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Sample records for genome studies progress

  1. Progress of genome wide association study in domestic animals

    PubMed Central

    2012-01-01

    Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described. PMID:22958308

  2. Identifying the genomic determinants of aging and longevity in human population studies: progress and challenges.

    PubMed

    Deelen, Joris; Beekman, Marian; Capri, Miriam; Franceschi, Claudio; Slagboom, P Eline

    2013-04-01

    Human lifespan variation is mainly determined by environmental factors, whereas the genetic contribution is 25-30% and expected to be polygenic. Two complementary fields go hand in hand in order to unravel the mechanisms of biological aging: genomic and biomarker research. Explorative and candidate gene studies of the human genome by genetic, transcriptomic, and epigenomic approaches have resulted in the identification of a limited number of interesting positive linkage regions, genes, and pathways that contribute to lifespan variation. The possibilities to further exploit these findings are rapidly increasing through the use of novel technologies, such as next-generation sequencing. Genomic research is progressively being integrated with biomarker studies on aging, including the application of (noninvasive) deep phenotyping and omics data - generated using novel technologies - in a wealth of studies in human populations. Hence, these studies may assist in obtaining a more holistic perspective on the role of the genome in aging and lifespan regulation. PMID:23423909

  3. Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics

    PubMed Central

    Stranger, Barbara E.; Stahl, Eli A.; Raj, Towfique

    2011-01-01

    Enormous progress in mapping complex traits in humans has been made in the last 5 yr. There has been early success for prevalent diseases with complex phenotypes. These studies have demonstrated clearly that, while complex traits differ in their underlying genetic architectures, for many common disorders the predominant pattern is that of many loci, individually with small effects on phenotype. For some traits, loci of large effect have been identified. For almost all complex traits studied in humans, the sum of the identified genetic effects comprises only a portion, generally less than half, of the estimated trait heritability. A variety of hypotheses have been proposed to explain why this might be the case, including untested rare variants, and gene–gene and gene–environment interaction. Effort is currently being directed toward implementation of novel analytic approaches and testing rare variants for association with complex traits using imputed variants from the publicly available 1000 Genomes Project resequencing data and from direct resequencing of clinical samples. Through integration with annotations and functional genomic data as well as by in vitro and in vivo experimentation, mapping studies continue to characterize functional variants associated with complex traits and address fundamental issues such as epistasis and pleiotropy. This review focuses primarily on the ways in which genome-wide association studies (GWASs) have revolutionized the field of human quantitative genetics. PMID:21115973

  4. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

    PubMed Central

    Kouri, Naomi; Ross, Owen A.; Dombroski, Beth; Younkin, Curtis S.; Serie, Daniel J.; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A.; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; McLean, Catriona A.; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B.; Farlow, Martin R.; Grafman, Jordan; Huey, Edward D.; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T.; Kretzschmar, Hans A.; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L.; Vonsattel, Jean Paul G.; Van Deerlin, Vivianna M.; Grossman, Murray; Hurtig, Howard I.; Gross, Rachel G.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M.; Wenning, Gregor K.; White, Charles L.; Höglinger, Günter U.; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I.; Crook, Julia; Parisi, Joseph E.; Boeve, Bradley F.; Josephs, Keith A.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Graff-Radford, Neill R.; Litvan, Irene; Younkin, Steven G.; Wang, Li-San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D.; Dickson, Dennis W.

    2015-01-01

    Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein). PMID:26077951

  5. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.

    PubMed

    Kouri, Naomi; Ross, Owen A; Dombroski, Beth; Younkin, Curtis S; Serie, Daniel J; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; McLean, Catriona A; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B; Farlow, Martin R; Grafman, Jordan; Huey, Edward D; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T; Kretzschmar, Hans A; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L; Vonsattel, Jean Paul G; Van Deerlin, Vivianna M; Grossman, Murray; Hurtig, Howard I; Gross, Rachel G; Arnold, Steven E; Trojanowski, John Q; Lee, Virginia M; Wenning, Gregor K; White, Charles L; Höglinger, Günter U; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I; Crook, Julia; Parisi, Joseph E; Boeve, Bradley F; Josephs, Keith A; Wszolek, Zbigniew K; Uitti, Ryan J; Graff-Radford, Neill R; Litvan, Irene; Younkin, Steven G; Wang, Li-San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D; Dickson, Dennis W

    2015-01-01

    Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein). PMID:26077951

  6. Genome-Wide Association Studies: Progress in Identifying Genetic Biomarkers in Common, Complex Diseases

    PubMed Central

    Kingsmore, Stephen F.; Lindquist, Ingrid E.; Mudge, Joann; Beavis, William D.

    2007-01-01

    Novel, comprehensive approaches for biomarker discovery and validation are urgently needed. One particular area of methodologic need is for discovery of novel genetic biomarkers in complex diseases and traits. Here, we review recent successes in the use of genome wide association (GWA) approaches to identify genetic biomarkers in common human diseases and traits. Such studies are yielding initial insights into the allelic architecture of complex traits. In general, it appears that complex diseases are associated with many common polymorphisms, implying profound genetic heterogeneity between affected individuals. PMID:19662211

  7. Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment.

    PubMed

    Hu, X; Pickering, E H; Hall, S K; Naik, S; Liu, Y C; Soares, H; Katz, E; Paciga, S A; Liu, W; Aisen, P S; Bales, K R; Samad, T A; John, S L

    2011-01-01

    Alzheimer's disease (AD) is the leading cause of dementia among the elderly population; however, knowledge about genetic risk factors involved in disease progression is limited. We conducted a genome-wide association study (GWAS) using clinical decline as measured by changes in the Clinical Dementia Rating-sum of boxes as a quantitative trait to test for single-nucleotide polymorphisms (SNPs) that were associated with the rate of progression in 822 Caucasian subjects of amnestic mild cognitive impairment (MCI). There was no significant association with disease progress for any of the recently identified disease susceptibility variants in CLU, CR1, PICALM, BIN1, EPHA1, MS4A6A, MS4A4E or CD33 following multiple testing correction. We did, however, identify multiple novel loci that reached genome-wide significance at the 0.01 level. These top variants (rs7840202 at chr8 in UBR5: P=4.27 × 10(-14); rs11637611 with a cluster of SNPs at chr15q23 close to the Tay-Sachs disease locus: P=1.07 × 10(-15); and rs12752888 at chr1: P=3.08 × 10(-11)) were also associated with a significant decline in cognition as well as the conversion of subjects with MCI to a diagnosis of AD. Taken together, these variants define approximately 16.6% of the MCI sub-population with a faster rate of decline independent of the other known disease risk factors. In addition to providing new insights into protein pathways that may be involved with the progress to AD in MCI subjects, these variants if further validated may enable the identification of a more homogeneous population of subjects at an earlier stage of disease for testing novel hypotheses and/or therapies in the clinical setting. PMID:22833209

  8. Mosquito genomics: progress and challenges.

    PubMed

    Severson, David W; Behura, Susanta K

    2012-01-01

    The whole-genome sequencing of mosquitoes has facilitated our understanding of fundamental biological processes at their basic molecular levels and holds potential for application to mosquito control and prevention of mosquito-borne disease transmission. Draft genome sequences are available for Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus. Collectively, these represent the major vectors of African malaria, dengue fever and yellow fever viruses, and lymphatic filariasis, respectively. Rapid advances in genome technologies have revealed detailed information on genome architecture as well as phenotype-specific transcriptomics and proteomics. These resources allow for detailed comparative analyses within and across populations as well as species. Next-generation sequencing technologies will likely promote a proliferation of genome sequences for additional mosquito species as well as for individual insects. Here we review the current status of genome research in mosquitoes and identify potential areas for further investigations. PMID:21942845

  9. Current Progress in Sports Genomics.

    PubMed

    Ahmetov, Ildus I; Fedotovskaya, Olga N

    2015-01-01

    Understanding the genetic architecture of athletic performance is an important step in the development of methods for talent identification in sport. Research concerned with molecular predictors has highlighted a number of potentially important DNA polymorphisms contributing to predisposition to success in certain types of sport. This review summarizes the evidence and mechanistic insights on the associations between DNA polymorphisms and athletic performance. A literature search (period: 1997-2014) revealed that at least 120 genetic markers are linked to elite athlete status (77 endurance-related genetic markers and 43 power/strength-related genetic markers). Notably, 11 (9%) of these genetic markers (endurance markers: ACE I, ACTN3 577X, PPARA rs4253778 G, PPARGC1A Gly482; power/strength markers: ACE D, ACTN3 Arg577, AMPD1 Gln12, HIF1A 582Ser, MTHFR rs1801131 C, NOS3 rs2070744 T, PPARG 12Ala) have shown positive associations with athlete status in three or more studies, and six markers (CREM rs1531550 A, DMD rs939787 T, GALNT13 rs10196189 G, NFIA-AS1 rs1572312 C, RBFOX1 rs7191721 G, TSHR rs7144481 C) were identified after performing genome-wide association studies (GWAS) of African-American, Jamaican, Japanese, and Russian athletes. On the other hand, the significance of 29 (24%) markers was not replicated in at least one study. Future research including multicenter GWAS, whole-genome sequencing, epigenetic, transcriptomic, proteomic, and metabolomic profiling and performing meta-analyses in large cohorts of athletes is needed before these findings can be extended to practice in sport. PMID:26231489

  10. A Multiancestral Genome-Wide Exome Array Study of Alzheimer Disease, Frontotemporal Dementia, and Progressive Supranuclear Palsy

    PubMed Central

    Chen, Jason A.; Wang, Qing; Davis-Turak, Jeremy; Li, Yun; Karydas, Anna M.; Hsu, Sandy C.; Sears, Renee L.; Chatzopoulou, Doxa; Huang, Alden Y.; Wojta, Kevin J.; Klein, Eric; Lee, Jason; Beekly, Duane L.; Boxer, Adam; Faber, Kelley M.; Haase, Claudia M.; Miller, Josh; Poon, Wayne W.; Rosen, Ami; Rosen, Howard; Sapozhnikova, Anna; Shapira, Jill; Varpetian, Arousiak; Foroud, Tatiana M.; Levenson, Robert W.; Levey, Allan I.; Kukull, Walter A.; Mendez, Mario F.; Ringman, John; Chui, Helena; Cotman, Carl; DeCarli, Charles; Miller, Bruce L.; Geschwind, Daniel H.; Coppola, Giovanni

    2015-01-01

    IMPORTANCE Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wide level. OBJECTIVE To identify low-frequency coding variants that affect susceptibility to AD, FTD, and PSP. DESIGN, SETTING, AND PARTICIPANTS We used the Illumina HumanExome BeadChip array to genotype a large number of variants (most of which are low-frequency coding variants) in a cohort of patients with neurodegenerative disease (224 with AD, 168 with FTD, and 48 with PSP) and in 224 control individuals without dementia enrolled between 2005–2012 from multiple centers participating in the Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease (GIFT) Study. An additional multiancestral replication cohort of 240 patients with AD and 240 controls without dementia was used to validate suggestive findings. Variant-level association testing and gene-based testing were performed. MAIN OUTCOMES AND MEASURES Statistical association of genetic variants with clinical diagnosis of AD, FTD, and PSP. RESULTS Genetic variants typed by the exome array explained 44%, 53%, and 57% of the total phenotypic variance of AD, FTD, and PSP, respectively. An association with the known AD gene ABCA7 was replicated in several ancestries (discovery P = .0049, European P = .041, African American P = .043, and Asian P = .027), suggesting that exonic variants within this gene modify AD susceptibility. In addition, 2 suggestive candidate genes, DYSF (P = 5.53 × 10−5) and PAXIP1 (P = 2.26 × 10−4), were highlighted in patients with AD and differentially expressed in AD brain. Corroborating evidence from other exome array studies and gene expression data points toward potential involvement of these genes in the pathogenesis of AD. CONCLUSIONS AND RELEVANCE Low

  11. DOE Joint Genome Institute 2008 Progress Report

    SciTech Connect

    Gilbert, David

    2009-03-12

    dominated how sequencing was done in the last decade is being replaced by a variety of new processes and sequencing instruments. The JGI, with an increasing number of next-generation sequencers, whose throughput is 100- to 1,000-fold greater than the Sanger capillary-based sequencers, is increasingly focused in new directions on projects of scale and complexity not previously attempted. These new directions for the JGI come, in part, from the 2008 National Research Council report on the goals of the National Plant Genome Initiative as well as the 2007 National Research Council report on the New Science of Metagenomics. Both reports outline a crucial need for systematic large-scale surveys of the plant and microbial components of the biosphere as well as an increasing need for large-scale analysis capabilities to meet the challenge of converting sequence data into knowledge. The JGI is extensively discussed in both reports as vital to progress in these fields of major national interest. JGI's future plan for plants and microbes includes a systematic approach for investigation of these organisms at a scale requiring the special capabilities of the JGI to generate, manage, and analyze the datasets. JGI will generate and provide not only community access to these plant and microbial datasets, but also the tools for analyzing them. These activities will produce essential knowledge that will be needed if we are to be able to respond to the world's energy and environmental challenges. As the JGI Plant and Microbial programs advance, the JGI as a user facility is also evolving. The Institute has been highly successful in bending its technical and analytical skills to help users solve large complex problems of major importance, and that effort will continue unabated. The JGI will increasingly move from a central focus on 'one-off' user projects coming from small user communities to much larger scale projects driven by systematic and problem-focused approaches to selection of

  12. Overcoming Barriers to Progress in Exercise Genomics

    PubMed Central

    Bouchard, Claude

    2011-01-01

    This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. PMID:21697717

  13. Poultry Genome Sequences: Progress and Outstanding Challenges

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first build of the chicken genome sequence appeared in March 2004 – the first genome sequence of any animal agriculture species. That sequence was done primarily by whole genome shotgun Sanger sequencing, along with the use of an extensive BAC contig-based physical map to assemble the sequence ...

  14. Comprehensive nucleosome mapping of the human genome in cancer progression

    PubMed Central

    Druliner, Brooke R.; Vera, Daniel; Johnson, Ruth; Ruan, Xiaoyang; Apone, Lynn M.; Dimalanta, Eileen T.; Stewart, Fiona J.; Boardman, Lisa; Dennis, Jonathan H.

    2016-01-01

    Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation. PMID:26735342

  15. Genomics and disease progression in IgA nephritis.

    PubMed

    Woo, Keng Thye; Lau, Yeow Kok; Choong, Hui Lin; Tan, Han Khim; Foo, Marjorie Wy; Lee, Evan Jc; Anantharaman, Vathsala; Lee, Grace Sl; Yap, Hui Kim; Yi, Zhao; Fook-Chong, Stephanie; Wong, Kok Seng; Chan, Choong Meng

    2013-12-01

    Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21. PMID:24463829

  16. [Genome plasticity and catabolic potential of pseudomonas cepacia]. Progress report

    SciTech Connect

    1993-12-31

    This progress report describes efforts directed at understanding the genomic structure of Pseudomonas cepacia. Variously reported are descriptions of the replicons in the genome, organization of macrorestriction fragments comprising the genome, use of a Tn-5- 751S to insertionally inactivate and map selected genes, construction of IS407 derivatives containing a trimethoprim resistance marker and SwaI site, and analysis of nucleotide sequences of IS401 and IS408.

  17. Human Genome Program Report. Part 1, Overview and Progress

    DOE R&D Accomplishments Database

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  18. Human genome program report. Part 1, overview and progress

    SciTech Connect

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  19. Integrated genomic characterization of IDH1-mutant glioma malignant progression

    PubMed Central

    Bai, Hanwen; Harmanci, Akdes Serin; Erson-Omay, E Zeynep; Li, Jie; Coşkun, Süleyman; Simon, Matthias; Krischek, Boris; Özduman, Koray; Omay, S Bülent; Sorensen, Eric A; Turcan, Şevin; Bakırcığlu, Mehmet; Carrión-Grant, Geneive; Murray, Phillip B; Clark, Victoria E; Ercan-Sencicek, A Gulhan; Knight, James; Sencar, Leman; Altınok, Selin; Kaulen, Leon D; Gülez, Burcu; Timmer, Marco; Schramm, Johannes; Mishra-Gorur, Ketu; Henegariu, Octavian; Moliterno, Jennifer; Louvi, Angeliki; Chan, Timothy A; Tannheimer, Stacey L; Pamir, M Necmettin; Vortmeyer, Alexander O; Bilguvar, Kaya; Yasuno, Katsuhito; Günel, Murat

    2016-01-01

    Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors1. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigenetic silencing of developmental transcription factor genes bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extraterminal (BET) family as a potential therapeutic approach. PMID:26618343

  20. Studying Culicoides vectors of BTV in the post-genomic era: resources, bottlenecks to progress and future directions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Culicoides biting midges (Diptera: Ceratopogonidae) are a major vector group responsible for the biological transmission of a wide variety of globally significant arboviruses, including bluetongue virus (BTV). In this review we examine current biological resources for the study of this genus, with a...

  1. The Cassava Genome: Current Progress, Future Directions.

    PubMed

    Prochnik, Simon; Marri, Pradeep Reddy; Desany, Brian; Rabinowicz, Pablo D; Kodira, Chinnappa; Mohiuddin, Mohammed; Rodriguez, Fausto; Fauquet, Claude; Tohme, Joseph; Harkins, Timothy; Rokhsar, Daniel S; Rounsley, Steve

    2012-03-01

    The starchy swollen roots of cassava provide an essential food source for nearly a billion people, as well as possibilities for bioenergy, yet improvements to nutritional content and resistance to threatening diseases are currently impeded. A 454-based whole genome shotgun sequence has been assembled, which covers 69% of the predicted genome size and 96% of protein-coding gene space, with genome finishing underway. The predicted 30,666 genes and 3,485 alternate splice forms are supported by 1.4 M expressed sequence tags (ESTs). Maps based on simple sequence repeat (SSR)-, and EST-derived single nucleotide polymorphisms (SNPs) already exist. Thanks to the genome sequence, a high-density linkage map is currently being developed from a cross between two diverse cassava cultivars: one susceptible to cassava brown streak disease; the other resistant. An efficient genotyping-by-sequencing (GBS) approach is being developed to catalog SNPs both within the mapping population and among diverse African farmer-preferred varieties of cassava. These resources will accelerate marker-assisted breeding programs, allowing improvements in disease-resistance and nutrition, and will help us understand the genetic basis for disease resistance. PMID:22523606

  2. 2013 Progress Report -- DOE Joint Genome Institute

    SciTech Connect

    2013-11-01

    In October 2012, we introduced a 10-Year Strategic Vision [http://bit.ly/JGI-Vision] for the Institute. A central focus of this Strategic Vision is to bridge the gap between sequenced genomes and an understanding of biological functions at the organism and ecosystem level. This involves the continued massive-scale generation of sequence data, complemented by orthogonal new capabilities to functionally annotate these large sequence data sets. Our Strategic Vision lays out a path to guide our decisions and ensure that the evolving set of experimental and computational capabilities available to DOE JGI users will continue to enable groundbreaking science.

