether all amino acid sites involved in the disease have not been identified. Using a resampling technique, we developed a statistical test that takes account of the nonindependence of the sites sampled. Further, when multiple sites in the genetic region are involved in disease, the test statistic gives a closer fit to the null expectation when some--compared with none--of the true predisposing factors are included in the haplotype analysis. Although the haplotype method cannot distinguish between very highly correlated sites in one population, ethnic comparisons may help identify the true predisposing factors. The haplotype method was applied to insulin-dependent diabetes mellitus (IDDM) HLA class II DQA1-DQB1 data from Caucasian, African, and Japanese populations. Our results indicate that the combination DQA1#52 (Arg predisposing) DQB1#57 (Asp protective), which has been proposed as an important IDDM agent, does not include all the predisposing elements. With rheumatoid arthritis HLA class II DRB1 data, the results were consistent with the shared-epitope hypothesis. PMID:9042931

Gene drive systems for insect disease vectors.

PubMed

Sinkins, Steven P; Gould, Fred

2006-06-01

The elegant mechanisms by which naturally occurring selfish genetic elements, such as transposable elements, meiotic drive genes, homing endonuclease genes and Wolbachia, spread at the expense of their hosts provide some of the most fascinating and remarkable subjects in evolutionary genetics. These elements also have enormous untapped potential to be used in the control of some of the world's most devastating diseases. Effective gene drive systems for spreading genes that can block the transmission of insect-borne pathogens are much needed. Here we explore the potential of natural gene drive systems and discuss the artificial constructs that could be envisaged for this purpose.

Detecting authorized and unauthorized genetically modified organisms containing vip3A by real-time PCR and next-generation sequencing.

PubMed

Liang, Chanjuan; van Dijk, Jeroen P; Scholtens, Ingrid M J; Staats, Martijn; Prins, Theo W; Voorhuijzen, Marleen M; da Silva, Andrea M; Arisi, Ana Carolina Maisonnave; den Dunnen, Johan T; Kok, Esther J

2014-04-01

The growing number of biotech crops with novel genetic elements increasingly complicates the detection of genetically modified organisms (GMOs) in food and feed samples using conventional screening methods. Unauthorized GMOs (UGMOs) in food and feed are currently identified through combining GMO element screening with sequencing the DNA flanking these elements. In this study, a specific and sensitive qPCR assay was developed for vip3A element detection based on the vip3Aa20 coding sequences of the recently marketed MIR162 maize and COT102 cotton. Furthermore, SiteFinding-PCR in combination with Sanger, Illumina or Pacific BioSciences (PacBio) sequencing was performed targeting the flanking DNA of the vip3Aa20 element in MIR162. De novo assembly and Basic Local Alignment Search Tool searches were used to mimic UGMO identification. PacBio data resulted in relatively long contigs in the upstream (1,326 nucleotides (nt); 95 % identity) and downstream (1,135 nt; 92 % identity) regions, whereas Illumina data resulted in two smaller contigs of 858 and 1,038 nt with higher sequence identity (>99 % identity). Both approaches outperformed Sanger sequencing, underlining the potential for next-generation sequencing in UGMO identification.

Proteomics technique opens new frontiers in mobilome research.

PubMed

Davidson, Andrew D; Matthews, David A; Maringer, Kevin

2017-01-01

A large proportion of the genome of most eukaryotic organisms consists of highly repetitive mobile genetic elements. The sum of these elements is called the "mobilome," which in eukaryotes is made up mostly of transposons. Transposable elements contribute to disease, evolution, and normal physiology by mediating genetic rearrangement, and through the "domestication" of transposon proteins for cellular functions. Although 'omics studies of mobilome genomes and transcriptomes are common, technical challenges have hampered high-throughput global proteomics analyses of transposons. In a recent paper, we overcame these technical hurdles using a technique called "proteomics informed by transcriptomics" (PIT), and thus published the first unbiased global mobilome-derived proteome for any organism (using cell lines derived from the mosquito Aedes aegypti ). In this commentary, we describe our methods in more detail, and summarise our major findings. We also use new genome sequencing data to show that, in many cases, the specific genomic element expressing a given protein can be identified using PIT. This proteomic technique therefore represents an important technological advance that will open new avenues of research into the role that proteins derived from transposons and other repetitive and sequence diverse genetic elements, such as endogenous retroviruses, play in health and disease.

Characterization of noncoding regulatory DNA in the human genome.

PubMed

Elkon, Ran; Agami, Reuven

2017-08-08

Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria.

PubMed

El Salabi, Allaaeddin; Walsh, Timothey R; Chouchani, Chedly

2013-05-01

Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.

Current strategies for mobilome research

PubMed Central

Jørgensen, Tue S.; Kiil, Anne S.; Hansen, Martin A.; Sørensen, Søren J.; Hansen, Lars H.

2015-01-01

Mobile genetic elements (MGEs) are pivotal for bacterial evolution and adaptation, allowing shuffling of genes even between distantly related bacterial species. The study of these elements is biologically interesting as the mode of genetic propagation is kaleidoscopic and important, as MGEs are the main vehicles of the increasing bacterial antibiotic resistance that causes thousands of human deaths each year. The study of MGEs has previously focused on plasmids from individual isolates, but the revolution in sequencing technology has allowed the study of mobile genomic elements of entire communities using metagenomic approaches. The problem in using metagenomic sequencing for the study of MGEs is that plasmids and other mobile elements only comprise a small fraction of the total genetic content that are difficult to separate from chromosomal DNA based on sequence alone. The distinction between plasmid and chromosome is important as the mobility and regulation of genes largely depend on their genetic context. Several different approaches have been proposed that specifically enrich plasmid DNA from community samples. Here, we review recent approaches used to study entire plasmid pools from complex environments, and point out possible future developments for and pitfalls of these approaches. Further, we discuss the use of the PacBio long-read sequencing technology for MGE discovery. PMID:25657641

Clinical exome sequencing reports: current informatics practice and future opportunities.

PubMed

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine; Cole, Justin; Bartlett, Christopher; Lin, Simon

2017-11-01

The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments-certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetics and the investigation of developmental delay/intellectual disability.

PubMed

Srour, Myriam; Shevell, Michael

2014-04-01

Global developmental delay and intellectual disabilities are common reasons for diagnostic assessment by paediatricians. There are a multiplicity of possible causes many of which have genetic, management and treatment implications for the child and family. Genetic causes are estimated to be responsible for approximately a quarter to one-half of identified cases. The multiplicity of individually rare genetic causes challenges the practitioner with respect to the selection of diagnostic tests and accurate diagnosis. To assist the practitioner practice guidelines have been formulated and these are reviewed and summarised in this particular article.

A chemical genetic strategy identify the PHOSTIN, a synthetic molecule that triggers phosphate starvation responses in Arabidopsis thaliana.

PubMed

Bonnot, Clémence; Pinson, Benoît; Clément, Mathilde; Bernillon, Stéphane; Chiarenza, Serge; Kanno, Satomi; Kobayashi, Natsuko; Delannoy, Etienne; Nakanishi, Tomoko M; Nussaume, Laurent; Desnos, Thierry

2016-01-01

Plants display numerous strategies to cope with phosphate (Pi)-deficiency. Despite multiple genetic studies, the molecular mechanisms of low-Pi-signalling remain unknown. To validate the interest of chemical genetics to investigate this pathway we discovered and analysed the effects of PHOSTIN (PSN), a drug mimicking Pi-starvation in Arabidopsis. We assessed the effects of PSN and structural analogues on the induction of Pi-deficiency responses in mutants and wild-type and followed their accumulation in plants organs by high pressure liquid chromotography (HPLC) or mass-spectrophotometry. We show that PSN is cleaved in the growth medium, releasing its active motif (PSN11), which accumulates in plants roots. Despite the overaccumulation of Pi in the roots of treated plants, PSN11 elicits both local and systemic Pi-starvation effects. Nevertheless, albeit that the transcriptional activation of low-Pi genes by PSN11 is lost in the phr1;phl1 double mutant, neither PHO1 nor PHO2 are required for PSN11 effects. The range of local and systemic responses to Pi-starvation elicited, and their dependence on the PHR1/PHL1 function suggests that PSN11 affects an important and early step of Pi-starvation signalling. Its independence from PHO1 and PHO2 suggest the existence of unknown pathway(s), showing the usefulness of PSN and chemical genetics to bring new elements to this field. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

IBSEM: An Individual-Based Atlantic Salmon Population Model.

PubMed

Castellani, Marco; Heino, Mikko; Gilbey, John; Araki, Hitoshi; Svåsand, Terje; Glover, Kevin A

2015-01-01

Ecology and genetics can influence the fate of individuals and populations in multiple ways. However, to date, few studies consider them when modelling the evolutionary trajectory of populations faced with admixture with non-local populations. For the Atlantic salmon, a model incorporating these elements is urgently needed because many populations are challenged with gene-flow from non-local and domesticated conspecifics. We developed an Individual-Based Salmon Eco-genetic Model (IBSEM) to simulate the demographic and population genetic change of an Atlantic salmon population through its entire life-cycle. Processes such as growth, mortality, and maturation are simulated through stochastic procedures, which take into account environmental variables as well as the genotype of the individuals. IBSEM is based upon detailed empirical data from salmon biology, and parameterized to reproduce the environmental conditions and the characteristics of a wild population inhabiting a Norwegian river. Simulations demonstrated that the model consistently and reliably reproduces the characteristics of the population. Moreover, in absence of farmed escapees, the modelled populations reach an evolutionary equilibrium that is similar to our definition of a 'wild' genotype. We assessed the sensitivity of the model in the face of assumptions made on the fitness differences between farm and wild salmon, and evaluated the role of straying as a buffering mechanism against the intrusion of farm genes into wild populations. These results demonstrate that IBSEM is able to capture the evolutionary forces shaping the life history of wild salmon and is therefore able to model the response of populations under environmental and genetic stressors.

Genetic evolution and clinical impact in extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

PubMed

Chong, Yong; Ito, Yoshikiyo; Kamimura, Tomohiko

2011-10-01

The emergence of extended-spectrum β-lactamase (ESBL)-producing bacteria, particularly Escherichia coli and Klebsiella pneumoniae, is now a critical concern for the development of therapies against bacterial infection. ESBLs consist of three major genetic groups: TEM, SHV, and CTX-M types. Nosocomial infections due to TEM and SHV-producing K. pneumoniae strains were frequently documented until the late 1990s. The number of reports on community-acquired infections caused by CTX-M-producing E. coli strains have dramatically increased over the last decade; however, K. pneumoniae strains, of either the TEM or SHV types, are persistent and important ESBL producers. The spread of ESBL genes is associated with various mobile genetic elements, such as transposons, insertion sequences, and integrons. The rapid dissemination of ESBL genes of the CTX-M type may be related to highly complicated genetic structures. These structures harboring ESBL genes and mobile elements are found in a variety of plasmids, which often carry many other antibiotic resistance genes. Multidrug-resistant CTX-M-15-producing E. coli strains disseminate worldwide. Efficient mobile elements and plasmids may have accelerated the genetic diversity and the rapid spread of ESBL genes, and their genetic evolution has caused an emerging threat to the bacteria for which few effective drugs have been identified. Copyright © 2011 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ochiai, Yoshihiro

Heat-conduction analysis under steady state without heat generation can easily be treated by the boundary element method. However, in the case with heat conduction with heat generation can approximately be solved without a domain integral by an improved multiple-reciprocity boundary element method. The convention multiple-reciprocity boundary element method is not suitable for complicated heat generation. In the improved multiple-reciprocity boundary element method, on the other hand, the domain integral in each step is divided into point, line, and area integrals. In order to solve the problem, the contour lines of heat generation, which approximate the actual heat generation, are used.

De novo mutations in regulatory elements in neurodevelopmental disorders

PubMed Central

Short, Patrick J.; McRae, Jeremy F.; Gallone, Giuseppe; Sifrim, Alejandro; Won, Hyejung; Geschwind, Daniel H.; Wright, Caroline F.; Firth, Helen V; FitzPatrick, David R.; Barrett, Jeffrey C.; Hurles, Matthew E.

2018-01-01

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders. PMID:29562236

The impact of transposable elements on mammalian development.

PubMed

Garcia-Perez, Jose L; Widmann, Thomas J; Adams, Ian R

2016-11-15

Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that have a significant impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and discuss how the somatic activity of TEs can influence gene regulatory networks. © 2016. Published by The Company of Biologists Ltd.

Adaptive Process Control with Fuzzy Logic and Genetic Algorithms

NASA Technical Reports Server (NTRS)

Karr, C. L.

1993-01-01

Researchers at the U.S. Bureau of Mines have developed adaptive process control systems in which genetic algorithms (GA's) are used to augment fuzzy logic controllers (FLC's). GA's are search algorithms that rapidly locate near-optimum solutions to a wide spectrum of problems by modeling the search procedures of natural genetics. FLC's are rule based systems that efficiently manipulate a problem environment by modeling the 'rule-of-thumb' strategy used in human decision-making. Together, GA's and FLC's possess the capabilities necessary to produce powerful, efficient, and robust adaptive control systems. To perform efficiently, such control systems require a control element to manipulate the problem environment, an analysis element to recognize changes in the problem environment, and a learning element to adjust to the changes in the problem environment. Details of an overall adaptive control system are discussed. A specific laboratory acid-base pH system is used to demonstrate the ideas presented.

Genetic algorithms in adaptive fuzzy control

NASA Technical Reports Server (NTRS)

Karr, C. Lucas; Harper, Tony R.

1992-01-01

Researchers at the U.S. Bureau of Mines have developed adaptive process control systems in which genetic algorithms (GA's) are used to augment fuzzy logic controllers (FLC's). GA's are search algorithms that rapidly locate near-optimum solutions to a wide spectrum of problems by modeling the search procedures of natural genetics. FLC's are rule based systems that efficiently manipulate a problem environment by modeling the 'rule-of-thumb' strategy used in human decision making. Together, GA's and FLC's possess the capabilities necessary to produce powerful, efficient, and robust adaptive control systems. To perform efficiently, such control systems require a control element to manipulate the problem environment, an analysis element to recognize changes in the problem environment, and a learning element to adjust fuzzy membership functions in response to the changes in the problem environment. Details of an overall adaptive control system are discussed. A specific computer-simulated chemical system is used to demonstrate the ideas presented.

The ENCODE project: implications for psychiatric genetics.

PubMed

Kavanagh, D H; Dwyer, S; O'Donovan, M C; Owen, M J

2013-05-01

The ENCyclopedia Of DNA Elements (ENCODE) project is a public research consortium that aims to identify all functional elements of the human genome sequence. The project comprised 1640 data sets, from 147 different cell type and the findings were released in a coordinated set of 34 publications across several journals. The ENCODE publications report that 80.4% of the human genome displays some functionality. These data have important implications for interpreting results from large-scale genetics studies. We reviewed some of the key findings from the ENCODE publications and discuss how they can influence or inform further investigations into the genetic factors contributing to neuropsychiatric disorders.

Selecting Random Distributed Elements for HIFU using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Zhou, Yufeng

2011-09-01

As an effective and noninvasive therapeutic modality for tumor treatment, high-intensity focused ultrasound (HIFU) has attracted attention from both physicians and patients. New generations of HIFU systems with the ability to electrically steer the HIFU focus using phased array transducers have been under development. The presence of side and grating lobes may cause undesired thermal accumulation at the interface of the coupling medium (i.e. water) and skin, or in the intervening tissue. Although sparse randomly distributed piston elements could reduce the amplitude of grating lobes, there are theoretically no grating lobes with the use of concave elements in the new phased array HIFU. A new HIFU transmission strategy is proposed in this study, firing a number of but not all elements for a certain period and then changing to another group for the next firing sequence. The advantages are: 1) the asymmetric position of active elements may reduce the side lobes, and 2) each element has some resting time during the entire HIFU ablation (up to several hours for some clinical applications) so that the decreasing efficiency of the transducer due to thermal accumulation is minimized. Genetic algorithm was used for selecting randomly distributed elements in a HIFU array. Amplitudes of the first side lobes at the focal plane were used as the fitness value in the optimization. Overall, it is suggested that the proposed new strategy could reduce the side lobe and the consequent side-effects, and the genetic algorithm is effective in selecting those randomly distributed elements in a HIFU array.

Genetics Home Reference: adiposis dolorosa

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes The cause of adiposis dolorosa is unknown. The condition is thought to have a genetic component because a few families with multiple affected family members have been reported. ...

Multiple capacitors for natural genetic variation in Drosophila melanogaster.

PubMed

Takahashi, Kazuo H

2013-03-01

Cryptic genetic variation (CGV) or a standing genetic variation that is not ordinarily expressed as a phenotype is released when the robustness of organisms is impaired under environmental or genetic perturbations. Evolutionary capacitors modulate the amount of genetic variation exposed to natural selection and hidden cryptically; they have a fundamental effect on the evolvability of traits on evolutionary timescales. In this study, I have demonstrated the effects of multiple genomic regions of Drosophila melanogaster on CGV in wing shape. I examined the effects of 61 genomic deficiencies on quantitative and qualitative natural genetic variation in the wing shape of D. melanogaster. I have identified 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome. Furthermore, five genomic deficiencies uncovered qualitative CGV in wing morphology. These findings suggest that CGV in wing shape of wild-type D. melanogaster is regulated by multiple capacitors with divergent functions. Future analysis of genes encompassed by these genomic regions would help elucidate novel capacitor genes and better understand the general features of capacitors regarding natural genetic variation. © 2012 Blackwell Publishing Ltd.

Tricholoma matsutake in a natural Pinus densiflora forest: correspondence between above- and below-ground genets, association with multiple host trees and alteration of existing ectomycorrhizal communities.

PubMed

Lian, Chunlan; Narimatsu, Maki; Nara, Kazuhide; Hogetsu, Taizo

2006-01-01

Tricholoma matsutake (matsutake) is an ectomycorrhizal (ECM) fungus that produces economically important mushrooms in Japan. Here, we use microsatellite markers to identify genets of matsutake sporocarps and below-ground ECM tips, as well as associated host genotypes of Pinus densiflora. We also studied ECM fungal community structure inside, beneath and outside the matsutake fairy rings, using morphological and internal transcribed spacer (ITS) polymorphism analysis. Based on sporocarp samples, one to four genets were found within each fairy ring, and no genetic differentiation among six sites was detected. Matsutake ECM tips were only found beneath fairy rings and corresponded with the genotypes of the above-ground sporocarps. We detected nine below-ground matsutake genets, all of which colonized multiple pine trees (three to seven trees per genet). The ECM fungal community beneath fairy rings was species-poor and significantly differed from those inside and outside the fairy rings. We conclude that matsutake genets occasionally establish from basidiospores and expand on the root systems of multiple host trees. Although matsutake mycelia suppress other ECM fungi during expansion, most of them may recover after the passage of the fairy rings.

Nutritional and Genetic Determinants of Early Puberty

DTIC Science & Technology

2007-06-01

AD_________________ Award Number: W81XWH-04-1-0575 TITLE: Nutritional and Genetic Determinants...CONTRACT NUMBER Nutritional and Genetic Determinants of Early Puberty 5b. GRANT NUMBER W81XWH-04-1-0575 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...later in life. Nutritional factors during childhood and puberty, and inherited genetic factors are suspected to interact in modulating these early

Complex genomic rearrangement in CCS-LacZ transgenic mice.

PubMed

Stroud, Dina Myers; Darrow, Bruce J; Kim, Sang Do; Zhang, Jie; Jongbloed, Monique R M; Rentschler, Stacey; Moskowitz, Ivan P G; Seidman, Jonathan; Fishman, Glenn I

2007-02-01

The cardiac conduction system (CCS)-lacZ insertional mouse mutant strain genetically labels the developing and mature CCS. This pattern of expression is presumed to reflect the site of transgene integration rather than regulatory elements within the transgene proper. We sought to characterize the genomic structure of the integration locus and identify nearby gene(s) that might potentially confer the observed CCS-specific transcription. We found rearrangement of chromosome 7 between regions D1 and E1 with altered transcription of multiple genes in the D1 region. Several lines of evidence suggested that regulatory elements from at least one gene, Slco3A1, influenced CCS-restricted reporter gene expression. In embryonic hearts, Slco3A1 was expressed in a spatial pattern similar to the CCS-lacZ transgene and was similarly neuregulin-responsive. At later stages, however, expression patterns of the transgene and Slco3A1 diverged, suggesting that the Slco3A1 locus may be necessary, but not sufficient to confer CCS-specific transgene expression in the CCS-lacZ line. (c) 2007 Wiley-Liss, Inc.

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

PubMed

Painter, Jodie N; Kaufmann, Susanne; O'Mara, Tracy A; Hillman, Kristine M; Sivakumaran, Haran; Darabi, Hatef; Cheng, Timothy H T; Pearson, John; Kazakoff, Stephen; Waddell, Nicola; Hoivik, Erling A; Goode, Ellen L; Scott, Rodney J; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; French, Juliet D; Salvesen, Helga B; Pollock, Pamela M; Thompson, Deborah J; Spurdle, Amanda B; Edwards, Stacey L

2016-06-02

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

PubMed

Gu, Yulong; Warren, James Roy; Day, Karen Jean

2011-01-01

This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."

Genetic variation and virulence of Autographa californica multiple nucleopolyhedrovirus and Trichoplusia ni single nucleopolyhedrovirus isolates

USDA-ARS?s Scientific Manuscript database

To determine the genetic diversity within the baculovirus species Autographa calfornica multiple nucleopolyhedrovirus (AcMNPV; Baculoviridae: Alphabaculovirus), a PCR-based method was used to identify and classify baculoviruses found in virus samples from the lepidopteran host species A. californi...

Etiology in psychiatry: embracing the reality of poly‐gene‐environmental causation of mental illness

PubMed Central

Uher, Rudolf; Zwicker, Alyson

2017-01-01

Intriguing findings on genetic and environmental causation suggest a need to reframe the etiology of mental disorders. Molecular genetics shows that thousands of common and rare genetic variants contribute to mental illness. Epidemiological studies have identified dozens of environmental exposures that are associated with psychopathology. The effect of environment is likely conditional on genetic factors, resulting in gene‐environment interactions. The impact of environmental factors also depends on previous exposures, resulting in environment‐environment interactions. Most known genetic and environmental factors are shared across multiple mental disorders. Schizophrenia, bipolar disorder and major depressive disorder, in particular, are closely causally linked. Synthesis of findings from twin studies, molecular genetics and epidemiological research suggests that joint consideration of multiple genetic and environmental factors has much greater explanatory power than separate studies of genetic or environmental causation. Multi‐factorial gene‐environment interactions are likely to be a generic mechanism involved in the majority of cases of mental illness, which is only partially tapped by existing gene‐environment studies. Future research may cut across psychiatric disorders and address poly‐causation by considering multiple genetic and environmental measures across the life course with a specific focus on the first two decades of life. Integrative analyses of poly‐causation including gene‐environment and environment‐environment interactions can realize the potential for discovering causal types and mechanisms that are likely to generate new preventive and therapeutic tools. PMID:28498595

The adequacy of informed consent forms in genetic research in Oman: a pilot study.

PubMed

Al-Riyami, Asya; Jaju, Deepali; Jaju, Sanjay; Silverman, Henry J

2011-08-01

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms. © 2011 Blackwell Publishing Ltd.

Selfish DNA: homing endonucleases find a home.

PubMed

Edgell, David R

2009-02-10

Self-splicing group I introns come in two flavours - those with a homing endonuclease to promote mobility of the intron, and those without an endonuclease. How homing endonucleases and self-splicing introns associate to form a composite selfish genetic element is a question of long-standing interest. Recent work has revealed that a shared characteristic of both introns and endonucleases, the targeting of conserved sequences, may provide the impetus for the evolution of composite mobile genetic elements.

Genetic diversity among isolates of Autographa californica multiple nucleopolyhedrovirus

USDA-ARS?s Scientific Manuscript database

Our knowledge of genetic variation at the nucleotide sequence level of Autographa californica multiple nucleopolyhedrovirus (AcMNPV; Baculoviridae: Alphabaculovirus) derives from complete genome sequences of the C6 clonal isolate of AcMNPV and the R1 and CL3 clonal isolates of AcMNPV variants Rachip...

Proteomics technique opens new frontiers in mobilome research

PubMed Central

Davidson, Andrew D.; Matthews, David A.

2017-01-01

ABSTRACT A large proportion of the genome of most eukaryotic organisms consists of highly repetitive mobile genetic elements. The sum of these elements is called the “mobilome,” which in eukaryotes is made up mostly of transposons. Transposable elements contribute to disease, evolution, and normal physiology by mediating genetic rearrangement, and through the “domestication” of transposon proteins for cellular functions. Although ‘omics studies of mobilome genomes and transcriptomes are common, technical challenges have hampered high-throughput global proteomics analyses of transposons. In a recent paper, we overcame these technical hurdles using a technique called “proteomics informed by transcriptomics” (PIT), and thus published the first unbiased global mobilome-derived proteome for any organism (using cell lines derived from the mosquito Aedes aegypti). In this commentary, we describe our methods in more detail, and summarise our major findings. We also use new genome sequencing data to show that, in many cases, the specific genomic element expressing a given protein can be identified using PIT. This proteomic technique therefore represents an important technological advance that will open new avenues of research into the role that proteins derived from transposons and other repetitive and sequence diverse genetic elements, such as endogenous retroviruses, play in health and disease. PMID:28932623

Extrachromosomal genetic elements in Micrococcus.

PubMed

Dib, Julián Rafael; Liebl, Wolfgang; Wagenknecht, Martin; Farías, María Eugenia; Meinhardt, Friedhelm

2013-01-01

Micrococci are Gram-positive G + C-rich, nonmotile, nonspore-forming actinomycetous bacteria. Micrococcus comprises ten members, with Micrococcus luteus being the type species. Representatives of the genus play important roles in the biodegradation of xenobiotics, bioremediation processes, production of biotechnologically important enzymes or bioactive compounds, as test strains in biological assays for lysozyme and antibiotics, and as infective agents in immunocompromised humans. The first description of plasmids dates back approximately 28 years, when several extrachromosomal elements ranging in size from 1.5 to 30.2 kb were found in Micrococcus luteus. Up to the present, a number of circular plasmids conferring antibiotic resistance, the ability to degrade aromatic compounds, and osmotolerance are known, as well as cryptic elements with unidentified functions. Here, we review the Micrococcus extrachromosomal traits reported thus far including phages and the only quite recently described large linear extrachromosomal genetic elements, termed linear plasmids, which range in size from 75 kb (pJD12) to 110 kb (pLMA1) and which confer putative advantageous capabilities, such as antibiotic or heavy metal resistances (inferred from sequence analyses and curing experiments). The role of the extrachromosomal elements for the frequently proven ecological and biotechnological versatility of the genus will be addressed as well as their potential for the development and use as genetic tools.

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

Host–parasite genotypic interactions in the honey bee: the dynamics of diversity

PubMed Central

Evison, Sophie E F; Fazio, Geraldine; Chappell, Paula; Foley, Kirsten; Jensen, Annette B; Hughes, William O H

2013-01-01

Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within-colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host–parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host–parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects. PMID:23919163

Host-parasite genotypic interactions in the honey bee: the dynamics of diversity.

PubMed

Evison, Sophie E F; Fazio, Geraldine; Chappell, Paula; Foley, Kirsten; Jensen, Annette B; Hughes, William O H

2013-07-01

Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within-colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host-parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host-parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects.

[Future challenges in multiple sclerosis].

PubMed

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

LEOPARD syndrome

MedlinePlus

Multiple lentigines syndrome; Noonan syndrome with multiple lentigines ... Genetics Home Reference -- ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines National Organization for Rare Disorders -- ...

Two Kinds of "Elements" and the Dialectic between Synthetic-deductive and Analytic-genetic Approaches in Mathematics.

ERIC Educational Resources Information Center

Steiner, Hans-Georg

1988-01-01

Describes two kinds of elements in mathematics: Euclid's and Bourbaki's. Discusses some criticisms on the two concepts of elements from a philosophical, methodological, and didactical point of view. Suggests a complementarist view and several implications for mathematics education. (YP)

Moderate Multiple Parentage and Low Genetic Variation Reduces the Potential for Genetic Incompatibility Avoidance Despite High Risk of Inbreeding

PubMed Central

Tuni, Cristina; Goodacre, Sara; Bechsgaard, Jesper; Bilde, Trine

2012-01-01

Background Polyandry is widespread throughout the animal kingdom. In the absence of direct benefits of mating with different males, the underlying basis for polyandry is enigmatic because it can carry considerable costs such as elevated exposure to sexual diseases, physical injury or other direct fitness costs. Such costs may be balanced by indirect genetic benefits to the offspring of polyandrous females. We investigated polyandry and patterns of parentage in the spider Stegodyphus lineatus. This species experiences relatively high levels of inbreeding as a result of its spatial population structure, philopatry and limited male mating dispersal. Polyandry may provide an opportunity for post mating inbreeding avoidance that reduces the risk of genetic incompatibilities arising from incestuous matings. However, multiple mating carries direct fitness costs to females suggesting that genetic benefits must be substantial to counter direct costs. Methodology/Principal Findings Genetic parentage analyses in two populations from Israel and a Greek island, showed mixed-brood parentage in approximately 50% of the broods. The number of fathers ranged from 1–2 indicating low levels of multiple parentage and there was no evidence for paternity bias in mixed-broods from both populations. Microsatellite loci variation suggested limited genetic variation within populations, especially in the Greek island population. Relatedness estimates among females in the maternal generation and potentially interacting individuals were substantial indicating full-sib and half-sib relationships. Conclusions/Significance Three lines of evidence indicate limited potential to obtain substantial genetic benefits in the form of reduced inbreeding. The relatively low frequency of multiple parentage together with low genetic variation among potential mates and the elevated risk of mating among related individuals as corroborated by our genetic data suggest that there are limited actual outbreeding opportunities for polyandrous females. Polyandry in S. lineatus is thus unlikely to be maintained through adaptive female choice. PMID:22235316

Mammalian skin cell biology: at the interface between laboratory and clinic.

PubMed

Watt, Fiona M

2014-11-21

Mammalian skin research represents the convergence of three complementary disciplines: cell biology, mouse genetics, and dermatology. The skin provides a paradigm for current research in cell adhesion, inflammation, and tissue stem cells. Here, I discuss recent insights into the cell biology of skin. Single-cell analysis has revealed that human epidermal stem cells are heterogeneous and differentiate in response to multiple extrinsic signals. Live-cell imaging, optogenetics, and cell ablation experiments show skin cells to be remarkably dynamic. High-throughput, genome-wide approaches have yielded unprecedented insights into the circuitry that controls epidermal stem cell fate. Last, integrative biological analysis of human skin disorders has revealed unexpected functions for elements of the skin that were previously considered purely structural. Copyright © 2014, American Association for the Advancement of Science.

Pathogenicity Island Cross Talk Mediated by Recombination Directionality Factors Facilitates Excision from the Chromosome.

PubMed

Carpenter, Megan R; Rozovsky, Sharon; Boyd, E Fidelma

2015-12-14

Pathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase-mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. In this study, we examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential for Vibrio cholerae host colonization: Vibrio pathogenicity island 1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1 and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1- and VPI-2-encoded integrases. We demonstrated that the RDFs Vibrio excision factor A (VefA) and VefB bind at the attachment sites (overlapping the int promoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition, V. cholerae RDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs. Deciphering the mechanisms of pathogenicity island excision is necessary for understanding the evolution and spread of these elements to their nonpathogenic counterparts. Such mechanistic insight would assist in predicting the mobility of uncharacterized genetic elements. This study identified extensive RDF-mediated cross talk between two nonhomologous VPIs and demonstrated the dual functionality of RDF proteins: (i) inducing PAI excision and (ii) acting as transcriptional regulators. Findings from this study may be implicated in determining the mobilome contribution of other bacteria with multiple MIGEs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Disease-associated variants in different categories of disease located in distinct regulatory elements.

PubMed

Ma, Meng; Ru, Ying; Chuang, Ling-Shiang; Hsu, Nai-Yun; Shi, Li-Song; Hakenberg, Jörg; Cheng, Wei-Yi; Uzilov, Andrew; Ding, Wei; Glicksberg, Benjamin S; Chen, Rong

2015-01-01

The invention of high throughput sequencing technologies has led to the discoveries of hundreds of thousands of genetic variants associated with thousands of human diseases. Many of these genetic variants are located outside the protein coding regions, and as such, it is challenging to interpret the function of these genetic variants by traditional genetic approaches. Recent genome-wide functional genomics studies, such as FANTOM5 and ENCODE have uncovered a large number of regulatory elements across hundreds of different tissues or cell lines in the human genome. These findings provide an opportunity to study the interaction between regulatory elements and disease-associated genetic variants. Identifying these diseased-related regulatory elements will shed light on understanding the mechanisms of how these variants regulate gene expression and ultimately result in disease formation and progression. In this study, we curated and categorized 27,558 Mendelian disease variants, 20,964 complex disease variants, 5,809 cancer predisposing germline variants, and 43,364 recurrent cancer somatic mutations. Compared against nine different types of regulatory regions from FANTOM5 and ENCODE projects, we found that different types of disease variants show distinctive propensity for particular regulatory elements. Mendelian disease variants and recurrent cancer somatic mutations are 22-fold and 10- fold significantly enriched in promoter regions respectively (q<0.001), compared with allele-frequency-matched genomic background. Separate from these two categories, cancer predisposing germline variants are 27-fold enriched in histone modification regions (q<0.001), 10-fold enriched in chromatin physical interaction regions (q<0.001), and 6-fold enriched in transcription promoters (q<0.001). Furthermore, Mendelian disease variants and recurrent cancer somatic mutations share very similar distribution across types of functional effects. We further found that regulatory regions are located within over 50% coding exon regions. Transcription promoters, methylation regions, and transcription insulators have the highest density of disease variants, with 472, 239, and 72 disease variants per one million base pairs, respectively. Disease-associated variants in different disease categories are preferentially located in particular regulatory elements. These results will be useful for an overall understanding about the differences among the pathogenic mechanisms of various disease-associated variants.

Disease-associated variants in different categories of disease located in distinct regulatory elements

PubMed Central

2015-01-01

Background The invention of high throughput sequencing technologies has led to the discoveries of hundreds of thousands of genetic variants associated with thousands of human diseases. Many of these genetic variants are located outside the protein coding regions, and as such, it is challenging to interpret the function of these genetic variants by traditional genetic approaches. Recent genome-wide functional genomics studies, such as FANTOM5 and ENCODE have uncovered a large number of regulatory elements across hundreds of different tissues or cell lines in the human genome. These findings provide an opportunity to study the interaction between regulatory elements and disease-associated genetic variants. Identifying these diseased-related regulatory elements will shed light on understanding the mechanisms of how these variants regulate gene expression and ultimately result in disease formation and progression. Results In this study, we curated and categorized 27,558 Mendelian disease variants, 20,964 complex disease variants, 5,809 cancer predisposing germline variants, and 43,364 recurrent cancer somatic mutations. Compared against nine different types of regulatory regions from FANTOM5 and ENCODE projects, we found that different types of disease variants show distinctive propensity for particular regulatory elements. Mendelian disease variants and recurrent cancer somatic mutations are 22-fold and 10- fold significantly enriched in promoter regions respectively (q<0.001), compared with allele-frequency-matched genomic background. Separate from these two categories, cancer predisposing germline variants are 27-fold enriched in histone modification regions (q<0.001), 10-fold enriched in chromatin physical interaction regions (q<0.001), and 6-fold enriched in transcription promoters (q<0.001). Furthermore, Mendelian disease variants and recurrent cancer somatic mutations share very similar distribution across types of functional effects. We further found that regulatory regions are located within over 50% coding exon regions. Transcription promoters, methylation regions, and transcription insulators have the highest density of disease variants, with 472, 239, and 72 disease variants per one million base pairs, respectively. Conclusions Disease-associated variants in different disease categories are preferentially located in particular regulatory elements. These results will be useful for an overall understanding about the differences among the pathogenic mechanisms of various disease-associated variants. PMID:26110593

Method and systems for collecting data from multiple fields of view

NASA Technical Reports Server (NTRS)

Schwemmer, Geary K. (Inventor)

2002-01-01

Systems and methods for processing light from multiple fields (48, 54, 55) of view without excessive machinery for scanning optical elements. In an exemplary embodiment of the invention, multiple holographic optical elements (41, 42, 43, 44, 45), integrated on a common film (4), diffract and project light from respective fields of view.

The genetic links between the big five personality traits and general interest domains.

PubMed

Kandler, Christian; Bleidorn, Wiebke; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M

2011-12-01

This is the first genetically informative study in which multiple informants were used to quantify the genetic and environmental sources of individual differences in general interests as well as the phenotypic and genetic links between general interests and Big Five personality traits. Self-reports and two peer ratings from 844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs, were collected. Multiple-rater scores (composites) revealed that the averaged levels of genetic and environmental effects on seven broad interest domains were similar to those on personality traits. Multivariate analyses showed that about 35% of the genetic and 9% of the environmental variance in interests were explained by personality domains, in particular by Openness. The findings suggest that interests cannot easily be considered as a byproduct of the interactions between personality genotypes and the environmental influences but rather as an internal regulation of behavior with an own genetic basis.

Genetic conflict and sex chromosome evolution

PubMed Central

Meiklejohn, Colin D; Tao, Yun

2009-01-01

Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed in the germline, the distribution of genes in the genome, and the evolution of hybrid sterility between species. PMID:19931208

Conjoin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sjaardema, Gregory

2010-08-06

Conjoin is a code for joining sequentially in time multiple exodusII database files. It is used to create a single results or restart file from multiple results or restart files which typically arise as the result of multiple restarted analyses. The resulting output file will be the union of the input files with a status variable indicating the status of each element at the various time planes.Combining multiple exodusII files arising from a restarted analysis or combining multiple exodusII files arising from a finite element analysis with dynamic topology changes.

Prenatal Genetic Counseling (For Parents)

MedlinePlus

... Before you meet with a genetic counselor in person, you may be asked to gather information about your family history. The counselor will want to know of any relatives with genetic disorders, multiple miscarriages, ...

The interaction of genotype and environment determines variation in the maize kernal ionome

USDA-ARS?s Scientific Manuscript database

Plants obtain soil-resident elements that support growth and metabolism via water-mediated flow due to transpiration and active transport processes. The availability of elements in the environment can interact with the genetic capacity of the organism to modulate element uptake through plastic adapt...

High proportions of Staphylococcus epidermidis in dental caries harbor multiple classes of antibiotics resistance, significantly increase inflammatory interleukins in dental pulps.

PubMed

Devang Divakar, Darshan; Muzaheed; Aldeyab, Sultan Salem; Alfawaz, Sara A; AlKheraif, Abdulaziz Abdullah; Ahmed Khan, Aftab

2017-08-01

Staphylococcus epidermidis is one of most prevalent in dental caries or dental pulp which has the capability of horizontal genetic transfer between different bacterial species in the oropharynx, suggesting that it may evolve with the dissemination of resistant determinants, This study was performed to molecularly characterize and differentiate S. epidermidis isolated from dental caries and healthy individual. Also, two important cytokines in inflammation were assayed caused due to S. epidermidis of health and dental caries sources. Dental caries strains were more resistant with high MIC 50 and MIC 90 value. These isolates also showed the presence of mecA gene and another virulence gene i. e sea and seb comparatively more than healthy individual isolates. SCCmec types, III and IV was more prevalent in dental caries isolates where an as healthy individual was more non-typable. Additionally, the quantity of IL-1β and IL-8 caused due to dental caries isolates was seen more which indicate dental caries isolates are able to induce. This study showed that S. epidermidis a normal flora of oropharyngeal are more diverse to those strains which cause dental caries. S. epidermidis owns a prodigious genetic plasticity that permits to obtain, lose or regulate genetic elements that provide compensations to improve its colonization in the host. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethylene Inhibits Cell Proliferation of the Arabidopsis Root Meristem1[OPEN

PubMed Central

Street, Ian H.; Aman, Sitwat; Zubo, Yan; Ramzan, Aleena; Wang, Xiaomin; Shakeel, Samina N.; Kieber, Joseph J.; Schaller, G. Eric

2015-01-01

The root system of plants plays a critical role in plant growth and survival, with root growth being dependent on both cell proliferation and cell elongation. Multiple phytohormones interact to control root growth, including ethylene, which is primarily known for its role in controlling root cell elongation. We find that ethylene also negatively regulates cell proliferation at the root meristem of Arabidopsis (Arabidopsis thaliana). Genetic analysis indicates that the inhibition of cell proliferation involves two pathways operating downstream of the ethylene receptors. The major pathway is the canonical ethylene signal transduction pathway that incorporates CONSTITUTIVE TRIPLE RESPONSE1, ETHYLENE INSENSITIVE2, and the ETHYLENE INSENSITIVE3 family of transcription factors. The secondary pathway is a phosphorelay based on genetic analysis of receptor histidine kinase activity and mutants involving the type B response regulators. Analysis of ethylene-dependent gene expression and genetic analysis supports SHORT HYPOCOTYL2, a repressor of auxin signaling, as one mediator of the ethylene response and furthermore, indicates that SHORT HYPOCOTYL2 is a point of convergence for both ethylene and cytokinin in negatively regulating cell proliferation. Additional analysis indicates that ethylene signaling contributes but is not required for cytokinin to inhibit activity of the root meristem. These results identify key elements, along with points of cross talk with cytokinin and auxin, by which ethylene negatively regulates cell proliferation at the root apical meristem. PMID:26149574

Simulation of the M13 life cycle II: Investigation of the control mechanisms of M13 infection and establishment of the carrier state.

PubMed

Smeal, Steven W; Schmitt, Margaret A; Pereira, Ronnie Rodrigues; Prasad, Ashok; Fisk, John D

2017-01-01

Bacteriophage M13 is a true parasite of bacteria, able to co-opt the infected cell and control the production of progeny across many cellular generations. Here, our genetically-structured simulation of M13 is applied to quantitatively dissect the interplay between the host cellular environment and the controlling interactions governing the phage life cycle during the initial establishment of infection and across multiple cell generations. Multiple simulations suggest that phage-encoded feedback interactions constrain the utilization of host DNA polymerase, RNA polymerase and ribosomes. The simulation reveals the importance of p5 translational attenuation in controlling the production of phage double-stranded DNA and suggests an underappreciated role for p5 translational self-attenuation in resource allocation. The control elements active in a single generation are sufficient to reproduce the experimentally-observed multigenerational curing of the phage infection. Understanding the subtleties of regulation will be important for maximally exploiting M13 particles as scaffolds for nanoscale devices. Copyright © 2016 Elsevier Inc. All rights reserved.

The genetic structure of the A mating-type locus of Lentinula edodes.

PubMed

Au, Chun Hang; Wong, Man Chun; Bao, Dapeng; Zhang, Meiyan; Song, Chunyan; Song, Wenhua; Law, Patrick Tik Wan; Kües, Ursula; Kwan, Hoi Shan

2014-02-10

The Shiitake mushroom, Lentinula edodes (Berk.) Pegler is a tetrapolar basidiomycete with two unlinked mating-type loci, commonly called the A and B loci. Identifying the mating-types in shiitake is important for enhancing the breeding and cultivation of this economically-important edible mushroom. Here, we identified the A mating-type locus from the first draft genome sequence of L. edodes and characterized multiple alleles from different monokaryotic strains. Two intron-length polymorphism markers were developed to facilitate rapid molecular determination of A mating-type. L. edodes sequences were compared with those of known tetrapolar and bipolar basidiomycete species. The A mating-type genes are conserved at the homeodomain region across the order Agaricales. However, we observed unique genomic organization of the locus in L. edodes which exhibits atypical gene order and multiple repetitive elements around its A locus. To our knowledge, this is the first known exception among Homobasidiomycetes, in which the mitochondrial intermediate peptidase (mip) gene is not closely linked to A locus. Copyright © 2013 Elsevier B.V. All rights reserved.

Genome diversity and divergence in Drosophila mauritiana: multiple signatures of faster X evolution.

PubMed

Garrigan, Daniel; Kingan, Sarah B; Geneva, Anthony J; Vedanayagam, Jeffrey P; Presgraves, Daven C

2014-09-04

Drosophila mauritiana is an Indian Ocean island endemic species that diverged from its two sister species, Drosophila simulans and Drosophila sechellia, approximately 240,000 years ago. Multiple forms of incomplete reproductive isolation have evolved among these species, including sexual, gametic, ecological, and intrinsic postzygotic barriers, with crosses among all three species conforming to Haldane's rule: F(1) hybrid males are sterile and F(1) hybrid females are fertile. Extensive genetic resources and the fertility of hybrid females have made D. mauritiana, in particular, an important model for speciation genetics. Analyses between D. mauritiana and both of its siblings have shown that the X chromosome makes a disproportionate contribution to hybrid male sterility. But why the X plays a special role in the evolution of hybrid sterility in these, and other, species remains an unsolved problem. To complement functional genetic analyses, we have investigated the population genomics of D. mauritiana, giving special attention to differences between the X and the autosomes. We present a de novo genome assembly of D. mauritiana annotated with RNAseq data and a whole-genome analysis of polymorphism and divergence from ten individuals. Our analyses show that, relative to the autosomes, the X chromosome has reduced nucleotide diversity but elevated nucleotide divergence; an excess of recurrent adaptive evolution at its protein-coding genes; an excess of recent, strong selective sweeps; and a large excess of satellite DNA. Interestingly, one of two centimorgan-scale selective sweeps on the D. mauritiana X chromosome spans a region containing two sex-ratio meiotic drive elements and a high concentration of satellite DNA. Furthermore, genes with roles in reproduction and chromosome biology are enriched among genes that have histories of recurrent adaptive protein evolution. Together, these genome-wide analyses suggest that genetic conflict and frequent positive natural selection on the X chromosome have shaped the molecular evolutionary history of D. mauritiana, refining our understanding of the possible causes of the large X-effect in speciation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Giftedness and Genetics: The Emergenic-Epigenetic Model and Its Implications

ERIC Educational Resources Information Center

Simonton, Dean Keith

2005-01-01

The genetic endowment underlying giftedness may operate in a far more complex manner than often expressed in most theoretical accounts of the phenomenon. First, an endowment may be emergenic. That is, a gift may consist of multiple traits (multidimensional) that are inherited in a multiplicative (configurational), rather than an additive (simple)…

Developing Pedagogical Tools to Improve Teaching Multiple Models of the Gene in High School

ERIC Educational Resources Information Center

Auckaraaree, Nantaya

2013-01-01

Multiple models of the gene are used to explore genetic phenomena in scientific practices and in the classroom. In genetics curricula, the classical and molecular models are presented in disconnected domains. Research demonstrates that, without explicit connections, students have difficulty developing an understanding of the gene that spans…

Integrating Genetic, Psychopharmacological and Neuroimaging Studies: A Converging Methods Approach to Understanding the Neurobiology of ADHD

ERIC Educational Resources Information Center

Durston, Sarah; Konrad, Kerstin

2007-01-01

This paper aims to illustrate how combining multiple approaches can inform us about the neurobiology of ADHD. Converging evidence from genetic, psychopharmacological and functional neuroimaging studies has implicated dopaminergic fronto-striatal circuitry in ADHD. However, while the observation of converging evidence from multiple vantage points…

Phlebotomy and the Amish Inspired this Geneticist - TCGA

Cancer.gov

Dr. Stacey Gabriel began her career in genetics while working on a rare disease in the Amish. Learn more about her experience witnessing the human element of genetics in this TCGA in Action Researcher Profile.

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

PubMed Central

Demongeot, Jacques; Goles, Eric; Morvan, Michel; Noual, Mathilde; Sené, Sylvain

2010-01-01

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally. PMID:20700525

Origin and Evolution of European Community-Acquired Methicillin-Resistant Staphylococcus aureus

PubMed Central

Wirth, Thierry; Andersen, Paal S.; Skov, Robert L.; De Grassi, Anna; Simões, Patricia Martins; Tristan, Anne; Petersen, Andreas; Aziz, Maliha; Kiil, Kristoffer; Cirković, Ivana; Udo, Edet E.; del Campo, Rosa; Vuopio-Varkila, Jaana; Ahmad, Norazah; Tokajian, Sima; Peters, Georg; Schaumburg, Frieder; Olsson-Liljequist, Barbro; Givskov, Michael; Driebe, Elizabeth E.; Vigh, Henrik E.; Shittu, Adebayo; Ramdani-Bougessa, Nadjia; Rasigade, Jean-Philippe; Price, Lance B.; Vandenesch, Francois; Larsen, Anders R.; Laurent, Frederic

2014-01-01

ABSTRACT Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. PMID:25161186

Altering Genomic Integrity: Heavy Metal Exposure Promotes Transposable Element-Mediated Damage.

PubMed

Morales, Maria E; Servant, Geraldine; Ade, Catherine; Roy-Engel, Astrid M

2015-07-01

Maintenance of genomic integrity is critical for cellular homeostasis and survival. The active transposable elements (TEs) composed primarily of three mobile element lineages LINE-1, Alu, and SVA comprise approximately 30% of the mass of the human genome. For the past 2 decades, studies have shown that TEs significantly contribute to genetic instability and that TE-caused damages are associated with genetic diseases and cancer. Different environmental exposures, including several heavy metals, influence how TEs interact with its host genome increasing their negative impact. This mini-review provides some basic knowledge on TEs, their contribution to disease, and an overview of the current knowledge on how heavy metals influence TE-mediated damage.

Genetics Home Reference: nonsyndromic aplasia cutis congenita

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Nonsyndromic aplasia cutis congenita can have different causes, and often the cause is unknown. Because the condition is sometimes found in multiple members of a family, it is thought to have a genetic component; ...

The novel conjugative transposon tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes.

PubMed

Santagati, Maria; Iannelli, Francesco; Cascone, Carmela; Campanile, Floriana; Oggioni, Marco R; Stefani, Stefania; Pozzi, Gianni

2003-01-01

The macrolide efflux gene mef(A) of the Streptococcus pyogenes clinical strain 2812A was found to be carried by a 52-kb chromosomal genetic element that could be transferred by conjugation to the chromosome of other streptococcal species. The characteristics of this genetic element are typical of conjugative transposons and was named Tn1207.3. The size of Tn1207.3 was established by pulsed-field gel electrophoresis (PFGE), and DNA sequencing analysis showed that the 7,244 bp at the left end of Tn1207.3 were identical to those of the pneumococcal Tn1207.1 element. Tn1207.3-like genetic elements were found to be inserted at a single specific chromosomal site in 12 different clinical isolates S. pyogenes exhibiting the M phenotype of resistance to macrolides and carrying the mef(A) gene. Tn1207.3 was transferred from S. pyogenes 2812A to Streptococcus pneumoniae, and sequence analysis carried out on six independent transconjugants showed that insertion of Tn1207.3 in the pneumococcal genome always occurred at a single specific site as in Tn1207.1. Using MF2, a representative S. pneumoniae transconjugant, as a donor, Tn1207.3 was transferred again by conjugation to S. pyogenes and Streptococcus gordonii. The previously described nonconjugative element Tn1207.1 of S. pneumoniae appears to be a defective element, part of a longer conjugative transposon that carries mef(A) and is found in clinical isolates of S. pyogenes.

Understanding genetics: Analysis of secondary students' conceptual status

NASA Astrophysics Data System (ADS)

Tsui, Chi-Yan; Treagust, David F.

2007-02-01

This article explores the conceptual change of students in Grades 10 and 12 in three Australian senior high schools when the teachers included computer multimedia to a greater or lesser extent in their teaching of a genetics course. The study, underpinned by a multidimensional conceptual-change framework, used an interpretive approach and a case-based design with multiple data collection methods. Over 4-8 weeks, the students learned genetics in classroom lessons that included BioLogica activities, which feature multiple representations. Results of the online tests and interview tasks revealed that most students improved their understanding of genetics as evidenced in the development of genetics reasoning. However, using Thorley's (1990) status analysis categories, a cross-case analysis of the gene conceptions of 9 of the 26 students interviewed indicated that only 4 students' postinstructional conceptions were intelligible-plausible-fruitful. Students' conceptual change was consistent with classroom teaching and learning. Findings suggested that multiple representations supported conceptual understanding of genetics but not in all students. It was also shown that status can be a viable hallmark enabling researchers to identify students' conceptual change that would otherwise be less accessible. Thorley's method for analyzing conceptual status is discussed.

Genetic variation, multiple paternity, and measures of reproductive success in the critically endangered hawksbill turtle (Eretmochelys imbricata).

PubMed

González-Garza, Blanca Idalia; Stow, Adam; Sánchez-Teyer, Lorenzo Felipe; Zapata-Pérez, Omar

2015-12-01

The Yucatán Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs.

26 CFR 1.72-5 - Expected return.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the joint and survivor annuity element 110.40 Multiple from Table I (male, age 60) 18.2 Number of... anticipatable with respect to the joint and survivor annuity element 124.80 Multiple from Table V (age 60) 24.2... annuity payments to be received annually by the multiple shown in Table I or V (whichever is applicable...

26 CFR 1.72-5 - Expected return.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the joint and survivor annuity element 110.40 Multiple from Table I (male, age 60) 18.2 Number of... anticipatable with respect to the joint and survivor annuity element 124.80 Multiple from Table V (age 60) 24.2... annuity payments to be received annually by the multiple shown in Table I or V (whichever is applicable...

26 CFR 1.72-5 - Expected return.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the joint and survivor annuity element 110.40 Multiple from Table I (male, age 60) 18.2 Number of... anticipatable with respect to the joint and survivor annuity element 124.80 Multiple from Table V (age 60) 24.2... annuity payments to be received annually by the multiple shown in Table I or V (whichever is applicable...

26 CFR 1.72-5 - Expected return.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the joint and survivor annuity element 110.40 Multiple from Table I (male, age 60) 18.2 Number of... anticipatable with respect to the joint and survivor annuity element 124.80 Multiple from Table V (age 60) 24.2... annuity payments to be received annually by the multiple shown in Table I or V (whichever is applicable...