  3. A Review of Catfish Genomics: Progress and Perspectives

    PubMed Central

    2003-01-01

    Catfish is one of the lower teleosts whose genome research is important for evolutionary genomics. As the major aquaculture species in the USA, its genome research also has practical and economical implications. Much progress has been made in recent years, including the development of large numbers of molecular markers, the construction of framework genetic linkage maps, the identification of putative markers involved in performance traits, and the development of genomic resources. Repetitive elements have been identified and characterized in the catfish genome that should facilitate physical analysis of the catfish genome. A large number of genes or full-length cDNAs have been analysed using genomic approaches, providing information on gene structure, gene evolution and gene expression in relation to functions. Catfish genome research has come to a stage when physical mapping through BAC contig construction is greatly demanded, in order to develop regional markers for QTL analysis and for large-scale comparative mapping. The current effort in large-scale EST analysis and type I marker mapping should further enhance research efficiency through comparative mapping. Candidate gene identification is being accelerated through the use of cDNA microarrays. PMID:18629126

  4. Research progress of plant population genomics based on high-throughput sequencing.

    PubMed

    Yunsheng, Wang

    2016-08-01

    Population genomics, a new paradigm for population genetics, combine the concepts and techniques of genomics with the theoretical system of population genetics and improve our understanding of microevolution through identification of site-specific effect and genome-wide effects using genome-wide polymorphic sites genotypeing. With the appearance and improvement of the next generation high-throughput sequencing technology, the numbers of plant species with complete genome sequences increased rapidly and large scale resequencing has also been carried out in recent years. Parallel sequencing has also been done in some plant species without complete genome sequences. These studies have greatly promoted the development of population genomics and deepened our understanding of the genetic diversity, level of linking disequilibium, selection effect, demographical history and molecular mechanism of complex traits of relevant plant population at a genomic level. In this review, I briely introduced the concept and research methods of population genomics and summarized the research progress of plant population genomics based on high-throughput sequencing. I also discussed the prospect as well as existing problems of plant population genomics in order to provide references for related studies. PMID:27531607

  5. In situ quantification of genomic instability in breast cancer progression

    SciTech Connect

    Ortiz de Solorzano, Carlos; Chin, Koei; Gray, Joe W.; Lockett, Stephen J.

    2003-05-15

    Genomic instability is a hallmark of breast and other solid cancers. Presumably caused by critical telomere reduction, GI is responsible for providing the genetic diversity required in the multi-step progression of the disease. We have used multicolor fluorescence in situ hybridization and 3D image analysis to quantify genomic instability cell-by-cell in thick, intact tissue sections of normal breast epithelium, preneoplastic lesions (usual ductal hyperplasia), ductal carcinona is situ or invasive carcinoma of the breast. Our in situ-cell by cell-analysis of genomic instability shows an important increase of genomic instability in the transition from hyperplasia to in situ carcinoma, followed by a reduction of instability in invasive carcinoma. This pattern suggests that the transition from hyperplasia to in situ carcinoma corresponds to telomere crisis and invasive carcinoma is a consequence of telomerase reactivation afertelomere crisis.

  6. White matter lesion progression: A genome-wide search for genetic influences

    PubMed Central

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C; DeCarli, Charles; Fornage, Myriam; Sigurdsson, Sigurdur; Srikanth, Velandai; Trompet, Stella; Verhaaren, Benjamin FJ; Wolf, Christiane; Yang, Qiong; Adams, Hieab HH; Amouyel, Philippe; Beiser, Alexa; Buckley, Brendan M; Callisaya, Michele; Chauhan, Ganesh; de Craen, Anton JM; Dufouil, Carole; van Duijn, Cornelia M; Ford, Ian; Freudenberger, Paul; Gottesman, Rebecca F; Gudnason, Vilmundur; Heiss, Gerardo; Hofman, Albert; Lumley, Thomas; Martinez, Oliver; Mazoyer, Bernard; Moran, Chris; Niessen, Wiro J.; Phan, Thanh; Psaty, Bruce M; Satizabal, Claudia L; Sattar, Naveed; Schilling, Sabrina; Shibata, Dean K; Slagboom, P Eline; Smith, Albert; Stott, David J; Taylor, Kent D; Thomson, Russell; Töglhofer, Anna M; Tzourio, Christophe; van Buchem, Mark; Wang, Jing; Westendorp, Rudi GJ; Windham, B Gwen; Vernooij, Meike W; Zijdenbos, Alex; Beare, Richard; Debette, Stéphanie; Ikram, M Arfan; Jukema, J Wouter; Launer, Lenore J; Longstreth, W T; Mosley, Thomas H; Seshadri, Sudha; Schmidt, Helena; Schmidt, Reinhold

    2016-01-01

    Background and Purpose White matter lesion (WML) progression on magnetic resonance imaging (MRI) is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in seven cohorts risk models including demographics, vascular risk factors plus single nucleotide polymorphisms (SNPs) that have been shown to be associated cross-sectionally with WML in the current and previous association studies. Results A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no SNPs achieved genome-wide significance (p-value < 5×10−8). Four loci were suggestive (p-value < 1×10−5) of an association with WML progression: 10q24.32 (rs10883817, p=1.46×10−6); 12q13.13 (rs4761974, p=8.71×10−7); 20p12.1 (rs6135309, p=3.69×10−6); and 4p15.31 (rs7664442, p=2.26×10−6). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors and baseline WML burden. Conclusions Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, life-style or host-related biological factors. PMID:26451028

  7. Personal genomes in progress: from the Human Genome Project to the Personal Genome Project

    PubMed Central

    Lunshof (Co-first author), Jeantine E.; Bobe (Co-first author), Jason; Aach, John; Angrist, Misha; V. Thakuria, Joseph; Vorhaus, Daniel B.; R. Hoehe (Co-last author), Margret; Church (Co-last author), George M.

    2010-01-01

    The cost of a diploid human genome sequence has dropped from about $70M to $2000 since 2007- even as the standards for redundancy have increased from 7x to 40x in order to improve call rates. Coupled with the low return on investment for common single-nucleotide polymorphisms, this has caused a significant rise in interest in correlating genome sequences with comprehensive environmental and trait data (GET). The cost of electronic health records, imaging, and microbial, immunological, and behavioral data are also dropping quickly. Sharing such integrated GET datasets and their interpretations with a diversity of researchers and research subjects highlights the need for informed-consent models capable of addressing novel privacy and other issues, as well as for flexible data-sharing resources that make materials and data available with minimum restrictions on use. This article examines the Personal Genome Project's effort to develop a GET database as a public genomics resource broadly accessible to both researchers and research participants, while pursuing the highest standards in research ethics. PMID:20373666

  8. Progresses in proton radioactivity studies

    NASA Astrophysics Data System (ADS)

    Ferreira, L. S.; Maglione, E.

    2016-07-01

    In the present talk, we will discuss recent progresses in the theoretical study of proton radioactivity and their impact on the present understanding of nuclear structure at the extremes of proton stability.

  9. Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient’s outcome in advanced colorectal cancer: the CORIOLAN study

    PubMed Central

    2014-01-01

    Background Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. Methods/Design CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC. Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps. Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Discussion Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging

  10. Progress in TILLING as a tool for functional genomics and improvement of crops.

    PubMed

    Chen, Liang; Hao, Liugen; Parry, Martin A J; Phillips, Andrew L; Hu, Yin-Gang

    2014-05-01

    Food security is a global concern and substantial yield increases in crops are required to feed the growing world population. Mutagenesis is an important tool in crop improvement and is free of the regulatory restrictions imposed on genetically modified organisms. Targeting Induced Local Lesions in Genomes (TILLING), which combines traditional chemical mutagenesis with high-throughput genome-wide screening for point mutations in desired genes, offers a powerful way to create novel mutant alleles for both functional genomics and improvement of crops. TILLING is generally applicable to genomes whether small or large, diploid or even allohexaploid, and shows great potential to address the major challenge of linking sequence information to the function of genes and to modulate key traits for plant breeding. TILLING has been successfully applied in many crop species and recent progress in TILLING is summarized below, especially on the developments in mutation detection technology, application of TILLING in gene functional studies and crop breeding. The potential of TILLING/EcoTILLING for functional genetics and crop improvement is also discussed. Furthermore, a small-scale forward strategy including backcross and selfing was conducted to release the potential mutant phenotypes masked in M2 (or M3) plants. PMID:24618006

  11. Adaptive radiations: From field to genomic studies

    PubMed Central

    Hodges, Scott A.; Derieg, Nathan J.

    2009-01-01

    Adaptive radiations were central to Darwin's formation of his theory of natural selection, and today they are still the centerpiece for many studies of adaptation and speciation. Here, we review the advantages of adaptive radiations, especially recent ones, for detecting evolutionary trends and the genetic dissection of adaptive traits. We focus on Aquilegia as a primary example of these advantages and highlight progress in understanding the genetic basis of flower color. Phylogenetic analysis of Aquilegia indicates that flower color transitions proceed by changes in the types of anthocyanin pigments produced or their complete loss. Biochemical, crossing, and gene expression studies have provided a wealth of information about the genetic basis of these transitions in Aquilegia. To obtain both enzymatic and regulatory candidate genes for the entire flavonoid pathway, which produces anthocyanins, we used a combination of sequence searches of the Aquilegia Gene Index, phylogenetic analyses, and the isolation of novel sequences by using degenerate PCR and RACE. In total we identified 34 genes that are likely involved in the flavonoid pathway. A number of these genes appear to be single copy in Aquilegia and thus variation in their expression may have been key for floral color evolution. Future studies will be able to use these sequences along with next-generation sequencing technologies to follow expression and sequence variation at the population level. The genetic dissection of other adaptive traits in Aquilegia should also be possible soon as genomic resources such as whole-genome sequencing become available. PMID:19528644

  12. Adaptive radiations: from field to genomic studies.

    PubMed

    Hodges, Scott A; Derieg, Nathan J

    2009-06-16

    Adaptive radiations were central to Darwin's formation of his theory of natural selection, and today they are still the centerpiece for many studies of adaptation and speciation. Here, we review the advantages of adaptive radiations, especially recent ones, for detecting evolutionary trends and the genetic dissection of adaptive traits. We focus on Aquilegia as a primary example of these advantages and highlight progress in understanding the genetic basis of flower color. Phylogenetic analysis of Aquilegia indicates that flower color transitions proceed by changes in the types of anthocyanin pigments produced or their complete loss. Biochemical, crossing, and gene expression studies have provided a wealth of information about the genetic basis of these transitions in Aquilegia. To obtain both enzymatic and regulatory candidate genes for the entire flavonoid pathway, which produces anthocyanins, we used a combination of sequence searches of the Aquilegia Gene Index, phylogenetic analyses, and the isolation of novel sequences by using degenerate PCR and RACE. In total we identified 34 genes that are likely involved in the flavonoid pathway. A number of these genes appear to be single copy in Aquilegia and thus variation in their expression may have been key for floral color evolution. Future studies will be able to use these sequences along with next-generation sequencing technologies to follow expression and sequence variation at the population level. The genetic dissection of other adaptive traits in Aquilegia should also be possible soon as genomic resources such as whole-genome sequencing become available. PMID:19528644

  13. The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression

    PubMed Central

    Oh, Jung D.; Kling-Bäckhed, Helene; Giannakis, Marios; Xu, Jian; Fulton, Robert S.; Fulton, Lucinda A.; Cordum, Holland S.; Wang, Chunyan; Elliott, Glendoria; Edwards, Jennifer; Mardis, Elaine R.; Engstrand, Lars G.; Gordon, Jeffrey I.

    2006-01-01

    Helicobacter pylori produces acute superficial gastritis in nearly all of its human hosts. However, a subset of individuals develops chronic atrophic gastritis (ChAG), a condition characterized in part by diminished numbers of acid-producing parietal cells and increased risk for development of gastric adenocarcinoma. Previously, we used a gnotobiotic transgenic mouse model with an engineered ablation of parietal cells to show that loss of parietal cells provides an opportunity for a H. pylori isolate from a patient with ChAG (HPAG1) to bind to, enter, and persist within gastric stem cells. This finding raises the question of how ChAG influences H. pylori genome evolution, physiology, and tumorigenesis. Here we describe the 1,596,366-bp HPAG1 genome. Custom HPAG1 Affymetrix GeneChips, representing 99.6% of its predicted ORFs, were used for whole-genome genotyping of additional H. pylori ChAG isolates obtained from Swedish patients enrolled in a case-control study of gastric cancer, as well as ChAG- and cancer-associated isolates from an individual who progressed from ChAG to gastric adenocarcinoma. The results reveal a shared gene signature among ChAG strains, as well as genes that may have been lost or gained during progression to adenocarcinoma. Whole-genome transcriptional profiling of HPAG1’s response to acid during in vitro growth indicates that genes encoding components of metal uptake and utilization pathways, outer membrane proteins, and virulence factors are among those associated with H. pylori’s adaptation to ChAG. PMID:16788065

  14. Research progress of genome editing and derivative technologies in plants.

    PubMed

    Qiwei, Shan; Caixia, Gao

    2015-10-01

    Genome editing technologies using engineered nucleases have been widely used in many model organisms. Genome editing with sequence-specific nuclease (SSN) creates DNA double-strand breaks (DSBs) in the genomic target sites that are primarily repaired by the non-homologous end joining (NHEJ) or homologous recombination (HR) pathways, which can be employed to achieve targeted genome modifications such as gene mutations, insertions, replacements or chromosome rearrangements. There are three major SSNs─zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. In contrast to ZFN and TALEN, which require substantial protein engineering to each DNA target, the CRISPR/Cas9 system requires only a change in the guide RNA. For this reason, the CRISPR/Cas9 system is a simple, inexpensive and versatile tool for genome engineering. Furthermore, a modified version of the CRISPR/Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression, such as activation, depression and epigenetic regulation. In this review, we summarize the development and applications of genome editing technologies for basic research and biotechnology, as well as highlight challenges and future directions, with particular emphasis on plants. PMID:26496748

  15. Progress of targeted genome modification approaches in higher plants.

    PubMed

    Cardi, Teodoro; Neal Stewart, C

    2016-07-01

    Transgene integration in plants is based on illegitimate recombination between non-homologous sequences. The low control of integration site and number of (trans/cis)gene copies might have negative consequences on the expression of transferred genes and their insertion within endogenous coding sequences. The first experiments conducted to use precise homologous recombination for gene integration commenced soon after the first demonstration that transgenic plants could be produced. Modern transgene targeting categories used in plant biology are: (a) homologous recombination-dependent gene targeting; (b) recombinase-mediated site-specific gene integration; (c) oligonucleotide-directed mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools enable precise gene replacement or stacking with exogenous sequences and targeted mutagenesis of endogeneous sequences. The possibility to engineer chimeric designer nucleases, which are able to target virtually any genomic site, and use them for inducing double-strand breaks in host DNA create new opportunities for both applied plant breeding and functional genomics. CRISPR is the most recent technology available for precise genome editing. Its rapid adoption in biological research is based on its inherent simplicity and efficacy. Its utilization, however, depends on available sequence information, especially for genome-wide analysis. We will review the approaches used for genome modification, specifically those for affecting gene integration and modification in higher plants. For each approach, the advantages and limitations will be noted. We also will speculate on how their actual commercial development and implementation in plant breeding will be affected by governmental regulations. PMID:27025856

  16. Bacterial genome reduction using the progressive clustering of deletions via yeast sexual cycling

    PubMed Central

    Assad-Garcia, Nacyra; Kostylev, Maxim; Noskov, Vladimir N.; Wise, Kim S.; Karas, Bogumil J.; Stam, Jason; Montague, Michael G.; Hanly, Timothy J.; Enriquez, Nico J.; Ramon, Adi; Goldgof, Gregory M.; Richter, R. Alexander; Vashee, Sanjay; Chuang, Ray-Yuan; Winzeler, Elizabeth A.; Hutchison, Clyde A.; Gibson, Daniel G.; Smith, Hamilton O.; Glass, John I.; Venter, J. Craig

    2015-01-01

    The availability of genetically tractable organisms with simple genomes is critical for the rapid, systems-level understanding of basic biological processes. Mycoplasma bacteria, with the smallest known genomes among free-living cellular organisms, are ideal models for this purpose, but the natural versions of these cells have genome complexities still too great to offer a comprehensive view of a fundamental life form. Here we describe an efficient method for reducing genomes from these organisms by identifying individually deletable regions using transposon mutagenesis and progressively clustering deleted genomic segments using meiotic recombination between the bacterial genomes harbored in yeast. Mycoplasmal genomes subjected to this process and transplanted into recipient cells yielded two mycoplasma strains. The first simultaneously lacked eight singly deletable regions of the genome, representing a total of 91 genes and ∼10% of the original genome. The second strain lacked seven of the eight regions, representing 84 genes. Growth assay data revealed an absence of genetic interactions among the 91 genes under tested conditions. Despite predicted effects of the deletions on sugar metabolism and the proteome, growth rates were unaffected by the gene deletions in the seven-deletion strain. These results support the feasibility of using single-gene disruption data to design and construct viable genomes lacking multiple genes, paving the way toward genome minimization. The progressive clustering method is expected to be effective for the reorganization of any mega-sized DNA molecules cloned in yeast, facilitating the construction of designer genomes in microbes as well as genomic fragments for genetic engineering of higher eukaryotes. PMID:25654978

  17. Ancient population genomics and the study of evolution

    PubMed Central

    Parks, M.; Subramanian, S.; Baroni, C.; Salvatore, M. C.; Zhang, G.; Millar, C. D.; Lambert, D. M.

    2015-01-01

    Recently, the study of ancient DNA (aDNA) has been greatly enhanced by the development of second-generation DNA sequencing technologies and targeted enrichment strategies. These developments have allowed the recovery of several complete ancient genomes, a result that would have been considered virtually impossible only a decade ago. Prior to these developments, aDNA research was largely focused on the recovery of short DNA sequences and their use in the study of phylogenetic relationships, molecular rates, species identification and population structure. However, it is now possible to sequence a large number of modern and ancient complete genomes from a single species and thereby study the genomic patterns of evolutionary change over time. Such a study would herald the beginnings of ancient population genomics and its use in the study of evolution. Species that are amenable to such large-scale studies warrant increased research effort. We report here progress on a population genomic study of the Adélie penguin (Pygoscelis adeliae). This species is ideally suited to ancient population genomic research because both modern and ancient samples are abundant in the permafrost conditions of Antarctica. This species will enable us to directly address many of the fundamental questions in ecology and evolution. PMID:25487332

  18. Challenges of flow-cytometric estimation of nuclear genome size in orchids, a plant group with both whole-genome and progressively partial endoreplication.