Mapping of Ionomic Traits in Mimulus guttatus Reveals Mo and Cd QTLs That Colocalize with MOT1 Homologues

PubMed Central

Lowry, David B.; Sheng, Calvin C.; Zhu, Zhirui; Juenger, Thomas E.; Lahner, Brett; Salt, David E.; Willis, John H.

2012-01-01

Natural variation in the regulation of the accumulation of mineral nutrients and trace elements in plant tissues is crucial to plant metabolism, development, and survival across different habitats. Studies of the genetic basis of natural variation in nutrient metabolism have been facilitated by the development of ionomics. Ionomics is a functional genomic approach for the identification of the genes and gene networks that regulate the elemental composition, or ionome, of an organism. In this study, we evaluated the genetic basis of divergence in elemental composition between an inland annual and a coastal perennial accession of Mimulus guttatus using a recombinant inbred line (RIL) mapping population. Out of 20 elements evaluated, Mo and Cd were the most divergent in accumulation between the two accessions and were highly genetically correlated in the RILs across two replicated experiments. We discovered two major quantitative trait loci (QTL) for Mo accumulation, the largest of which consistently colocalized with a QTL for Cd accumulation. Interestingly, both Mo QTLs also colocalized with the two M. guttatus homologues of MOT1, the only known plant transporter to be involved in natural variation in molybdate uptake. PMID:22292026

Optical mapping reveals a large genetic inversion between two methicillin-resistant Staphylococcus aureus strains.

PubMed

Shukla, Sanjay K; Kislow, Jennifer; Briska, Adam; Henkhaus, John; Dykes, Colin

2009-09-01

Staphylococcus aureus is a highly versatile and evolving bacterium of great clinical importance. S. aureus can evolve by acquiring single nucleotide polymorphisms and mobile genetic elements and by recombination events. Identification and location of novel genomic elements in a bacterial genome are not straightforward, unless the whole genome is sequenced. Optical mapping is a new tool that creates a high-resolution, in situ ordered restriction map of a bacterial genome. These maps can be used to determine genomic organization and perform comparative genomics to identify genomic rearrangements, such as insertions, deletions, duplications, and inversions, compared to an in silico (virtual) restriction map of a known genome sequence. Using this technology, we report here the identification, approximate location, and characterization of a genetic inversion of approximately 500 kb of a DNA element between the NRS387 (USA800) and FPR3757 (USA300) strains. The presence of the inversion and location of its junction sites were confirmed by site-specific PCR and sequencing. At both the left and right junction sites in NRS387, an IS1181 element and a 73-bp sequence were identified as inverted repeats, which could explain the possible mechanism of the inversion event.

Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster

PubMed Central

Simoni, Alekos; Siniscalchi, Carla; Chan, Yuk-Sang; Huen, David S.; Russell, Steven; Windbichler, Nikolai; Crisanti, Andrea

2014-01-01

Selfish genes are DNA elements that increase their rate of genetic transmission at the expense of other genes in the genome and can therefore quickly spread within a population. It has been suggested that selfish elements could be exploited to modify the genome of entire populations for medical and ecological applications. Here we report that transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) can be engineered into site-specific synthetic selfish elements (SSEs) and demonstrate their transmission of up to 70% in the Drosophila germline. We show here that SSEs can spread via DNA break-induced homologous recombination, a process known as ‘homing’ similar to that observed for homing endonuclease genes (HEGs), despite their fundamentally different modes of DNA binding and cleavage. We observed that TALEN and ZFN have a reduced capability of secondary homing compared to HEG as their repetitive structure had a negative effect on their genetic stability. The modular architecture of ZFNs and TALENs allows for the rapid design of novel SSEs against specific genomic sequences making them potentially suitable for the genetic engineering of wild-type populations of animals and plants, in applications such as gene replacement or population suppression of pest species. PMID:24803674

Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island

PubMed Central

Sanna, Alessandro; Pretti, Salvatore; Marcello, Alberto; Mannu, Carla; Targhetta, Clara; Bruno, Graziella; Songini, Marco

2015-01-01

Background Type 1 diabetes incidence presents a decreasing gradient in Europe from the Nordic countries to the Mediterranean ones. Exception to this gradient is represented by Sardinia, the second largest Mediterranean island whose population shows the highest incidence in Europe, after Finland. The genetic features of this population have created a fertile ground for the epidemic of the disease, however, as well as being strikingly high, the incidence rate has suddenly presented a continuous increase from the ‘50s, not explainable by accumulation of new genetic variants. Several environmental factors have been taken into account, possibly interacting with the genetic/epigenetic scenario, but there are no strong evidences to date. Methods The present study investigated the hypothesis that geochemical elements could create permissive environmental conditions for autoimmune diabetes. An ecological analysis was performed to test possible correlations between the values of eight elements in stream sediments and type 1 diabetes incidence rate in Sardinia. Results Analyses revealed negative associations between elements, such as Co, Cr, Cu, Mn, Ni, Zn, and type 1 diabetes incidence. Conclusions The results suggest a possible protective role of some elements against the onset of the disease. PMID:26559814

The human genome: a multifractal analysis

PubMed Central

2011-01-01

Background Several studies have shown that genomes can be studied via a multifractal formalism. Recently, we used a multifractal approach to study the genetic information content of the Caenorhabditis elegans genome. Here we investigate the possibility that the human genome shows a similar behavior to that observed in the nematode. Results We report here multifractality in the human genome sequence. This behavior correlates strongly on the presence of Alu elements and to a lesser extent on CpG islands and (G+C) content. In contrast, no or low relationship was found for LINE, MIR, MER, LTRs elements and DNA regions poor in genetic information. Gene function, cluster of orthologous genes, metabolic pathways, and exons tended to increase their frequencies with ranges of multifractality and large gene families were located in genomic regions with varied multifractality. Additionally, a multifractal map and classification for human chromosomes are proposed. Conclusions Based on these findings, we propose a descriptive non-linear model for the structure of the human genome, with some biological implications. This model reveals 1) a multifractal regionalization where many regions coexist that are far from equilibrium and 2) this non-linear organization has significant molecular and medical genetic implications for understanding the role of Alu elements in genome stability and structure of the human genome. Given the role of Alu sequences in gene regulation, genetic diseases, human genetic diversity, adaptation and phylogenetic analyses, these quantifications are especially useful. PMID:21999602

IBSEM: An Individual-Based Atlantic Salmon Population Model

PubMed Central

Castellani, Marco; Heino, Mikko; Gilbey, John; Araki, Hitoshi; Svåsand, Terje; Glover, Kevin A.

2015-01-01

Ecology and genetics can influence the fate of individuals and populations in multiple ways. However, to date, few studies consider them when modelling the evolutionary trajectory of populations faced with admixture with non-local populations. For the Atlantic salmon, a model incorporating these elements is urgently needed because many populations are challenged with gene-flow from non-local and domesticated conspecifics. We developed an Individual-Based Salmon Eco-genetic Model (IBSEM) to simulate the demographic and population genetic change of an Atlantic salmon population through its entire life-cycle. Processes such as growth, mortality, and maturation are simulated through stochastic procedures, which take into account environmental variables as well as the genotype of the individuals. IBSEM is based upon detailed empirical data from salmon biology, and parameterized to reproduce the environmental conditions and the characteristics of a wild population inhabiting a Norwegian river. Simulations demonstrated that the model consistently and reliably reproduces the characteristics of the population. Moreover, in absence of farmed escapees, the modelled populations reach an evolutionary equilibrium that is similar to our definition of a ‘wild’ genotype. We assessed the sensitivity of the model in the face of assumptions made on the fitness differences between farm and wild salmon, and evaluated the role of straying as a buffering mechanism against the intrusion of farm genes into wild populations. These results demonstrate that IBSEM is able to capture the evolutionary forces shaping the life history of wild salmon and is therefore able to model the response of populations under environmental and genetic stressors. PMID:26383256

Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis.

PubMed

Wang, Yanqun; Liu, Di; Shi, Weifeng; Lu, Roujian; Wang, Wenling; Zhao, Yanjie; Deng, Yao; Zhou, Weimin; Ren, Hongguang; Wu, Jun; Wang, Yu; Wu, Guizhen; Gao, George F; Tan, Wenjie

2015-09-08

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus. The recent outbreak of MERS-CoV in South Korea has attracted global media attention due to the speed of spread and onward transmission. Here, we present the complete genome of the first imported MERS-CoV case in China and demonstrate genetic recombination events between group 3 and group 5 of clade B that may have implications for the transmissibility of MERS-CoV. Copyright © 2015 Wang et al.

Multispecies genetic objectives in spatial conservation planning.

PubMed

Nielsen, Erica S; Beger, Maria; Henriques, Romina; Selkoe, Kimberly A; von der Heyden, Sophie

2017-08-01

Growing threats to biodiversity and global alteration of habitats and species distributions make it increasingly necessary to consider evolutionary patterns in conservation decision making. Yet, there is no clear-cut guidance on how genetic features can be incorporated into conservation-planning processes, despite multiple molecular markers and several genetic metrics for each marker type to choose from. Genetic patterns differ between species, but the potential tradeoffs among genetic objectives for multiple species in conservation planning are currently understudied. We compared spatial conservation prioritizations derived from 2 metrics of genetic diversity (nucleotide and haplotype diversity) and 2 metrics of genetic isolation (private haplotypes and local genetic differentiation) in mitochondrial DNA of 5 marine species. We compared outcomes of conservation plans based only on habitat representation with plans based on genetic data and habitat representation. Fewer priority areas were selected for conservation plans based solely on habitat representation than on plans that included habitat and genetic data. All 4 genetic metrics selected approximately similar conservation-priority areas, which is likely a result of prioritizing genetic patterns across a genetically diverse array of species. Largely, our results suggest that multispecies genetic conservation objectives are vital to creating protected-area networks that appropriately preserve community-level evolutionary patterns. © 2016 Society for Conservation Biology.

The Regulatory Properties of Autonomous Subtelomeric P Elements Are Sensitive to a Suppressor of Variegation in Drosophila Melanogaster

PubMed Central

Ronsseray, S.; Lehmann, M.; Nouaud, D.; Anxolabehere, D.

1996-01-01

Genetic recombination was used in Drosophila melanogaster to isolate P elements, inserted at the telomeres of X chromosomes (cytological site 1A) from natural populations, in a genetic background devoid of other P elements. We show that complete maternally inherited P repression in the germline (P cytotype) can be elicited by only two autonomous P elements at 1A and that a single element at this site has partial regulatory properties. The analysis of the surrounding chromosomal regions of the P elements at 1A shows that in all cases these elements are flanked by Telomeric Associated Sequences, tandemly repetitive noncoding sequences that have properties of heterochromatin. In addition, we show that the regulatory properties of P elements at 1A can be inhibited by some of the mutant alleles of the Su(var)205 gene and by a deficiency of this gene. However, the regulatory properties of reference P strains (Harwich and Texas 007) are not impaired by Su(var)205 mutations. Su(var)205 encodes Heterochromatin Protein 1 (HP1). These results suggest that the HP1 dosage effect on the P element properties is site-dependent and could involve the structure of the chromatin. PMID:8844154

Genetics Home Reference: esophageal atresia/tracheoesophageal fistula

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Isolated EA/TEF is considered to be a multifactorial condition, which means that multiple gene variations and environmental factors likely contribute to its occurrence. ...

The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks.

PubMed

Morozova, Tatiana V; Goldman, David; Mackay, Trudy F C; Anholt, Robert R H

2012-02-20

Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms.

Inherited genetic variants associated with occurrence of multiple primary melanoma.

PubMed

Gibbs, David C; Orlow, Irene; Kanetsky, Peter A; Luo, Li; Kricker, Anne; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Sharma, Ajay; La Pilla, Emily; From, Lynn; Busam, Klaus J; Cust, Anne E; Ollila, David W; Begg, Colin B; Berwick, Marianne; Thomas, Nancy E

2015-06-01

Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. ©2015 American Association for Cancer Research.

Inherited genetic variants associated with occurrence of multiple primary melanoma

PubMed Central

Gibbs, David C.; Orlow, Irene; Kanetsky, Peter A.; Luo, Li; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Sharma, Ajay; La Pilla, Emily; From, Lynn; Busam, Klaus J.; Cust, Anne E.; Ollila, David W.; Begg, Colin B.; Berwick, Marianne; Thomas, Nancy E.

2015-01-01

Recent studies including genome-wide association studies have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 single nucleotide polymorphisms (SNP) from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% CIs were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma while NCOA6 rs4911442 approached significance (P = 0.06). The GEM study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. PMID:25837821

Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models

PubMed Central

Wang, Yifan; Liu, Aiyi; Mills, James L.; Boehnke, Michael; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Xiong, Momiao; Wu, Colin O.; Fan, Ruzong

2015-01-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks’s Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. PMID:25809955

Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.

PubMed

Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong

2015-05-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.

Genetics and education: the ethics of shaping human identity.

PubMed

Ravitsky, Vardit

2002-10-01

This paper suggests an analogy between education and genetic interventions as means of shaping the identity of children and future adults. It proposes to look at issues discussed in the philosophy of education as a possible source of insight for ethical guidelines regarding future genetic interventions. The paper focuses on situations of conflict between parents and state regarding the authority to determine the child s best interests. It describes the current formulation of the conflict in the literature as lacking the crucial element of the child s right to a cultural identity. It argues that this element is a necessary component in an ethical analysis of the child s best interests in a multicultural, liberal society which respects diversity. The paper therefore proposes a better model for the moral evaluation of identity-shaping decisions and offers some implications of this model for genetics.

Genetic consequences of trumpeter swan (Cygnus buccinator) reintroductions

USGS Publications Warehouse

Ransler, F.A.; Quinn, T.W.; Oyler-McCance, S.J.

2011-01-01

Relocation programs are often initiated to restore threatened species to previously occupied portions of their range. A primary challenge of restoration efforts is to translocate individuals in a way that prevents loss of genetic diversity and decreases differentiation relative to source populations-a challenge that becomes increasingly difficult when remnant populations of the species are already genetically depauperate. Trumpeter swans were previously extirpated in the entire eastern half of their range. Physical translocations of birds over the last 70 years have restored the species to portions of its historical range. Despite the long history of management, there has been little monitoring of the genetic outcomes of these restoration attempts. We assessed the consequences of this reintroduction program by comparing patterns of genetic variation at 17 microsatellite loci across four restoration flocks (three wild-released, one captive) and their source populations. We found that a wild-released population established from a single source displayed a trend toward reduced genetic diversity relative to and significant genetic differentiation from its source population, though small founder population effects may also explain this pattern. Wild-released flocks restored from multiple populations maintained source levels of genetic variation and lacked significant differentiation from at least one of their sources. Further, the flock originating from a single source revealed significantly lower levels of genetic variation than those established from multiple sources. The distribution of genetic variation in the captive flock was similar to its source. While the case of trumpeter swans provides evidence that restorations from multiple versus single source populations may better preserve natural levels of genetic diversity, more studies are needed to understand the general applicability of this management strategy. ?? 2010 Springer Science+Business Media B.V. (outside the USA).

NanoSIMS analysis of Bacillus spores for forensics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, P K; Davisson, M L; Velsko, S P

2010-02-23

The threat associated with the potential use of radiological, nuclear, chemical and biological materials in terrorist acts has resulted in new fields of forensic science requiring the application of state-of-the-science analytical techniques. Since the anthrax letter attacks in the United States in the fall of 2001, there has been increased interest in physical and chemical characterization of bacterial spores. While molecular methods are powerful tools for identifying genetic differences, other methods may be able to differentiate genetically identical samples based on physical and chemical properties, as well as provide complimentary information, such as methods of production and approximate date ofmore » production. Microanalysis has the potential to contribute significantly to microbial forensics. Bacillus spores are highly structured, consisting of a core, cortex, coat, and in some species, an exosporium. This structure provides a template for constraining elemental abundance differences at the nanometer scale. The primary controls on the distribution of major elements in spores are likely structural and physiological. For example, P and Ca are known to be abundant in the spore core because that is where P-rich nucleic acids and Cadipicolinic acid are located, respectively. Trace elements are known to bind to the spore coat but the controls on these elements are less well understood. Elemental distributions and abundances may be directly related to spore production, purification and stabilization methodologies, which are of particular interest for forensic investigation. To this end, we are developing a high-resolution secondary ion mass spectrometry method using a Cameca NanoSIMS 50 to study the distribution and abundance of trace elements in bacterial spores. In this presentation we will review and compare methods for preparing and analyzing samples, as well as review results on the distribution and abundance of elements in bacterial spores. We use NanoSIMS to directly image samples as well as depth profile samples. The directly imaged samples are sectioned to present a flat surface for analysis. We use focused ion beam (FIB) milling to top-cut individual spores to create flat surfaces for NanoSIMS analysis. Depth profiling can be used on whole spores, which are consumed in the process of analysis. The two methods generate comparable results, with the expected distribution of P and Ca. Ca-compatible elements, such as Mg and Mn, are found to follow the distribution of Ca. The distribution of other elements will be discussed. We envision the first application of this methodology will be to sample matching for trace samples. Towards this end, we are generating a baseline data set for samples produced by multiple laboratories. Preliminary results suggest that this method provides significant probative value for identifying samples produced by the same method in the same laboratory, as well as coming from the same initial production run. The results of this study will be presented.« less

The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks

PubMed Central

2012-01-01

Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms. PMID:22348705

Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes

DTIC Science & Technology

2013-03-14

SUPPLEMENTARY NOTES 14. ABSTRACT Autism is an extremely common and heterogeneous neurodevelopmental disorder. While genetic factors are known to play...AFRL-SA-WP-TR-2013-0013 Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes...Genetic Mapping for the Discovery of Autism Susceptibility Genes 5a. CONTRACT NUMBER N/A 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6

Sparse matrix multiplications for linear scaling electronic structure calculations in an atom-centered basis set using multiatom blocks.

PubMed

Saravanan, Chandra; Shao, Yihan; Baer, Roi; Ross, Philip N; Head-Gordon, Martin

2003-04-15

A sparse matrix multiplication scheme with multiatom blocks is reported, a tool that can be very useful for developing linear-scaling methods with atom-centered basis functions. Compared to conventional element-by-element sparse matrix multiplication schemes, efficiency is gained by the use of the highly optimized basic linear algebra subroutines (BLAS). However, some sparsity is lost in the multiatom blocking scheme because these matrix blocks will in general contain negligible elements. As a result, an optimal block size that minimizes the CPU time by balancing these two effects is recovered. In calculations on linear alkanes, polyglycines, estane polymers, and water clusters the optimal block size is found to be between 40 and 100 basis functions, where about 55-75% of the machine peak performance was achieved on an IBM RS6000 workstation. In these calculations, the blocked sparse matrix multiplications can be 10 times faster than a standard element-by-element sparse matrix package. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 24: 618-622, 2003

Multiple methods integration for structural mechanics analysis and design

NASA Technical Reports Server (NTRS)

Housner, J. M.; Aminpour, M. A.

1991-01-01

A new research area of multiple methods integration is proposed for joining diverse methods of structural mechanics analysis which interact with one another. Three categories of multiple methods are defined: those in which a physical interface are well defined; those in which a physical interface is not well-defined, but selected; and those in which the interface is a mathematical transformation. Two fundamental integration procedures are presented that can be extended to integrate various methods (e.g., finite elements, Rayleigh Ritz, Galerkin, and integral methods) with one another. Since the finite element method will likely be the major method to be integrated, its enhanced robustness under element distortion is also examined and a new robust shell element is demonstrated.

Multiple Myeloma Genomics: A Systematic Review.

PubMed

Weaver, Casey J; Tariman, Joseph D

2017-08-01

This integrative review describes the genomic variants that have been found to be associated with poor prognosis in patients diagnosed with multiple myeloma (MM). Second, it identifies MM genetic and genomic changes using next-generation sequencing, specifically whole-genome sequencing or exome sequencing. A search for peer-reviewed articles through PubMed, EBSCOhost, and DePaul WorldCat Libraries Worldwide yielded 33 articles that were included in the final analysis. The most commonly reported genetic changes were KRAS, NRAS, TP53, FAM46C, BRAF, DIS3, ATM, and CCND1. These genetic changes play a role in the pathogenesis of MM, prognostication, and therapeutic targets for novel therapies. MM genetics and genomics are expanding rapidly; oncology nurse clinicians must have basic competencies in genetics and genomics to help patients understand the complexities of genetic and genomic alterations and be able to refer patients to appropriate genomic professionals if needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic susceptibility to lung cancer—light at the end of the tunnel?

PubMed Central

Christiani, David C.

2013-01-01

Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer is cigarette smoking. Additionally, there are multiple genetic factors, which may also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate genes leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and patterns of genetic risk may be useful in the earlier detection and treatment of lung cancer patients. PMID:23349013

Identification, variation and transcription of pneumococcal repeat sequences

PubMed Central

2011-01-01

Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

Component mode synthesis and large deflection vibration of complex structures. Volume 3: Multiple-mode nonlinear free and forced vibrations of beams using finite element method

NASA Technical Reports Server (NTRS)

Mei, Chuh; Shen, Mo-How

1987-01-01

Multiple-mode nonlinear forced vibration of a beam was analyzed by the finite element method. Inplane (longitudinal) displacement and inertia (IDI) are considered in the formulation. By combining the finite element method and nonlinear theory, more realistic models of structural response are obtained more easily and faster.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

PubMed Central

Jahanshad, Neda; Kochunov, Peter; Sprooten, Emma; Mandl, René C.; Nichols, Thomas E.; Almassy, Laura; Blangero, John; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Martin, Nicholas G.; McMahon, Katie L.; Medland, Sarah E.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Hulshoff Pol, Hilleke E.; Bastin, Mark E.; McIntosh, Andrew M.; Deary, Ian J.; Thompson, Paul M.; Glahn, David C.

2013-01-01

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/). PMID:23629049

Genetic parameters for first lactation test-day milk flow in Holstein cows.

PubMed

Laureano, M M M; Bignardi, A B; El Faro, L; Cardoso, V L; Albuquerque, L G

2012-01-01

Genetic parameters for test-day milk flow (TDMF) of 2175 first lactations of Holstein cows were estimated using multiple-trait and repeatability models. The models included the direct additive genetic effect as a random effect and contemporary group (defined as the year and month of test) and age of cow at calving (linear and quadratic effect) as fixed effects. For the repeatability model, in addition to the effects cited, the permanent environmental effect of the animal was also included as a random effect. Variance components were estimated using the restricted maximum likelihood method in single- and multiple-trait and repeatability analyses. The heritability estimates for TDMF ranged from 0.23 (TDMF 6) to 0.32 (TDMF 2 and TDMF 4) in single-trait analysis and from 0.28 (TDMF 7 and TDMF 10) to 0.37 (TDMF 4) in multiple-trait analysis. In general, higher heritabilities were observed at the beginning of lactation until the fourth month. Heritability estimated with the repeatability model was 0.27 and the coefficient of repeatability for first lactation TDMF was 0.66. The genetic correlations were positive and ranged from 0.72 (TDMF 1 and 10) to 0.97 (TDMF 4 and 5). The results indicate that milk flow should respond satisfactorily to selection, promoting rapid genetic gains because the estimated heritabilities were moderate to high. Higher genetic gains might be obtained if selection was performed in the TDMF 4. Both the repeatability model and the multiple-trait model are adequate for the genetic evaluation of animals in terms of milk flow, but the latter provides more accurate estimates of breeding values.

Transcriptional activation of Mina by Sp1/3 factors.

PubMed

Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

2013-01-01

Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.

Transcriptional Activation of Mina by Sp1/3 Factors

PubMed Central

Lian, Shangli; Potula, Hari Hara S. K.; Pillai, Meenu R.; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

2013-01-01

Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5′ region [1]. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays – reporter, gel shift and chromatin immunoprecipitation – to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways. PMID:24324617

Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens

PubMed Central

Wales, Andrew D.; Davies, Robert H.

2015-01-01

Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations. PMID:27025641

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics

PubMed Central

Gillings, Michael R.; Paulsen, Ian T.; Tetu, Sasha G.

2015-01-01

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century. PMID:26371047

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics.

PubMed

Gillings, Michael R; Paulsen, Ian T; Tetu, Sasha G

2015-09-08

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century.

MACRO: a combined microchip-PCR and microarray system for high-throughput monitoring of genetically modified organisms.

PubMed

Shao, Ning; Jiang, Shi-Meng; Zhang, Miao; Wang, Jing; Guo, Shu-Juan; Li, Yang; Jiang, He-Wei; Liu, Cheng-Xi; Zhang, Da-Bing; Yang, Li-Tao; Tao, Sheng-Ce

2014-01-21

The monitoring of genetically modified organisms (GMOs) is a primary step of GMO regulation. However, there is presently a lack of effective and high-throughput methodologies for specifically and sensitively monitoring most of the commercialized GMOs. Herein, we developed a multiplex amplification on a chip with readout on an oligo microarray (MACRO) system specifically for convenient GMO monitoring. This system is composed of a microchip for multiplex amplification and an oligo microarray for the readout of multiple amplicons, containing a total of 91 targets (18 universal elements, 20 exogenous genes, 45 events, and 8 endogenous reference genes) that covers 97.1% of all GM events that have been commercialized up to 2012. We demonstrate that the specificity of MACRO is ~100%, with a limit of detection (LOD) that is suitable for real-world applications. Moreover, the results obtained of simulated complex samples and blind samples with MACRO were 100% consistent with expectations and the results of independently performed real-time PCRs, respectively. Thus, we believe MACRO is the first system that can be applied for effectively monitoring the majority of the commercialized GMOs in a single test.

A formulation of the foundations of genetics and evolution.

PubMed

Bahr, Brian Edward

2016-05-01

This paper proposes a formulation of theories of the foundations of genetics and evolution that can be used to mathematically simulate phenotype expression, reproduction, mutation, and natural selection. It will be shown that Mendelian inheritance can be mathematically simulated with expressions involving matrices and that these expressions can also simulate phenomena that are modifications to Mendel's basic principles, like alleles that give rise to quantitative effects and traits that are the expression of multiple alleles and/or multiple genetic loci. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability.

PubMed

Reggiani, Claudio; Coppens, Sandra; Sekhara, Tayeb; Dimov, Ivan; Pichon, Bruno; Lufin, Nicolas; Addor, Marie-Claude; Belligni, Elga Fabia; Digilio, Maria Cristina; Faletra, Flavio; Ferrero, Giovanni Battista; Gerard, Marion; Isidor, Bertrand; Joss, Shelagh; Niel-Bütschi, Florence; Perrone, Maria Dolores; Petit, Florence; Renieri, Alessandra; Romana, Serge; Topa, Alexandra; Vermeesch, Joris Robert; Lenaerts, Tom; Casimir, Georges; Abramowicz, Marc; Bontempi, Gianluca; Vilain, Catheline; Deconinck, Nicolas; Smits, Guillaume

2017-07-19

Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders. Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play. Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients' clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories. While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

PubMed Central

Garin, Intza; Edghill, Emma L.; Akerman, Ildem; Rubio-Cabezas, Oscar; Rica, Itxaso; Locke, Jonathan M.; Maestro, Miguel Angel; Alshaikh, Adnan; Bundak, Ruveyde; del Castillo, Gabriel; Deeb, Asma; Deiss, Dorothee; Fernandez, Juan M.; Godbole, Koumudi; Hussain, Khalid; O’Connell, Michele; Klupa, Thomasz; Kolouskova, Stanislava; Mohsin, Fauzia; Perlman, Kusiel; Sumnik, Zdenek; Rial, Jose M.; Ugarte, Estibaliz; Vasanthi, Thiruvengadam; Johnstone, Karen; Flanagan, Sarah E.; Martínez, Rosa; Castaño, Carlos; Patch, Ann-Marie; Fernández-Rebollo, Eduardo; Raile, Klemens; Morgan, Noel; Harries, Lorna W.; Castaño, Luis; Ellard, Sian; Ferrer, Jorge; de Nanclares, Guiomar Perez; Hattersley, Andrew T.