    PubMed

    Trávníček, Pavel; Ponert, Jan; Urfus, Tomáš; Jersáková, Jana; Vrána, Jan; Hřibová, Eva; Doležel, Jaroslav; Suda, Jan

    2015-10-01

    Nuclear genome size is an inherited quantitative trait of eukaryotic organisms with both practical and biological consequences. A detailed analysis of major families is a promising approach to fully understand the biological meaning of the extensive variation in genome size in plants. Although Orchidaceae accounts for ∼10% of the angiosperm diversity, the knowledge of patterns and dynamics of their genome size is limited, in part due to difficulties in flow cytometric analyses. Cells in various somatic tissues of orchids undergo extensive endoreplication, either whole-genome or partial, and the G1-phase nuclei with 2C DNA amounts may be lacking, resulting in overestimated genome size values. Interpretation of DNA content histograms is particularly challenging in species with progressively partial endoreplication, in which the ratios between the positions of two neighboring DNA peaks are lower than two. In order to assess distributions of nuclear DNA amounts and identify tissue suitable for reliable estimation of nuclear DNA content, we analyzed six different tissue types in 48 orchid species belonging to all recognized subfamilies. Although traditionally used leaves may provide incorrect C-values, particularly in species with progressively partial endoreplication, young ovaries and pollinaria consistently yield 2C and 1C peaks of their G1-phase nuclei, respectively, and are, therefore, the most suitable parts for genome size studies in orchids. We also provide new DNA C-values for 22 orchid genera and 42 species. Adhering to the proposed methodology would allow for reliable genome size estimates in this largest plant family. Although our research was limited to orchids, the need to find a suitable tissue with dominant 2C peak of G1-phase nuclei applies to all endopolyploid species. PMID:25929591

  19. Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology–Genomic Integration Analysis

    PubMed Central

    Natrajan, Rachael; Sailem, Heba; Mardakheh, Faraz K.; Arias Garcia, Mar; Tape, Christopher J.; Dowsett, Mitch; Bakal, Chris; Yuan, Yinyin

    2016-01-01

    Background The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters. Methods and Findings We developed a quantitative measure of microenvironmental heterogeneity along three spatial dimensions (3-D) in solid tumors, termed the tumor ecosystem diversity index (EDI), using fully automated histology image analysis coupled with statistical measures commonly used in ecology. This measure was compared with disease-specific survival, key mutations, genome-wide copy number, and expression profiling data in a retrospective study of 510 breast cancer patients as a test set and 516 breast cancer patients as an independent validation set. In high-grade (grade 3) breast cancers, we uncovered a striking link between high microenvironmental heterogeneity measured by EDI and a poor prognosis that cannot be explained by tumor size, genomics, or any other data types. However, this association was not observed in low-grade (grade 1 and 2) breast cancers. The prognostic value of EDI was superior to known prognostic factors and was enhanced with the addition of TP53 mutation status (multivariate analysis test set, p = 9 × 10−4, hazard ratio = 1.47, 95% CI 1.17–1.84; validation set, p = 0.0011, hazard ratio = 1.78, 95% CI 1.26–2.52). Integration with genome-wide profiling data identified losses of specific genes on 4p14 and 5q13 that were enriched in grade 3 tumors with high microenvironmental diversity that also substratified patients into poor prognostic groups. Limitations of this study include the number of cell types included in the model, that EDI has prognostic value only in grade 3 tumors, and that our spatial heterogeneity measure was dependent on spatial scale and tumor size. Conclusions To

  20. Progress of the rainbow trout reference genome assembly project

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rainbow trout are the most widely cultivated cold freshwater fish in the world and an important model species for many research areas. Despite this importance, the complex nature of the rainbow trout genome (pseudotetraploid and high repeat content) has hindered the production of a high-quality refe...

  1. Genomic Data and Cooperation Result in Faster Progress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genotypes for 38,416 markers of 5,335 Holstein bulls were combined with traditional evaluations to test predictive ability. Genomic evaluations were significantly (P < .0001) more accurate than official parent averages for all 27 traits tested. Squared correlations with future daughter deviations av...

  2. Invited review: Genomic selection in dairy cattle: progress and challenges.

    PubMed

    Hayes, B J; Bowman, P J; Chamberlain, A J; Goddard, M E

    2009-02-01

    A new technology called genomic selection is revolutionizing dairy cattle breeding. Genomic selection refers to selection decisions based on genomic breeding values (GEBV). The GEBV are calculated as the sum of the effects of dense genetic markers, or haplotypes of these markers, across the entire genome, thereby potentially capturing all the quantitative trait loci (QTL) that contribute to variation in a trait. The QTL effects, inferred from either haplotypes or individual single nucleotide polymorphism markers, are first estimated in a large reference population with phenotypic information. In subsequent generations, only marker information is required to calculate GEBV. The reliability of GEBV predicted in this way has already been evaluated in experiments in the United States, New Zealand, Australia, and the Netherlands. These experiments used reference populations of between 650 and 4,500 progeny-tested Holstein-Friesian bulls, genotyped for approximately 50,000 genome-wide markers. Reliabilities of GEBV for young bulls without progeny test results in the reference population were between 20 and 67%. The reliability achieved depended on the heritability of the trait evaluated, the number of bulls in the reference population, the statistical method used to estimate the single nucleotide polymorphism effects in the reference population, and the method used to calculate the reliability. A common finding in 3 countries (United States, New Zealand, and Australia) was that a straightforward BLUP method for estimating the marker effects gave reliabilities of GEBV almost as high as more complex methods. The BLUP method is attractive because the only prior information required is the additive genetic variance of the trait. All countries included a polygenic effect (parent average breeding value) in their GEBV calculation. This inclusion is recommended to capture any genetic variance not associated with the markers, and to put some selection pressure on low

  3. Loss of photoreceptorness and gain of genomic alterations in retinoblastoma reveal tumor progression

    PubMed Central

    Kooi, Irsan E.; Mol, Berber M.; Moll, Annette C.; van der Valk, Paul; de Jong, Marcus C.; de Graaf, Pim; van Mil, Saskia E.; Schouten-van Meeteren, Antoinette Y.N.; Meijers-Heijboer, Hanne; Kaspers, Gertjan L.; te Riele, Hein; Cloos, Jacqueline; Dorsman, Josephine C.

    2015-01-01

    Background Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1−/− retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1−/− tumors seemed more dichotomous, differences within the RB1−/− tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared with tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation Molecular, clinical and histopathological differences between RB1−/− tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Research in context Retinoblastoma is an ocular childhood cancer commonly caused by mutations in the RB1 gene. In order to determine optimal treatment, tumor subtyping is considered critically important. However, except for very rare retinoblastomas without an RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do exist. Our study shows that retinoblastomas are highly diverse but rather than reflecting distinct tumor types with

  4. The Multifunctions of WD40 Proteins in Genome Integrity and Cell Cycle Progression

    PubMed Central

    Zhang, Caiguo; Zhang, Fan

    2015-01-01

    Eukaryotic genome encodes numerous WD40 repeat proteins, which generally function as platforms of protein-protein interactions and are involved in numerous biological process, such as signal transduction, gene transcriptional regulation, protein modifications, cytoskeleton assembly, vesicular trafficking, DNA damage and repair, cell death and cell cycle progression. Among these diverse functions, genome integrity maintenance and cell cycle progression are extremely important as deregulation of them is clinically linked to uncontrolled proliferative diseases such as cancer. Thus, we mainly summarize and discuss the recent understanding of WD40 proteins and their molecular mechanisms linked to genome stability and cell cycle progression in this review, thereby demonstrating their pervasiveness and importance in cellular networks. PMID:25653723

  5. DOE project on genome mapping and sequencing. Progress report, 1992

    SciTech Connect

    Evans, G.A.

    1992-12-31

    These efforts on the human genome project were initiated in September, 1990, to contribute towards completion of the human genome project physical mapping effort. In the original application, the authors proposed a novel strategy for constructing a physical map of human chromosome 11, based upon techniques derived in this group and by others. The original goals were to (1) produce a set of cosmid reference clones mapped to specific sites by high resolution fluorescence in situ hybridization, (2) produce a set of associated STS sequences and PCR primers for each site, (3) isolate YAC clones corresponding to each STS and, (4) construct YAC contigs such that > 90% of the chromosome would be covered by contigs of 2 mb or greater. Since that time, and with the advent of new technology and reagents, the strategy has been modified slightly but still retains the same goals as originally proposed. The authors have added a project to produce chromosome 11-specific cDNAs and determine the map location and DNA sequence of a selected portion of them.

  6. Metabolite-based genome-wide association studies in plants.

    PubMed

    Luo, Jie

    2015-04-01

    The plant metabolome is the readout of plant physiological status and is regarded as the bridge between the genome and the phenome of plants. Unraveling the natural variation and the underlying genetic basis of plant metabolism has received increasing interest from plant biologists. Enabled by the recent advances in high-throughput profiling and genotyping technologies, metabolite-based genome-wide association study (mGWAS) has emerged as a powerful alternative forward genetics strategy to dissect the genetic and biochemical bases of metabolism in model and crop plants. In this review, recent progress and applications of mGWAS in understanding the genetic control of plant metabolism and in interactive functional genomics and metabolomics are presented. Further directions and perspectives of mGWAS in plants are also discussed. PMID:25637954

  7. Final progress report, Construction of a genome-wide highly characterized clone resource for genome sequencing

    SciTech Connect

    Nierman, William C.

    2000-02-14

    At TIGR, the human Bacterial Artificial Chromosome (BAC) end sequencing and trimming were with an overall sequencing success rate of 65%. CalTech human BAC libraries A, B, C and D as well as Roswell Park Cancer Institute's library RPCI-11 were used. To date, we have generated >300,000 end sequences from >186,000 human BAC clones with an average read length {approx}460 bp for a total of 141 Mb covering {approx}4.7% of the genome. Over sixty percent of the clones have BAC end sequences (BESs) from both ends representing over five-fold coverage of the genome by the paired-end clones. The average phred Q20 length is {approx}400 bp. This high accuracy makes our BESs match the human finished sequences with an average identity of 99% and a match length of 450 bp, and a frequency of one match per 12.8 kb contig sequence. Our sample tracking has ensured a clone tracking accuracy of >90%, which gives researchers a high confidence in (1) retrieving the right clone from the BA C libraries based on the sequence matches; and (2) building a minimum tiling path of sequence-ready clones across the genome and genome assembly scaffolds.

  8. Progressive genomic instability in the FVB/KrasLA2 mouse model of lung cancer

    PubMed Central

    To, Minh D.; Quigley, David A.; Mao, Jian-Hua; Rosario, Reyno Del; Hsu, Jeff; Hodgson, Graeme; Jacks, Tyler; Balmain, Allan

    2011-01-01

    Alterations in DNA copy number contribute to the development and progression of cancers and are common in epithelial tumors. We have used array Comparative Genomic Hybridization (aCGH) to visualize DNA copy number alterations across the genomes of lung tumors in the KrasLA2 model of lung cancer. Copy number gain involving the Kras locus, as focal amplification or whole chromosome gain, is the most common alteration in these tumors, and with a prevalence that increased significantly with increasing tumor size. Furthermore, Kras amplification was the only major genomic event among the smallest lung tumors, suggesting that this alteration occurs early during the development of mutant Kras driven lung cancers. Recurring gains and deletions of other chromosomes occur progressively more frequently among larger tumors. These results are in contrast to a previous aCGH analysis of lung tumors from KrasLA2 mice on a mixed genetic background, in which relatively few DNA copy number alterations were observed regardless of tumor size. Our model features the KrasLA2 allele on the inbred FVB/N mouse strain, and in this genetic background there is a highly statistically significant increase in level of genomic instability with increasing tumor size. These data suggest that recurring DNA copy alterations are important for tumor progression in the KrasLA2 model of lung cancer, and that the requirement for these alterations may be dependent on the genetic background of the mouse strain. PMID:21807965

  9. Nuclear spectroscopic studies. Progress report

    SciTech Connect

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.

    1996-01-16

    This report describes progress in the experimental nuclear physics program of the University of Tennessee, Knoxville. It presents findings related to properties of high-spin states, low-energy levels of nuclei far from stability, and high-energy heavy-ion physics, as well as a brief description of the Joint Institute of Heavy Ion Research (a collaboration between the University of Tennessee, Vanderbilt University, and Oak Ridge National Laboratory) and its activities (particularly those of the last few years), and a list of publications. 89 refs., 18 figs., 5 tabs.

  10. The origins and progress of genomics research on Tef (Eragrostis tef).

    PubMed

    Girma, Dejene; Assefa, Kebebew; Chanyalew, Solomon; Cannarozzi, Gina; Kuhlemeier, Cris; Tadele, Zerihun

    2014-06-01

    Tef, Eragrostis tef (Zucc.) Trotter, is the most important cereal in Ethiopia. Tef is cultivated by more than five million small-scale farmers annually and constitutes the staple food for more than half of the population of 80 million. The crop is preferred by both farmers and consumers due to its beneficial traits associated with its agronomy and utilization. The genetic and phenotypic diversity of tef in Ethiopia is a national treasure of potentially global importance. In order for this diversity to be effectively conserved and utilized, a better understanding at the genomic level is necessary. In the recent years, tef has become the subject of genomic research in Ethiopia and abroad. Genomic-assisted tef improvement holds tremendous potential for improving productivity, thereby benefiting the smallholder farmers who have cultivated and relied on the crop for thousands of years. It is hoped that such research endeavours will provide solutions to some of the age-old problems of tef's husbandry. In this review, we provide a brief description of the genesis and progress of tef genomic research to date, suggest ways to utilize the genomic tools developed so far, discuss the potential of genomics to enable sustainable conservation and use of tef genetic diversity and suggest opportunities for the future research. PMID:24891040

  11. From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges

    PubMed Central

    Bianchi, Diana W

    2015-01-01

    Thus far, the focus of personalized medicine has been the prevention and treatment of conditions that affect adults. Although advances in genetic technology have been applied more frequently to prenatal diagnosis than to fetal treatment, genetic and genomic information is beginning to influence pregnancy management. Recent developments in sequencing the fetal genome combined with progress in understanding fetal physiology using gene expression arrays indicate that we could have the technical capabilities to apply an individualized medicine approach to the fetus. Here I review recent advances in prenatal genetic diagnostics, the challenges associated with these new technologies and how the information derived from them can be used to advance fetal care. Historically, the goal of prenatal diagnosis has been to provide an informed choice to prospective parents. We are now at a point where that goal can and should be expanded to incorporate genetic, genomic and transcriptomic data to develop new approaches to fetal treatment. PMID:22772565

  12. ING2 controls the progression of DNA replication forks to maintain genome stability

    PubMed Central

    Larrieu, Delphine; Ythier, Damien; Binet, Romuald; Brambilla, Christian; Brambilla, Elisabeth; Sengupta, Sagar; Pedeux, Rémy

    2009-01-01

    Inhibitor of growth 2 (ING2) is a candidate tumour suppressor gene the expression of which is frequently lost in tumours. Here, we identified a new function for ING2 in the control of DNA replication and in the maintenance of genome stability. Global replication rate was markedly reduced during normal S-phase in small interfering RNA (siRNA) ING2 cells, as seen in a DNA fibre spreading experiment. Accordingly, we found that ING2 interacts with proliferating cell nuclear antigen and regulates its amount to the chromatin fraction, allowing normal replication progression and normal cell proliferation. Deregulation of DNA replication has been previously associated with genome instability. Hence, a high proportion of siRNA ING2 cells presented endoreduplication of their genome as well as an increased frequency of sister chromatid exchange. Thus, we propose for the first time that ING2 might function as a tumour suppressor gene by directly maintaining DNA integrity. PMID:19730436

  13. Genome-Wide Association Studies of Cancer

    PubMed Central

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  14. Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection

    PubMed Central

    Quinn, Meghan; Xiang, Shi-Hua

    2016-01-01

    Ovine progressive pneumonia virus (OPPV) is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease. PMID:26950733

  15. Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability

    PubMed Central

    Iimori, Makoto; Watanabe, Sugiko; Kiyonari, Shinichi; Matsuoka, Kazuaki; Sakasai, Ryo; Saeki, Hiroshi; Oki, Eiji; Kitao, Hiroyuki; Maehara, Yoshihiko

    2016-01-01

    Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability. PMID:27030108

  16. Polyphosphate is involved in cell cycle progression and genomic stability in Saccharomyces cerevisiae.

    PubMed

    Bru, Samuel; Martínez-Laínez, Joan Marc; Hernández-Ortega, Sara; Quandt, Eva; Torres-Torronteras, Javier; Martí, Ramón; Canadell, David; Ariño, Joaquin; Sharma, Sushma; Jiménez, Javier; Clotet, Josep

    2016-08-01

    Polyphosphate (polyP) is a linear chain of up to hundreds of inorganic phosphate residues that is necessary for many physiological functions in all living organisms. In some bacteria, polyP supplies material to molecules such as DNA, thus playing an important role in biosynthetic processes in prokaryotes. In the present study, we set out to gain further insight into the role of polyP in eukaryotic cells. We observed that polyP amounts are cyclically regulated in Saccharomyces cerevisiae, and those mutants that cannot synthesise (vtc4Δ) or hydrolyse polyP (ppn1Δ, ppx1Δ) present impaired cell cycle progression. Further analysis revealed that polyP mutants show delayed nucleotide production and increased genomic instability. Based on these findings, we concluded that polyP not only maintains intracellular phosphate concentrations in response to fluctuations in extracellular phosphate levels, but also muffles internal cyclic phosphate fluctuations, such as those produced by the sudden demand of phosphate to synthetize deoxynucleotides just before and during DNA duplication. We propose that the presence of polyP in eukaryotic cells is required for the timely and accurate duplication of DNA. PMID:27072996

  17. [Meibomian gland morphology study progression].