2010-01-01

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (−3.2 SD score vs. −2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man. PMID:20133622

Chemical studies of H chondrites. I - Mobile trace elements and gas retention ages

NASA Technical Reports Server (NTRS)

Lingner, David W.; Huston, Ted J.; Hutson, Melinda; Lipschutz, Michael E.

1987-01-01

Trends for 16 trace elements (Ag, As, Au, Bi, Cd, Co, Cs, Ga, In, K, Rb, Sb, Se, Te, Tl, and Zn), chosen to span a broad geochemical and thermal response range, in 44 H4-6 chondrites, differ widely from those in L4-6 chondrites. In particular, H chondrites classified as heavily shocked petrologically do not necessarily exhibit Ar-40 loss and vice versa. The clear-cut causal relationship between siderophile and mobile element loss with increasing late shock seen in L chondrites is not generally evident in the H group. H chondrite parent material experienced an early high temperature genetic episode that mobilized a substantial proportion of these trace elements so that later thermal episodes resulted in more subtle, collateral fractionations. Mildly shocked L chondrites escaped this early high temperature event, indicating that the two most numerous meteorite groups differ fundamentally in genetic history.

The perceived and predicted implications of psychiatric genetic knowledge among persons with multiple cases of depression in the family.

PubMed

Laegsgaard, M M; Stamp, A S; Hall, E O C; Mors, O

2010-12-01

Psychiatric genetic research raises hope regarding better treatment and prevention, but also regarding a possible de-stigmatizing effect of attributing mental illness to genetics. This study explores i) the impact on family relations of participating in a genetic study; ii) the impact of biogenetic attributions on perceptions of depression and stigma and iii) the perceived benefits and concerns regarding psychiatric genetic testing. Focus groups were conducted with 17 participants suffering from depression, with multiple cases of depression in the family, and previously participating in a genetic study. Participating in a genetic study caused more openness about depression in most families. A biogenetic explanation of depression was perceived as having the potential of diminishing self stigma. Testing of self and children was widely accepted, whereas prenatal testing raised concern. Persons suffering from depression may benefit from endorsing a biogenetic explanation, especially in relation to self-understanding and self-stigma. © 2010 John Wiley & Sons A/S.

Characterization of a complex context containing mecA but lacking genes encoding cassette chromosome recombinases in Staphylococcus haemolyticus

PubMed Central

2013-01-01

Background Methicillin resistance determinant mecA is generally transferred by SCCmec elements. However, the mecA gene might not be carried by a SCCmec in a Staphylococcus haemolyticus clinical isolate, WCH1, as no cassette chromosome recombinase genes were detected. Therefore, the genetic context of mecA in WCH1 was investigated. Results A 40-kb region containing mecA was obtained from WCH1, bounded by orfX at one end and several orfs of S. haemolyticus core chromosome at the other. This 40-kb region was very complex in structure with multiple genetic components that appeared to have different origins. For instance, the 3.7-kb structure adjacent to orfX was almost identical to that on the chromosome of Staphylococcus epidermidis RP62a but was absent from S. haemolyticus JCSC1435. Terminal inverted repeats of SCC were found but no ccr genes could be detected. mecA was bracketed by two copies of IS431, which was flanked by 8-bp direct target repeat sequence (DR). Conclusions The presence of 8-bp DR suggests that the two copies of IS431 might have formed a composite transposon for mobilizing mecA. This finding is of significance as multiple copies of IS431 are commonly present in the contexts of mecA, which might have the potential to form various composite transposons that could mediate the mobilization of mecA. This study also provides an explanation for the absence of ccr in some staphylococci isolates carrying mecA. PMID:23521926

Characterization of a complex context containing mecA but lacking genes encoding cassette chromosome recombinases in Staphylococcus haemolyticus.

PubMed

Zong, Zhiyong

2013-03-22

Methicillin resistance determinant mecA is generally transferred by SCCmec elements. However, the mecA gene might not be carried by a SCCmec in a Staphylococcus haemolyticus clinical isolate, WCH1, as no cassette chromosome recombinase genes were detected. Therefore, the genetic context of mecA in WCH1 was investigated. A 40-kb region containing mecA was obtained from WCH1, bounded by orfX at one end and several orfs of S. haemolyticus core chromosome at the other. This 40-kb region was very complex in structure with multiple genetic components that appeared to have different origins. For instance, the 3.7-kb structure adjacent to orfX was almost identical to that on the chromosome of Staphylococcus epidermidis RP62a but was absent from S. haemolyticus JCSC1435. Terminal inverted repeats of SCC were found but no ccr genes could be detected. mecA was bracketed by two copies of IS431, which was flanked by 8-bp direct target repeat sequence (DR). The presence of 8-bp DR suggests that the two copies of IS431 might have formed a composite transposon for mobilizing mecA. This finding is of significance as multiple copies of IS431 are commonly present in the contexts of mecA, which might have the potential to form various composite transposons that could mediate the mobilization of mecA. This study also provides an explanation for the absence of ccr in some staphylococci isolates carrying mecA.

Identifying micro-inversions using high-throughput sequencing reads.

PubMed

He, Feifei; Li, Yang; Tang, Yu-Hang; Ma, Jian; Zhu, Huaiqiu

2016-01-11

The identification of inversions of DNA segments shorter than read length (e.g., 100 bp), defined as micro-inversions (MIs), remains challenging for next-generation sequencing reads. It is acknowledged that MIs are important genomic variation and may play roles in causing genetic disease. However, current alignment methods are generally insensitive to detect MIs. Here we develop a novel tool, MID (Micro-Inversion Detector), to identify MIs in human genomes using next-generation sequencing reads. The algorithm of MID is designed based on a dynamic programming path-finding approach. What makes MID different from other variant detection tools is that MID can handle small MIs and multiple breakpoints within an unmapped read. Moreover, MID improves reliability in low coverage data by integrating multiple samples. Our evaluation demonstrated that MID outperforms Gustaf, which can currently detect inversions from 30 bp to 500 bp. To our knowledge, MID is the first method that can efficiently and reliably identify MIs from unmapped short next-generation sequencing reads. MID is reliable on low coverage data, which is suitable for large-scale projects such as the 1000 Genomes Project (1KGP). MID identified previously unknown MIs from the 1KGP that overlap with genes and regulatory elements in the human genome. We also identified MIs in cancer cell lines from Cancer Cell Line Encyclopedia (CCLE). Therefore our tool is expected to be useful to improve the study of MIs as a type of genetic variant in the human genome. The source code can be downloaded from: http://cqb.pku.edu.cn/ZhuLab/MID .

Genetic Architecture of Lacunar Stroke.

PubMed

Traylor, Matthew; Bevan, Steve; Baron, Jean-Claude; Hassan, Ahamad; Lewis, Cathryn M; Markus, Hugh S

2015-09-01

Lacunar strokes comprise ≈20% of all strokes. Despite this frequency, their pathogenesis is poorly understood. Previous genome-wide association studies in lacunar stroke have been disappointing, which may be because of phenotypic heterogeneity. Pathological and radiological studies suggest that there may be different pathologies underlying lacunar strokes. This has led to the suggestion of 2 subtypes: isolated lacunar infarcts and multiple lacunar infarcts and leukoaraiosis. We performed genome-wide analyses in a magnetic resonance imaging-verified cohort of 1012 younger onset lacunar stroke cases and 964 controls. Using these data, we first estimated the heritability of lacunar stroke and its 2 hypothesized subtypes, and secondly, we determined whether this is enriched for regulatory regions in the genome, as defined by data from Encyclopedia of DNA Elements (ENCODE) and other sources. Finally, we determine the evidence for a polygenic contribution from rare variation to lacunar stroke and its subtypes. Our results indicate a substantial heritable component to magnetic resonance imaging-verified lacunar stroke (20%-25%) and its 2 subtypes (isolated lacunar infarct, 15%-18%; multiple lacunar infarcts/leukoaraiosis, 23%-28%). This heritable component is significantly enriched for sites affecting expression of genes. In addition, we show that the risk of the 2 subtypes of lacunar stroke in isolation, but not in combination, is associated with rare variation in the genome. Lacunar stroke, when defined on magnetic resonance imaging, is a highly heritable complex disease. Much of this heritability arises from regions of the genome affecting gene regulation. Rare variation affects 2 subtypes of lacunar in isolation, suggesting that they may have distinct genetic susceptibility factors. © 2015 The Authors.

Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system.

PubMed

Hsu, Li-Yang; Harris, Simon R; Chlebowicz, Monika A; Lindsay, Jodi A; Koh, Tse-Hsien; Krishnan, Prabha; Tan, Thean-Yen; Hon, Pei-Yun; Grubb, Warren B; Bentley, Stephen D; Parkhill, Julian; Peacock, Sharon J; Holden, Matthew T G

2015-04-23

In the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe. We investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population. Our results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations.

Optimization of shape control of a cantilever beam using dielectric elastomer actuators

NASA Astrophysics Data System (ADS)

Liu, Chong; Mao, Boyong; Huang, Gangting; Wu, Qichen; Xie, Shilin; Xu, Minglong

2018-05-01

Dielectric elastomer (DE) is a kind of smart soft material that has many advantages such as large deformation, fast response, lightweight and easy synthesis. These features make dielectric elastomer a suitable material for actuators. This article focuses on the shape control of a cantilever beam by using dielectric elastomer actuators. The shape control equation in finite element formulation of the cantilever beam partially covered with dielectric elastomer actuators is derived based on the constitutive equation of dielectric elastomer material by using Hamilton principle. The actuating forces produced by dielectric elastomer actuators depend on the number of layers, the position and the actuation voltage of dielectric elastomer actuators. First, effects of these factors on the shape control accuracy when one pair or multiple pairs of actuators are employed are simulated, respectively. The simulation results demonstrate that increasing the number of actuators or the number of layers can improve the control effect and reduce the actuation voltages effectively. Second, to achieve the optimal shape control effect, the position of the actuators and the drive voltages are all determined using a genetic algorithm. The robustness of the genetic algorithm is analyzed. Moreover, the implications of using one pair and multiple pairs of actuators to drive the cantilever beam to the expected shape are investigated. The results demonstrate that a small number of actuators with optimal placement and optimal voltage values can achieve the shape control of the beam effectively. Finally, a preliminary experimental verification of the control effect is carried out, which shows the correctness of the theoretical method.

IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas.

PubMed

Valera, Alexandra; Balagué, Olga; Colomo, Luis; Martínez, Antonio; Delabie, Jan; Taddesse-Heath, Lekidelu; Jaffe, Elaine S; Campo, Elías

2010-11-01

Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in the immunocompromised or elderly patients. Although the clinical and pathologic characteristics of these tumors have been defined, the genetic alterations involved in their pathogenesis are not well known. In this study, we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization in 42 PBL and 3 extracavitary primary effusion lymphomas. MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumors. MYC rearrangements were more common in Epstein-Barr virus (EBV)-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumors (P<0.05). No rearrangements of BCL2, BCL6, MALT1, or PAX5 were detected in any PBL but gains of these loci were observed in 31% to 41% of the cases examined. Twelve of the 40 PBL in which 3 or more loci could be investigated had multiple simultaneous gains in 3 or more loci. No differences in the survival of the patients according to MYC were observed but the 4 patients with the longest survival (>50 mo) had no or low number of gains (<3). No rearrangements of any of these loci were seen in the primary effusion lymphomas. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.

Informed decision-making in elective major vascular surgery: analysis of 145 surgeon-patient consultations.

PubMed

Etchells, Edward; Ferrari, Michel; Kiss, Alex; Martyn, Nikki; Zinman, Deborah; Levinson, Wendy

2011-06-01

Prior studies show significant gaps in the informed decision-making process, a central goal of surgical care. These studies have been limited by their focus on low-risk decisions, single visits rather than entire consultations, or both. Our objectives were, first, to rate informed decision-making for major elective vascular surgery based on audiotapes of actual physician-patient conversations and, second, to compare ratings of informed decision-making for first visits to ratings for multiple visits by the same patient over time. We prospectively enrolled patients for whom vascular surgical treatment was a potential option at a tertiary care outpatient vascular surgery clinic. We audio-taped all surgeon-patient conversations, including multiple visits when necessary, until a decision was made. Using an existing method, we evaluated the transcripts for elements of decision-making, including basic elements (e.g., an explanation of the clinical condition), intermediate elements (e.g., risks and benefits) and complex elements (e.g., uncertainty around the decision). We analyzed 145 surgeon-patient consultations. Overall, 45% of consultations contained complex elements, whereas 23% did not contain the basic elements of decision-making. For the 67 consultations that involved multiple visits, ratings were significantly higher when evaluating all visits (50% complex elements) compared with evaluating only the first visit (33% complex elements, p < 0.001.) We found that 45% of consultations contained complex elements, which is higher than prior studies with similar methods. Analyzing decision-making over multiple visits yielded different results than analyzing decision-making for single visits.

Genetically engineered acidophilic heterotrophic bacteria by bacteriophage transduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, T.E.; Bruhn, D.F.; Bulmer, D.F.

1989-05-10

A bacteriophage capable of infecting acidophilic heterotrophic bacteria and processes for genetically engineering acidophilic bacteria for biomining or sulfur removal from coal are disclosed. The bacteriophage is capable of growth in cells existing at pH at or below 3.0. Lytic forms of the phage introduced into areas experiencing acid drainage kill the bacteria causing such drainage. Lysogenic forms of the phage having genes for selective removal of metallic or nonmetallic elements can be introduced into acidophilic bacteria to effect removal of the desired element from ore or coal. 1 fig., 1 tab.

Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans.

PubMed

He, Kan; Zhou, Tao; Shao, Jiaofang; Ren, Xiaoliang; Zhao, Zhongying; Liu, Dahai

2014-03-01

Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.

German politics of genetic engineering and its deconstruction.

PubMed

Gottweis, H

1995-05-01

Policy-making, as exemplified by biotechnology policy, can be understood as an attempt to manage a field of discursivity, to construct regularity in a dispersed multitude of combinable elements. Following this perspective of politics as a textual process, the paper interprets the politicization of genetic engineering in Germany as a defence of the political as a regime of heterogeneity, as a field of 'dissensus' rather than 'consensus', and a rejection of the idea that the framing of technological transformation is an autonomous process. From its beginning in the early 1970s, genetic engineering was symbolically entrenched as a key technology of the future, and as an integral element of the German politics of modernization. Attempts by new social movements and the Green Party to displace the egalitarian imaginary of democratic discourse into the politics of genetic engineering were construed by the political élites as an attack on the political order of post-World War II Germany. The 1990 Genetic Engineering Law attempted a closure of this controversy. But it is precisely the homogenizing idiom of this 'settlement' which continues to nourish the social movements and their radical challenge to the definitions and codings of the politics of genetic engineering.

Huanglongbing: An overview of a complex pathosystem ravaging the world's citrus.

PubMed

da Graça, John V; Douhan, Greg W; Halbert, Susan E; Keremane, Manjunath L; Lee, Richard F; Vidalakis, Georgios; Zhao, Hongwei

2016-04-01

Citrus huanglongbing (HLB) has become a major disease and limiting factor of production in citrus areas that have become infected. The destruction to the affected citrus industries has resulted in a tremendous increase to support research that in return has resulted in significant information on both applied and basic knowledge concerning this important disease to the global citrus industry. Recent research indicates the relationship between citrus and the causal agent of HLB is shaped by multiple elements, in which host defense responses may also play an important role. This review is intended to provide an overview of the importance of HLB to a wider audience of plant biologists. Recent advances on host-pathogen interactions, population genetics and vectoring of the causal agent are discussed. © 2015 Institute of Botany, Chinese Academy of Sciences.

Habit Reversal Therapy for Body-Focused Repetitive Behaviors in Williams Syndrome: A Case Study

PubMed Central

Klein-Tasman, Bonita P.

2013-01-01

Williams syndrome (WS) is genetic neurodevelopmental disorder with a well-characterized cognitive and behavioral phenotype. Research has consistently demonstrated high rates of psychopathology in this population; however, little research has examined the use of empirically-supported psychosocial interventions in those with WS. The current case study reports on the use of Habit Reversal Therapy (HRT) to treat multiple body-focused repetitive behaviors in a child with WS. Although HRT is a well-established cognitive-behavioral intervention for body-focused repetitive behaviors, it has been infrequently used in populations with developmental disabilities. An etiologically-informed approach was used to adapt HRT to fit the known behavioral and cognitive phenotype of WS. Results suggest that HRT may be beneficial for this population. Modified treatment elements are described and future research areas highlighted. PMID:24357918

Influence of within year treatments and between year environmental differences on peach leaf ash and carbon isotopic discrimination responses

USDA-ARS?s Scientific Manuscript database

Plant ash content is related to water use efficiency (WUE) (dry matter accumulation per unit of transpiration) and Delta 13C in a range of C3 species. In breeding programs, the genetic x environment interaction is measured with multiple locations and multiple years of evaluation but the genetic x e...

Chromosome size in diploid eukaryotic species centers on the average length with a conserved boundary

USDA-ARS?s Scientific Manuscript database

Understanding genome and chromosome evolution is important for understanding genetic inheritance and evolution. Universal events comprising DNA replication, transcription, repair, mobile genetic element transposition, chromosome rearrangements, mitosis, and meiosis underlie inheritance and variation...

The Genetic Basis of Upland/Lowland Ecotype Divergence in Switchgrass (Panicum virgatum)

PubMed Central

Milano, Elizabeth R.; Lowry, David B.; Juenger, Thomas E.

2016-01-01

The evolution of locally adapted ecotypes is a common phenomenon that generates diversity within plant species. However, we know surprisingly little about the genetic mechanisms underlying the locally adapted traits involved in ecotype formation. The genetic architecture underlying locally adapted traits dictates how an organism will respond to environmental selection pressures, and has major implications for evolutionary ecology, conservation, and crop breeding. To understand the genetic architecture underlying the divergence of switchgrass (Panicum virgatum) ecotypes, we constructed a genetic mapping population through a four-way outbred cross between two northern upland and two southern lowland accessions. Trait segregation in this mapping population was largely consistent with multiple independent loci controlling the suite of traits that characterizes ecotype divergence. We assembled a joint linkage map using ddRADseq, and mapped quantitative trait loci (QTL) for traits that are divergent between ecotypes, including flowering time, plant size, physiological processes, and disease resistance. Overall, we found that most QTL had small to intermediate effects. While we identified colocalizing QTL for multiple traits, we did not find any large-effect QTL that clearly controlled multiple traits through pleiotropy or tight physical linkage. These results indicate that ecologically important traits in switchgrass have a complex genetic basis, and that similar loci may underlie divergence across the geographic range of the ecotypes. PMID:27613751

Shedding subspecies: The influence of genetics on reptile subspecies taxonomy.

PubMed

Torstrom, Shannon M; Pangle, Kevin L; Swanson, Bradley J

2014-07-01

The subspecies concept influences multiple aspects of biology and management. The 'molecular revolution' altered traditional methods (morphological traits) of subspecies classification by applying genetic analyses resulting in alternative or contradictory classifications. We evaluated recent reptile literature for bias in the recommendations regarding subspecies status when genetic data were included. Reviewing characteristics of the study, genetic variables, genetic distance values and noting the species concepts, we found that subspecies were more likely elevated to species when using genetic analysis. However, there was no predictive relationship between variables used and taxonomic recommendation. There was a significant difference between the median genetic distance values when researchers elevated or collapsed a subspecies. Our review found nine different concepts of species used when recommending taxonomic change, and studies incorporating multiple species concepts were more likely to recommend a taxonomic change. Since using genetic techniques significantly alter reptile taxonomy there is a need to establish a standard method to determine the species-subspecies boundary in order to effectively use the subspecies classification for research and conservation purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

Thermionic nuclear reactor with internal heat distribution and multiple duct cooling

DOEpatents

Fisher, C.R.; Perry, L.W. Jr.

1975-11-01

A Thermionic Nuclear Reactor is described having multiple ribbon-like coolant ducts passing through the core, intertwined among the thermionic fuel elements to provide independent cooling paths. Heat pipes are disposed in the core between and adjacent to the thermionic fuel elements and the ribbon ducting, for the purpose of more uniformly distributing the heat of fission among the thermionic fuel elements and the ducts.

Comprehensive Fuel Spray Modeling and Impacts on Chamber Acoustics in Combustion Dynamics Simulations

DTIC Science & Technology

2013-05-01

multiple swirler configurations and fuel injector locations at atmospheric pressure con- ditions. Both single-element and multiple-element LDI...the swirl number, Reynolds’ number and injector location in the LDI element. Besides the multi-phase flow characteristics, several experimen- tal...region downstream of the fuel injector on account of a sta- ble and compact precessing vortex core. Recent ex- periments conducted by the Purdue group have

Right-Brain/Left-Brain Integrated Associative Processor Employing Convertible Multiple-Instruction-Stream Multiple-Data-Stream Elements

NASA Astrophysics Data System (ADS)

Hayakawa, Hitoshi; Ogawa, Makoto; Shibata, Tadashi

2005-04-01

A very large scale integrated circuit (VLSI) architecture for a multiple-instruction-stream multiple-data-stream (MIMD) associative processor has been proposed. The processor employs an architecture that enables seamless switching from associative operations to arithmetic operations. The MIMD element is convertible to a regular central processing unit (CPU) while maintaining its high performance as an associative processor. Therefore, the MIMD associative processor can perform not only on-chip perception, i.e., searching for the vector most similar to an input vector throughout the on-chip cache memory, but also arithmetic and logic operations similar to those in ordinary CPUs, both simultaneously in parallel processing. Three key technologies have been developed to generate the MIMD element: associative-operation-and-arithmetic-operation switchable calculation units, a versatile register control scheme within the MIMD element for flexible operations, and a short instruction set for minimizing the memory size for program storage. Key circuit blocks were designed and fabricated using 0.18 μm complementary metal-oxide-semiconductor (CMOS) technology. As a result, the full-featured MIMD element is estimated to be 3 mm2, showing the feasibility of an 8-parallel-MIMD-element associative processor in a single chip of 5 mm× 5 mm.

Exploring the possibility of modeling a genetic counseling guideline using agile methodology.

PubMed

Choi, Jeeyae

2013-01-01

Increased demand of genetic counseling services heightened the necessity of a computerized genetic counseling decision support system. In order to develop an effective and efficient computerized system, modeling of genetic counseling guideline is an essential step. Throughout this pilot study, Agile methodology with United Modeling Language (UML) was utilized to model a guideline. 13 tasks and 14 associated elements were extracted. Successfully constructed conceptual class and activity diagrams revealed that Agile methodology with UML was a suitable tool to modeling a genetic counseling guideline.

Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water

PubMed Central

Schwartz, Thomas; Armant, Olivier; Bretschneider, Nancy; Hahn, Alexander; Kirchen, Silke; Seifert, Martin; Dötsch, Andreas

2015-01-01

The fitness of sensitive and resistant Pseudomonas aeruginosa in different aquatic environments depends on genetic capacities and transcriptional regulation. Therefore, an antibiotic-sensitive isolate PA30 and a multi-resistant isolate PA49 originating from waste waters were compared via whole genome and transcriptome Illumina sequencing after exposure to municipal waste water and tap water. A number of different genomic islands (e.g. PAGIs, PAPIs) were identified in the two environmental isolates beside the highly conserved core genome. Exposure to tap water and waste water exhibited similar transcriptional impacts on several gene clusters (antibiotic and metal resistance, genetic mobile elements, efflux pumps) in both environmental P. aeruginosa isolates. The MexCD-OprJ efflux pump was overexpressed in PA49 in response to waste water. The expression of resistance genes, genetic mobile elements in PA49 was independent from the water matrix. Consistently, the antibiotic sensitive strain PA30 did not show any difference in expression of the intrinsic resistance determinants and genetic mobile elements. Thus, the exposure of both isolates to polluted waste water and oligotrophic tap water resulted in similar expression profiles of mentioned genes. However, changes in environmental milieus resulted in rather unspecific transcriptional responses than selected and stimuli-specific gene regulation. PMID:25186059

Movable Genetic Elements: Detection of Changes in Maize DNA at the Shrunken Locus Due to the Intervention of Ds Elements

DOE R&D Accomplishments Database

Burr, B.; Burr, F.A.

1980-05-28

This report describes our initial attempts at the molecular characterization of a maize controlling element. We have prepared a cDNA probe and used it to detect changes at a locus where Ds elements are found. Evidence of their presence are indicated by changes in the restriction patterns, but there is as yet no information on the physical nature of the controlling elements nor on the kinds of rearrangements they cause.

Pre-orthographic character string processing and parietal cortex: a role for visual attention in reading?

PubMed

Lobier, Muriel; Peyrin, Carole; Le Bas, Jean-François; Valdois, Sylviane

2012-07-01

The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetic addiction: selfish gene's strategy for symbiosis in the genome.

PubMed

Mochizuki, Atsushi; Yahara, Koji; Kobayashi, Ichizo; Iwasa, Yoh

2006-02-01

The evolution and maintenance of the phenomenon of postsegregational host killing or genetic addiction are paradoxical. In this phenomenon, a gene complex, once established in a genome, programs death of a host cell that has eliminated it. The intact form of the gene complex would survive in other members of the host population. It is controversial as to why these genetic elements are maintained, due to the lethal effects of host killing, or perhaps some other properties are beneficial to the host. We analyzed their population dynamics by analytical methods and computer simulations. Genetic addiction turned out to be advantageous to the gene complex in the presence of a competitor genetic element. The advantage is, however, limited in a population without spatial structure, such as that in a well-mixed liquid culture. In contrast, in a structured habitat, such as the surface of a solid medium, the addiction gene complex can increase in frequency, irrespective of its initial density. Our demonstration that genomes can evolve through acquisition of addiction genes has implications for the general question of how a genome can evolve as a community of potentially selfish genes.

Estimation of the size of genetic bottlenecks in cell-to-cell movement of soil-borne wheat mosaic virus and the possible role of the bottlenecks in speeding up selection of variations in trans-acting genes or elements.