    PubMed

    Wang, Yuqian; Dong, Nuo; Wu, Huping

    2014-04-01

    The meibomian gland (MG) in the eyelids, which is the largest sebaceous gland throughout the body, synthesize and secrete lipids to form the superficial tear film layer. It plays a key role in maintaining the ocular surface health. Abnormalities in meibomian gland morphology lead to meibomian gland dysfunction, which is the main cause of evaporative dry eye. Study on meibomian gland morphology will contribute significantly to the diagnosis and treatment of meibomian gland dysfunction. This review is just focusing on the current studies about techniques to visualize the morphology of the MG and changes of meibomian gland morphology related to diseases. PMID:24931156

  18. Nuclear spectroscopic studies. Progress report

    SciTech Connect

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1994-02-18

    The Nuclear Physics group at UTK is involved in heavy-ion physics including both nuclear structure and reaction mechanisms. During the last year experimental work has been in 3 broad areas: structure of nuclei at high angular momentum, structure of nuclei far from stability, and ultra-relativistic heavy-ion physics. Results in these areas are described in this document under: properties of high-spin states, study of low-energy levels of nuclei far from stability, and high-energy heavy-ion physics (PHENIX, etc.). Another important component of the work is theoretical interpretation of experimental results (Joint Institute for Heavy Ion Research).

  19. Progressive hemifacial atrophy. A natural history study.

    PubMed Central

    Miller, M T; Spencer, M A

    1995-01-01

    PURPOSE: To describe two very different natural history courses in 2 patients with hemifacial atrophy. Progressive hemifacial atrophy (Parry-Romberg syndrome, Romberg syndrome, PHA) is characterized by slowly progressive atrophy, frequently involving only one side of the face, primarily affecting the subcutaneous tissue and fat. The onset usually occurs during the first 2 decades of life. The cause and pathophysiology are unknown. Ophthalmic involvement is common, with progressive enophthalmos a frequent finding. Pupillary disturbances, heterochromia, uveitis, pigmentary disturbances of the ocular fundus, and restrictive strabismus have also been reported. Neurologic findings may be present, but the natural history and progression of ocular findings are often not described in the literature. METHODS: We studied the records and present findings of 2 patients with progressive hemifacial atrophy who were observed in our institution over a 10-year period. RESULTS: Both patients showed progression of ophthalmic findings, primarily on the affected side. One patient has had chronic uveitis with secondary cataract and glaucoma, in addition to retinal pigmentary changes. She also had a third-nerve paresis of the contralateral eye and mild seizure activity. The other patient had mild uveitis, some progression of unilateral retinal pigmentary changes, and a significant increase in hyperopia in the affected eye, in addition to hypotony at age 19 without a clear cause, but with secondary retinal and refractive changes. CONCLUSION: Ocular manifestations of progressive hemifacial atrophy are varied, but can progress from mild visual impairment to blindness. Images FIGURE 1 FIGURE 2 FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 6 PMID:8719679

  20. Drosophila Sld5 is essential for normal cell cycle progression and maintenance of genomic integrity

    SciTech Connect

    Gouge, Catherine A.; Christensen, Tim W.

    2010-09-10

    Research highlights: {yields} Drosophila Sld5 interacts with Psf1, PPsf2, and Mcm10. {yields} Haploinsufficiency of Sld5 leads to M-phase delay and genomic instability. {yields} Sld5 is also required for normal S phase progression. -- Abstract: Essential for the normal functioning of a cell is the maintenance of genomic integrity. Failure in this process is often catastrophic for the organism, leading to cell death or mis-proliferation. Central to genomic integrity is the faithful replication of DNA during S phase. The GINS complex has recently come to light as a critical player in DNA replication through stabilization of MCM2-7 and Cdc45 as a member of the CMG complex which is likely responsible for the processivity of helicase activity during S phase. The GINS complex is made up of 4 members in a 1:1:1:1 ratio: Psf1, Psf2, Psf3, And Sld5. Here we present the first analysis of the function of the Sld5 subunit in a multicellular organism. We show that Drosophila Sld5 interacts with Psf1, Psf2, and Mcm10 and that mutations in Sld5 lead to M and S phase delays with chromosomes exhibiting hallmarks of genomic instability.

  1. Genome-wide association studies in pediatric chronic kidney disease.

    PubMed

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression. PMID:26490952

  2. Nuclear spectroscopic studies. Progress report

    SciTech Connect

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1993-02-08

    The Nuclear Physics group at the University of Tennessee, Knoxville is involved in several aspects of heavy-ion physics including both nuclear structure and reaction mechanisms. While our main emphasis is on experimental problems involving heavy-ion accelerators, we have maintained a strong collaboration with several theorists in order to best pursue the physics of our measurements. During the last year we have led several experiments at the Holifield Heavy Ion Research Facility and participated in others at Argonne National Laboratory. Also, we continue to be very active in the collaboration to study ultra-relativistic heavy ion physics utilizing the SPS accelerator at CERN in Geneva, Switzerland and in a RHIC detector R&D project. Our experimental work is in four broad areas: (1) the structure of nuclei at high angular momentum, (2) heavy-ion induced transfer reactions, (3) the structure of nuclei far from stability, and (4) ultra-relativistic heavy-ion physics. The results of studies in these particular areas will be described in this document in sections IIA, IIB, IIC, and IID, respectively. Areas (1), (3), and (4) concentrate on the structure of nuclear matter in extreme conditions of rotational motion, imbalance of neutrons and protons, or very high temperature and density. Area (2) pursues the transfer of nucleons to states with high angular momentum, both to learn about their structure and to understand the transfer of particles, energy, and angular momentum in collisions between heavy ions. An important component of our program is the strong emphasis on the theoretical aspects of nuclear structure and reactions.

  3. Genomics and disease resistance studies in livestock☆

    PubMed Central

    Bishop, Stephen C; Woolliams, John A

    2014-01-01

    This paper considers the application of genetic and genomic techniques to disease resistance, the interpretation of data arising from such studies and the utilisation of the research outcomes to breed animals for enhanced resistance. Resistance and tolerance are defined and contrasted, factors affecting the analysis and interpretation of field data presented, and appropriate experimental designs discussed. These general principles are then applied to two detailed case studies, infectious pancreatic necrosis in Atlantic salmon and bovine tuberculosis in dairy cattle, and the lessons learnt are considered in detail. It is concluded that the rate limiting step in disease genetic studies will generally be provision of adequate phenotypic data, and its interpretation, rather than the genomic resources. Lastly, the importance of cross-disciplinary dialogue between the animal health and animal genetics communities is stressed. PMID:26339300

  4. Genome-wide association studies in pharmacogenomics.

    PubMed

    Daly, Ann K

    2010-04-01

    Genome-wide association (GWA) studies for pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. Until now, only the largest effects have been detected, partly because of the challenges of obtaining large numbers of cases for pharmacogenomic studies. Since 2007, a range of pharmacogenomics GWA studies have been published that have identified several interesting and novel associations between drug responses or reactions and clinically relevant loci, showing the value of this approach. PMID:20300088

  5. Basic Studies: A Description and Progress Report.

    ERIC Educational Resources Information Center

    Johnson, Charles N.; And Others

    This is a description and a progress report of the Basic Studies Program at Tarrant County Junior College (Texas), a 1-year program in general education designed for students who rank in the lower quarter of their junior college class and who have experienced little academic success in the past. Communications, humanities, social science, natural…

  6. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.

    PubMed

    Rose, Amy E; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega Y Saenz de Miera, Eleazar C; Medicherla, Ratna; Christos, Paul J; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman

    2011-04-01

    Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. PMID:21343389

  7. Comparison of genomic abnormalities between BRCAX and sporadic breast cancers studied by comparative genomic hybridization.

    PubMed

    Gronwald, Jacek; Jauch, Anna; Cybulski, Cezary; Schoell, Brigitte; Böhm-Steuer, Barbara; Lener, Marcin; Grabowska, Ewa; Górski, Bohdan; Jakubowska, Anna; Domagała, Wenancjusz; Chosia, Maria; Scott, Rodney J; Lubiński, Jan

    2005-03-20

    Very little is known about the chromosomal regions harbouring genes involved in initiation and progression of BRCAX-associated breast cancers. We applied comparative genomic hybridization (CGH) to identify the most frequent genomic imbalances in 18 BRCAX hereditary breast cancers and compared them to chromosomal aberrations detected in a group of 27 sporadic breast cancers. The aberrations observed most frequently in BRCAX tumours were gains of 8q (83%), 19q (67%), 19p (61%), 20q (61%), 1q (56%), 17q (56%) and losses of 8p (56%), 11q (44%) and 13q (33%). The sporadic cases most frequently showed gains of 1q (67%), 8q (48%), 17q (37%), 16p (33%), 19q (33%) and losses of 11q (26%), 8p (22%) and 16q (19%). Losses of 8p and gains 8q, 19 as well as gains of 20q (with respect to ductal tumours only) were detected significantly more often in BRCAX than in sporadic breast cancers. Analysis of 8p-losses and 8q-gains showed that these aberrations are early events in the tumorigenesis of BRCAX tumors. The findings of this report indicate similarities between BRCAX and BRCA2 tumours, possibly suggesting a common pathway of disease. These findings need confirmation by more extensive studies because only a limited number of cases were analysed and there are relatively few reports published. PMID:15540206

  8. Translation of genomics and epigenomics in prostate cancer: progress and promising directions

    PubMed Central

    Liu, Wennuan; Xu, Jianfeng

    2016-01-01

    During the last several years, exciting discoveries have been made in prostate cancer (PCa) as a result of significant advances in genomic technology and information. For example, using genome-wide association studies, more than 100 inherited genetic variants associated with PCa risk have been identified. Similarly, with the use of next-generation sequencing, various types of recurrent somatic DNA alterations in prostate tumors have been revealed. Some of these discoveries have potential clinical application to supplement existing tools for better decision-making regarding the need for screening, biopsy, and treatment of PCa. However, because of the complexity of these genomic findings and incomplete understanding of the genetics of this multifactorial disease, this potential has not yet been fully realized. PMID:27270344

  9. Applying genomics to the study of complex disease.

    PubMed

    Juran, Brian D; Lazaridis, Konstantinos N

    2007-02-01

    The interest in dissecting the genetic and environmental components of complex human disease is growing, fueled by the emerging advances in the field of genomics and related disciplines. Improved understanding of the pathogenesis of complex liver diseases such as gallbladder stones, nonalcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma remains a goal of the clinical and experimental hepatologist alike. Despite the scientific progress and technological advancement, elucidating the underlying mechanisms of complex hepatic diseases from the genomic standpoint will be demanding. Complexity of genomic structure and function, disease heterogeneity, influence of the environment on disease development and progression, and epigenetics all contribute to the challenge. To overcome these obstacles, novel conceptual frameworks regarding biological systems and human diseases are necessary in addition to a coordinated endeavor among different scientific disciplines. Deciphering in an integrated fashion the genomic, transcriptional, and translational aspects of the pathogenesis of complex liver diseases will lead to their better prediction, diagnostics, and treatment. PMID:17295173

  10. Sinbase: an integrated database to study genomics, genetics and comparative genomics in Sesamum indicum.

    PubMed

    Wang, Linhai; Yu, Jingyin; Li, Donghua; Zhang, Xiurong

    2015-01-01

    Sesame (Sesamum indicum L.) is an ancient and important oilseed crop grown widely in tropical and subtropical areas. It belongs to the gigantic order Lamiales, which includes many well-known or economically important species, such as olive (Olea europaea), leonurus (Leonurus japonicus) and lavender (Lavandula spica), many of which have important pharmacological properties. Despite their importance, genetic and genomic analyses on these species have been insufficient due to a lack of reference genome information. The now available S. indicum genome will provide an unprecedented opportunity for studying both S. indicum genetic traits and comparative genomics. To deliver S. indicum genomic information to the worldwide research community, we designed Sinbase, a web-based database with comprehensive sesame genomic, genetic and comparative genomic information. Sinbase includes sequences of assembled sesame pseudomolecular chromosomes, protein-coding genes (27,148), transposable elements (372,167) and non-coding RNAs (1,748). In particular, Sinbase provides unique and valuable information on colinear regions with various plant genomes, including Arabidopsis thaliana, Glycine max, Vitis vinifera and Solanum lycopersicum. Sinbase also provides a useful search function and data mining tools, including a keyword search and local BLAST service. Sinbase will be updated regularly with new features, improvements to genome annotation and new genomic sequences, and is freely accessible at http://ocri-genomics.org/Sinbase/. PMID:25480115

  11. Human genome libraries. Final progress report, February 1, 1994--August 31, 1997

    SciTech Connect

    Kao, Fa-Ten

    1998-01-01

    The goal of this program is to use a novel technology of chromosome microdissection and microcloning to construct chromosome region-specific libraries as resources for various human genome program studies. Region specific libraries have been constructed for the entire human chromosomes 2 and 18.

  12. Genome-Wide Association Studies: A Primer

    PubMed Central

    Corvin, Aiden; Craddock, Nick; Sullivan, Patrick F.

    2014-01-01

    There have been nearly 400genome-wide association studies published since 2005. The GWAS approach has been exceptionally successful in identifying common genetic variants that predispose to a variety of complex human diseases and biochemical and anthropometric traits. Although this approach is relatively new, there are many excellent reviews of different aspects of the GWAS method. Here, we provide a primer, an annotated overview of the GWAS method with particular reference to psychiatric genetics. We dissect the GWAS methodology into its components and provide a brief description with citations and links to reviews that cover the topic in detail. PMID:19895722

  13. Genome-wide association studies in neurology

    PubMed Central

    Tan, Meng-Shan; Jiang, Teng

    2014-01-01

    Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWAS in common neurological diseases, including Stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, migraine, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, restless legs syndrome, intracranial aneurysm, human prion diseases and moyamoya disease. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of potential therapeutic agents. PMID:25568877

  14. [Progress in molecular biology study of DNA computer].

    PubMed

    Zhang, Zhi-Zhou; Zhao, Jian; He, Lin

    2003-09-01

    DNA (deoxyribonucleotide acids) computer is an emerging new study area that basically combines molecular biology study of DNA molecules and computational study on how to employ these specific molecules to calculate. In 1994 Adleman described his pioneering research on DNA computing in Science. This is the first experimental report on DNA computer study. In 2001 Benenson et al published a paper in Nature regarding a programmable and autonomous DNA computing device. Because of its Turing-like functions, the device is regarded as another milestone progress for DNA computer study. The main features of DNA computer are massively parallel computing ability and potential enormous data storage capacity. Comparing with conventional electronic computers, DNA molecules provide conceptually a revolution in computing, and more and more implications have been found in various disciplines. DNA computer studies have brought great progress not only in its own computing mechanisms, but also in DNA manipulation technologies especially nano-technology. This article presents the basic principles of DNA computer, its applications, its important relationship with genomic research and our comments on all above issues. PMID:14577383

  15. A new model army: Emerging fish models to study the genomics of vertebrate Evo-Devo.

    PubMed

    Braasch, Ingo; Peterson, Samuel M; Desvignes, Thomas; McCluskey, Braedan M; Batzel, Peter; Postlethwait, John H

    2015-06-01

    Many fields of biology--including vertebrate Evo-Devo research--are facing an explosion of genomic and transcriptomic sequence information and a multitude of fish species are now swimming in this "genomic tsunami." Here, we first give an overview of recent developments in sequencing fish genomes and transcriptomes that identify properties of fish genomes requiring particular attention and propose strategies to overcome common challenges in fish genomics. We suggest that the generation of chromosome-level genome assemblies--for which we introduce the term "chromonome"--should be a key component of genomic investigations in fish because they enable large-scale conserved synteny analyses that inform orthology detection, a process critical for connectivity of genomes. Orthology calls in vertebrates, especially in teleost fish, are complicated by divergent evolution of gene repertoires and functions following two rounds of genome duplication in the ancestor of vertebrates and a third round at the base of teleost fish. Second, using examples of spotted gar, basal teleosts, zebrafish-related cyprinids, cavefish, livebearers, icefish, and lobefin fish, we illustrate how next generation sequencing technologies liberate emerging fish systems from genomic ignorance and transform them into a new model army to answer longstanding questions on the genomic and developmental basis of their biodiversity. Finally, we discuss recent progress in the genetic toolbox for the major fish models for functional analysis, zebrafish, and medaka, that can be transferred to many other fish species to study in vivo the functional effect of evolutionary genomic change as Evo-Devo research enters the postgenomic era. PMID:25111899

  16. A New Model Army: Emerging fish models to study the genomics of vertebrate Evo-Devo

    PubMed Central

    Braasch, Ingo; Peterson, Samuel M.; Desvignes, Thomas; McCluskey, Braedan M.; Batzel, Peter; Postlethwait, John H.