PubMed

Miyashita, Shuhei; Kishino, Hirohisa

2010-02-01

Genetic bottlenecks facilitate the fixation and extinction of variants in populations, and viral populations are no exception to this theory. To examine the existence of genetic bottlenecks in cell-to-cell movement of plant RNA viruses, we prepared constructs for Soil-borne wheat mosaic virus RNA2 vectors carrying two different fluorescent proteins, yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP). Coinoculation of host plant leaves with the two RNA2 vectors and the wild-type RNA1 showed separation of the two vector RNA2s, mostly within seven to nine cell-to-cell movements from individual initially coinfected cells. Our statistical analysis showed that the number of viral RNA genomes establishing infection in adjacent cells after the first cell-to-cell movement from an initially infected cell was 5.97 +/- 0.22 on average and 5.02 +/- 0.29 after the second cell-to-cell movement. These results indicate that plant RNA viruses may generally face narrow genetic bottlenecks in every cell-to-cell movement. Furthermore, our model suggests that, rather than suffering from fitness losses caused by the bottlenecks, the plant RNA viruses are utilizing the repeated genetic bottlenecks as an essential element of rapid selection of their adaptive variants in trans-acting genes or elements to respond to host shifting and changes in the growth conditions of the hosts.

Construction of 2,4,6-Trinitrotoluene Biosensors with Novel Sensing Elements from Escherichia coli K-12 MG1655.

PubMed

Tan, Junjie; Kan, Naipeng; Wang, Wei; Ling, Jingyi; Qu, Guolong; Jin, Jing; Shao, Yu; Liu, Gang; Chen, Huipeng

2015-06-01

Detection of 2,4,6-trinitrotoluene (TNT) has been extensively studied since it is a common explosive filling for landmines, posing significant threats to the environment and human safety. The rapid advances in synthetic biology give new hope to detect such toxic and hazardous compounds in a more sensitive and safe way. Biosensor construction anticipates finding sensing elements able to detect TNT. As TNT can induce some physiological responses in E. coli, it may be useful to define the sensing elements from E. coli to detect TNT. An E. coli MG1655 genomic promoter library containing nearly 5,400 elements was constructed. Five elements, yadG, yqgC, aspC, recE, and topA, displayed high sensing specificity to TNT and its indicator compounds 1,3-DNB and 2,4-DNT. Based on this, a whole cell biosensor was constructed using E. coli, in which green fluorescent protein was positioned downstream of the five sensing elements via genetic fusion. The threshold value, detection time, EC200 value, and other aspects of five sensing elements were determined and the minimum responding concentration to TNT was 4.75 mg/L. According to the synthetic biology, the five sensing elements enriched the reservoir of TNT-sensing elements, and provided a more applicable toolkit to be applied in genetic routes and live systems of biosensors in future.

Medea selfish genetic elements as tools for altering traits of wild populations: a theoretical analysis.

PubMed

Ward, Catherine M; Su, Jessica T; Huang, Yunxin; Lloyd, Alun L; Gould, Fred; Hay, Bruce A

2011-04-01

One strategy for controlling transmission of insect-borne disease involves replacing the native insect population with transgenic animals unable to transmit disease. Population replacement requires a drive mechanism to ensure the rapid spread of linked transgenes, the presence of which may result in a fitness cost to carriers. Medea selfish genetic elements have the feature that when present in a female, only offspring that inherit the element survive, a behavior that can lead to spread. Here, we derive equations that describe the conditions under which Medea elements with a fitness cost will spread, and the equilibrium allele frequencies are achieved. Of particular importance, we show that whenever Medea spreads, the non-Medea genotype is driven out of the population, and we estimate the number of generations required to achieve this goal for Medea elements with different fitness costs and male-only introduction frequencies. Finally, we characterize two contexts in which Medea elements with fitness costs drive the non-Medea allele from the population: an autosomal element in which not all Medea-bearing progeny of a Medea-bearing mother survive, and an X-linked element in species in which X/Y individuals are male. Our results suggest that Medea elements can drive population replacement under a wide range of conditions. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Predictive hypotheses are ineffectual in resolving complex biochemical systems.

PubMed

Fry, Michael

2018-03-20

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

Isolation and partial characterization of a root-specific promoter for stacking multiple traits into cassava (Manihot esculenta CRANTZ).

PubMed

Gbadegesin, M A; Beeching, J R

2011-06-07

Cassava can be cultivated on impoverished soils with minimum inputs, and its storage roots are a staple food for millions in Africa. However, these roots are low in bioavailable nutrients and in protein content, contain cyanogenic glycosides, and suffer from a very short post-harvest shelf-life, and the plant is susceptible to viral and bacterial diseases prevalent in Africa. The demand for improvement of cassava with respect to these traits comes from both farmers and national agricultural institutions. Genetic improvement of cassava cultivars by molecular biology techniques requires the availability of appropriate genes, a system to introduce these genes into cassava, and the use of suitable gene promoters. Cassava root-specific promoter for auxin-repressed protein was isolated using the gene walking approach, starting with a cDNA sequence. In silico analysis of promoter sequences revealed putative cis-acting regulatory elements, including root-specific elements, which may be required for gene expression in vascular tissues. Research on the activities of this promoter is continuing, with the development of plant expression cassettes for transformation into major African elite lines and farmers' preferred cassava cultivars to enable testing of tissue-specific expression patterns in the field.

Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by transpositional insertion of a piggyBac vector.

PubMed

Lobo, N F; Hua-Van, A; Li, X; Nolen, B M; Fraser, M J

2002-04-01

Mosquito-vectored diseases such as yellow fever and dengue fever continue to have a substantial impact on human populations world-wide. Novel strategies for control of these mosquito vectored diseases can arise through the development of reliable systems for genetic manipulation of the insect vector. A piggyBac vector marked with the Drosophila melanogaster cinnabar (cn) gene was used to transform the white-eyed khw strain of Aedes aegypti. Microinjection of preblastoderm embryos resulted in four families of cinnabar transformed insects. An overall transformation frequency of 4%, with a range of 0% to as high as 13% for individual experiments, was achieved when using a heat-shock induced transposase providing helper plasmid. Southern hybridizations indicated multiple insertion events in three of four transgenic lines, while the presence of duplicated target TTAA sites at either ends of individual insertions confirmed characteristic piggyBac transposition events in these three transgenic lines. The transgenic phenotype has remained stable for more than twenty generations. The transformations effected using the piggyBac element establish the potential of this element as a germ-line transformation vector for Aedine mosquitoes.

Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

PubMed

Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

2017-08-01

Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

PubMed

Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

2008-12-23

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster.

PubMed

Simoni, Alekos; Siniscalchi, Carla; Chan, Yuk-Sang; Huen, David S; Russell, Steven; Windbichler, Nikolai; Crisanti, Andrea

2014-06-01

Selfish genes are DNA elements that increase their rate of genetic transmission at the expense of other genes in the genome and can therefore quickly spread within a population. It has been suggested that selfish elements could be exploited to modify the genome of entire populations for medical and ecological applications. Here we report that transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) can be engineered into site-specific synthetic selfish elements (SSEs) and demonstrate their transmission of up to 70% in the Drosophila germline. We show here that SSEs can spread via DNA break-induced homologous recombination, a process known as 'homing' similar to that observed for homing endonuclease genes (HEGs), despite their fundamentally different modes of DNA binding and cleavage. We observed that TALEN and ZFN have a reduced capability of secondary homing compared to HEG as their repetitive structure had a negative effect on their genetic stability. The modular architecture of ZFNs and TALENs allows for the rapid design of novel SSEs against specific genomic sequences making them potentially suitable for the genetic engineering of wild-type populations of animals and plants, in applications such as gene replacement or population suppression of pest species. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optimization of the sources in local hyperthermia using a combined finite element-genetic algorithm method.

PubMed

Siauve, N; Nicolas, L; Vollaire, C; Marchal, C

2004-12-01

This article describes an optimization process specially designed for local and regional hyperthermia in order to achieve the desired specific absorption rate in the patient. It is based on a genetic algorithm coupled to a finite element formulation. The optimization method is applied to real human organs meshes assembled from computerized tomography scans. A 3D finite element formulation is used to calculate the electromagnetic field in the patient, achieved by radiofrequency or microwave sources. Space discretization is performed using incomplete first order edge elements. The sparse complex symmetric matrix equation is solved using a conjugate gradient solver with potential projection pre-conditionning. The formulation is validated by comparison of calculated specific absorption rate distributions in a phantom to temperature measurements. A genetic algorithm is used to optimize the specific absorption rate distribution to predict the phases and amplitudes of the sources leading to the best focalization. The objective function is defined as the specific absorption rate ratio in the tumour and healthy tissues. Several constraints, regarding the specific absorption rate in tumour and the total power in the patient, may be prescribed. Results obtained with two types of applicators (waveguides and annular phased array) are presented and show the faculties of the developed optimization process.

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England

PubMed Central

2010-01-01

Background As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Methods Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Results Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Conclusions Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions. PMID:20470377

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England.

PubMed

Bennett, Catherine L; Burke, Sarah E; Burton, Hilary; Farndon, Peter A

2010-05-14

As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions.

Genetic relationships between detailed reproductive traits and performance traits in Holstein-Friesian dairy cattle.

PubMed

Carthy, T R; Ryan, D P; Fitzgerald, A M; Evans, R D; Berry, D P

2016-02-01

The objective of the study was to estimate the genetic relationships between detailed reproductive traits derived from ultrasound examination of the reproductive tract and a range of performance traits in Holstein-Friesian dairy cows. The performance traits investigated included calving performance, milk production, somatic cell score (i.e., logarithm transformation of somatic cell count), carcass traits, and body-related linear type traits. Detailed reproductive traits included (1) resumed cyclicity at the time of examination, (2) multiple ovulations, (3) early ovulation, (4) heat detection, (5) ovarian cystic structures, (6) embryo loss, and (7) uterine score, measured on a 1 (little or no fluid with normal tone) to 4 (large quantity of fluid with a flaccid tone) scale, based on the tone of the uterine wall and the quantity of fluid present in the uterus. (Co)variance components were estimated using a repeatability animal linear mixed model. Genetic merit for greater milk, fat, and protein yield was associated with a reduced ability to resume cyclicity postpartum (genetic correlations ranged from -0.25 to -0.15). Higher genetic merit for milk yield was also associated with a greater genetic susceptibility to multiple ovulations. Genetic predisposition to elevated somatic cell score was associated with a decreased likelihood of cyclicity postpartum (genetic correlation of -0.32) and a greater risk of both multiple ovulations (genetic correlation of 0.25) and embryo loss (genetic correlation of 0.32). Greater body condition score was genetically associated with an increased likelihood of resumption of cyclicity postpartum (genetic correlation of 0.52). Genetically heavier, fatter carcasses with better conformation were also associated with an increased likelihood of resumed cyclicity by the time of examination (genetic correlations ranged from 0.24 to 0.41). Genetically heavier carcasses were associated with an inferior uterine score as well as a greater predisposition to embryo loss. Despite the overall antagonistic relationship between reproductive performance and both milk and carcass traits, not all detailed aspects of reproduction performance exhibited an antagonistic relationship. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Designed Proteins Induce the Formation of Nanocage-containing Extracellular Vesicles

PubMed Central

Votteler, Jörg; Ogohara, Cassandra; Yi, Sue; Hsia, Yang; Nattermann, Una; Belnap, David M.; King, Neil P.; Sundquist, Wesley I.

2017-01-01

Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids, and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids1,2 or proteins3–5, but strategies for engineering hybrid biological materials are only beginning to emerge6,7. Here, we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses. We refer to these hybrid biomaterials as Enveloped Protein Nanocages (EPNs). Robust EPN biogenesis required protein sequence elements that encode three distinct functions: membrane binding, self-assembly, and recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery8. A variety of synthetic proteins with these functional elements induced EPN biogenesis, highlighting the modularity and generality of the design strategy. Biochemical and electron cryomicroscopic (cryo-EM) analyses revealed that one design, EPN-01, comprised small (~100 nm) vesicles containing multiple protein nanocages that closely matched the structure of the designed 60-subunit self-assembling scaffold9. EPNs that incorporated the vesicular stomatitis viral glycoprotein (VSV-G) could fuse with target cells and deliver their contents, thereby transferring cargoes from one cell to another. These studies show how proteins can be programmed to direct the formation of hybrid biological materials that perform complex tasks, and establish EPNs as a novel class of designed, modular, genetically-encoded nanomaterials that can transfer molecules between cells. PMID:27919066

Saturation of recognition elements blocks evolution of new tRNA identities

PubMed Central

Saint-Léger, Adélaïde; Bello, Carla; Dans, Pablo D.; Torres, Adrian Gabriel; Novoa, Eva Maria; Camacho, Noelia; Orozco, Modesto; Kondrashov, Fyodor A.; Ribas de Pouplana, Lluís

2016-01-01

Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure. PMID:27386510

Effects of multiple founder populations on spatial genetic structure of reintroduced American martens.

PubMed

Williams, Bronwyn W; Scribner, Kim T

2010-01-01

Reintroductions and translocations are increasingly used to repatriate or increase probabilities of persistence for animal and plant species. Genetic and demographic characteristics of founding individuals and suitability of habitat at release sites are commonly believed to affect the success of these conservation programs. Genetic divergence among multiple source populations of American martens (Martes americana) and well documented introduction histories permitted analyses of post-introduction dispersion from release sites and development of genetic clusters in the Upper Peninsula (UP) of Michigan <50 years following release. Location and size of spatial genetic clusters and measures of individual-based autocorrelation were inferred using 11 microsatellite loci. We identified three genetic clusters in geographic proximity to original release locations. Estimated distances of effective gene flow based on spatial autocorrelation varied greatly among genetic clusters (30-90 km). Spatial contiguity of genetic clusters has been largely maintained with evidence for admixture primarily in localized regions, suggesting recent contact or locally retarded rates of gene flow. Data provide guidance for future studies of the effects of permeabilities of different land-cover and land-use features to dispersal and of other biotic and environmental factors that may contribute to the colonization process and development of spatial genetic associations.

Males and Females Contribute Unequally to Offspring Genetic Diversity in the Polygynandrous Mating System of Wild Boar

PubMed Central

Pérez-González, Javier; Costa, Vânia; Santos, Pedro; Slate, Jon; Carranza, Juan; Fernández-Llario, Pedro; Zsolnai, Attila; Monteiro, Nuno M.; Anton, István; Buzgó, József; Varga, Gyula; Beja-Pereira, Albano

2014-01-01

The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa) has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation. PMID:25541986

USE OF GENOTOXIC ACTIVITY PROFILES IN ASSESSMENT OF CARCINOGENESIS AND TRANSMISSIBLE GENETIC EFFECTS

EPA Science Inventory

A methodology has been developed to display and evaluate multiple test quantitative information on genetic toxicants for purposes of assessing carcinogenesis and transmissible genetic effects. ose Information is collected from the open literature: either the lowest effective dose...

Mobility and generation of mosaic non-autonomous transposons by Tn3-derived inverted-repeat miniature elements (TIMEs).

PubMed

Szuplewska, Magdalena; Ludwiczak, Marta; Lyzwa, Katarzyna; Czarnecki, Jakub; Bartosik, Dariusz

2014-01-01

Functional transposable elements (TEs) of several Pseudomonas spp. strains isolated from black shale ore of Lubin mine and from post-flotation tailings of Zelazny Most in Poland, were identified using a positive selection trap plasmid strategy. This approach led to the capture and characterization of (i) 13 insertion sequences from 5 IS families (IS3, IS5, ISL3, IS30 and IS1380), (ii) isoforms of two Tn3-family transposons--Tn5563a and Tn4662a (the latter contains a toxin-antitoxin system), as well as (iii) non-autonomous TEs of diverse structure, ranging in size from 262 to 3892 bp. The non-autonomous elements transposed into AT-rich DNA regions and generated 5- or 6-bp sequence duplications at the target site of transposition. Although these TEs lack a transposase gene, they contain homologous 38-bp-long terminal inverted repeat sequences (IRs), highly conserved in Tn5563a and many other Tn3-family transposons. The simplest elements of this type, designated TIMEs (Tn3 family-derived Inverted-repeat Miniature Elements) (262 bp), were identified within two natural plasmids (pZM1P1 and pLM8P2) of Pseudomonas spp. It was demonstrated that TIMEs are able to mobilize segments of plasmid DNA for transposition, which results in the generation of more complex non-autonomous elements, resembling IS-driven composite transposons in structure. Such transposon-like elements may contain different functional genetic modules in their core regions, including plasmid replication systems. Another non-autonomous element "captured" with a trap plasmid was a TIME derivative containing a predicted resolvase gene and a res site typical for many Tn3-family transposons. The identification of a portable site-specific recombination system is another intriguing example confirming the important role of non-autonomous TEs of the TIME family in shuffling genetic information in bacterial genomes. Transposition of such mosaic elements may have a significant impact on diversity and evolution, not only of transposons and plasmids, but also of other types of mobile genetic elements.

Analysis of a Near Field MIMO Wireless Channel Using 5.6 GHz Dipole Antennas

NASA Astrophysics Data System (ADS)

Maricar, Mohamed Ismaeel; Gradoni, Gabriele; Greedy, Steve; Ivrlac, Michel T.; Nossek, Josef A.; Phang, Sendy; Creagh, Stephen C.; Tanner, Gregor; Thomas, David W. P.

2016-05-01

Understanding the impact of interference upon the performance of a multiple input multiple output (MIMO) based device is of paramount importance in ensuring a design is both resilient and robust. In this work the effect of element-element interference in the creation of multiple channels of a wireless link approaching the near-field regime is studied. The elements of the 2-antenna transmit- and receive-arrays are chosen to be identical folded dipole antennas operating at 5.6 GHz. We find that two equally strong channels can be created even if the antennas interact at sub-wavelength distances, thus confirming previous theoretical predictions.

NON-MENDELIAN ETIOLOGIC FACTORS IN NEUROPSYCHIATRIC ILLNESS: PLEIOTROPY, EPIGENETICS, AND CONVERGENCE

PubMed Central

Deutsch, Curtis K; McIlvane, William J

2013-01-01

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms. PMID:23095384

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

PubMed Central

Chen, Laura P.; Beck, Anita E.; Tsuchiya, Karen D.; Chow, Penny M.; Mirzaa, Ghayda M.; Wiester, Rebecca T.

2015-01-01

Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements

PubMed Central

Tharakaraman, Kannan; Mariño-Ramírez, Leonardo; Sheetlin, Sergey L; Landsman, David; Spouge, John L

2006-01-01

Background Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances. PMID:16961919

Genes That Bias Mendelian Segregation

PubMed Central

Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion. PMID:24830502

Genes that bias Mendelian segregation.

PubMed

Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

Period doubling induced by thermal noise amplification in genetic circuits.

PubMed

Ruocco, G; Fratalocchi, A

2014-11-18

Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an "elemental" genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise.

Aerodynamic Optimization of a Supersonic Bending Body Projectile by a Vector-Evaluated Genetic Algorithm

DTIC Science & Technology

2016-12-01

Evaluated Genetic Algorithm prepared by Justin L Paul Academy of Applied Science 24 Warren Street Concord, NH 03301 under contract W911SR...Supersonic Bending Body Projectile by a Vector-Evaluated Genetic Algorithm prepared by Justin L Paul Academy of Applied Science 24 Warren Street... Genetic Algorithm 5a. CONTRACT NUMBER W199SR-15-2-001 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Justin L Paul 5d. PROJECT

Genetic Diversity of Plasmodium falciparum in Haiti: Insights from Microsatellite Markers

PubMed Central

Carter, Tamar E.; Malloy, Halley; Existe, Alexandre; Memnon, Gladys; St. Victor, Yves; Okech, Bernard A.; Mulligan, Connie J.

2015-01-01

Hispaniola, comprising Haiti and the Dominican Republic, has been identified as a candidate for malaria elimination. However, incomplete surveillance data in Haiti hamper efforts to assess the impact of ongoing malaria control interventions. Characteristics of the genetic diversity of Plasmodium falciparum populations can be used to assess parasite transmission, which is information vital to evaluating malaria elimination efforts. Here we characterize the genetic diversity of P. falciparum samples collected from patients at seven sites in Haiti using 12 microsatellite markers previously employed in population genetic analyses of global P. falciparum populations. We measured multiplicity of infections, level of genetic diversity, degree of population geographic substructure, and linkage disequilibrium (defined as non-random association of alleles from different loci). For low transmission populations like Haiti, we expect to see few multiple infections, low levels of genetic diversity, high degree of population structure, and high linkage disequilibrium. In Haiti, we found low levels of multiple infections (12.9%), moderate to high levels of genetic diversity (mean number of alleles per locus = 4.9, heterozygosity = 0.61), low levels of population structure (highest pairwise Fst = 0.09 and no clustering in principal components analysis), and moderate linkage disequilibrium (ISA = 0.05, P<0.0001). In addition, population bottleneck analysis revealed no evidence for a reduction in the P. falciparum population size in Haiti. We conclude that the high level of genetic diversity and lack of evidence for a population bottleneck may suggest that Haiti’s P. falciparum population has been stable and discuss the implications of our results for understanding the impact of malaria control interventions. We also discuss the relevance of parasite population history and other host and vector factors when assessing transmission intensity from genetic diversity data. PMID:26462203

Gene genealogies for genetic association mapping, with application to Crohn's disease

PubMed Central

Burkett, Kelly M.; Greenwood, Celia M. T.; McNeney, Brad; Graham, Jinko

2013-01-01

A gene genealogy describes relationships among haplotypes sampled from a population. Knowledge of the gene genealogy for a set of haplotypes is useful for estimation of population genetic parameters and it also has potential application in finding disease-predisposing genetic variants. As the true gene genealogy is unknown, Markov chain Monte Carlo (MCMC) approaches have been used to sample genealogies conditional on data at multiple genetic markers. We previously implemented an MCMC algorithm to sample from an approximation to the distribution of the gene genealogy conditional on haplotype data. Our approach samples ancestral trees, recombination and mutation rates at a genomic focal point. In this work, we describe how our sampler can be used to find disease-predisposing genetic variants in samples of cases and controls. We use a tree-based association statistic that quantifies the degree to which case haplotypes are more closely related to each other around the focal point than control haplotypes, without relying on a disease model. As the ancestral tree is a latent variable, so is the tree-based association statistic. We show how the sampler can be used to estimate the posterior distribution of the latent test statistic and corresponding latent p-values, which together comprise a fuzzy p-value. We illustrate the approach on a publicly-available dataset from a study of Crohn's disease that consists of genotypes at multiple SNP markers in a small genomic region. We estimate the posterior distribution of the tree-based association statistic and the recombination rate at multiple focal points in the region. Reassuringly, the posterior mean recombination rates estimated at the different focal points are consistent with previously published estimates. The tree-based association approach finds multiple sub-regions where the case haplotypes are more genetically related than the control haplotypes, and that there may be one or multiple disease-predisposing loci. PMID:24348515

Patterns of genetic diversity reveal multiple introductions and recurrent founder effects during range expansion in invasive populations of Geranium carolinianum (Geraniaceae)

PubMed Central

Shirk, R Y; Hamrick, J L; Zhang, C; Qiang, S

2014-01-01

Genetic diversity, and thus the adaptive potential of invasive populations, is largely based on three factors: patterns of genetic diversity in the species' native range, the number and location of introductions and the number of founding individuals per introduction. Specifically, reductions in genetic diversity (‘founder effects') should be stronger for species with low within-population diversity in their native range and few introductions of few individuals to the invasive range. We test these predictions with Geranium carolinianum, a winter annual herb native to North America and invasive in China. We measure the extent of founder effects using allozymes and microsatellites, and ask whether this is consistent with its colonization history and patterns of diversity in the native range. In the native range, genetic diversity is higher and structure is lower than expected based on life history traits. In China, our results provide evidence for multiple introductions near Nanjing, Jiangsu province, with subsequent range expansion to the west and south. Patterns of genetic diversity across China reveal weak founder effects that are driven largely by low-diversity populations at the expansion front, away from the introduction location. This suggests that reduced diversity in China has resulted from successive founder events during range expansion, and that the loss of genetic diversity in the Nanjing area was mitigated by multiple introductions from diverse source populations. This has implications for the future of G. carolinianum in China, as continued gene flow among populations should eventually increase genetic diversity within the more recently founded populations. PMID:24346497

Single kernel ionomic profiles are highly heritable indicators of genetic and environmental influences on elemental accumulation in maize grain (Zea mays)

USDA-ARS?s Scientific Manuscript database

The ionome, or elemental profile, of a maize kernel represents at least two distinct ideas. First, the collection of elements within the kernel are food, feed and feedstocks for people, animals and industrial processes. Second, the ionome of the kernel represents a developmental end point that can s...

SINEs.

PubMed

Kramerov, Dmitri A; Vassetzky, Nikita S

2011-01-01

Short interspersed elements (SINEs) are mobile genetic elements that invade the genomes of many eukaryotes. Since their discovery about 30 years ago, many gaps in our understanding of the biology and function of SINEs have been filled. This review summarizes the past and recent advances in the studies of SINEs. The structure and origin of SINEs as well as the processes involved in their amplification, transcription, RNA processing, reverse transcription, and integration of a SINE copy into the genome are considered. Then we focus on the significance of SINEs for the host genomes. While these genomic parasites can be deleterious to the cell, the long-term being in the genome has made SINEs a valuable source of genetic variation providing regulatory elements for gene expression, alternative splice sites, polyadenylation signals, and even functional RNA genes. Copyright © 2011 John Wiley & Sons, Ltd.

Regulation of ion homeostasis in plants: current approaches and future challenges.

PubMed

Rouached, Hatem; Secco, David; Arpat, Bulak A

2010-05-01

The dependency of plants on essential macro- and micro-elements to complete their life cycle serves as a major entry point of these elements into the global food web. However, plants often face depletion of one or more essential elements limiting their growth. Thus, in modern agriculture, improving plant mineral nutrition has gained fundamental importance in order to address the issue of sustainable food resources for the growing world population. Heavy fertilization of soil was, for long time, chosen as a strategy to cope with the deficiency of these elements. Yet, this strategy is neither economically nor ecologically conceivable at long-term. As an alternative, genetic and breeding approaches that provide plants new characteristics enabling them to grow in nutrient-depleted soils, has become a major focal interest. The research emphasis so far has been on elucidating the molecular physiology of individual nutritive elements. However, in practice, application of such knowledge is hindered by complex cross-talks, which are emerging in the face of new data, between these elements. Developing integrative approaches, combining genetic, comparative genomics and 'omics' platforms, is crucial to untangle the interconnected signaling networks regulating ion homeostasis in plants.

Role of the horizontal gene exchange in evolution of pathogenic Mycobacteria.

PubMed

Reva, Oleg; Korotetskiy, Ilya; Ilin, Aleksandr

2015-01-01

Mycobacterium tuberculosis is one of the most dangerous human pathogens, the causative agent of tuberculosis. While this pathogen is considered as extremely clonal and resistant to horizontal gene exchange, there are many facts supporting the hypothesis that on the early stages of evolution the development of pathogenicity of ancestral Mtb has started with a horizontal acquisition of virulence factors. Episodes of infections caused by non-tuberculosis Mycobacteria reported worldwide may suggest a potential for new pathogens to appear. If so, what is the role of horizontal gene transfer in this process? Availing of accessibility of complete genomes sequences of multiple pathogenic, conditionally pathogenic and saprophytic Mycobacteria, a genome comparative study was performed to investigate the distribution of genomic islands among bacteria and identify ontological links between these mobile elements. It was shown that the ancient genomic islands from M. tuberculosis still may be rooted to the pool of mobile genetic vectors distributed among Mycobacteria. A frequent exchange of genes was observed between M. marinum and several saprophytic and conditionally pathogenic species. Among them M. avium was the most promiscuous species acquiring genetic materials from diverse origins. Recent activation of genetic vectors circulating among Mycobacteria potentially may lead to emergence of new pathogens from environmental and conditionally pathogenic Mycobacteria. The species which require monitoring are M. marinum and M. avium as they eagerly acquire genes from different sources and may become donors of virulence gene cassettes to other micro-organisms.