    2014-01-01

    Many fields of biology – including vertebrate Evo-Devo research – are facing an explosion of genomic and transcriptomic sequence information and a multitude of fish species are now swimming in this ‘genomic tsunami’. Here, we first give an overview of recent developments in sequencing fish genomes and transcriptomes that identify properties of fish genomes requiring particular attention and propose strategies to overcome common challenges in fish genomics. We suggest that the generation of chromosome-level genome assemblies - for which we introduce the term ‘chromonome’ – should be a key component of genomic investigations in fish because they enable large-scale conserved synteny analyses that inform orthology detection, a process critical for connectivity of genomes. Orthology calls in vertebrates, especially in teleost fish, are complicated by divergent evolution of gene repertoires and functions following two rounds of genome duplication in the ancestor of vertebrates and a third round at the base of teleost fish. Second, using examples of spotted gar, basal teleosts, zebrafish-related cyprinids, cavefish, livebearers, icefish, and lobefin fish, we illustrate how next generation sequencing technologies liberate emerging fish systems from genomic ignorance and transform them into a new model army to answer longstanding questions on the genomic and developmental basis of their biodiversity. Finally, we discuss recent progress in the genetic toolbox for the major fish models for functional analysis, zebrafish and medaka, that can be transferred to many other fish species to study in vivo the functional effect of evolutionary genomic change as Evo-Devo research enters the postgenomic era. PMID:25111899

  17. PROGRESSIVE RECRUITMENT OF RUNX2 TO GENOMIC TARGETS DESPITE DECREASING EXPRESSION DURING OSTEOBLAST DIFFERENTIATION

    PubMed Central

    Pregizer, Steven; Baniwal, Sanjeev K.; Yan, Xiting; Borok, Zea; Frenkel, Baruch

    2008-01-01

    The mRNAs encoding Runx2, a master osteoblast transcription factor, and its target gene Osteocalcin (OC), are commonly used as markers of osteoblast differentiation. We found that while OC mRNA levels do indeed increase during development of the osteoblast phenotype in MC3T3-E1 cultures, Runx2 mRNA levels surprisingly decrease. Neither translational control of Runx2 (based on Western analysis) nor regulation of its DNA-binding ability (assessed by electrophoretic mobility shift assay) could explain the unexpected opposite patterns of Runx2 and OC expression. Instead, a series of ChIP assays during osteoblast differentiation revealed that early on, when Runx2 protein amount and DNA-binding activity are maximal, it is practically absent from the OC promoter. At later stages, Runx2 is recruited to the OC promoter while Runx2 mRNA, protein, and in vitro DNA binding progressively decrease. We also followed Runx2 occupancy at a novel genomic target discovered by ChIP-Chip analysis of cells in which the OC promoter is maximally occupied. The results revealed that Runx2 is recruited to this locus and to the OC promoter with a remarkably similar temporal pattern . These observations highlight a mechanism that restrains Runx2-mediated transcriptional control by confining its access to genomic targets to a narrow window of time. The need for such stringent control is consistent with the severe consequences of Runx2 over-expression in vivo. PMID:18821584

  18. Application of genomics-assisted breeding for generation of climate resilient crops: progress and prospects.

    PubMed

    Kole, Chittaranjan; Muthamilarasan, Mehanathan; Henry, Robert; Edwards, David; Sharma, Rishu; Abberton, Michael; Batley, Jacqueline; Bentley, Alison; Blakeney, Michael; Bryant, John; Cai, Hongwei; Cakir, Mehmet; Cseke, Leland J; Cockram, James; de Oliveira, Antonio Costa; De Pace, Ciro; Dempewolf, Hannes; Ellison, Shelby; Gepts, Paul; Greenland, Andy; Hall, Anthony; Hori, Kiyosumi; Hughes, Stephen; Humphreys, Mike W; Iorizzo, Massimo; Ismail, Abdelbagi M; Marshall, Athole; Mayes, Sean; Nguyen, Henry T; Ogbonnaya, Francis C; Ortiz, Rodomiro; Paterson, Andrew H; Simon, Philipp W; Tohme, Joe; Tuberosa, Roberto; Valliyodan, Babu; Varshney, Rajeev K; Wullschleger, Stan D; Yano, Masahiro; Prasad, Manoj

    2015-01-01

    Climate change affects agricultural productivity worldwide. Increased prices of food commodities are the initial indication of drastic edible yield loss, which is expected to increase further due to global warming. This situation has compelled plant scientists to develop climate change-resilient crops, which can withstand broad-spectrum stresses such as drought, heat, cold, salinity, flood, submergence and pests, thus helping to deliver increased productivity. Genomics appears to be a promising tool for deciphering the stress responsiveness of crop species with adaptation traits or in wild relatives toward identifying underlying genes, alleles or quantitative trait loci. Molecular breeding approaches have proven helpful in enhancing the stress adaptation of crop plants, and recent advances in high-throughput sequencing and phenotyping platforms have transformed molecular breeding to genomics-assisted breeding (GAB). In view of this, the present review elaborates the progress and prospects of GAB for improving climate change resilience in crops, which is likely to play an ever increasing role in the effort to ensure global food security. PMID:26322050

  19. Application of genomics-assisted breeding for generation of climate resilient crops: Progress and prospects

    SciTech Connect

    Kole, Chittaranjan; Muthamiliarasan, Mehanathan; Henry, Robert; Edwards, David; Sharma, Rishu; Abberton, Michael; Batley, Jacqueline; Bentley, Alison; Blakeney, Michael; Bryant, John; Cai, Hongwei; Cakir, Mehmet; Cseke, Leland J.; Cockram, James; de Oliveira, Antonio Costa; De Pace, Ciro; Dempewolf, Hannes; Ellison, Shelby; Gepts, Paul; Greenland, Andy; Hall, Anthony; Hori, Kiyosumi; Hughes, Stephen; Humphreys, Mike W.; Iorizzo, Massimo; Ismail, Abdelgabi M.; Marshall, Athole; Mayes, Sean; Nguyen, Henry T.; Ogbannaya, Francis C.; Ortiz, Rodomiro; Paterson, Andrew H.; Simon, Philipp W.; Tohme, Joe; Tuberosa, Roberto; Valliyodan, Babu; Varshney, Rajeev K.; Wullschleger, Stan D.; Yano, Masahiro; Prasad, Manoj

    2015-08-11

    Climate change affects agricultural productivity worldwide. Increased prices of food commodities are the initial indication of drastic edible yield loss, which is expected to increase further due to global warming. This situation has compelled plant scientists to develop climate change-resilient crops, which can withstand broad-spectrum stresses such as drought, heat, cold, salinity, flood, submergence and pests, thus helping to deliver increased productivity. Genomics appears to be a promising tool for deciphering the stress responsiveness of crop species with adaptation traits or in wild relatives toward identifying underlying genes, alleles or quantitative trait loci. Molecular breeding approaches have proven helpful in enhancing the stress adaptation of crop plants, and recent advances in high-throughput sequencing and phenotyping platforms have transformed molecular breeding to genomics-assisted breeding (GAB). In view of this, the present review elaborates the progress and prospects of GAB for improving climate change resilience in crops, which is likely to play an ever increasing role in the effort to ensure global food security.

  20. Application of genomics-assisted breeding for generation of climate resilient crops: Progress and prospects

    DOE PAGESBeta

    Kole, Chittaranjan; Muthamiliarasan, Mehanathan; Henry, Robert; Edwards, David; Sharma, Rishu; Abberton, Michael; Batley, Jacqueline; Bentley, Alison; Blakeney, Michael; Bryant, John; et al

    2015-08-11

    Climate change affects agricultural productivity worldwide. Increased prices of food commodities are the initial indication of drastic edible yield loss, which is expected to increase further due to global warming. This situation has compelled plant scientists to develop climate change-resilient crops, which can withstand broad-spectrum stresses such as drought, heat, cold, salinity, flood, submergence and pests, thus helping to deliver increased productivity. Genomics appears to be a promising tool for deciphering the stress responsiveness of crop species with adaptation traits or in wild relatives toward identifying underlying genes, alleles or quantitative trait loci. Molecular breeding approaches have proven helpful inmore » enhancing the stress adaptation of crop plants, and recent advances in high-throughput sequencing and phenotyping platforms have transformed molecular breeding to genomics-assisted breeding (GAB). In view of this, the present review elaborates the progress and prospects of GAB for improving climate change resilience in crops, which is likely to play an ever increasing role in the effort to ensure global food security.« less

  1. Application of genomics-assisted breeding for generation of climate resilient crops: progress and prospects

    PubMed Central

    Kole, Chittaranjan; Muthamilarasan, Mehanathan; Henry, Robert; Edwards, David; Sharma, Rishu; Abberton, Michael; Batley, Jacqueline; Bentley, Alison; Blakeney, Michael; Bryant, John; Cai, Hongwei; Cakir, Mehmet; Cseke, Leland J.; Cockram, James; de Oliveira, Antonio Costa; De Pace, Ciro; Dempewolf, Hannes; Ellison, Shelby; Gepts, Paul; Greenland, Andy; Hall, Anthony; Hori, Kiyosumi; Hughes, Stephen; Humphreys, Mike W.; Iorizzo, Massimo; Ismail, Abdelbagi M.; Marshall, Athole; Mayes, Sean; Nguyen, Henry T.; Ogbonnaya, Francis C.; Ortiz, Rodomiro; Paterson, Andrew H.; Simon, Philipp W.; Tohme, Joe; Tuberosa, Roberto; Valliyodan, Babu; Varshney, Rajeev K.; Wullschleger, Stan D.; Yano, Masahiro; Prasad, Manoj

    2015-01-01

    Climate change affects agricultural productivity worldwide. Increased prices of food commodities are the initial indication of drastic edible yield loss, which is expected to increase further due to global warming. This situation has compelled plant scientists to develop climate change-resilient crops, which can withstand broad-spectrum stresses such as drought, heat, cold, salinity, flood, submergence and pests, thus helping to deliver increased productivity. Genomics appears to be a promising tool for deciphering the stress responsiveness of crop species with adaptation traits or in wild relatives toward identifying underlying genes, alleles or quantitative trait loci. Molecular breeding approaches have proven helpful in enhancing the stress adaptation of crop plants, and recent advances in high-throughput sequencing and phenotyping platforms have transformed molecular breeding to genomics-assisted breeding (GAB). In view of this, the present review elaborates the progress and prospects of GAB for improving climate change resilience in crops, which is likely to play an ever increasing role in the effort to ensure global food security. PMID:26322050

  2. Deregulated expression of DNA polymerase β is involved in the progression of genomic instability

    PubMed Central

    Luo, Qingying; Lai, Yanhao; Liu, Shukun; Wu, Mei; Liu, Yuan; Zhang, Zunzhen

    2013-01-01

    Deregulated expression of DNA polymerase beta (pol β) has been implicated in genomic instability that leads to tumorigenesis, yet the mechanisms underlying the pol β-mediated genetic instability remain elusive. In this study, we investigated the roles of deregulated expression of pol β in spontaneous and xenobiotic-induced genetic instability using mouse embryonic fibroblasts (MEFs) that express distinct pol β levels (wild-type, null and over-expression) as a model system. Three genetic instability endpoints, DNA strand breaks, chromosome breakage and gene mutation, were examined under various expression levels of pol β by comet assay, micronuclei test and hprt mutation assay. Our results demonstrate that neither pol β deficiency nor pol β over-expression is sufficient for accumulation of spontaneous DNA damage that promotes a hyper-proliferation phenotype. However, pol β null cells exhibit increased sensitivity to exogenous DNA damaging agents with increased genomic instability compared with pol β wild-type and over-expression cells. This finding suggests that a pol β deficiency may underlie genomic instability induced by exogenous DNA damaging agents. Interestingly, pol β over-expression cells exhibit less chromosomal or DNA damage, but display a higher hprt mutation frequency upon methyl methanesulfonate exposure compared with the other two cell types. Our results therefore indicate that an excessive amount of pol β may promote genomic instability, presumably through an error-prone repair response, although it enhances overall BER capacity for induced DNA damage. PMID:22576475

  3. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    PubMed Central

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke; Knoop, Ann S.; Jensen, Jeanette D.; Bak, Martin; Mollenhauer, Jan; Kruse, Torben A.; Thomassen, Mads

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence. PMID:25730902

  4. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era.

    PubMed

    Verstraeten, Aline; Theuns, Jessie; Van Broeckhoven, Christine

    2015-03-01

    Parkinson disease (PD) and Parkinson-plus syndromes are genetically heterogeneous neurological diseases. Initial studies into the genetic causes of PD relied on classical molecular genetic approaches in well-documented case families. More recently, these approaches have been combined with exome sequencing and together have identified 15 causal genes. Additionally, genome-wide association studies (GWASs) have discovered over 25 genetic risk factors. Elucidation of the genetic architecture of sporadic and familial parkinsonism, however, has lagged behind that of simple Mendelian conditions, suggesting the existence of features confounding genetic data interpretation. Here we discuss the successes and potential pitfalls of gene discovery in PD and related disorders in the post-genomic era. With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies. PMID:25703649

  5. Genome-wide association study for semen quality traits in German Warmblood stallions.

    PubMed

    Gottschalk, Maren; Metzger, Julia; Martinsson, Gunilla; Sieme, Harald; Distl, Ottmar

    2016-08-01

    We performed a genome-wide association study for semen quality traits in 139 German Warmblood stallions. Stallions were genotyped using the Illumina equine SNP50 Beadchip. Traits analysed were de-regressed estimated breeding values (EBVs) for gel-free volume, sperm concentration, total number of sperm, progressive motility and the total number of progressively motile sperm. The GWAS revealed 29 SNPs on 12 different chromosomes as genome-wide significantly associated with semen quality traits. For ten genomic regions we could retrieve candidate genes influencing stallion fertility. Among the candidate genes, we could find the genes encoding cysteine-rich secretory proteins (CRISP1, CRISP2 and CRISP3). This was the first GWAS in horses performed for semen quality traits. PMID:27334685

  6. Genome-wide association study of swine farrowing traits. Part I: Genetic and genomic parameter estimates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary objective of this study was to determine genetic and genomic parameters among swine farrowing traits. Genetic parameters were obtained by using MTDFREML and genomic parameters were obtained using GenSel. Genetic and residual variances obtained from MTDFREML were used as priors for the ...

  7. SNPLims: a data management system for genome wide association studies

    PubMed Central

    Orro, Alessandro; Guffanti, Guia; Salvi, Erika; Macciardi, Fabio; Milanesi, Luciano

    2008-01-01

    Background Recent progresses in genotyping technologies allow the generation high-density genetic maps using hundreds of thousands of genetic markers for each DNA sample. The availability of this large amount of genotypic data facilitates the whole genome search for genetic basis of diseases. We need a suitable information management system to efficiently manage the data flow produced by whole genome genotyping and to make it available for further analyses. Results We have developed an information system mainly devoted to the storage and management of SNP genotype data produced by the Illumina platform from the raw outputs of genotyping into a relational database. The relational database can be accessed in order to import any existing data and export user-defined formats compatible with many different genetic analysis programs. After calculating family-based or case-control association study data, the results can be imported in SNPLims. One of the main features is to allow the user to rapidly identify and annotate statistically relevant polymorphisms from the large volume of data analyzed. Results can be easily visualized either graphically or creating ASCII comma separated format output files, which can be used as input to further analyses. Conclusions The proposed infrastructure allows to manage a relatively large amount of genotypes for each sample and an arbitrary number of samples and phenotypes. Moreover, it enables the users to control the quality of the data and to perform the most common screening analyses and identify genes that become “candidate” for the disease under consideration. PMID:18387201

  8. Genomic study of ossification of the posterior longitudinal ligament of the spine

    PubMed Central

    IKEGAWA, Shiro

    2014-01-01

    Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common disease after the middle age. OPLL frequently causes serious neurological problems due to compression of the spinal cord and/or nerve roots. OPLL occurs in patients with monogenic metabolic diseases including rickets/osteomalacia and hypoparathyroidism; however most of OPLL is idiopathic and is considered as a multi-factorial (polygenic) disease influenced by genetic and environmental factors. Genomic studies for the genetic factors of OPLL have been conducted, mainly in Japan, including linkage and association studies. This paper reviews the recent progress in the genomic study of OPLL and comments on its future direction. PMID:25504229

  9. Coordination: southeast continental shelf studies. Progress report

    SciTech Connect

    Menzel, D.W.

    1980-03-01

    The GABEX I experiment is designed to provide synoptic coverage of a series of Gulf Stream wave-like disturbances, the effect of these on the circulation of the entire shelf, and on biological and chemical processes. This study was initiated in February 1980 when current meter arrays were deployed. These meters will be removed in July 1980. In April three ships will simultaneously study the effects of Gulf Stream disturbances on the hydrography, chemistry, and biology of the shelf. One vessel will track a specific wave-like disturbance and provide synoptic coverage of the shelf area. The second vessel will determine the effect of shelf break processes on adjacent shelf water; and the third will study trace metal distributions in and outside of disturbances. Research progress is reported in continental shelf studies, nearshore and estuarine studies (diffusion of freshwater out of nearshore zone), tidal currents and material transport, and mixing of inlet plumes.

  10. The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.

    PubMed

    Gibson, William J; Hoivik, Erling A; Halle, Mari K; Taylor-Weiner, Amaro; Cherniack, Andrew D; Berg, Anna; Holst, Frederik; Zack, Travis I; Werner, Henrica M J; Staby, Kjersti M; Rosenberg, Mara; Stefansson, Ingunn M; Kusonmano, Kanthida; Chevalier, Aaron; Mauland, Karen K; Trovik, Jone; Krakstad, Camilla; Giannakis, Marios; Hodis, Eran; Woie, Kathrine; Bjorge, Line; Vintermyr, Olav K; Wala, Jeremiah A; Lawrence, Michael S; Getz, Gad; Carter, Scott L; Beroukhim, Rameen; Salvesen, Helga B

    2016-08-01

    Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed The Cancer Genome Atlas (TCGA) data, identifying new recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor gene NRIP1 in 12% of patients. We found that likely driver events were present in both primary and metastatic tissue samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites. PMID:27348297

  11. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

    PubMed

    Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-09-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  12. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

    PubMed Central

    Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-01-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  13. Review: Progress in the Researches on Insect Mitochondrial Genome and Analysis of Gene Order

    NASA Astrophysics Data System (ADS)

    Hu, Li; Jianyu, Gao; Haiyu, Liu; Wanzhi, Cai

    2009-04-01

    Insect mitochondrial genome is a double-stranded circular genomes which range from 14,503 bp to 19,571 bp in size. Nearly all the sequenced insect mitochondrial genomes encode 37 genes: two for rRNAs, 13 for proteins and 22 for tRNAs. This review compares and summarizes the features of complete mitochondrial genomes from 175 sequenced species of insects in 22 orders. The genomic organization, contents, gene order, and rearrangements of gene order are analyzed.

  14. Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

    Cancer.gov

    Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

  15. Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH.

    PubMed

    Selvarajah, S; Yoshimoto, M; Ludkovski, O; Park, P C; Bayani, J; Thorner, P; Maire, G; Squire, J A; Zielenska, M

    2008-01-01

    Osteosarcoma (OS) is characterized by an unstable karyotype which typically has a heterogeneous pattern of complex chromosomal abnormalities. High-resolution array comparative genomic hybridization (CGH) in combination with interphase fluorescence in situ hybridization (FISH) analyses provides a complete description of genomic imbalances together with an evaluation of the contribution of cell-to-cell variation to copy number changes. There have been no analyses to date documenting genomic signatures consistent with chromosomal instability mechanisms in OS tumors using array CGH. In this study, we utilized high-resolution array CGH to identify and characterize recurrent signatures of genomic imbalances using ten OS tumors. Comparison between the genomic profiles identified tumor groups with low, intermediate and high levels of genomic imbalance. Bands 6p22-->p21, 8q24 and 17p12--> p11.2 were consistently involved in high copy gain or amplification events. Since these three locations have been consistently associated with OS oncogenesis, FISH probes from each cytoband were used to derive an index of cellular heterogeneity for copy number within each region. OS with the highest degree of genomic imbalance also exhibited the most extreme cell-to-cell copy number variation. Significantly, the three OS with the most imbalance and genomic copy number heterogeneity also had the poorest response to preoperative chemotherapy. This genome wide analysis is the first utilizing oligonucleotide array CGH in combination with FISH analysis to derive genomic signatures of chromosomal instability in OS tumors by studying genomic imbalance and intercellular heterogeneity. This comprehensive genomic screening approach provides important insights concerning the mechanisms responsible for generating complex genomes. The resulting phenotypic diversity can generate tumors with a propensity for an aggressive disease course. A better understanding of the underlying mechanisms leading to OS

  16. Chronic Periodontitis Genome-wide Association Studies

    PubMed Central

    Rhodin, K.; Divaris, K.; North, K.E.; Barros, S.P.; Moss, K.; Beck, J.D.; Offenbacher, S.

    2014-01-01

    Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer rich data sources for the investigation of candidate genes, functional elements, and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen colonization (n = 1,020) from a cohort of adult Americans of European descent participating in the Atherosclerosis Risk in Communities study and employed a MAGENTA approach (i.e., meta-analysis gene set enrichment of variant associations) to obtain gene-centric and gene set association results corrected for gene size, number of single-nucleotide polymorphisms, and local linkage disequilibrium characteristics based on the human genome build 18 (National Center for Biotechnology Information build 36). We used the Gene Ontology, Ingenuity, KEGG, Panther, Reactome, and Biocarta databases for gene set enrichment analyses. Six genes showed evidence of statistically significant association: 4 with severe CP (NIN, p = 1.6 × 10−7; ABHD12B, p = 3.6 × 10−7; WHAMM, p = 1.7 × 10−6; AP3B2, p = 2.2 × 10−6) and 2 with high periodontal pathogen colonization (red complex–KCNK1, p = 3.4 × 10−7; Porphyromonas gingivalis–DAB2IP, p = 1.0 × 10−6). Top-ranked genes for moderate CP were HGD (p = 1.4 × 10−5), ZNF675 (p = 1.5 × 10−5), TNFRSF10C (p = 2.0 × 10−5), and EMR1 (p = 2.0 × 10−5). Loci containing NIN, EMR1, KCNK1, and DAB2IP had showed suggestive evidence of association in the earlier single-nucleotide polymorphism–based analyses, whereas WHAMM and AP2B2 emerged as novel candidates. The top gene sets included severe CP (“endoplasmic reticulum membrane,” “cytochrome P450,” “microsome,” and “oxidation reduction”) and moderate CP (“regulation of gene expression,” “zinc ion binding,” “BMP signaling pathway,” and “ruffle”). Gene-centric analyses offer a promising avenue for efficient interrogation of large-scale GWAS data. These results highlight genes in previously identified loci and

  17. Genes with Relevance for Early to Late Progression of Colon Carcinoma Based on Combined Genomic and Transcriptomic Information from the Same Patients

    PubMed Central

    Lagerstedt, Kristina K.; Kristiansson, Erik; Lönnroth, Christina; Andersson, Marianne; Iresjö, Britt-Marie; Gustafsson, Annika; Hansson, Elisabeth; Kressner, Ulf; Nordgren, Svante; Enlund, Fredrik; Lundholm, Kent

    2010-01-01

    Background: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. Methods: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. Results: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A–D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. Conclusions: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in

  18. CRISPR/Cas9 genome editing throws descriptive 3-D genome folding studies for a loop.

    PubMed

    Beagan, Jonathan A; Phillips-Cremins, Jennifer E

    2016-07-01

    CRISPR/Cas9 genome editing studies have recently shed new light into the causal link between the linear DNA sequence and 3-D chromatin architecture. Here we describe current models for the folding of genomes into a nested hierarchy of higher-order structures and discuss new insights into the organizing principles governing genome folding at each length scale. WIREs Syst Biol Med 2016, 8:286-299. doi: 10.1002/wsbm.1338 For further resources related to this article, please visit the WIREs website. PMID:27265842

  19. Galaxy tools to study genome diversity

    PubMed Central

    2013-01-01

    Background Intra-species genetic variation can be used to investigate population structure, selection, and gene flow in non-model vertebrates; and due to the plummeting costs for genome sequencing, it is now possible for small labs to obtain full-genome variation data from their species of interest. However, those labs may not have easy access to, and familiarity with, computational tools to analyze those data. Results We have created a suite of tools for the Galaxy web server aimed at handling nucleotide and amino-acid polymorphisms discovered by full-genome sequencing of several individuals of the same species, or using a SNP genotyping microarray. In addition to providing user-friendly tools, a main goal is to make published analyses reproducible. While most of the examples discussed in this paper deal with nuclear-genome diversity in non-human vertebrates, we also illustrate the application of the tools to fungal genomes, human biomedical data, and mitochondrial sequences. Conclusions This project illustrates that a small group can design, implement, test, document, and distribute a Galaxy tool collection to meet the needs of a particular community of biologists. PMID:24377391

  20. [Advances in Genomics Studies for Coronary Artery Disease].

    PubMed

    Wang, Ying; Zhu, Hui-juan; Zeng, Yong

    2015-08-01

    Coronary artery disease (CAD) is one of the major life-threatening diseases. In addition to traditional risk factors including age, sex, smoking, hypertension,and diabetes, genomic studies have shown that CAD has obvious genetic predisposition. In recent years, the rapid advances in genomics shed new light on early diagnosis, risk stratification and new treatment targets. PMID:26564468

  1. Data management for genomic mapping applications: A case study

    SciTech Connect

    Markowitz, V.M.; Lewis, S.; McCarthy, J.; Olken, F.; Zorn, M.

    1992-05-01

    In this paper we describe a new approach to the construction of data management systems for genomic mapping applications in molecular biology, genetics, and plant breeding. We discuss the architecture of such systems and propose an incremental approach to the development of such systems. We illustrate the proposed approach and architecture with a case study of a prototype data management system for genomic maps.

  2. Genomic Study of Cardiovascular Continuum Comorbidity

    PubMed Central

    Makeeva, O. A.; Sleptsov, A. A.; Kulish, E. V.; Barbarash, O. L.; Mazur, A. M.; Prokhorchuk, E. B.; Chekanov, N. N.; Stepanov, V. A.; Puzyrev, V. P.

    2015-01-01

    Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non–random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the “My Gene” genomic service (www.i–gene.ru). An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype “IHD only,” including those in the APOB, CD226, NKX2–5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the “IHD and AH” phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the

  3. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    PubMed Central

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  4. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement.

    PubMed

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  5. Database management research for the Human Genome Project: Progress report, 7/1/96-3/15/97

    SciTech Connect

    Goodman, N.

    1997-03-01

    Progress is reported on the development of software that works in conjunction with database management systems (DBMSs) in ways that are useful for genomics. This new release of LabBase has two major advantages over the previous version, namely it runs on the Sybase relational DBMS rather than ObjectStore and offers more complete data modeling features than the previous version so is suitable for more kinds of genetic databases.

  6. FY-1979 progress report. Hydrotransport plugging study.

    SciTech Connect

    Eyler, L.L.; Lombardo, N.J.

    1980-01-01

    The objective of the Hydrotransport Plugging Study is to investigate phenomena associated with predicting the onset and occurrence of plugging in pipeline transport of coal. This study addresses large particle transport plugging phenomena that may be encountered in run-of-mine operations. The project is being conducted in four tasks: review and analysis of current capabilities and available data, analytical modeling, experimental investigations, and unplugging and static start-up. This report documents work completed in FY-1979 as well as work currently in progress. A review of currently available prediction methods was completed. Applicability of the methods to large particle hydrotransport and the prediction of plugging was evaluated. It was determined that available models were inadequate, either because they are empirical and tuned to a given solid or because they are simplified analytical models incapable of accounting for a wide range of parameters. Complicated regression curve fit models lacking a physical basis cannot be extrapolated with confidence. Several specific conclusions were reached: Recent developments in mechanistic modeling, describing flow conditions at the limit of stationary deposition, provide the best basis for prediction and extrapolation of large particle flow. Certain modeled phenomena require further analytical and experimental investigation to improve confidence levels. Experimental work needs to be performed to support modeling and to provide an adequate data base for comparison purposes. No available model permits treatment of solids mixtures such as coal and rock.

  7. A progress report on seismic model studies

    USGS Publications Warehouse

    Healy, J.H.; Mangan, G.B.

    1963-01-01

    The value of seismic-model studies as an aid to understanding wave propagation in the Earth's crust was recognized by early investigators (Tatel and Tuve, 1955). Preliminary model results were very promising, but progress in model seismology has been restricted by two problems: (1) difficulties in the development of models with continuously variable velocity-depth functions, and (2) difficulties in the construction of models of adequate size to provide a meaningful wave-length to layer-thickness ratio. The problem of a continuously variable velocity-depth function has been partly solved by a technique using two-dimensional plate models constructed by laminating plastic to aluminum, so that the ratio of plastic to aluminum controls the velocity-depth function (Healy and Press, 1960). These techniques provide a continuously variable velocity-depth function, but it is not possible to construct such models large enough to study short-period wave propagation in the crust. This report describes improvements in our ability to machine large models. Two types of models are being used: one is a cylindrical aluminum tube machined on a lathe, and the other is a large plate machined on a precision planer. Both of these modeling techniques give promising results and are a significant improvement over earlier efforts.

  8. Tracking the progression of speciation: variable patterns of introgression across the genome provide insights on the species delimitation between progenitor-derivative spruces (Picea mariana × P. rubens).

    PubMed

    de Lafontaine, Guillaume; Prunier, Julien; Gérardi, Sébastien; Bousquet, Jean

    2015-10-01

    The genic species concept implies that while most of the genome can be exchanged somewhat freely between species through introgression, some genomic regions remain impermeable to interspecific gene flow. Hence, interspecific differences can be maintained despite ongoing gene exchange within contact zones. This study assessed the heterogeneous patterns of introgression at gene loci across the hybrid zone of an incipient progenitor-derivative species pair, Picea mariana (black spruce) and Picea rubens (red spruce). The spruce taxa likely diverged in geographic isolation during the Pleistocene and came into secondary contact during late Holocene. A total of 300 SNPs distributed across the 12 linkage groups (LG) of black spruce were genotyped for 385 individual trees from 33 populations distributed across the allopatric zone of each species and within the zone of sympatry. An integrative framework combining three population genomic approaches was used to scan the genomes, revealing heterogeneous patterns of introgression. A total of 23 SNPs scattered over 10 LG were considered impermeable to introgression and putatively under diverging selection. These loci revealed the existence of impermeable genomic regions forming the species boundary and are thus indicative of ongoing speciation between these two genetic lineages. Another 238 SNPs reflected selectively neutral diffusion across the porous species barrier. Finally, 39 highly permeable SNPs suggested ancestral polymorphism along with balancing selection. The heterogeneous patterns of introgression across the genome indicated that the speciation process between black spruce and red spruce is young and incomplete, albeit some interspecific differences are maintained, allowing ongoing species divergence even in sympatry. The approach developed in this study can be used to track the progression of ongoing speciation processes. PMID:26346701

  9. Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma.

    PubMed

    Hijiya, Naoki; Tsukamoto, Yoshiyuki; Nakada, Chisato; Tung Nguyen, Lam; Kai, Tomoki; Matsuura, Keiko; Shibata, Kohei; Inomata, Masafumi; Uchida, Tomohisa; Tokunaga, Akinori; Amada, Kohei; Shirao, Kuniaki; Yamada, Yasunari; Mori, Hiromu; Takeuchi, Ichiro; Seto, Masao; Aoki, Masahiro; Takekawa, Mutsuhiro; Moriyama, Masatsugu

    2016-05-01

    The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN. We demonstrate that the frequency of genomic copy-number aberrations significantly increased during the course of invasion, and the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, an MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter as well as in invasive carcinomas due to genomic loss. Restoration of DUSP4 expression in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Accordingly, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model and significantly extended survival. Collectively, our findings demonstrate a genetic mechanism by which pancreatic precursor lesions progress to invasive carcinomas and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling. Cancer Res; 76(9); 2612-25. ©2016 AACR. PMID:26941286

  10. Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression.

    PubMed

    Ramesh, Vignesh; Ganesan, Kumaresan

    2016-10-01

    Development of targeted therapeutics is still at its early stage for hepatocellular carcinoma (HCC) due to the incomplete understanding of the confounding regulations at signaling pathway level. In this investigation, gene co-expression-based networking and integrative functional genomic modeling of HCC mRNA profiles as signaling processes were employed to understand the complex signaling cascades involved in HCC development toward understanding the avenues for targeted therapeutics. Multiple sets of genes and molecular biological processes involved during HCC development were identified from this integrative analysis: (i) Loss of liver cellular features due to the reduced HNF4A & PPAR signaling in the early stages of HCC, (ii) activated inflammatory and stress signals in the cirrhosis stages and (iii) highly activated cellular proliferation with the activated E2F-MYC oncogenic signaling with the gain of embryonic liver stem cell-like features in the advanced stage tumors. Upon connecting these gene-sets with the established drug sensitivity-related gene signatures, targeted therapeutic strategies for the heterogeneous HCC conditions have been identified. PPAR agonist class of drugs for early stage HCC conditions, anti-inflammatory drugs for cirrhosis and topoisomerase inhibitors for the advanced HCC conditions were inferred. Integrative functional genomic analysis of HCC transcriptome profiles at the context of signaling pathways has defined the key molecular processes involved in HCC development. Further, the study highlights the stage-specific and pathway focused targeted therapeutics for HCC. These findings deserve extensive preclinical explorations toward the establishment of targeted therapeutics. PMID:27194100

  11. [Genome-wide association study on complex diseases: study design and genetic markers].

    PubMed

    Yan, Wei-Li

    2008-04-01

    Genome-wide association study used to be a dream of geneticists years ago, but now it came true. Since the first paper reported the finding of genetic variation contributing to human age-related macular degeneration by genome-wide association study in 2005, a numbers of whole genome studies have been published. The present paper reviewed some common comments in whole genome association study on complex diseases, including achievements of genome-wide association studies on complex traits or diseases, principles of study design, selection of genetic marker in genome, and comparisons of different commercial products for whole genome association study. Finally a newly defined genetic variation, copy number variation, was briefly introduced. This paper also summarized the shortcomings of current genome-wide association studies and perspectives of its future. PMID:18424408

  12. Study of heavy flavored particles. Progress report

    SciTech Connect

    Not Available

    1991-12-31

    This report discusses progress on the following topics: time-of- flight system; charmed baryon production and decays; D decays to baryons; measurement of sigma plus particles magnetic moments; and strong interaction coupling. (LSP)

  13. Genomics Study of Gastric Cancer and Its Molecular Subtypes.

    PubMed

    Yuen, Siu Tsan; Leung, Suet Yi

    2016-01-01

    Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation). Recent advances in genomic technology have led to an improved understanding of the driver gene mutational profile, gene expression, and epigenetic alterations that underlie each of the subgroups, with therapeutic implications in some of these alterations. There have been attempts to classify gastric cancers based on these genomic features, with an aim to improve prognostication and predict responsiveness to specific drug therapy. The eventual aims of these genomic studies are to develop deep biological insights into the carcinogenic pathway in each of these subtypes. Future large-scale drug screening strategies may then be able to link these genomic features to drug responsiveness, eventually leading to genome-guided personalized medicine with improved cure rates. PMID:27573784

  14. The Global Invertebrate Genomics Alliance (GIGA): Developing Community Resources to Study Diverse Invertebrate Genomes

    PubMed Central

    2014-01-01

    Over 95% of all metazoan (animal) species comprise the “invertebrates,” but very few genomes from these organisms have been sequenced. We have, therefore, formed a “Global Invertebrate Genomics Alliance” (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major challenges (e.g., species selection, sample collection and storage, sequence assembly, annotation, analytical tools) associated with genome/transcriptome sequencing across a large taxonomic spectrum. We aim to promote standards that will facilitate comparative approaches to invertebrate genomics and collaborations across the international scientific community. Candidate study taxa include species from Porifera, Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida, Bryozoa, and Platyhelminthes, among others. GIGA will target 7000 noninsect/nonnematode species, with an emphasis on marine taxa because of the unrivaled phyletic diversity in the oceans. Priorities for selecting invertebrates for sequencing will include, but are not restricted to, their phylogenetic placement; relevance to organismal, ecological, and conservation research; and their importance to fisheries and human health. We highlight benefits of sequencing both whole genomes (DNA) and transcriptomes and also suggest policies for genomic-level data access and sharing based on transparency and inclusiveness. The GIGA Web site (http://giga.nova.edu) has been launched to facilitate this collaborative venture. PMID:24336862

  15. The Global Invertebrate Genomics Alliance (GIGA): developing community resources to study diverse invertebrate genomes.

    PubMed

    Bracken-Grissom, Heather; Collins, Allen G; Collins, Timothy; Crandall, Keith; Distel, Daniel; Dunn, Casey; Giribet, Gonzalo; Haddock, Steven; Knowlton, Nancy; Martindale, Mark; Medina, Mónica; Messing, Charles; O'Brien, Stephen J; Paulay, Gustav; Putnam, Nicolas; Ravasi, Timothy; Rouse, Greg W; Ryan, Joseph F; Schulze, Anja; Wörheide, Gert; Adamska, Maja; Bailly, Xavier; Breinholt, Jesse; Browne, William E; Diaz, M Christina; Evans, Nathaniel; Flot, Jean-François; Fogarty, Nicole; Johnston, Matthew; Kamel, Bishoy; Kawahara, Akito Y; Laberge, Tammy; Lavrov, Dennis; Michonneau, François; Moroz, Leonid L; Oakley, Todd; Osborne, Karen; Pomponi, Shirley A; Rhodes, Adelaide; Santos, Scott R; Satoh, Nori; Thacker, Robert W; Van de Peer, Yves; Voolstra, Christian R; Welch, David Mark; Winston, Judith; Zhou, Xin

    2014-01-01

    Over 95% of all metazoan (animal) species comprise the "invertebrates," but very few genomes from these organisms have been sequenced. We have, therefore, formed a "Global Invertebrate Genomics Alliance" (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major challenges (e.g., species selection, sample collection and storage, sequence assembly, annotation, analytical tools) associated with genome/transcriptome sequencing across a large taxonomic spectrum. We aim to promote standards that will facilitate comparative approaches to invertebrate genomics and collaborations across the international scientific community. Candidate study taxa include species from Porifera, Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida, Bryozoa, and Platyhelminthes, among others. GIGA will target 7000 noninsect/nonnematode species, with an emphasis on marine taxa because of the unrivaled phyletic diversity in the oceans. Priorities for selecting invertebrates for sequencing will include, but are not restricted to, their phylogenetic placement; relevance to organismal, ecological, and conservation research; and their importance to fisheries and human health. We highlight benefits of sequencing both whole genomes (DNA) and transcriptomes and also suggest policies for genomic-level data access and sharing based on transparency and inclusiveness. The GIGA Web site (http://giga.nova.edu) has been launched to facilitate this collaborative venture. PMID:24336862

  16. 2012 U.S. Department of Energy: Joint Genome Institute: Progress Report

    SciTech Connect

    Gilbert, David

    2013-01-01

    The mission of the U.S. Department of Energy Joint Genome Institute (DOE JGI) is to serve the diverse scientific community as a user facility, enabling the application of large-scale genomics and analysis of plants, microbes, and communities of microbes to address the DOE mission goals in bioenergy and the environment. The DOE JGI's sequencing efforts fall under the Eukaryote Super Program, which includes the Plant and Fungal Genomics Programs; and the Prokaryote Super Program, which includes the Microbial Genomics and Metagenomics Programs. In 2012, several projects made news for their contributions to energy and environment research.