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands.

PubMed

Bradley, Kevin M; Benner, Steven A

2014-01-01

Synthetic biologists wishing to self-assemble large DNA (L-DNA) constructs from small DNA fragments made by automated synthesis need fragments that hybridize predictably. Such predictability is difficult to obtain with nucleotides built from just the four standard nucleotides. Natural DNA's peculiar combination of strong and weak G:C and A:T pairs, the context-dependence of the strengths of those pairs, unimolecular strand folding that competes with desired interstrand hybridization, and non-Watson-Crick interactions available to standard DNA, all contribute to this unpredictability. In principle, adding extra nucleotides to the genetic alphabet can improve the predictability and reliability of autonomous DNA self-assembly, simply by increasing the information density of oligonucleotide sequences. These extra nucleotides are now available as parts of artificially expanded genetic information systems (AEGIS), and tools are now available to generate entirely standard DNA from AEGIS DNA during PCR amplification. Here, we describe the OligArch (for "oligonucleotide architecting") software, an application that permits synthetic biologists to engineer optimally self-assembling DNA constructs from both six- and eight-letter AEGIS alphabets. This software has been used to design oligonucleotides that self-assemble to form complete genes from 20 or more single-stranded synthetic oligonucleotides. OligArch is therefore a key element of a scalable and integrated infrastructure for the rapid and designed engineering of biology.

The Evolution of Campylobacter jejuni and Campylobacter coli

PubMed Central

Sheppard, Samuel K.; Maiden, Martin C.J.

2015-01-01

The global significance of Campylobacter jejuni and Campylobacter coli as gastrointestinal human pathogens has motivated numerous studies to characterize their population biology and evolution. These bacteria are a common component of the intestinal microbiota of numerous bird and mammal species and cause disease in humans, typically via consumption of contaminated meat products, especially poultry meat. Sequence-based molecular typing methods, such as multilocus sequence typing (MLST) and whole genome sequencing (WGS), have been instructive for understanding the epidemiology and evolution of these bacteria and how phenotypic variation relates to the high degree of genetic structuring in C. coli and C. jejuni populations. Here, we describe aspects of the relatively short history of coevolution between humans and pathogenic Campylobacter, by reviewing research investigating how mutation and lateral or horizontal gene transfer (LGT or HGT, respectively) interact to create the observed population structure. These genetic changes occur in a complex fitness landscape with divergent ecologies, including multiple host species, which can lead to rapid adaptation, for example, through frame-shift mutations that alter gene expression or the acquisition of novel genetic elements by HGT. Recombination is a particularly strong evolutionary force in Campylobacter, leading to the emergence of new lineages and even large-scale genome-wide interspecies introgression between C. jejuni and C. coli. The increasing availability of large genome datasets is enhancing understanding of Campylobacter evolution through the application of methods, such as genome-wide association studies, but MLST-derived clonal complex designations remain a useful method for describing population structure. PMID:26101080

A targeted genetic modifier screen links the SWI2/SNF2 protein domino to growth and autophagy genes in Drosophila melanogaster.

PubMed

Kwon, Matt Hyoung; Callaway, Heather; Zhong, Jim; Yedvobnick, Barry

2013-05-20

Targeted genetic studies can facilitate phenotypic analyses and provide important insights into development and other complex processes. The SWI2/SNF2 DNA-dependent ATPase Domino (Dom) of Drosophila melanogaster, a component of the Tip60 acetyltransferase complex, has been associated with a wide spectrum of cellular processes at multiple developmental stages. These include hematopoiesis, cell proliferation, homeotic gene regulation, histone exchange during DNA repair, and Notch signaling. To explore the wider gene network associated with Dom action, we used RNAi directed against domino (dom) to mediate loss-of-function at the wing margin, a tissue that is readily scored for phenotypic changes. Dom RNAi driven through GAL4-UAS elicited dominant wing nicking that responded phenotypically to the dose of dom and other loci known to function with dom. We screened for phenotypic modifiers of this wing phenotype among 2500 transpositions of the EP P element and found both enhancers and suppressors. Several classes of modifier were obtained, including those encoding transcription factors, RNA regulatory proteins, and factors that regulate cell growth, proliferation and autophagy, a lysosomal degradation pathway that affects cell growth under conditions of starvation and stress. Our analysis is consistent with prior studies, suggesting that Dom acts pleiotropically as a positive effector of Notch signaling and a repressor of proliferation. This genetic system should facilitate screens for additional loci associated with Dom function, and complement biochemical approaches to their regulatory activity.

Neighborhood Disadvantage Alters the Origins of Children's Nonaggressive Conduct Problems

PubMed Central

Burt, S. Alexandra; Klump, Kelly L.; Gorman-Smith, Deborah; Neiderhiser, Jenae M.

2015-01-01

Neighborhood disadvantage plays a pivotal role in child mental health, including child antisocial behavior (e.g., lying, theft, vandalism; assault, cruelty). Prior studies have indicated that shared environmental influences on youth antisocial behavior increase with increasing disadvantage, but have been unable to confirm that these findings persist once various selection confounds are considered. The current study sought to fill this gap in the literature, examining whether and how neighborhood disadvantage alters the genetic and environmental origins of child antisocial behavior. Our sample consisted of 2,054 child twins participating in the Michigan State University Twin Registry, half of whom were oversampled to reside in modestly-to-severely impoverished neighborhoods. We made use of an innovative set of nuclear twin family models, thereby allowing us to disambiguate between, and simultaneously estimate, multiple elements of the shared environment as well as genetic influences. Although there was no evidence that the etiology of aggressive antisocial behavior was moderated by neighborhood disadvantage, the etiology of non-aggressive antisocial behavior shifted dramatically with increasing neighborhood disadvantage. Sibling-level shared environmental influences were estimated to be near zero in the wealthiest neighborhoods, and increased dramatically in the most impoverished neighborhoods. By contrast, both genetic risk and family-level shared environmental transmission were significantly more influential in middle- and upper-class neighborhoods than in impoverished neighborhoods. Such results collectively highlight the profound role that pervasive neighborhood poverty plays in shaping the etiology of child non-aggressive antisocial behavior. Implications are discussed. PMID:27347447

Genetic diversity of environmental Vibrio cholerae O1 strains isolated in Northern Vietnam.

PubMed

Takemura, Taichiro; Murase, Kazunori; Maruyama, Fumito; Tran, Thi Luong; Ota, Atsushi; Nakagawa, Ichiro; Nguyen, Dong Tu; Ngo, Tu Cuong; Nguyen, Thi Hang; Tokizawa, Asako; Morita, Masatomo; Ohnishi, Makoto; Nguyen, Binh Minh; Yamashiro, Tetsu

2017-10-01

Cholera epidemics have been recorded periodically in Vietnam during the seventh cholera pandemic. Since cholera is a water-borne disease, systematic monitoring of environmental waters for Vibrio cholerae presence is important for predicting and preventing cholera epidemics. We conducted monitoring, isolation, and genetic characterization of V. cholerae strains in Nam Dinh province of Northern Vietnam from Jul 2013 to Feb 2015. In this study, four V. cholerae O1 strains were detected and isolated from 110 analyzed water samples (3.6%); however, none of them carried the cholera toxin gene, ctxA, in their genomes. Whole genome sequencing and phylogenetic analysis revealed that the four O1 isolates were separated into two independent clusters, and one of them diverged from a common ancestor with pandemic strains. The analysis of pathogenicity islands (CTX prophage, VPI-I, VPI-II, VSP-I, and VSP-II) indicated that one strain (VNND_2014Jun_6SS) harbored an unknown prophage-like sequence with high homology to vibriophage KSF-1 phi and VCY phi, identified from Bangladesh and the USA, respectively, while the other three strains carried tcpA gene with a distinct sequence demonstrating a separate clonal lineage. These results suggest that the aquatic environment can harbor highly divergent V. cholera strains and serve as a reservoir for multiple V. cholerae virulence-associated genes which may be exchanged via mobile genetic elements. Therefore, continuous monitoring and genetic characterization of V. cholerae strains in the environment should contribute to the early detection of the sources of infection and prevention of cholera outbreaks as well as to understanding the natural ecology and evolution of V. cholerae. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis

PubMed Central

Wu, Yu; Zhao, Qing; Gao, Lei; Yu, Xiao-Min; Fang, Ping; Oliver, David J.; Xiang, Cheng-Bin

2010-01-01

Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a ‘sulphur-free’ solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance. PMID:20547563

Highly divergent ancient gene families in metagenomic samples are compatible with additional divisions of life.

PubMed

Lopez, Philippe; Halary, Sébastien; Bapteste, Eric

2015-10-26

Microbial genetic diversity is often investigated via the comparison of relatively similar 16S molecules through multiple alignments between reference sequences and novel environmental samples using phylogenetic trees, direct BLAST matches, or phylotypes counts. However, are we missing novel lineages in the microbial dark universe by relying on standard phylogenetic and BLAST methods? If so, how can we probe that universe using alternative approaches? We performed a novel type of multi-marker analysis of genetic diversity exploiting the topology of inclusive sequence similarity networks. Our protocol identified 86 ancient gene families, well distributed and rarely transferred across the 3 domains of life, and retrieved their environmental homologs among 10 million predicted ORFs from human gut samples and other metagenomic projects. Numerous highly divergent environmental homologs were observed in gut samples, although the most divergent genes were over-represented in non-gut environments. In our networks, most divergent environmental genes grouped exclusively with uncultured relatives, in maximal cliques. Sequences within these groups were under strong purifying selection and presented a range of genetic variation comparable to that of a prokaryotic domain. Many genes families included environmental homologs that were highly divergent from cultured homologs: in 79 gene families (including 18 ribosomal proteins), Bacteria and Archaea were less divergent than some groups of environmental sequences were to any cultured or viral homologs. Moreover, some groups of environmental homologs branched very deeply in phylogenetic trees of life, when they were not too divergent to be aligned. These results underline how limited our understanding of the most diverse elements of the microbial world remains, and encourage a deeper exploration of natural communities and their genetic resources, hinting at the possibility that still unknown yet major divisions of life have yet to be discovered.

Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis.

PubMed

Wu, Yu; Zhao, Qing; Gao, Lei; Yu, Xiao-Min; Fang, Ping; Oliver, David J; Xiang, Cheng-Bin

2010-07-01

Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a 'sulphur-free' solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance.

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...

Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension.

PubMed

Zhu, Xiaofeng; Feng, Tao; Tayo, Bamidele O; Liang, Jingjing; Young, J Hunter; Franceschini, Nora; Smith, Jennifer A; Yanek, Lisa R; Sun, Yan V; Edwards, Todd L; Chen, Wei; Nalls, Mike; Fox, Ervin; Sale, Michele; Bottinger, Erwin; Rotimi, Charles; Liu, Yongmei; McKnight, Barbara; Liu, Kiang; Arnett, Donna K; Chakravati, Aravinda; Cooper, Richard S; Redline, Susan

2015-01-08

Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Murine genetically engineered and human xenograft models of chronic lymphocytic leukemia.

PubMed

Chen, Shih-Shih; Chiorazzi, Nicholas

2014-07-01

Chronic lymphocytic leukemia (CLL) is a genetically complex disease, with multiple factors having an impact on onset, progression, and response to therapy. Genetic differences/abnormalities have been found in hematopoietic stem cells from patients, as well as in B lymphocytes of individuals with monoclonal B-cell lymphocytosis who may develop the disease. Furthermore, after the onset of CLL, additional genetic alterations occur over time, often causing disease worsening and altering patient outcomes. Therefore, being able to genetically engineer mouse models that mimic CLL or at least certain aspects of the disease will help us understand disease mechanisms and improve treatments. This notwithstanding, because neither the genetic aberrations responsible for leukemogenesis and progression nor the promoting factors that support these are likely identical in character or influences for all patients, genetically engineered mouse models will only completely mimic CLL when all of these factors are precisely defined. In addition, multiple genetically engineered models may be required because of the heterogeneity in susceptibility genes among patients that can have an effect on genetic and environmental characteristics influencing disease development and outcome. For these reasons, we review the major murine genetically engineered and human xenograft models in use at the present time, aiming to report the advantages and disadvantages of each. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic heterogeneity in autism: From single gene to a pathway perspective.

PubMed

An, Joon Yong; Claudianos, Charles

2016-09-01

The extreme genetic heterogeneity of autism spectrum disorder (ASD) represents a major challenge. Recent advances in genetic screening and systems biology approaches have extended our knowledge of the genetic etiology of ASD. In this review, we discuss the paradigm shift from a single gene causation model to pathway perturbation model as a guide to better understand the pathophysiology of ASD. We discuss recent genetic findings obtained through next-generation sequencing (NGS) and examine various integrative analyses using systems biology and complex networks approaches that identify convergent patterns of genetic elements associated with ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maize Germplasm Conservation in Southern California's Urban Gardens: Introduced Diversity Beyond ex situ and in situ Management.

PubMed

Heraty, Joanne M; Ellstrand, Norman C

Contemporary germplasm conservation studies largely focus on ex situ and in situ management of diversity within centers of genetic diversity. Transnational migrants who transport and introduce landraces to new locations may catalyze a third type of conservation that combines both approaches. Resulting populations may support reduced diversity as a result of evolutionary forces such as genetic drift, selection, and gene flow, yet they may also be more diverse as a result of multiple introductions, selective breeding and cross pollination among multiple introduced varietals. In this study, we measured the amount and structure of maize molecular genetic diversity in samples collected from home gardens and community gardens maintained by immigrant farmers in Southern California. We used the same markers to measure the genetic diversity and structure of commercially available maize varieties and compared our data to previously reported genetic diversity statistics of Mesoamerican landraces. Our results reveal that transnational dispersal creates an opportunity for the maintenance of maize genetic diversity beyond its recognized centers of diversity.

Update on Sporadic Colorectal Cancer Genetics.

PubMed

Hardiman, Karin M

2018-05-01

Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics.

PubMed

Pare, Guillaume; Mao, Shihong; Deng, Wei Q

2016-06-08

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance.

A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics

PubMed Central

Pare, Guillaume; Mao, Shihong; Deng, Wei Q.

2016-01-01

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance. PMID:27273519

Estimating the contribution of genetic variants to difference in incidence of disease between population groups.

PubMed

Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

2012-08-01

Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.

Estimating the contribution of genetic variants to difference in incidence of disease between population groups

PubMed Central

Moonesinghe, Ramal; Ioannidis, John PA; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

2012-01-01

Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene–environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal. PMID:22333905

Patient and Genetic Counselor Perceptions of In-person versus Telephone Genetic Counseling for Hereditary Breast/Ovarian Cancer

PubMed Central

Jacobs, Aryana S.; Schwartz, Marc D.; Valdimarsdottir, Heiddis; Nusbaum, Rachel H.; Hooker, Gillian W.; DeMarco, Tiffani A.; Heinzmann, Jessica E.; McKinnon, Wendy; McCormick, Shelley R.; Davis, Claire; Forman, Andrea D.; Lebensohn, Alexandra Perez; Dalton, Emily; Tully, Diana Moglia; Graves, Kristi D.; Similuk, Morgan; Kelly, Scott; Peshkin, Beth N.

2016-01-01

Telephone genetic counseling (TC) for high-risk women interested in BRCA1/2 testing has been shown to yield positive outcomes comparable to usual care (UC; in-person) genetic counseling. However, little is known about how genetic counselors perceive the delivery of these alternate forms of genetic counseling. As part of a randomized trial of TC versus UC, genetic counselors completed a 5-item genetic counselor process questionnaire (GCQ) assessing key elements of pre-test sessions (information delivery, emotional support, addressing questions and concerns, tailoring of session, and facilitation of decision- making) with the 479 female participants (TC, N=236; UC, N=243). The GCQ scores did not differ for TC vs. UC sessions (t (477) = 0.11, p = 0.910). However, multivariate analysis showed that participant race/ethnicity significantly predicted genetic counselor perceptions (β = 0.172, p<0.001) in that the GCQ scores were lower for minorities in TC and UC. Exploratory analyses suggested that GCQ scores may be associated with patient preference for UC versus TC (t (79) = 2.21, p=0.030). Additionally, we found that genetic counselor ratings of session effectiveness were generally concordant with patient perceptions of the session. These data indicate that genetic counselors perceive that key components of TC can be delivered as effectively as UC, and that these elements may contribute to specific aspects of patient satisfaction. However, undefined process differences may be present which account for lower counselor perceptions about the effectiveness of their sessions with minority women (i.e., those other than non-Hispanic Whites). We discuss other potential clinical and research implications of our findings. PMID:26969308

Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements.

PubMed

Zhu, Lingxiang; Yan, Zhongqiang; Zhang, Zhaojun; Zhou, Qiming; Zhou, Jinchun; Wakeland, Edward K; Fang, Xiangdong; Xuan, Zhenyu; Shen, Dingxia; Li, Quan-Zhen

2013-01-01

The emergence and rapid spreading of multidrug-resistant Acinetobacter baumannii strains has become a major health threat worldwide. To better understand the genetic recombination related with the acquisition of drug-resistant elements during bacterial infection, we performed complete genome analysis on three newly isolated multidrug-resistant A. baumannii strains from Beijing using next-generation sequencing technology. Whole genome comparison revealed that all 3 strains share some common drug resistant elements including carbapenem-resistant bla OXA-23 and tetracycline (tet) resistance islands, but the genome structures are diversified among strains. Various genomic islands intersperse on the genome with transposons and insertions, reflecting the recombination flexibility during the acquisition of the resistant elements. The blood-isolated BJAB07104 and ascites-isolated BJAB0868 exhibit high similarity on their genome structure with most of the global clone II strains, suggesting these two strains belong to the dominant outbreak strains prevalent worldwide. A large resistance island (RI) of about 121-kb, carrying a cluster of resistance-related genes, was inserted into the ATPase gene on BJAB07104 and BJAB0868 genomes. A 78-kb insertion element carrying tra-locus and bla OXA-23 island, can be either inserted into one of the tniB gene in the 121-kb RI on the chromosome, or transformed to conjugative plasmid in the two BJAB strains. The third strains of this study, BJAB0715, which was isolated from spinal fluid, exhibit much more divergence compared with above two strains. It harbors multiple drug-resistance elements including a truncated AbaR-22-like RI on its genome. One of the unique features of this strain is that it carries both bla OXA-23 and bla OXA-58 genes on its genome. Besides, an Acinetobacter lwoffii adeABC efflux element was found inserted into the ATPase position in BJAB0715. Our comparative analysis on currently completed Acinetobacter baumannii genomes revealed extensive and dynamic genome organizations, which may facilitate the bacteria to acquire drug-resistance elements into their genomes.

Radiation detector having a multiplicity of individual detecting elements

DOEpatents

Whetten, Nathan R.; Kelley, John E.

1985-01-01

A radiation detector has a plurality of detector collection element arrays immersed in a radiation-to-electron conversion medium. Each array contains a multiplicity of coplanar detector elements radially disposed with respect to one of a plurality of positions which at least one radiation source can assume. Each detector collector array is utilized only when a source is operative at the associated source position, negating the necessity for a multi-element detector to be moved with respect to an object to be examined. A novel housing provides the required containment of a high-pressure gas conversion medium.

Diagnostic use of computational retrotransposon detection: Successful definition of pathogenetic mechanism in a ciliopathy phenotype.

PubMed

Takenouchi, Toshiki; Kuchikata, Tomu; Yoshihashi, Hiroshi; Fujiwara, Mineko; Uehara, Tomoko; Miyama, Sahoko; Yamada, Shiro; Kosaki, Kenjiro

2017-05-01

Among more than 5,000 human monogenic disorders with known causative genes, transposable element insertion of a Long Interspersed Nuclear Element 1 (LINE1, L1) is known as the mechanistic basis in only 13 genetic conditions. Meckel-Gruber syndrome is a rare ciliopathy characterized by occipital encephalocele and cystic kidney disease. Here, we document a boy with occipital encephalocele, post-axial polydactyly, and multicystic renal disease. A medical exome analysis detected a heterozygous frameshift mutation, c.4582_4583delCG p.(Arg1528Serfs*17) in CC2D2A in the maternally derived allele. The further use of a dedicated bioinformatics algorithm for detecting retrotransposon insertions led to the detection of an L1 insertion affecting exon 7 in the paternally derived allele. The complete sequencing and sequence homology analysis of the inserted L1 element showed that the L1 element was classified as L1HS (L1 human specific) and that the element had intact open reading frames in the two L1-encoded proteins. This observation ranks Meckel-Gruber syndrome as only the 14th disorder to be caused by an L1 insertion among more than 5,000 known human genetic disorders. Although a transposable element detection algorithm is not included in the current best-practice next-generation sequencing analysis, the present observation illustrates the utility of such an algorithm, which would require modest computational time and resources. Whether the seemingly infrequent recognition of L1 insertion in the pathogenesis of human genetic diseases might simply reflect a lack of appropriate detection methods remains to be seen. © 2017 Wiley Periodicals, Inc.

Composite Spectrometer Prisms

NASA Technical Reports Server (NTRS)

Breckinridge, J. B.; Page, N. A.; Rodgers, J. M.

1985-01-01

Efficient linear dispersive element for spectrometer instruments achieved using several different glasses in multiple-element prism. Good results obtained in both two-and three-element prisms using variety of different glass materials.

Structure and Genetic Content of the Megaplasmids of Neurotoxigenic Clostridium butyricum Type E Strains from Italy

PubMed Central

Iacobino, Angelo; Scalfaro, Concetta; Franciosa, Giovanna

2013-01-01

We determined the genetic maps of the megaplasmids of six neutoroxigenic Clostridium butyricum type E strains from Italy using molecular and bioinformatics techniques. The megaplasmids are circular, not linear as we had previously proposed. The differently-sized megaplasmids share a genetic region that includes structural, metabolic and regulatory genes. In addition, we found that a 168 kb genetic region is present only in the larger megaplasmids of two tested strains, whereas it is absent from the smaller megaplasmids of the four remaining strains. The genetic region unique to the larger megaplasmids contains, among other features, a locus for clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated (cas) genes, i.e. a bacterial adaptive immune system providing sequence-specific protection from invading genetic elements. Some CRISPR spacer sequences of the neurotoxigenic C. butyricum type E strains showed homology to prophage, phage and plasmid sequences from closely related clostridia species or from distant species, all sharing the intestinal habitat, suggesting that the CRISPR locus might be involved in the microorganism adaptation to the human or animal intestinal environment. Besides, we report here that each of four distinct CRISPR spacers partially matched DNA sequences of different prophages and phages, at identical nucleotide locations. This suggests that, at least in neurotoxigenic C. butyricum type E, the CRISPR locus is potentially able to recognize the same conserved DNA sequence of different invading genetic elements, besides targeting sequences unique to previously encountered invading DNA, as currently predicted for a CRISPR locus. Thus, the results of this study introduce the possibility that CRISPR loci can provide resistance to a wider range of invading DNA elements than previously appreciated. Whether it is more advantageous for the peculiar neurotoxigenic C. butyricum type E strains to maintain or to lose the CRISPR-cas system remains an open question. PMID:23967192

Objective lens simultaneously optimized for pupil ghosting, wavefront delivery and pupil imaging

NASA Technical Reports Server (NTRS)

Olczak, Eugene G (Inventor)

2011-01-01

An objective lens includes multiple optical elements disposed between a first end and a second end, each optical element oriented along an optical axis. Each optical surface of the multiple optical elements provides an angle of incidence to a marginal ray that is above a minimum threshold angle. This threshold angle minimizes pupil ghosts that may enter an interferometer. The objective lens also optimizes wavefront delivery and pupil imaging onto an optical surface under test.

The Genetic Basis of Upland/Lowland Ecotype Divergence in Switchgrass (Panicum virgatum)

DOE PAGES

Milano, E. R.; Lowry, D. B.; Juenger, T. E.

2016-09-09

The evolution of locally adapted ecotypes is a common phenomenon that generates diversity within plant species. However, we know surprisingly little about the genetic mechanisms underlying the locally adapted traits involved in ecotype formation. The genetic architecture underlying locally adapted traits dictates how an organism will respond to environmental selection pressures, and has major implications for evolutionary ecology, conservation, and crop breeding. To understand the genetic architecture underlying the divergence of switchgrass (Panicum virgatum) ecotypes, we constructed a genetic mapping population through a four-way outbred cross between two northern upland and two southern lowland accessions. Trait segregation in this mappingmore » population was largely consistent with multiple independent loci controlling the suite of traits that characterizes ecotype divergence. We assembled a joint linkage map using ddRADseq, and mapped quantitative trait loci (QTL) for traits that are divergent between ecotypes, including flowering time, plant size, physiological processes, and disease resistance. Overall, we found that most QTL had small to intermediate effects. While we identified colocalizing QTL for multiple traits, we did not find any large-effect QTL that clearly controlled multiple traits through pleiotropy or tight physical linkage. These results indicate that ecologically important traits in switchgrass have a complex genetic basis, and that similar loci may underlie divergence across the geographic range of the ecotypes.« less

The Genetic Basis of Upland/Lowland Ecotype Divergence in Switchgrass (Panicum virgatum)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milano, E. R.; Lowry, D. B.; Juenger, T. E.

The evolution of locally adapted ecotypes is a common phenomenon that generates diversity within plant species. However, we know surprisingly little about the genetic mechanisms underlying the locally adapted traits involved in ecotype formation. The genetic architecture underlying locally adapted traits dictates how an organism will respond to environmental selection pressures, and has major implications for evolutionary ecology, conservation, and crop breeding. To understand the genetic architecture underlying the divergence of switchgrass (Panicum virgatum) ecotypes, we constructed a genetic mapping population through a four-way outbred cross between two northern upland and two southern lowland accessions. Trait segregation in this mappingmore » population was largely consistent with multiple independent loci controlling the suite of traits that characterizes ecotype divergence. We assembled a joint linkage map using ddRADseq, and mapped quantitative trait loci (QTL) for traits that are divergent between ecotypes, including flowering time, plant size, physiological processes, and disease resistance. Overall, we found that most QTL had small to intermediate effects. While we identified colocalizing QTL for multiple traits, we did not find any large-effect QTL that clearly controlled multiple traits through pleiotropy or tight physical linkage. These results indicate that ecologically important traits in switchgrass have a complex genetic basis, and that similar loci may underlie divergence across the geographic range of the ecotypes.« less

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

DTIC Science & Technology

2017-12-01

meaning that most men with prostate cancer have multiple, genetically distinct cancers. Pathologists cannot assess clonality by routine microscopic...Hence, in this proposal we utilized dual ERG/SPINK1 immunohistochemistry (IHC)—as a readout of clonal, mutually exclusive molecular subtypes—to assess...multiclonal (also referred to as multifocal), meaning that more than 80% of men with prostate cancer actually have multiple, genetically distinct

Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

PubMed

He, Dan; Kuhn, David; Parida, Laxmi

2016-06-15

Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

Hili Inhibits HIV Replication in Activated T Cells.