  17. Prospects and pitfalls in whole genome association studies

    PubMed Central

    Lawrence, Robert W; Evans, David M; Cardon, Lon R

    2005-01-01

    Recent large-scale studies of common genetic variation throughout the human genome are making it feasible to conduct whole genome studies of genotype–phenotype associations. Such studies have the potential to uncover novel contributors to common complex traits and thus lead to insights into the aetiology of multifactorial phenotypes. Despite this promise, it is important to recognize that the availability of genetic markers and the ability to assay them at realistic cost does not guarantee success of this approach. There are a number of practical issues that require close attention, some forms of allelic architecture are not readily amenable to the association approach with even the most rigorous design, and doubtless new hurdles will emerge as the studies begin. Here we discuss the promise and current challenges of the whole genome approach, and raise some issues to consider in interpreting the results of the first whole genome studies. PMID:16096108

  18. Progress in the search for genetic linkage with Tourette syndrome: An exclusion map covering more than 50% of the autosomal genome

    PubMed Central

    Pakstis, Andrew J.; Heutink, Peter; Pauls, David L.; Kurlan, Roger; van de Wetering, Ben J. M.; Leckman, James F.; Sandkuyl, Lodewijk A.; Kidd, Judith R.; Breedveld, Guido J.; Castiglione, Carmela M.; Weber, James; Sparkes, Robert S.; Cohen, Donald J.; Kidd, Kenneth K.; Oostra, Ben A.

    1991-01-01

    Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus. Several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder. Strong and clear evidence of linkage has not yet been produced for Tourette syndrome. This paper presents an overview of the methods and progress of the groups centered at Yale University and Erasmus University in excluding linkage from a large portion of the genome. Our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the United States, Canada, The Netherlands, and Norway. More than 50% (and perhaps as much as 66%) of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the Tourette syndrome pedigrees pooled for this summary. PMID:1990837

  19. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  20. Stories and Challenges of Genome Wide Association Studies in Livestock — A Review

    PubMed Central

    Sharma, Aditi; Lee, Jun Seop; Dang, Chang Gwon; Sudrajad, Pita; Kim, Hyeong Cheol; Yeon, Seong Heum; Kang, Hee Seol; Lee, Seung-Hwan

    2015-01-01

    Undoubtedly livestock is one of the major contributors to the economy of any country. The economic value of livestock includes meat, dairy products, fiber, fertilizer etc. Understanding and identifying the associations of quantitative trait loci (QTL) with the economically important traits is believed to substantially benefit the livestock industry. The past two decades have seen a flurry of interest in mapping the QTL associated with traits of economic importance on the genome. With the availability of single nucleotide polymorphism chip of various densities it is possible to identify regions, QTL and genes on the genome that explain the association and its effect on the phenotype under consideration. Remarkable advancement has been seen in genome wide association studies (GWAS) since its inception till the present day. In this review we describe the progress and challenges of GWAS in various livestock species. PMID:26194229

  1. Stories and Challenges of Genome Wide Association Studies in Livestock - A Review.

    PubMed

    Sharma, Aditi; Lee, Jun Seop; Dang, Chang Gwon; Sudrajad, Pita; Kim, Hyeong Cheol; Yeon, Seong Heum; Kang, Hee Seol; Lee, Seung-Hwan

    2015-10-01

    Undoubtedly livestock is one of the major contributors to the economy of any country. The economic value of livestock includes meat, dairy products, fiber, fertilizer etc. Understanding and identifying the associations of quantitative trait loci (QTL) with the economically important traits is believed to substantially benefit the livestock industry. The past two decades have seen a flurry of interest in mapping the QTL associated with traits of economic importance on the genome. With the availability of single nucleotide polymorphism chip of various densities it is possible to identify regions, QTL and genes on the genome that explain the association and its effect on the phenotype under consideration. Remarkable advancement has been seen in genome wide association studies (GWAS) since its inception till the present day. In this review we describe the progress and challenges of GWAS in various livestock species. PMID:26194229

  2. Using CAVE technology for functional genomics studies.

    PubMed

    Sensen, Christoph W

    2002-01-01

    We have established the first Java 3D-enabled CAVE (CAVE automated virtual environment). The Java application programming interface allows the complete separation of the program development from the program execution, opening new application domains for the CAVE technology. Programs can be developed on any Java-enabled computer platform, including Windows, Macintosh, and Linux workstations, and executed in the CAVE without modification. The introduction of Java, one of the major programming environments for bioinformatics, into the CAVE environment allows the rapid development applications for genome research, especially for the analysis of the spatial and temporal data that are being produced by functional genomics experiments. The CAVE technology will play a major role in the modeling of biological systems that is necessary to understand how these systems are organized and how they function. PMID:12614491

  3. Integrated Genome-Based Studies of Shewanella Ecophysiology

    SciTech Connect

    Zhou, Jizhong; He, Zhili

    2014-04-08

    As a part of the Shewanella Federation project, we have used integrated genomic, proteomic and computational technologies to study various aspects of energy metabolism of two Shewanella strains from a systems-level perspective.

  4. A SUPER Powerful Method for Genome Wide Association Study

    PubMed Central

    Pan, Yuchun; Buckler, Edward S.; Zhang, Zhiwu

    2014-01-01

    Genome-Wide Association Studies shed light on the identification of genes underlying human diseases and agriculturally important traits. This potential has been shadowed by false positive findings. The Mixed Linear Model (MLM) method is flexible enough to simultaneously incorporate population structure and cryptic relationships to reduce false positives. However, its intensive computational burden is prohibitive in practice, especially for large samples. The newly developed algorithm, FaST-LMM, solved the computational problem, but requires that the number of SNPs be less than the number of individuals to derive a rank-reduced relationship. This restriction potentially leads to less statistical power when compared to using all SNPs. We developed a method to extract a small subset of SNPs and use them in FaST-LMM. This method not only retains the computational advantage of FaST-LMM, but also remarkably increases statistical power even when compared to using the entire set of SNPs. We named the method SUPER (Settlement of MLM Under Progressively Exclusive Relationship) and made it available within an implementation of the GAPIT software package. PMID:25247812

  5. Mycobacterial species as case-study of comparative genome analysis.

    PubMed

    Zakham, F; Belayachi, L; Ussery, D; Akrim, M; Benjouad, A; El Aouad, R; Ennaji, M M

    2011-01-01

    The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species. PMID:21396338

  6. Progress towards the complete American cranberry (Vaccinium macrocarpon Ait.) plastid genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Next generation sequencing (NGS) technology has been rapidly adopted for sequencing complete plant genomes due to its high-throughput and cost effective benefits. Advances towards the complete plastid genome sequence of the cranberry cultivar “HyRed” are presented using in silico procedures. We used...

  7. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress.

    PubMed

    Lyon, Gholson J; Wang, Kai

    2012-01-01

    The pace of exome and genome sequencing is accelerating, with the identification of many new disease-causing mutations in research settings, and it is likely that whole exome or genome sequencing could have a major impact in the clinical arena in the relatively near future. However, the human genomics community is currently facing several challenges, including phenotyping, sample collection, sequencing strategies, bioinformatics analysis, biological validation of variant function, clinical interpretation and validity of variant data, and delivery of genomic information to various constituents. Here we review these challenges and summarize the bottlenecks for the clinical application of exome and genome sequencing, and we discuss ways for moving the field forward. In particular, we urge the need for clinical-grade sample collection, high-quality sequencing data acquisition, digitalized phenotyping, rigorous generation of variant calls, and comprehensive functional annotation of variants. Additionally, we suggest that a 'networking of science' model that encourages much more collaboration and online sharing of medical history, genomic data and biological knowledge, including among research participants and consumers/patients, will help establish causation and penetrance for disease causal variants and genes. As we enter this new era of genomic medicine, we envision that consumer-driven and consumer-oriented efforts will take center stage, thus allowing insights from the human genome project to translate directly back into individualized medicine. PMID:22830651

  8. The International Pea Genome Sequencing Project: Sequencing and Assembly Progresses Updates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International Consortium for the Pea Genome Sequencing (ICPG) includes scientists from six countries around the world. Its aim is to provide a high quality reference of the pea genome to the scientific community as well as to the pea breeder community. The consortium proposed a strategy that int...

  9. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress

    PubMed Central

    2012-01-01

    The pace of exome and genome sequencing is accelerating, with the identification of many new disease-causing mutations in research settings, and it is likely that whole exome or genome sequencing could have a major impact in the clinical arena in the relatively near future. However, the human genomics community is currently facing several challenges, including phenotyping, sample collection, sequencing strategies, bioinformatics analysis, biological validation of variant function, clinical interpretation and validity of variant data, and delivery of genomic information to various constituents. Here we review these challenges and summarize the bottlenecks for the clinical application of exome and genome sequencing, and we discuss ways for moving the field forward. In particular, we urge the need for clinical-grade sample collection, high-quality sequencing data acquisition, digitalized phenotyping, rigorous generation of variant calls, and comprehensive functional annotation of variants. Additionally, we suggest that a 'networking of science' model that encourages much more collaboration and online sharing of medical history, genomic data and biological knowledge, including among research participants and consumers/patients, will help establish causation and penetrance for disease causal variants and genes. As we enter this new era of genomic medicine, we envision that consumer-driven and consumer-oriented efforts will take center stage, thus allowing insights from the human genome project to translate directly back into individualized medicine. PMID:22830651

  10. Whole genome comparative studies between chicken and turkey and their implications for avian genome evolution

    PubMed Central

    Griffin, Darren K; Robertson, Lindsay B; Tempest, Helen G; Vignal, Alain; Fillon, Valérie; Crooijmans, Richard PMA; Groenen, Martien AM; Deryusheva, Svetlana; Gaginskaya, Elena; Carré, Wilfrid; Waddington, David; Talbot, Richard; Völker, Martin; Masabanda, Julio S; Burt, Dave W

    2008-01-01

    Background Comparative genomics is a powerful means of establishing inter-specific relationships between gene function/location and allows insight into genomic rearrangements, conservation and evolutionary phylogeny. The availability of the complete sequence of the chicken genome has initiated the development of detailed genomic information in other birds including turkey, an agriculturally important species where mapping has hitherto focused on linkage with limited physical information. No molecular study has yet examined conservation of avian microchromosomes, nor differences in copy number variants (CNVs) between birds. Results We present a detailed comparative cytogenetic map between chicken and turkey based on reciprocal chromosome painting and mapping of 338 chicken BACs to turkey metaphases. Two inter-chromosomal changes (both involving centromeres) and three pericentric inversions have been identified between chicken and turkey; and array CGH identified 16 inter-specific CNVs. Conclusion This is the first study to combine the modalities of zoo-FISH and array CGH between different avian species. The first insight into the conservation of microchromosomes, the first comparative cytogenetic map of any bird and the first appraisal of CNVs between birds is provided. Results suggest that avian genomes have remained relatively stable during evolution compared to mammalian equivalents. PMID:18410676

  11. From NGS assembly challenges to instability of fungal mitochondrial genomes: A case study in genome complexity.

    PubMed

    Misas, Elizabeth; Muñoz, José Fernando; Gallo, Juan Esteban; McEwen, Juan Guillermo; Clay, Oliver Keatinge

    2016-04-01

    The presence of repetitive or non-unique DNA persisting over sizable regions of a eukaryotic genome can hinder the genome's successful de novo assembly from short reads: ambiguities in assigning genome locations to the non-unique subsequences can result in premature termination of contigs and thus overfragmented assemblies. Fungal mitochondrial (mtDNA) genomes are compact (typically less than 100 kb), yet often contain short non-unique sequences that can be shown to impede their successful de novo assembly in silico. Such repeats can also confuse processes in the cell in vivo. A well-studied example is ectopic (out-of-register, illegitimate) recombination associated with repeat pairs, which can lead to deletion of functionally important genes that are located between the repeats. Repeats that remain conserved over micro- or macroevolutionary timescales despite such risks may indicate functionally or structurally (e.g., for replication) important regions. This principle could form the basis of a mining strategy for accelerating discovery of function in genome sequences. We present here our screening of a sample of 11 fully sequenced fungal mitochondrial genomes by observing where exact k-mer repeats occurred several times; initial analyses motivated us to focus on 17-mers occurring more than three times. Based on the diverse repeats we observe, we propose that such screening may serve as an efficient expedient for gaining a rapid but representative first insight into the repeat landscapes of sparsely characterized mitochondrial chromosomes. Our matching of the flagged repeats to previously reported regions of interest supports the idea that systems of persisting, non-trivial repeats in genomes can often highlight features meriting further attention. PMID:26970210

  12. Personal Commitment, Support and Progress in Doctoral Studies

    ERIC Educational Resources Information Center

    Martinsuo, Miia; Turkulainen, Virpi

    2011-01-01

    Earlier research on doctoral education has associated study progress with the student's own capabilities and faculty support. The purpose of this study is to investigate how students' personal commitment and various forms of support, as well as their complementary effects, explain progress in doctoral studies. Data were collected by a…

  13. Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

    PubMed Central

    Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

  14. Elucidating Genomic Characteristics of Lung Cancer Progression from In Situ to Invasive Adenocarcinoma

    PubMed Central

    Vinayanuwattikun, Chanida; Le Calvez-Kelm, Florence; Abedi-Ardekani, Behnoush; Zaridze, David; Mukeria, Anush; Voegele, Catherine; Vallée, Maxime; Purnomosari, Dewajani; Forey, Nathalie; Durand, Geoffroy; Byrnes, Graham; Mckay, James; Brennan, Paul; Scelo, Ghislaine

    2016-01-01

    To examine the diversity of somatic alterations and clonal evolution according to aggressiveness of disease, nineteen tumor-blood pairs of ‘formerly bronchiolo-alveolar carcinoma (BAC)’ which had been reclassified into preinvasive lesion (adenocarcinoma in situ; AIS), focal invasive lesion (minimally invasive adenocarcinoma; MIA), and invasive lesion (lepidic predominant adenocarcinoma; LPA and non-lepidic predominant adenocarcinoma; non-LPA) according to IASLC/ATS/ERS 2011 classification were explored by whole exome sequencing. Several distinct somatic alterations were observed compare to the lung adenocarcinoma study from the Cancer Genome Atlas (TCGA). There were higher numbers of tumors with significant APOBEC mutation fold enrichment (73% vs. 58% TCGA). The frequency of KRAS mutations was lower in our study (5% vs. 32% TCGA), while a higher number of mutations of RNA-splicing genes, RBM10 and U2AF1, were found (37% vs. 11% TCGA). We found neither mutational pattern nor somatic copy number alterations that were specific to AIS/MIA. We demonstrated that clonal cell fraction was the only distinctive feature that discriminated LPA/non-LPA from AIS/MIA. The broad range of clonal frequency signified a more branched clonal evolution at the time of diagnosis. Assessment of tumor clonal cell fraction might provide critical information for individualized therapy as a prognostic factor, however this needs further study. PMID:27545006

  15. Elucidating Genomic Characteristics of Lung Cancer Progression from In Situ to Invasive Adenocarcinoma.

    PubMed

    Vinayanuwattikun, Chanida; Le Calvez-Kelm, Florence; Abedi-Ardekani, Behnoush; Zaridze, David; Mukeria, Anush; Voegele, Catherine; Vallée, Maxime; Purnomosari, Dewajani; Forey, Nathalie; Durand, Geoffroy; Byrnes, Graham; Mckay, James; Brennan, Paul; Scelo, Ghislaine

    2016-01-01

    To examine the diversity of somatic alterations and clonal evolution according to aggressiveness of disease, nineteen tumor-blood pairs of 'formerly bronchiolo-alveolar carcinoma (BAC)' which had been reclassified into preinvasive lesion (adenocarcinoma in situ; AIS), focal invasive lesion (minimally invasive adenocarcinoma; MIA), and invasive lesion (lepidic predominant adenocarcinoma; LPA and non-lepidic predominant adenocarcinoma; non-LPA) according to IASLC/ATS/ERS 2011 classification were explored by whole exome sequencing. Several distinct somatic alterations were observed compare to the lung adenocarcinoma study from the Cancer Genome Atlas (TCGA). There were higher numbers of tumors with significant APOBEC mutation fold enrichment (73% vs. 58% TCGA). The frequency of KRAS mutations was lower in our study (5% vs. 32% TCGA), while a higher number of mutations of RNA-splicing genes, RBM10 and U2AF1, were found (37% vs. 11% TCGA). We found neither mutational pattern nor somatic copy number alterations that were specific to AIS/MIA. We demonstrated that clonal cell fraction was the only distinctive feature that discriminated LPA/non-LPA from AIS/MIA. The broad range of clonal frequency signified a more branched clonal evolution at the time of diagnosis. Assessment of tumor clonal cell fraction might provide critical information for individualized therapy as a prognostic factor, however this needs further study. PMID:27545006

  16. Dissecting ancestry genomic background in substance dependence genome-wide association studies

    PubMed Central

    Polimanti, Renato; Yang, Can; Zhao, Hongyu; Gelernter, Joel

    2015-01-01

    Aims To understand the role of ancestral genomic background in substance dependence (SD) genome-wide association studies (GWAS), we analyzed population diversity at genetic loci associated with SD traits and evaluated its effect on GWAS outcomes. Materials & methods We investigated 24 genes with variants associated with SD by GWAS; and 82 loci with putative subordinate roles with respect to SD-associated genes. Results We observed high ancestry-related frequency differences in common functional alleles in GWAS relevant genes and their interactive partners. Common functional alleles with high frequency differences demonstrated significant effects on the GWAS outcomes. Conclusion Population differences in SD GWAS outcomes seem not to be influenced by general variation across the genome, but by ancestry-related local haplotype structures at SD-associated loci. PMID:26267224

  17. Coordination: southeast continental shelf studies. Progress report

    SciTech Connect

    Menzel, D.W.

    1981-02-01

    The objectives are to identify important physical, chemical and biological processes which affect the transfer of materials on the southeast continental shelf, determine important parameters which govern observed temporal and spatial varibility on the continental shelf, determine the extent and modes of coupling between events at the shelf break and nearshore, and determine physical, chemical and biological exchange rates on the inner shelf. Progress in meeting these research objectives is presented. (ACR)

  18. 78 FR 47674 - Genome in a Bottle Consortium-Progress and Planning Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ...: select appropriate sources for whole genome RMs and identify or design synthetic DNA constructs that... and synthetic DNA RMs along with the methods (documentary standards) and reference data necessary...