PubMed

Peterlin, B Matija; Liu, Pingyang; Wang, Xiaoyun; Cary, Daniele; Shao, Wei; Leoz, Marie; Hong, Tian; Pan, Tao; Fujinaga, Koh

2017-06-01

P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4 + T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNA Arg (UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements. IMPORTANCE Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4 + T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements. Copyright © 2017 American Society for Microbiology.

Exploring Conceptual Change in Genetics Using a Multidimensional Interpretive Framework.

ERIC Educational Resources Information Center

Venville, Grady J.; Treagust, David F.

1998-01-01

Changes in grade 10 students' (n=79) conceptions of genes during genetics instruction was studied from multiple perspectives. Ontologically, most students moved from passive to active models of genes. Affectively, students were interested in genetics but unmotivated by microscopic mechanistic explanations; however, teaching approaches were…

Genomic Variation between Genetic lines of White Leghorns Differed in Resistance to Marek’s Disease

USDA-ARS?s Scientific Manuscript database

Genetic resistance to avian tumor virus-induced tumorigenesis and vaccine protective efficacy preventing such tumorigenicity are determined by multiple factors including host genetics, viral virulence, dose of challenge viruses, type of vaccine, vaccine dosage, and interval between vaccination and v...

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

PubMed

Morris, Gerwyn; Berk, Michael; Puri, Basant K

2018-04-01

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

Germline genetic variants with implications for disease risk and therapeutic outcomes.

PubMed

Pasternak, Amy L; Ward, Kristen M; Luzum, Jasmine A; Ellingrod, Vicki L; Hertz, Daniel L

2017-10-01

Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care. Copyright © 2017 the American Physiological Society.

Reconciling genetic evolution and the associative learning account of mirror neurons through data-acquisition mechanisms.

PubMed

Lotem, Arnon; Kolodny, Oren

2014-04-01

An associative learning account of mirror neurons should not preclude genetic evolution of its underlying mechanisms. On the contrary, an associative learning framework for cognitive development should seek heritable variation in the learning rules and in the data-acquisition mechanisms that construct associative networks, demonstrating how small genetic modifications of associative elements can give rise to the evolution of complex cognition.

Genetic covariance between components of male reproductive success: within-pair vs. extra-pair paternity in song sparrows

PubMed Central

Reid, J M; Arcese, P; Losdat, S

2014-01-01

The evolutionary trajectories of reproductive systems, including both male and female multiple mating and hence polygyny and polyandry, are expected to depend on the additive genetic variances and covariances in and among components of male reproductive success achieved through different reproductive tactics. However, genetic covariances among key components of male reproductive success have not been estimated in wild populations. We used comprehensive paternity data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) to estimate additive genetic variance and covariance in the total number of offspring a male sired per year outside his social pairings (i.e. his total extra-pair reproductive success achieved through multiple mating) and his liability to sire offspring produced by his socially paired female (i.e. his success in defending within-pair paternity). Both components of male fitness showed nonzero additive genetic variance, and the estimated genetic covariance was positive, implying that males with high additive genetic value for extra-pair reproduction also have high additive genetic propensity to sire their socially paired female's offspring. There was consequently no evidence of a genetic or phenotypic trade-off between male within-pair paternity success and extra-pair reproductive success. Such positive genetic covariance might be expected to facilitate ongoing evolution of polygyny and could also shape the ongoing evolution of polyandry through indirect selection. PMID:25186454

Elucidating the multiple genetic lineages and population genetic structure of the brooding coral Seriatopora (Scleractinia: Pocilloporidae) in the Ryukyu Archipelago

NASA Astrophysics Data System (ADS)

Nakajima, Yuichi; Nishikawa, Akira; Iguchi, Akira; Nagata, Tomofumi; Uyeno, Daisuke; Sakai, Kazuhiko; Mitarai, Satoshi

2017-06-01

The elucidation of species diversity and connectivity is essential for conserving coral reef communities and for understanding the characteristics of coral populations. To assess the species diversity, intraspecific genetic diversity, and genetic differentiation among populations of the brooding coral Seriatopora spp., we conducted phylogenetic and population genetic analyses using a mitochondrial DNA control region and microsatellites at ten sites in the Ryukyu Archipelago, Japan. At least three genetic lineages of Seriatopora (Seriatopora-A, -B, and -C) were detected in our specimens. We collected colonies morphologically similar to Seriatopora hystrix, but these may have included multiple, genetically distinct species. Although sexual reproduction maintains the populations of all the genetic lineages, Seriatopora-A and Seriatopora-C had lower genetic diversity than Seriatopora-B. We detected significant genetic differentiation in Seriatopora-B among the three populations as follows: pairwise F ST = 0.064-0.116 (all P = 0.001), pairwise G''ST = 0.107-0.209 (all P = 0.001). Additionally, only one migrant from an unsampled population was genetically identified within Seriatopora-B. Because the peak of the settlement of Seriatopora larvae is within 1 d and almost all larvae are settled within 5 d of spawning, our observations may be related to low dispersal ability. Populations of Seriatopora in the Ryukyu Archipelago will probably not recover unless there is substantial new recruitment from distant populations.

sp3-hybridized framework structure of group-14 elements discovered by genetic algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Manh Cuong; Zhao, Xin; Wang, Cai-Zhuang

2014-05-01

Group-14 elements, including C, Si, Ge, and Sn, can form various stable and metastable structures. Finding new metastable structures of group-14 elements with desirable physical properties for new technological applications has attracted a lot of interest. Using a genetic algorithm, we discovered a new low-energy metastable distorted sp3-hybridized framework structure of the group-14 elements. It has P42/mnm symmetry with 12 atoms per unit cell. The void volume of this structure is as large as 139.7Å3 for Si P42/mnm, and it can be used for gas or metal-atom encapsulation. Band-structure calculations show that P42/mnm structures of Si and Ge are semiconductingmore » with energy band gaps close to the optimal values for optoelectronic or photovoltaic applications. With metal-atom encapsulation, the P42/mnm structure would also be a candidate for rattling-mediated superconducting or used as thermoelectric materials.« less

Microarray analyses of Xylella fastidiosa provide evidence of coordinated transcription control of laterally transferred elements.

PubMed

Nunes, Luiz R; Rosato, Yoko B; Muto, Nair H; Yanai, Giane M; da Silva, Vivian S; Leite, Daniela B; Gonçalves, Edmilson R; de Souza, Alessandra A; Coletta-Filho, Helvécio D; Machado, Marcos A; Lopes, Silvio A; de Oliveira, Regina Costa

2003-04-01

Genetically distinct strains of the plant bacterium Xylella fastidiosa (Xf) are responsible for a variety of plant diseases, accounting for severe economic damage throughout the world. Using as a reference the genome of Xf 9a5c strain, associated with citrus variegated chlorosis (CVC), we developed a microarray-based comparison involving 12 Xf isolates, providing a thorough assessment of the variation in genomic composition across the group. Our results demonstrate that Xf displays one of the largest flexible gene pools characterized to date, with several horizontally acquired elements, such as prophages, plasmids, and genomic islands (GIs), which contribute up to 18% of the final genome. Transcriptome analysis of bacteria grown under different conditions shows that most of these elements are transcriptionally active, and their expression can be influenced in a coordinated manner by environmental stimuli. Finally, evaluation of the genetic composition of these laterally transferred elements identified differences that may help to explain the adaptability of Xf strains to infect such a wide range of plant species.

Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

PubMed

Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

2016-09-01

Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

Disproportionate Contributions of Select Genomic Compartments and Cell Types to Genetic Risk for Coronary Artery Disease

PubMed Central

Won, Hong-Hee; Natarajan, Pradeep; Dobbyn, Amanda; Jordan, Daniel M.; Roussos, Panos; Lage, Kasper; Raychaudhuri, Soumya

2015-01-01

Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function. First, we examined the heritability of MI/CAD according to genomic compartments. We observed that single nucleotide polymorphisms (SNPs) residing within nearby regulatory regions show significant polygenicity and contribute between 59–71% of the heritability for MI/CAD. Second, we showed that the polygenicity and heritability explained by these SNPs are enriched in histone modification marks in specific cell types. Third, we found that a statistically higher number of 45 MI/CAD-associated SNPs that have been identified from large-scale GWAS studies reside within certain functional elements of the genome, particularly in active enhancer and promoter regions. Finally, we observed significant heterogeneity of this signal across cell types, with strong signals observed within adipose nuclei, as well as brain and spleen cell types. These results suggest that the genetic etiology of MI/CAD is largely explained by tissue-specific regulatory perturbation within the human genome. PMID:26509271

Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.

PubMed

Schwartz, Thomas; Armant, Olivier; Bretschneider, Nancy; Hahn, Alexander; Kirchen, Silke; Seifert, Martin; Dötsch, Andreas

2015-01-01

The fitness of sensitive and resistant Pseudomonas aeruginosa in different aquatic environments depends on genetic capacities and transcriptional regulation. Therefore, an antibiotic-sensitive isolate PA30 and a multi-resistant isolate PA49 originating from waste waters were compared via whole genome and transcriptome Illumina sequencing after exposure to municipal waste water and tap water. A number of different genomic islands (e.g. PAGIs, PAPIs) were identified in the two environmental isolates beside the highly conserved core genome. Exposure to tap water and waste water exhibited similar transcriptional impacts on several gene clusters (antibiotic and metal resistance, genetic mobile elements, efflux pumps) in both environmental P. aeruginosa isolates. The MexCD-OprJ efflux pump was overexpressed in PA49 in response to waste water. The expression of resistance genes, genetic mobile elements in PA49 was independent from the water matrix. Consistently, the antibiotic sensitive strain PA30 did not show any difference in expression of the intrinsic resistance determinants and genetic mobile elements. Thus, the exposure of both isolates to polluted waste water and oligotrophic tap water resulted in similar expression profiles of mentioned genes. However, changes in environmental milieus resulted in rather unspecific transcriptional responses than selected and stimuli-specific gene regulation. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO) Radar Based on the Elements of the Covariance Matrix.

PubMed

Zhang, Zhengyan; Zhang, Jianyun; Zhou, Qingsong; Li, Xiaobo

2018-03-07

In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

Changes in gene expression between a soybean F1 hybrid and its parents are associated with agronomically valuable traits

USDA-ARS?s Scientific Manuscript database

Plant breeding consists of creating phenotypic and genetic diversity by hybridizing diverse parents and selecting progeny which have new combinations of targeted traits. Soybean [Glycine max (L.) Merr.] genetic diversity is limited because domesticated soybean has undergone multiple genetic bottlene...

The Arabidopsis thaliana mobilome and its impact at the species level.

PubMed

Quadrana, Leandro; Bortolini Silveira, Amanda; Mayhew, George F; LeBlanc, Chantal; Martienssen, Robert A; Jeddeloh, Jeffrey A; Colot, Vincent

2016-06-03

Transposable elements (TEs) are powerful motors of genome evolution yet a comprehensive assessment of recent transposition activity at the species level is lacking for most organisms. Here, using genome sequencing data for 211 Arabidopsis thaliana accessions taken from across the globe, we identify thousands of recent transposition events involving half of the 326 TE families annotated in this plant species. We further show that the composition and activity of the 'mobilome' vary extensively between accessions in relation to climate and genetic factors. Moreover, TEs insert equally throughout the genome and are rapidly purged by natural selection from gene-rich regions because they frequently affect genes, in multiple ways. Remarkably, loci controlling adaptive responses to the environment are the most frequent transposition targets observed. These findings demonstrate the pervasive, species-wide impact that a rich mobilome can have and the importance of transposition as a recurrent generator of large-effect alleles.

Review: the role of vitamin D in nervous system health and disease.

PubMed

DeLuca, G C; Kimball, S M; Kolasinski, J; Ramagopalan, S V; Ebers, G C

2013-08-01

Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis. © 2013 British Neuropathological Society.

Genomic signatures of evolutionary transitions from solitary to group living

PubMed Central

Kapheim, Karen M.; Pan, Hailin; Li, Cai; Salzberg, Steven L.; Puiu, Daniela; Magoc, Tanja; Robertson, Hugh M.; Hudson, Matthew E.; Venkat, Aarti; Fischman, Brielle J.; Hernandez, Alvaro; Yandell, Mark; Ence, Daniel; Holt, Carson; Yocum, George D.; Kemp, William P.; Bosch, Jordi; Waterhouse, Robert M.; Zdobnov, Evgeny M.; Stolle, Eckart; Kraus, F. Bernhard; Helbing, Sophie; Moritz, Robin F. A.; Glastad, Karl M.; Hunt, Brendan G.; Goodisman, Michael A. D.; Hauser, Frank; Grimmelikhuijzen, Cornelis J. P.; Pinheiro, Daniel Guariz; Nunes, Francis Morais Franco; Soares, Michelle Prioli Miranda; Tanaka, Érica Donato; Simões, Zilá Luz Paulino; Hartfelder, Klaus; Evans, Jay D.; Barribeau, Seth M.; Johnson, Reed M.; Massey, Jonathan H.; Southey, Bruce R.; Hasselmann, Martin; Hamacher, Daniel; Biewer, Matthias; Kent, Clement F.; Zayed, Amro; Blatti, Charles; Sinha, Saurabh; Johnston, J. Spencer; Hanrahan, Shawn J.; Kocher, Sarah D.; Wang, Jun; Robinson, Gene E.; Zhang, Guojie

2017-01-01

The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks. PMID:25977371

Social evolution. Genomic signatures of evolutionary transitions from solitary to group living.

PubMed

Kapheim, Karen M; Pan, Hailin; Li, Cai; Salzberg, Steven L; Puiu, Daniela; Magoc, Tanja; Robertson, Hugh M; Hudson, Matthew E; Venkat, Aarti; Fischman, Brielle J; Hernandez, Alvaro; Yandell, Mark; Ence, Daniel; Holt, Carson; Yocum, George D; Kemp, William P; Bosch, Jordi; Waterhouse, Robert M; Zdobnov, Evgeny M; Stolle, Eckart; Kraus, F Bernhard; Helbing, Sophie; Moritz, Robin F A; Glastad, Karl M; Hunt, Brendan G; Goodisman, Michael A D; Hauser, Frank; Grimmelikhuijzen, Cornelis J P; Pinheiro, Daniel Guariz; Nunes, Francis Morais Franco; Soares, Michelle Prioli Miranda; Tanaka, Érica Donato; Simões, Zilá Luz Paulino; Hartfelder, Klaus; Evans, Jay D; Barribeau, Seth M; Johnson, Reed M; Massey, Jonathan H; Southey, Bruce R; Hasselmann, Martin; Hamacher, Daniel; Biewer, Matthias; Kent, Clement F; Zayed, Amro; Blatti, Charles; Sinha, Saurabh; Johnston, J Spencer; Hanrahan, Shawn J; Kocher, Sarah D; Wang, Jun; Robinson, Gene E; Zhang, Guojie

2015-06-05

The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks. Copyright © 2015, American Association for the Advancement of Science.

From the primordial soup to self-driving cars: standards and their role in natural and technological innovation

PubMed Central

Wagner, Andreas; Ortman, Scott; Maxfield, Robert

2016-01-01

Standards are specifications to which the elements of a technology must conform. Here, we apply this notion to the biochemical ‘technologies' of nature, where objects like DNA and proteins, as well as processes like the regulation of gene activity are highly standardized. We introduce the concept of standards with multiple examples, ranging from the ancient genetic material RNA, to Palaeolithic stone axes, and digital electronics, and we discuss common ways in which standards emerge in nature and technology. We then focus on the question of how standards can facilitate technological and biological innovation. Innovation-enhancing standards include those of proteins and digital electronics. They share common features, such as that few standardized building blocks can be combined through standard interfaces to create myriad useful objects or processes. We argue that such features will also characterize the most innovation-enhancing standards of future technologies. PMID:26864893

Mechanisms of viral mutation.

PubMed

Sanjuán, Rafael; Domingo-Calap, Pilar

2016-12-01

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.

From the primordial soup to self-driving cars: standards and their role in natural and technological innovation.

PubMed

Wagner, Andreas; Ortman, Scott; Maxfield, Robert

2016-02-01

Standards are specifications to which the elements of a technology must conform. Here, we apply this notion to the biochemical 'technologies' of nature, where objects like DNA and proteins, as well as processes like the regulation of gene activity are highly standardized. We introduce the concept of standards with multiple examples, ranging from the ancient genetic material RNA, to Palaeolithic stone axes, and digital electronics, and we discuss common ways in which standards emerge in nature and technology. We then focus on the question of how standards can facilitate technological and biological innovation. Innovation-enhancing standards include those of proteins and digital electronics. They share common features, such as that few standardized building blocks can be combined through standard interfaces to create myriad useful objects or processes. We argue that such features will also characterize the most innovation-enhancing standards of future technologies. © 2016 The Author(s).

Chronobiology of bipolar disorder: therapeutic implication.

PubMed

Dallaspezia, Sara; Benedetti, Francesco

2015-08-01

Multiple lines of evidence suggest that psychopathological symptoms of bipolar disorder arise in part from a malfunction of the circadian system, linking the disease with an abnormal internal timing. Alterations in circadian rhythms and sleep are core elements in the disorders, characterizing both mania and depression and having recently been shown during euthymia. Several human genetic studies have implicated specific genes that make up the genesis of circadian rhythms in the manifestation of mood disorders with polymorphisms in molecular clock genes not only showing an association with the disorder but having also been linked to its phenotypic particularities. Many medications used to treat the disorder, such as antidepressant and mood stabilizers, affect the circadian clock. Finally, circadian rhythms and sleep researches have been the starting point of the developing of chronobiological therapies. These interventions are safe, rapid and effective and they should be considered first-line strategies for bipolar depression.

Piezoceramic Actuator Placement for Acoustic Control of Panels

NASA Technical Reports Server (NTRS)

Bevan, Jeffrey S.; Turner, Travis L. (Technical Monitor)

2001-01-01

Optimum placement of multiple traditional piezoceramic actuators is determined for active structural acoustic control of flat panels. The structural acoustic response is determined using acoustic radiation filters and structural surface vibration characteristics. Linear Quadratic Regulator (LQR) control is utilized to determine the optimum state feedback gain for active structural acoustic control. The optimum actuator location is determined by minimizing the structural acoustic radiated noise using a modified genetic algorithm. Experimental tests are conducted and compared to analytical results. Anisotropic piezoceramic actuators exhibits enhanced performance when compared to traditional isotropic piezoceramic actuators. As a result of the inherent isotropy, these advanced actuators develop strain along the principal material axis. The orientation of anisotropic actuators is investigated on the effect of structural vibration and acoustic control of curved and flat panels. A fully coupled shallow shell finite element formulation is developed to include anisotropic piezoceramic actuators for shell structures.

Piezoceramic Actuator Placement for Acoustic Control of Panels

NASA Technical Reports Server (NTRS)

Bevan, Jeffrey S.

2000-01-01

Optimum placement of multiple traditional piezoceramic actuators is determined for active structural acoustic control of flat panels. The structural acoustic response is determined using acoustic radiation filters and structural surface vibration characteristics. Linear Quadratic Regulator (LQR) control is utilized to determine the optimum state feedback gain for active structural acoustic control. The optimum actuator location is determined by minimizing the structural acoustic radiated noise using a modified genetic algorithm. Experimental tests are conducted and compared to analytical results. Anisotropic piezoceramic actuators exhibit enhanced performance when compared to traditional isotropic piezoceramic actuators. As a result of the inherent isotropy, these advanced actuators develop strain along the principal material axis. The orientation of anisotropic actuators is investigated on the effect of structural vibration and acoustic control of curved and flat panels. A fully coupled shallow shell finite element formulation is developed to include anisotropic piezoceramic actuators for shell structures.

Multiple cerebral arteriovenous malformations associated to rostral hypoplasia of the superior sagittal sinus: case report.

PubMed

TORNè, Ramon; Molina Jaque, Felipe A; Rodriguez-Hernandez, Ana; Arikan, Fuat; Lopez-Bermeo, Diego; Tomasello, Alejandro

2016-06-07

Multiple cerebral arteriovenous malformations (AVMs) are a rare occurrence usually associated with defined genetic disorders or a family history of cerebrovascular disease. The remaining cases cannot be associated to a genetic pathogenesis and are considered idiopathic. We report an extremely unusual case nor genetic neither idiopathic, but linked to an anatomical intracranial venous variation. The patient presented two independent frontal AVMs associated with rostral hypoplasia of the superior sagittal sinus. This anatomical variation may have induced frontal venous hypertension (VHT) triggering the development of the two AVMs. Throughout this intriguing case, we discuss the role of VHT in AVM development.

The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.

PubMed

Richardson, Sandra R; Doucet, Aurélien J; Kopera, Huira C; Moldovan, John B; Garcia-Perez, José Luis; Moran, John V

2015-04-01

Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.

Different Genetic Elements Carrying the tet(W) Gene in Two Human Clinical Isolates of Streptococcus suis▿ †

PubMed Central

Palmieri, Claudio; Princivalli, Maria Stella; Brenciani, Andrea; Varaldo, Pietro E.; Facinelli, Bruna

2011-01-01

The genetic support for tet(W), an emerging tetracycline resistance determinant, was studied in two strains of Streptococcus suis, SsCA and SsUD, both isolated in Italy from patients with meningitis. Two completely different tet(W)-carrying genetic elements, sharing only a tet(W)-containing segment barely larger than the gene, were found in the two strains. The one from strain SsCA was nontransferable, and aside from an erm(B)-containing insertion, it closely resembled a genomic island recently described in an S. suis Chinese human isolate in sequence, organization, and chromosomal location. The tet(W)-carrying genetic element from strain SsUD was transferable (at a low frequency) and, though apparently noninducible following mitomycin C treatment, displayed a typical phage organization and was named ΦSsUD.1. Its full sequence was determined (60,711 bp), the highest BLASTN score being Streptococcus pyogenes Φm46.1. ΦSsUD.1 exhibited a unique combination of antibiotic and heavy metal resistance genes. Besides tet(W), it contained a MAS (macrolide-aminoglycoside-streptothricin) fragment with an erm(B) gene having a deleted leader peptide and a cadC/cadA cadmium efflux cassette. The MAS fragment closely resembled the one recently described in pneumococcal transposons Tn6003 and Tn1545. These resistance genes found in the ΦSsUD.1 phage scaffold differed from, but were in the same position as, cargo genes carried by other streptococcal phages. The chromosome integration site of ΦSsUD.1 was at the 3′ end of a conserved tRNA uracil methyltransferase (rum) gene. This site, known to be an insertional hot spot for mobile elements in S. pyogenes, might play a similar role in S. suis. PMID:21115784

Different genetic elements carrying the tet(W) gene in two human clinical isolates of Streptococcus suis.

PubMed

Palmieri, Claudio; Princivalli, Maria Stella; Brenciani, Andrea; Varaldo, Pietro E; Facinelli, Bruna

2011-02-01

The genetic support for tet(W), an emerging tetracycline resistance determinant, was studied in two strains of Streptococcus suis, SsCA and SsUD, both isolated in Italy from patients with meningitis. Two completely different tet(W)-carrying genetic elements, sharing only a tet(W)-containing segment barely larger than the gene, were found in the two strains. The one from strain SsCA was nontransferable, and aside from an erm(B)-containing insertion, it closely resembled a genomic island recently described in an S. suis Chinese human isolate in sequence, organization, and chromosomal location. The tet(W)-carrying genetic element from strain SsUD was transferable (at a low frequency) and, though apparently noninducible following mitomycin C treatment, displayed a typical phage organization and was named ΦSsUD.1. Its full sequence was determined (60,711 bp), the highest BLASTN score being Streptococcus pyogenes Φm46.1. ΦSsUD.1 exhibited a unique combination of antibiotic and heavy metal resistance genes. Besides tet(W), it contained a MAS (macrolide-aminoglycoside-streptothricin) fragment with an erm(B) gene having a deleted leader peptide and a cadC/cadA cadmium efflux cassette. The MAS fragment closely resembled the one recently described in pneumococcal transposons Tn6003 and Tn1545. These resistance genes found in the ΦSsUD.1 phage scaffold differed from, but were in the same position as, cargo genes carried by other streptococcal phages. The chromosome integration site of ΦSsUD.1 was at the 3' end of a conserved tRNA uracil methyltransferase (rum) gene. This site, known to be an insertional hot spot for mobile elements in S. pyogenes, might play a similar role in S. suis.

Miniature inverted-repeat transposable element identification and genetic marker development in Agrostis

USDA-ARS?s Scientific Manuscript database

Creeping bentgrass (Agrostis stolonifera L.) is an important species to the turfgrass industry because of its adaptation for use in high quality turf stands such as golf course putting greens, tees, and fairways. A. stolonifera is a highly outcrossing allotetraploid making genetic marker developmen...

Invasion genetics of the Bermuda buttercup (Oxalis pes-caprae): complex intercontinental patterns of genetic diversity, polyploidy and heterostyly characterize both native and introduced populations.

PubMed

Ferrero, Victoria; Barrett, Spencer C H; Castro, Sílvia; Caldeirinha, Patrícia; Navarro, Luis; Loureiro, João; Rodríguez-Echeverría, Susana

2015-05-01

Genetic diversity in populations of invasive species is influenced by a variety of factors including reproductive systems, ploidy level, stochastic forces associated with colonization and multiple introductions followed by admixture. Here, we compare genetic variation in native and introduced populations of the clonal plant Oxalis pes-caprae to investigate the influence of reproductive mode and ploidy on levels of diversity. This species is a tristylous geophyte native to South Africa. Invasive populations throughout much of the introduced range are composed of a sterile clonal pentaploid short-styled form. We examined morph ratios, ploidy level, reproductive mode and genetic diversity at nuclear microsatellite loci in 10 and 12 populations from South Africa and the Western Mediterranean region, respectively. Flow cytometry confirmed earlier reports of diploids and tetraploids in the native range, with a single population containing pentaploid individuals. Introduced populations were composed mainly of pentaploids, but sexual tetraploids were also found. There was clear genetic differentiation between ploidy levels, but sexual populations from both regions were not significantly different in levels of diversity. Invasive populations of the pentaploid exhibited dramatically reduced levels of diversity but were not genetically uniform. The occurrence of mixed ploidy levels and stylar polymorphism in the introduced range is consistent with multiple introductions to the Western Mediterranean. This inference was supported by variation patterns at microsatellite loci. Our study indicates that some invasive populations of Oxalis pes-caprae are not entirely clonal, as often assumed, and multiple introductions and recombination have the potential to increase genetic variation in the introduced range. © 2014 John Wiley & Sons Ltd.

Strategies and approaches in plasmidome studies-uncovering plasmid diversity disregarding of linear elements?

PubMed

Dib, Julián R; Wagenknecht, Martin; Farías, María E; Meinhardt, Friedhelm

2015-01-01

The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which-despite their frequent occurrence in a large number of bacteria-are largely neglected in prevalent plasmidome conceptions.

copia-like retrotransposons are ubiquitous among plants.

PubMed Central

Voytas, D F; Cummings, M P; Koniczny, A; Ausubel, F M; Rodermel, S R

1992-01-01

Transposable genetic elements are assumed to be a feature of all eukaryotic genomes. Their identification, however, has largely been haphazard, limited principally to organisms subjected to molecular or genetic scrutiny. We assessed the phylogenetic distribution of copia-like retrotransposons, a class of transposable element that proliferates by reverse transcription, using a polymerase chain reaction assay designed to detect copia-like element reverse transcriptase sequences. copia-like retrotransposons were identified in 64 plant species as well as the photosynthetic protist Volvox carteri. The plant species included representatives from 9 of 10 plant divisions, including bryophytes, lycopods, ferns, gymnosperms, and angiosperms. DNA sequence analysis of 29 cloned PCR products and of a maize retrotransposon cDNA confirmed the identity of these sequences as copia-like reverse transcriptase sequences, thereby demonstrating that this class of retrotransposons is a ubiquitous component of plant genomes. Images PMID:1379734

ECUT: Energy Conversion and Utilization Technologies program - Biocatalysis research activity

NASA Technical Reports Server (NTRS)

Wilcox, R.

1984-01-01

The activities of the Biocatalysis Research Activity are organized into the Biocatalysis and Molecular Modeling work elements and a supporting planning and analysis function. In the Biocatalysis work element, progress is made in developing a method for stabilizing genetically engineered traits in microorganisms, refining a technique for monitoring cells that are genetically engineered, and identifying strains of fungi for highly efficient preprocessing of biomass for optimizing the efficiency of bioreactors. In the Molecular Modeling work element, a preliminary model of the behavior of enzymes is developed. A preliminary investigation of the potential for synthesizing enzymes for use in electrochemical processes is completed. Contact with industry and universities is made to define key biocatalysis technical issues and to broaden the range of potential participants in the activity. Analyses are conducted to identify and evaluate potential concepts for future research funding.

TEMPLE: analysing population genetic variation at transcription factor binding sites.

PubMed

Litovchenko, Maria; Laurent, Stefan

2016-11-01

Genetic variation occurring at the level of regulatory sequences can affect phenotypes and fitness in natural populations. This variation can be analysed in a population genetic framework to study how genetic drift and selection affect the evolution of these functional elements. However, doing this requires a good understanding of the location and nature of regulatory regions and has long been a major hurdle. The current proliferation of genomewide profiling experiments of transcription factor occupancies greatly improves our ability to identify genomic regions involved in specific DNA-protein interactions. Although software exists for predicting transcription factor binding sites (TFBS), and the effects of genetic variants on TFBS specificity, there are no tools currently available for inferring this information jointly with the genetic variation at TFBS in natural populations. We developed the software Transcription Elements Mapping at the Population LEvel (TEMPLE), which predicts TFBS, evaluates the effects of genetic variants on TFBS specificity and summarizes the genetic variation occurring at TFBS in intraspecific sequence alignments. We demonstrate that TEMPLE's TFBS prediction algorithms gives identical results to PATSER, a software distribution commonly used in the field. We also illustrate the unique features of TEMPLE by analysing TFBS diversity for the TF Senseless (SENS) in one ancestral and one cosmopolitan population of the fruit fly Drosophila melanogaster. TEMPLE can be used to localize TFBS that are characterized by strong genetic differentiation across natural populations. This will be particularly useful for studies aiming to identify adaptive mutations. TEMPLE is a java-based cross-platform software that easily maps the genetic diversity at predicted TFBSs using a graphical interface, or from the Unix command line. © 2016 John Wiley & Sons Ltd.

SXT/R391 integrative and conjugative elements in Proteus species reveal abundant genetic diversity and multidrug resistance

PubMed Central

Li, Xinyue; Du, Yu; Du, Pengcheng; Dai, Hang; Fang, Yujie; Li, Zhenpeng; Lv, Na; Zhu, Baoli; Kan, Biao; Wang, Duochun

2016-01-01

SXT/R391 integrative and conjugative elements (ICEs) are self-transmissible mobile genetic elements that are found in most members of Enterobacteriaceae. Here, we determined fifteen SXT/R391 ICEs carried by Proteus isolates from food (4.2%) and diarrhoea patients (17.3%). BLASTn searches against GenBank showed that the fifteen SXT/R391 ICEs were closely related to that from different Enterobacteriaceae species, including Proteus mirabilis. Using core gene phylogenetic analysis, the fifteen SXT/R391 ICEs were grouped into six distinct clusters, including a dominant cluster and three clusters that have not been previously reported in Proteus isolates. The SXT/R391 ICEs shared a common structure with a set of conserved genes, five hotspots and two variable regions, which contained more foreign genes, including drug-resistance genes. Notably, a class A β-lactamase gene was identified in nine SXT/R391 ICEs. Collectively, the ICE-carrying isolates carried resistance genes for 20 tested drugs. Six isolates were resistant to chloramphenicol, kanamycin, streptomycin, trimethoprim-sulfamethoxazole, sulfisoxazole and tetracycline, which are drug resistances commonly encoded by ICEs. Our results demonstrate abundant genetic diversity and multidrug resistance of the SXT/R391 ICEs carried by Proteus isolates, which may have significance for public health. It is therefore necessary to continuously monitor the antimicrobial resistance and related mobile elements among Proteus isolates. PMID:27892525

On a concurrent element-by-element preconditioned conjugate gradient algorithm for multiple load cases

NASA Technical Reports Server (NTRS)

Watson, Brian; Kamat, M. P.

1990-01-01

Element-by-element preconditioned conjugate gradient (EBE-PCG) algorithms have been advocated for use in parallel/vector processing environments as being superior to the conventional LDL(exp T) decomposition algorithm for single load cases. Although there may be some advantages in using such algorithms for a single load case, when it comes to situations involving multiple load cases, the LDL(exp T) decomposition algorithm would appear to be decidedly more cost-effective. The authors have outlined an EBE-PCG algorithm suitable for multiple load cases and compared its effectiveness to the highly efficient LDL(exp T) decomposition scheme. The proposed algorithm offers almost no advantages over the LDL(exp T) algorithm for the linear problems investigated on the Alliant FX/8. However, there may be some merit in the algorithm in solving nonlinear problems with load incrementation, but that remains to be investigated.

Implications of genetic testing for the insurance industry: the UK example.

PubMed

Raeburn, Sandy

2002-01-01

This report summarises the controversy of genetic tests and insurance, with a focus on the UK situation during the past decade. UK experience provides insight for future strategies to help people with genetic disadvantages make insurance provision for themselves and their families. Non-disclosure of genetic test results (already carried out for clinical purposes) may not benefit people at risk of genetic disorders or with positive genetic tests. The pressure of geneticists over a decade to prevent disclosure to insurers may have masked opportunities to use insurance to provide help for people with genetic disadvantages. To seize the opportunities now, there must be collaboration, not conflict. Politicians, geneticists, social scientists and all elements of the insurance industry can contribute to wise solutions.

What Use Is Population Genetics?

PubMed

Charlesworth, Brian

2015-07-01

The Genetic Society of America's Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth's research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation. Copyright © 2015 by the Genetics Society of America.

A systems approach defining constraints of the genome architecture on lineage selection and evolvability during somatic cancer evolution

PubMed Central

Rübben, Albert; Nordhoff, Ole

2013-01-01

Summary Most clinically distinguishable malignant tumors are characterized by specific mutations, specific patterns of chromosomal rearrangements and a predominant mechanism of genetic instability but it remains unsolved whether modifications of cancer genomes can be explained solely by mutations and selection through the cancer microenvironment. It has been suggested that internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution. A similar situation can be expected for somatic cancer evolution as molecular key mechanisms encountered in species evolution also constitute prevalent mutation mechanisms in human cancers. This assumption is developed into a systems approach of carcinogenesis which focuses on possible inner constraints of the genome architecture on lineage selection during somatic cancer evolution. The proposed systems approach can be considered an analogy to the concept of evolvability in species evolution. The principal hypothesis is that permissive or restrictive effects of the genome architecture on lineage selection during somatic cancer evolution exist and have a measurable impact. The systems approach postulates three classes of lineage selection effects of the genome architecture on somatic cancer evolution: i) effects mediated by changes of fitness of cells of cancer lineage, ii) effects mediated by changes of mutation probabilities and iii) effects mediated by changes of gene designation and physical and functional genome redundancy. Physical genome redundancy is the copy number of identical genetic sequences. Functional genome redundancy of a gene or a regulatory element is defined as the number of different genetic elements, regardless of copy number, coding for the same specific biological function within a cancer cell. Complex interactions of the genome architecture on lineage selection may be expected when modifications of the genome architecture have multiple and possibly opposed effects which manifest themselves at disparate times and progression stages. Dissection of putative mechanisms mediating constraints exerted by the genome architecture on somatic cancer evolution may provide an algorithm for understanding and predicting as well as modifying somatic cancer evolution in individual patients. PMID:23336076

PCR and magnetic bead-mediated target capture for the isolation of short interspersed nucleotide elements in fishes.

PubMed

Liu, Dong; Zhu, Guoli; Tang, Wenqiao; Yang, Jinquan; Guo, Hongyi

2012-01-01

Short interspersed nucleotide elements (SINEs), a type of retrotransposon, are widely distributed in various genomes with multiple copies arranged in different orientations, and cause changes to genes and genomes during evolutionary history. This can provide the basis for determining genome diversity, genetic variation and molecular phylogeny, etc. SINE DNA is transcribed into RNA by polymerase III from an internal promoter, which is composed of two conserved boxes, box A and box B. Here we present an approach to isolate novel SINEs based on these promoter elements. Box A of a SINE is obtained via PCR with only one primer identical to box B (B-PCR). Box B and its downstream sequence are acquired by PCR with one primer corresponding to box A (A-PCR). The SINE clone produced by A-PCR is selected as a template to label a probe with biotin. The full-length SINEs are isolated from the genomic pool through complex capture using the biotinylated probe bound to magnetic particles. Using this approach, a novel SINE family, Cn-SINE, from the genomes of Coilia nasus, was isolated. The members are 180-360 bp long. Sequence homology suggests that Cn-SINEs evolved from a leucine tRNA gene. This is the first report of a tRNA(Leu)-related SINE obtained without the use of a genomic library or inverse PCR. These results provide new insights into the origin of SINEs.

PCR and Magnetic Bead-Mediated Target Capture for the Isolation of Short Interspersed Nucleotide Elements in Fishes

PubMed Central

Liu, Dong; Zhu, Guoli; Tang, Wenqiao; Yang, Jinquan; Guo, Hongyi

2012-01-01

Short interspersed nucleotide elements (SINEs), a type of retrotransposon, are widely distributed in various genomes with multiple copies arranged in different orientations, and cause changes to genes and genomes during evolutionary history. This can provide the basis for determining genome diversity, genetic variation and molecular phylogeny, etc. SINE DNA is transcribed into RNA by polymerase III from an internal promoter, which is composed of two conserved boxes, box A and box B. Here we present an approach to isolate novel SINEs based on these promoter elements. Box A of a SINE is obtained via PCR with only one primer identical to box B (B-PCR). Box B and its downstream sequence are acquired by PCR with one primer corresponding to box A (A-PCR). The SINE clone produced by A-PCR is selected as a template to label a probe with biotin. The full-length SINEs are isolated from the genomic pool through complex capture using the biotinylated probe bound to magnetic particles. Using this approach, a novel SINE family, Cn-SINE, from the genomes of Coilia nasus, was isolated. The members are 180–360 bp long. Sequence homology suggests that Cn-SINEs evolved from a leucine tRNA gene. This is the first report of a tRNALeu-related SINE obtained without the use of a genomic library or inverse PCR. These results provide new insights into the origin of SINEs. PMID:22408437

International Congress on Transposable Elements (ICTE) 2012 in Saint Malo and the sea of TE stories.

PubMed

Ainouche, Abdelkader; Bétermier, Mireille; Chandler, Mick; Cordaux, Richard; Cristofari, Gaël; Deragon, Jean-Marc; Lesage, Pascale; Panaud, Olivier; Quesneville, Hadi; Vaury, Chantal; Vieira, Cristina; Vitte, Clémentine

2012-10-30

An international conference on Transposable Elements (TEs) was held 21-24 April 2012 in Saint Malo, France. Organized by the French Transposition Community (GDR Elements Génétiques Mobiles et Génomes, CNRS) and the French Society of Genetics (SFG), the conference's goal was to bring together researchers from around the world who study transposition in diverse organisms using multiple experimental approaches. The meeting drew more than 217 attendees and most contributed through poster presentations (117), invited talks and short talks selected from poster abstracts (48 in total). The talks were organized into four scientific sessions, focused on: impact of TEs on genomes, control of transposition, evolution of TEs and mechanisms of transposition. Here, we present highlights from the talks given during the platform sessions. The conference was sponsored by Alliance pour les sciences de la vie et de la santé (Aviesan), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut de recherche pour le développement (IRD), Institut national de la recherche agronomique (INRA), Université de Perpignan, Université de Rennes 1, Région Bretagne and Mobile DNA. CHAIR OF THE ORGANIZATION COMMITTEE: Jean-Marc Deragon ORGANIZERS: Abdelkader Ainouche, Mireille Bétermier, Mick Chandler, Richard Cordaux, Gaël Cristofari, Jean-Marc Deragon, Pascale Lesage, Didier Mazel, Olivier Panaud, Hadi Quesneville, Chantal Vaury, Cristina Vieira and Clémentine Vitte.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

Arabidopsis and the Genetic Potential for the Phytoremediation of Toxic Elemental and Organic Pollutants

PubMed Central

Cobbett, Christopher S.; Meagher, Richard B.

2002-01-01

In a process called phytoremediation, plants can be used to extract, detoxify, and/or sequester toxic pollutants from soil, water, and air. Phytoremediation may become an essential tool in cleaning the environment and reducing human and animal exposure to potential carcinogens and other toxins. Arabidopsis has provided useful information about the genetic, physiological, and biochemical mechanisms behind phytoremediation, and it is an excellent model genetic organism to test foreign gene expression. This review focuses on Arabidopsis studies concerning: 1) the remediation of elemental pollutants; 2) the remediation of organic pollutants; and 3) the phytoremediation genome. Elemental pollutants include heavy metals and metalloids (e.g., mercury, lead, cadmium, arsenic) that are immutable. The general goal of phytoremediation is to extract, detoxify, and hyperaccumulate elemental pollutants in above-ground plant tissues for later harvest. A few dozen Arabidopsis genes and proteins that play direct roles in the remediation of elemental pollutants are discussed. Organic pollutants include toxic chemicals such as benzene, benzo(a)pyrene, polychlorinated biphenyls, trichloroethylene, trinitrotoluene, and dichlorodiphenyltrichloroethane. Phytoremediation of organic pollutants is focused on their complete mineralization to harmless products, however, less is known about the potential of plants to act on complex organic chemicals. A preliminary survey of the Arabidopsis genome suggests that as many as 700 genes encode proteins that have the capacity to act directly on environmental pollutants or could be modified to do so. The potential of the phytoremediation proteome to be used to reduce human exposure to toxic pollutants appears to be enormous and untapped. PMID:22303204

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Genetic landscapes GIS Toolbox: tools to map patterns of genetic divergence and diversity.

USGS Publications Warehouse

Vandergast, Amy G.; Perry, William M.; Lugo, Roberto V.; Hathaway, Stacie A.

2011-01-01

The Landscape Genetics GIS Toolbox contains tools that run in the Geographic Information System software, ArcGIS, to map genetic landscapes and to summarize multiple genetic landscapes as average and variance surfaces. These tools can be used to visualize the distribution of genetic diversity across geographic space and to study associations between patterns of genetic diversity and geographic features or other geo-referenced environmental data sets. Together, these tools create genetic landscape surfaces directly from tables containing genetic distance or diversity data and sample location coordinates, greatly reducing the complexity of building and analyzing these raster surfaces in a Geographic Information System.

Eight-Element Antenna Array for LTE 3.4-3.8 GHz Mobile Handset Applications

NASA Astrophysics Data System (ADS)

Yang, Lingsheng; Ji, Ming; Cheng, Biyu; Ni, Bo

2017-05-01

In this letter, an eight-element Multiple-input multiple-output (MIMO) antenna system for LTE mobile handset applications is proposed. The antenna array consists of eight 3D inverted F-shaped antennas (3D-IFA), and the measured -10 dB impedance bandwidth is 3.2-3.9 GHz which can cover the LTE bands 42 and 43 (3.4-3.8 GHz). By controlling the rotation of the antenna elements, no less than 10 dB isolation between antenna elements can be obtained. After using the specially designed meandered slots on the ground as decoupling structures, the measured isolation can be further improved to higher than 13 dB between the antenna elements at the whole operating band.

Insights into population ecology and sexual selection in snakes through the application of DNA-based genetic markers.

PubMed

Gibbs, H L; Weatherhead, P J

2001-01-01

Hypervariable genetic markers have revolutionized studies of kinship, behavioral ecology, and population biology in vertebrate groups such as birds, but their use in snakes remains limited. To illustrate the value of such markers in snakes, we review studies that have used microsatellite DNA loci to analyze local population differentiation and parentage in snakes. Four ecologically distinct species of snakes all show evidence for differentiation at small spatial scales (2-15 km), but with substantial differences among species. This result highlights how genetic analysis can reveal hidden aspects of the natural history of difficult-to-observe taxa, and it raises important questions about the ecological factors that may contribute to restricted gene flow. A 3-year study of genetic parentage in marked populations of the northern water snake showed that (1) participation in mating aggregations was a poor predictor of genetic-based measures of reproductive success; (2) multiple paternity was high, yet there was no detectable fitness advantage to multiple mating by females; and (3) the opportunity for selection was far higher in males than in females due to a larger variance in male reproductive success, and yet this resulted in no detectable selection on morphological variation in males. Thus genetic markers have provided accurate measures of individual reproductive success in this species, an important step toward resolving the adaptive significance of key features including multiple paternity and reversed sexual size dimorphism. Overall these studies illustrate how genetic analyses of snakes provide previously unobtainable information of long-standing interest to behavioral ecologists.

Integrative Lifecourse and Genetic Analysis of Military Working Dogs

DTIC Science & Technology

2014-12-01

Award Number: W81XWH-11-2-0226 TITLE: Integrative Lifecourse and Genetic Analysis of Military Working Dogs PRINCIPAL INVESTIGATOR: Kun Huang...Integrative Lifecourse and Genetic Analysis of Military Working Dogs 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-2-0226 5c. PROGRAM ELEMENT NUMBER...of the military working dog population. There are several critical aspects to meeting the aims of this proposal. 1) development of data driven

Genetic and Functional Heterogeneity of Tumors in Neurofibromatosis 2

DTIC Science & Technology

2015-05-01

Award Number: W81XWH-13-1-0093 TITLE: Genetic and Functional Heterogeneity of Tumors in Neurofibromatosis 2 PRINCIPAL INVESTIGATOR: James F...Genetic and Functional Heterogeneity of Tumors in Neurofibromatosis 2 5a. CONTRACT NUMBER W81XWH-13-1-0093 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...confirm genes and processes that contribute to NF2 tumor formation and assess their effects on cellular phenotypes. 15. SUBJECT TERMS Neurofibromatosis

Selected isotope ratio measurements of light metallic elements (Li, Mg, Ca, and Cu) by multiple collector ICP-MS

PubMed Central

Platzner, Thomas I.; Segal, Irina

2007-01-01

The unique capabilities of multiple collector inductively coupled mass spectrometry (MC-ICP-MS) for high precision isotope ratio measurements in light elements as Li, Mg, Ca, and Cu are reviewed in this paper. These elements have been intensively studied at the Geological Survey of Israel (GSI) and other laboratories over the past few years, and the methods used to obtain high precision isotope analyses are discussed in detail. The scientific study of isotopic fractionation of these elements is significant for achieving a better understanding of geochemical and biochemical processes in nature and the environment. PMID:17962922

Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.

PubMed

Viana, Joana; Hannon, Eilis; Dempster, Emma; Pidsley, Ruth; Macdonald, Ruby; Knox, Olivia; Spiers, Helen; Troakes, Claire; Al-Saraj, Safa; Turecki, Gustavo; Schalkwyk, Leonard C; Mill, Jonathan

2017-01-01

Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease. © The Author 2016. Published by Oxford University Press.

Redox flow batteries having multiple electroactive elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei; Li, Liyu; Yang, Zhenguo

Introducing multiple redox reactions with a suitable voltage range can improve the energy density of redox flow battery (RFB) systems. One example includes RFB systems utilizing multiple redox pairs in the positive half cell, the negative half cell, or in both. Such RFB systems can have a negative electrolyte, a positive electrolyte, and a membrane between the negative electrolyte and the positive electrolyte, in which at least two electrochemically active elements exist in the negative electrolyte, the positive electrolyte, or both.

Human predisposition to cognitive impairment and its relation with environmental exposure to potentially toxic elements.

PubMed

Cabral Pinto, Marina M S; Marinho-Reis, A Paula; Almeida, Agostinho; Ordens, Carlos M; Silva, Maria M V G; Freitas, Sandra; Simões, Mário R; Moreira, Paula I; Dinis, Pedro A; Diniz, M Luísa; Ferreira da Silva, Eduardo A; Condesso de Melo, M Teresa

2017-03-09

New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson's, Alzheimer's and sclerosis diseases. This study proposes a multidisciplinary approach combining neurosciences, psychology and environmental sciences while integrating socio-economic, neuropsychological, environmental and health data. We present the preliminary results of a neuropsychological assessment carried out in elderly residents of the industrial city of Estarreja. A battery of cognitive tests and a personal questionnaire were administered to the participants. Multivariate analysis and multiple linear regression analysis were used to identify potential relationships between the cognitive status of the participants and environmental exposure to potentially toxic elements. The results suggest a relationship between urinary PTEs levels and the incidence of cognitive disorders. They also point towards water consumption habits and profession as relevant factors of exposure. Linear regression models show that aluminium (R 2  = 38%), cadmium (R 2  = 11%) and zinc (R 2  = 6%) are good predictors of the scores of the Mini-Mental State Examination cognitive test. Median contents (µg/l) in groundwater are above admissible levels for drinking water for aluminium (371), iron (860), manganese (250), and zinc (305). While the World Health Organization does not provide health-based reference values for aluminium, results obtained from this study suggest that it may have an important role in the cognitive status of the elderly. Urine proved to be a suitable biomarker of exposure both to elements with low and high excretion rates.

Promoter library-based module combination (PLMC) technology for optimization of threonine biosynthesis in Corynebacterium glutamicum.

PubMed

Wei, Liang; Xu, Ning; Wang, Yiran; Zhou, Wei; Han, Guoqiang; Ma, Yanhe; Liu, Jun

2018-05-01

Due to the lack of efficient control elements and tools, the fine-tuning of gene expression in the multi-gene metabolic pathways is still a great challenge for engineering microbial cell factories, especially for the important industrial microorganism Corynebacterium glutamicum. In this study, the promoter library-based module combination (PLMC) technology was developed to efficiently optimize the expression of genes in C. glutamicum. A random promoter library was designed to contain the putative - 10 (NNTANANT) and - 35 (NNGNCN) consensus motifs, and refined through a three-step screening procedure to achieve numerous genetic control elements with different strength levels, including fluorescence-activated cell sorting (FACS) screening, agar plate screening, and 96-well plate screening. Multiple conventional strategies were employed for further precise characterizations of the promoter library, such as real-time quantitative PCR, sodium dodecyl sulfate polyacrylamide gel electrophoresis, FACS analysis, and the lacZ reporter system. These results suggested that the established promoter elements effectively regulated gene expression and showed varying strengths over a wide range. Subsequently, a multi-module combination technology was created based on the efficient promoter elements for combination and optimization of modules in the multi-gene pathways. Using this technology, the threonine biosynthesis pathway was reconstructed and optimized by predictable tuning expression of five modules in C. glutamicum. The threonine titer of the optimized strain was significantly improved to 12.8 g/L, an approximate 6.1-fold higher than that of the control strain. Overall, the PLMC technology presented in this study provides a rapid and effective method for combination and optimization of multi-gene pathways in C. glutamicum.

Grains of connectivity: analysis at multiple spatial scales in landscape genetics.

PubMed

Galpern, Paul; Manseau, Micheline; Wilson, Paul

2012-08-01

Landscape genetic analyses are typically conducted at one spatial scale. Considering multiple scales may be essential for identifying landscape features influencing gene flow. We examined landscape connectivity for woodland caribou (Rangifer tarandus caribou) at multiple spatial scales using a new approach based on landscape graphs that creates a Voronoi tessellation of the landscape. To illustrate the potential of the method, we generated five resistance surfaces to explain how landscape pattern may influence gene flow across the range of this population. We tested each resistance surface using a raster at the spatial grain of available landscape data (200 m grid squares). We then used our method to produce up to 127 additional grains for each resistance surface. We applied a causal modelling framework with partial Mantel tests, where evidence of landscape resistance is tested against an alternative hypothesis of isolation-by-distance, and found statistically significant support for landscape resistance to gene flow in 89 of the 507 spatial grains examined. We found evidence that major roads as well as the cumulative effects of natural and anthropogenic disturbance may be contributing to the genetic structure. Using only the original grid surface yielded no evidence for landscape resistance to gene flow. Our results show that using multiple spatial grains can reveal landscape influences on genetic structure that may be overlooked with a single grain, and suggest that coarsening the grain of landcover data may be appropriate for highly mobile species. We discuss how grains of connectivity and related analyses have potential landscape genetic applications in a broad range of systems. © 2012 Blackwell Publishing Ltd.

A computational interactome for prioritizing genes associated with complex agronomic traits in rice (Oryza sativa).

PubMed

Liu, Shiwei; Liu, Yihui; Zhao, Jiawei; Cai, Shitao; Qian, Hongmei; Zuo, Kaijing; Zhao, Lingxia; Zhang, Lida

2017-04-01

Rice (Oryza sativa) is one of the most important staple foods for more than half of the global population. Many rice traits are quantitative, complex and controlled by multiple interacting genes. Thus, a full understanding of genetic relationships will be critical to systematically identify genes controlling agronomic traits. We developed a genome-wide rice protein-protein interaction network (RicePPINet, http://netbio.sjtu.edu.cn/riceppinet) using machine learning with structural relationship and functional information. RicePPINet contained 708 819 predicted interactions for 16 895 non-transposable element related proteins. The power of the network for discovering novel protein interactions was demonstrated through comparison with other publicly available protein-protein interaction (PPI) prediction methods, and by experimentally determined PPI data sets. Furthermore, global analysis of domain-mediated interactions revealed RicePPINet accurately reflects PPIs at the domain level. Our studies showed the efficiency of the RicePPINet-based method in prioritizing candidate genes involved in complex agronomic traits, such as disease resistance and drought tolerance, was approximately 2-11 times better than random prediction. RicePPINet provides an expanded landscape of computational interactome for the genetic dissection of agronomically important traits in rice. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.