  19. Study of Transposable Elements and Their Genomic Impact.

    PubMed

    Muñoz-Lopez, Martin; Vilar-Astasio, Raquel; Tristan-Ramos, Pablo; Lopez-Ruiz, Cesar; Garcia-Pérez, Jose L

    2016-01-01

    Transposable elements (TEs) have been considered traditionally as junk DNA, i.e., DNA sequences that despite representing a high proportion of genomes had no evident cellular functions. However, over the last decades, it has become undeniable that not only TE-derived DNA sequences have (and had) a fundamental role during genome evolution, but also TEs have important implications in the origin and evolution of many genomic disorders. This concise review provides a brief overview of the different types of TEs that can be found in genomes, as well as a list of techniques and methods used to study their impact and mobilization. Some of these techniques will be covered in detail in this Method Book. PMID:26895043

  20. Progress in the study of drug nanocrystals.

    PubMed

    Shi, Jing; Guo, Fei; Zheng, Aiping; Zhang, Xiaoyan; Sun, Jianxu

    2015-12-01

    The poor water solubility of many candidate drugs remains a major obstacle to their development and clinical use, especially for oral drug delivery. Nanocrystal technology can improve the solubility and dissolution rates of many poorly water-soluble drugs very effectively, significantly improving their oral bioavailability and decreasing the food effect. For this reason, this technology is becoming a key area of drug delivery research. This review presents much of the recent progress in nanocrystal drug pharmaceuticals, including the characteristics, composition, preparation technology, and clinical applications of these drugs. Finally, the effect of nanocrystal technology on insoluble drugs is quantified and described. PMID:26817271

  1. Integrated genome based studies of Shewanella ecophysiology

    SciTech Connect

    Saffarini, Daad A

    2013-03-07

    Progress is reported in these areas: Regulation of anaerobic respiration by cAMP receptor protein and role of adenylate cyclases; Identification of an octaheme c cytochrome as the terminal sulfite reductase in S. oneidensis MR-1; Identification and analysis of components of the electron transport chains that lead to reduction of thiosulfate, tetrathionate, and elemental sulfur in MR-1; Involvement of pili and flagella in metal reduction by S. oneidensis MR-1; and work suggesting that HemN1 is the major enzyme that is involved in heme biosynthesis under anaerobic conditions.

  2. [Progress of non-genomic action of estrogen and its impact on female reproduction].

    PubMed

    Yu, Lin-Lin; Yuan, Dong-Zhi; Zhang, Shi-Mao; Yue, Li-Min

    2016-08-25

    Estrogen is one of the steroid hormones. Besides the genomic action mediated by its intracellular receptor on target cells, there is now increasing body of evidence indicating that estrogen also has non-genomic action. For the non-genomic action, estrogen binds to its receptor on cell membrane, subsequently rapidly activates various intracellular signaling pathways, such as PLC/Ca(2+), ERK/MAPK, cAMP-PKA, PI3K-AKT-NOS, and finally induces biological effects. The non-genomic effects of estrogen on physiologic and pathologic processes have been found in many tissues within the reproductive, nervous and cardiovascular systems and bone etc. In reproductive system, it has been demonstrated that estrogen plays important roles in follicle development, fertilization and embryo implantation, and it is involved in the genesis and development of genital tract tumors and breast cancer. In this review, we focus on the general characteristics of non-genomic action of estrogen, its main nonnuclear signaling pathways and physiological and pathological significance, especially its influences in female reproductive functions. PMID:27546514

  3. Genome-wide alterations of the DNA replication program during tumor progression

    NASA Astrophysics Data System (ADS)

    Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.

    2016-08-01

    Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.

  4. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  5. Studying Genome Heterogeneity within the Arbuscular Mycorrhizal Fungal Cytoplasm

    PubMed Central

    Halary, Sébastien; Bapteste, Eric; Hijri, Mohamed

    2015-01-01

    Although heterokaryons have been reported in nature, multicellular organisms are generally assumed genetically homogeneous. Here, we investigate the case of arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The growth advantages they confer to their hosts are of great potential benefit to sustainable agricultural practices. However, measuring genetic diversity for these coenocytes is a major challenge: Within the same cytoplasm, AMF contain thousands of nuclei and show extremely high levels of genetic variation for some loci. The extent and physical location of polymorphism within and between AMF genomes is unclear. We used two complementary strategies to estimate genetic diversity in AMF, investigating polymorphism both on a genome scale and in putative single copy loci. First, we used data from whole-genome pyrosequencing of four AMF isolates to describe genetic diversity, based on a conservative network-based clustering approach. AMF isolates showed marked differences in genome-wide diversity patterns in comparison to a panel of control fungal genomes. This clustering approach further allowed us to provide conservative estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative single copy genomic markers, which we investigated by massive parallel amplicon sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most loci showed high polymorphism, with up to 103 alleles per marker. This polymorphism could be distributed within or between nuclei. However, we argue that the Rhizophagus isolates under study might be heterokaryotic, at least for the putative single copy markers we studied. Considering that genetic information is the main resource for identification of AMF, we suggest that special attention is warranted for the study of these ecologically important organisms. PMID:25573960

  6. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  7. Genome-wide effects of acute progressive feed restriction in liver and white adipose tissue

    SciTech Connect

    Pohjanvirta, Raimo Boutros, Paul C.; Moffat, Ivy D.; Linden, Jere; Wendelin, Dominique; Okey, Allan B.

    2008-07-01

    Acute progressive feed restriction (APFR) represents a specific form of caloric restriction in which feed availability is increasingly curtailed over a period of a few days to a few weeks. It is often used for control animals in toxicological and pharmacological studies on compounds causing body weight loss to equalize weight changes between experimental and control groups and thereby, intuitively, to also set their metabolic states to the same phase. However, scientific justification for this procedure is lacking. In the present study, we analyzed by microarrays the impact on hepatic gene expression in rats of two APFR regimens that caused identical diminution of body weight (19%) but differed slightly in duration (4 vs. 10 days). In addition, white adipose tissue (WAT) was also subjected to the transcriptomic analysis on day-4. The data revealed that the two regimens led to distinct patterns of differentially expressed genes in liver, albeit some major pathways of energy metabolism were similarly affected (particularly fatty acid and amino acid catabolism). The reason for the divergence appeared to be entrainment by the longer APFR protocol of peripheral oscillator genes, which resulted in derailment of circadian rhythms and consequent interaction of altered diurnal fluctuations with metabolic adjustments in gene expression activities. WAT proved to be highly unresponsive to the 4-day APFR as only 17 mRNA levels were influenced by the treatment. This study demonstrates that body weight is a poor proxy of metabolic state and that the customary protocols of feed restriction can lead to rhythm entrainment.

  8. Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996

    SciTech Connect

    Lim, C.S.; Xu, R.X.; Wang, M.

    1996-12-31

    Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).

  9. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

    PubMed Central

    Serrano, Lourdes; Martínez-Redondo, Paloma; Marazuela-Duque, Anna; Vazquez, Berta N.; Dooley, Scott J.; Voigt, Philipp; Beck, David B.; Kane-Goldsmith, Noriko; Tong, Qiang; Rabanal, Rosa M.; Fondevila, Dolors; Muñoz, Purificación; Krüger, Marcus; Tischfield, Jay A.; Vaquero, Alejandro

    2013-01-01

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1–3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle. PMID:23468428

  10. Progressive engineering of a homing endonuclease genome editing reagent for the murine X-linked immunodeficiency locus.

    PubMed

    Wang, Yupeng; Khan, Iram F; Boissel, Sandrine; Jarjour, Jordan; Pangallo, Joseph; Thyme, Summer; Baker, David; Scharenberg, Andrew M; Rawlings, David J

    2014-06-01

    LAGLIDADG homing endonucleases (LHEs) are compact endonucleases with 20-22 bp recognition sites, and thus are ideal scaffolds for engineering site-specific DNA cleavage enzymes for genome editing applications. Here, we describe a general approach to LHE engineering that combines rational design with directed evolution, using a yeast surface display high-throughput cleavage selection. This approach was employed to alter the binding and cleavage specificity of the I-Anil LHE to recognize a mutation in the mouse Bruton tyrosine kinase (Btk) gene causative for mouse X-linked immunodeficiency (XID)-a model of human X-linked agammaglobulinemia (XLA). The required re-targeting of I-AniI involved progressive resculpting of the DNA contact interface to accommodate nine base differences from the native cleavage sequence. The enzyme emerging from the progressive engineering process was specific for the XID mutant allele versus the wild-type (WT) allele, and exhibited activity equivalent to WT I-AniI in vitro and in cellulo reporter assays. Fusion of the enzyme to a site-specific DNA binding domain of transcription activator-like effector (TALE) resulted in a further enhancement of gene editing efficiency. These results illustrate the potential of LHE enzymes as specific and efficient tools for therapeutic genome engineering. PMID:24682825

  11. A genome-wide association study on amyotrophic lateral sclerosis in the Taiwanese Han population.

    PubMed

    Chen, Chi-Jim; Chen, Chien-Ming; Pai, Tun-Wen; Chang, Hao-Teng; Hwang, Chi-Shin

    2016-06-01

    Identification of mutations in patients with amyotrophic lateral sclerosis (ALS) in a genome-wide association study can reveal possible biomarkers of such a rapidly progressive and fatal neurodegenerative disease. It was observed that significant single nucleotide polymorphisms vary when the tested population changes from one ethnic group to another. To identify new loci associated with ALS susceptibility in the Taiwanese Han population, we performed a genome-wide association study on 94 patients with sporadic ALS and 376 matched controls. We uncovered two new susceptibility loci at 13q14.3 (rs2785946) and 11q25 (rs11224052). In addition, we analyzed the functions of all the associated genes among 54 significant single nucleotide polymorphisms using Gene Ontology annotations, and the results showed several statistically significant neural- and muscle-related Gene Ontology terms and the associated diseases. PMID:26580837

  12. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma

    PubMed Central

    Chahal, Harvind S.; Wu, Wenting; Ransohoff, Katherine J.; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Hinds, David A.; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10−8, logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  13. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.

    PubMed

    Chahal, Harvind S; Wu, Wenting; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Hinds, David A; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  14. Using high-throughput genomics to study hepatitis C: what determines the outcome of infection?

    PubMed

    Walters, Kathie-Anne; Katze, Michael G

    2009-03-01

    High-throughput genomic methods are now being used to study a wide variety of viral diseases, in an effort to understand how host responses to infection can lead either to efficient elimination of the pathogen or the development of severe disease. This article reviews how gene expression studies are addressing important clinical issues related to hepatitis C virus infection, in which some 15-25% of infected individuals are able to clear the virus without treatment, while the remainder progress to chronic liver disease that can lead to cirrhosis and death. Similar methods are also being used in an effort to identify the mechanisms underlying the failure of some hepatitis C patients to respond to interferon-alpha/ribavirin therapy. By providing a detailed picture of virus-host interactions, high-throughput genomics could potentially lead to the identification of novel cellular targets for the treatment of hepatitis C. PMID:19135090

  15. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    SciTech Connect

    TIEDJE, JAMES M; KONSTANTINIDIS, KOSTAS; WORDEN, MARK

    2014-01-08

    The aim of the work reported is to study Shewanella population genomics, and to understand the evolution, ecophysiology, and speciation of Shewanella. The tasks supporting this aim are: to study genetic and ecophysiological bases defining the core and diversification of Shewanella species; to determine gene content patterns along redox gradients; and to Investigate the evolutionary processes, patterns and mechanisms of Shewanella.

  16. The ten years (2004-2014): Progress in peanut genetics and genomics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant breeding, genetics, and genomics play a critical role in sustainable agriculture specifically in improving crop productivity, quality, and resistance to pests and diseases. The germplasm collections have been treasures of crop genetic resources. Utilization of the collections of wild peanut sp...

  17. Developing genomics tools for the western corn rootworm - Progress and promise

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cooperative efforts among a number of interested scientists and institutions in the U.S. and Europe are being undertaken to expand genomics resources for the western corn rootworm (Diabrotica virgifera virgifera). Such resources include development of hundreds of single nucleotide polymorphism (SNP...

  18. Generating genomic tools for blueberry improvement -- an update of our progress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is increased demand for and consumption of blueberries worldwide because of their many recognized health benefits. Great strides have been made in blueberry cultivar development since its domestication using traditional breeding approaches. However, genomic tools are lacking in blueberry, whic...

  19. Genome-wide association study for longevity with whole-genome sequencing in 3 cattle breeds.

    PubMed

    Zhang, Qianqian; Guldbrandtsen, Bernt; Thomasen, Jørn Rind; Lund, Mogens Sandø; Sahana, Goutam

    2016-09-01

    Longevity is an important economic trait in dairy production. Improvements in longevity could increase the average number of lactations per cow, thereby affecting the profitability of the dairy cattle industry. Improved longevity for cows reduces the replacement cost of stock and enables animals to achieve the highest production period. Moreover, longevity is an indirect indicator of animal welfare. Using whole-genome sequencing variants in 3 dairy cattle breeds, we carried out an association study and identified 7 genomic regions in Holstein and 5 regions in Red Dairy Cattle that were associated with longevity. Meta-analyses of 3 breeds revealed 2 significant genomic regions, located on chromosomes 6 (META-CHR6-88MB) and 18 (META-CHR18-58MB). META-CHR6-88MB overlaps with 2 known genes: neuropeptide G-protein coupled receptor (NPFFR2; 89,052,210-89,059,348 bp) and vitamin D-binding protein precursor (GC; 88,695,940-88,739,180 bp). The NPFFR2 gene was previously identified as a candidate gene for mastitis resistance. META-CHR18-58MB overlaps with zinc finger protein 717 (ZNF717; 58,130,465-58,141,877 bp) and zinc finger protein 613 (ZNF613; 58,115,782-58,117,110 bp), which have been associated with calving difficulties. Information on longevity-associated genomic regions could be used to find causal genes/variants influencing longevity and exploited to improve the reliability of genomic prediction. PMID:27289149

  20. [Research progress on case-control study].

    PubMed

    Zhang, F F; Liu, Z D; Zhang, C X; Jiang, B F

    2016-04-10

    Several new varients related to the case-control designs have been developed in the recent decades, and this article briefly summarized four new designs: two-stage design, case-specular study, exposure-crossover study and case-case-time-control study. This paper involved principles of study design, requisites for application, advantages and disadvantages on all the studies. PMID:27087230

  1. Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient.

    PubMed

    Zondervan, Krina T; Rahmioglu, Nilufer; Morris, Andrew P; Nyholt, Dale R; Montgomery, Grant W; Becker, Christian M; Missmer, Stacey A

    2016-07-01

    Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments. PMID:27513026

  2. Accurate Computation of Survival Statistics in Genome-Wide Studies

    PubMed Central

    Vandin, Fabio; Papoutsaki, Alexandra; Raphael, Benjamin J.; Upfal, Eli

    2015-01-01

    A key challenge in genomics is to identify genetic variants that distinguish patients with different survival time following diagnosis or treatment. While the log-rank test is widely used for this purpose, nearly all implementations of the log-rank test rely on an asymptotic approximation that is not appropriate in many genomics applications. This is because: the two populations determined by a genetic variant may have very different sizes; and the evaluation of many possible variants demands highly accurate computation of very small p-values. We demonstrate this problem for cancer genomics data where the standard log-rank test leads to many false positive associations between somatic mutations and survival time. We develop and analyze a novel algorithm, Exact Log-rank Test (ExaLT), that accurately computes the p-value of the log-rank statistic under an exact distribution that is appropriate for any size populations. We demonstrate the advantages of ExaLT on data from published cancer genomics studies, finding significant differences from the reported p-values. We analyze somatic mutations in six cancer types from The Cancer Genome Atlas (TCGA), finding mutations with known association to survival as well as several novel associations. In contrast, standard implementations of the log-rank test report dozens-hundreds of likely false positive associations as more significant than these known associations. PMID:25950620

  3. Quality Control Procedures for Genome Wide Association Studies

    PubMed Central

    Turner, Stephen; Armstrong, Loren L.; Bradford, Yuki; Carlson, Christopher S.; Crawford, Dana C.; Crenshaw, Andrew T.; de Andrade, Mariza; Doheny, Kimberly F.; Haines, Jonathan L.; Hayes, Geoffrey; Jarvik, Gail; Jiang, Lan; Kullo, Iftikhar J.; Li, Rongling; Ling, Hua; Manolio, Teri A.; Matsumoto, Martha; McCarty, Catherine A.; McDavid, Andrew N.; Mirel, Daniel B.; Paschall, Justin E.; Pugh, Elizabeth W.; Rasmussen, Luke V.; Wilke, Russell A.; Zuvich, Rebecca L.; Ritchie, Marylyn D.

    2011-01-01

    Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of complex disease. The recent application of GWAS to clinic-based cohorts has also yielded genetic predictors of clinical outcomes. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. With each new dataset, new realities are discovered about GWAS data and best practices continue to be developed. The Genomics Workgroup of the National Human Genome Research Institute (NHGRI) funded electronic Medical Records and Genomics (eMERGE) network has invested considerable effort in developing strategies for QC of these data. The lessons learned by this group will be valuable for other investigators dealing with large scale genomic datasets. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the eMERGE network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. In this protocol we discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research. PMID:21234875

  4. Case-control association studies with matching and genomic controlling.

    PubMed

    Lee, Wen-Chung

    2004-07-01

    Family-based association studies have gained in popularity for mapping disease-susceptibility gene(s) of complex diseases. However, recruiting family controls is often more difficult than recruiting unrelated controls. The author proposes a case-control study, where the possible biases due to population stratification are controlled by matching in the design stage and by genomic controlling in the data-analytic stage. The matching is based on a set of "stratum-delineating variables," such as, race, ethnicity, nationality, ancestry, and birthplace; and the genomic controlling is based on typing a number of null markers across the genome and applying the principle of multiplicative scaling of chi-square distribution. It pays to match carefully to have a higher proportion of correctly matched sets, as computer simulation showed that this would increase the power of the study. If matching is crude, one loses power but still has the correct type I error rate after genomic controlling. Power studies showed that the numbers of affected subjects required for the pair-matched study are comparable to those required by the case-parents design, if the study was conducted in a homogeneous population. As the (control-to-case) matching ratio increases, the number of affected subjects required decreases. With matching ratio tending toward infinity, the number required shrinks roughly by half. The case-control study with matching and genomic controlling frees us from family bondage, and the genetic problem as complicated as mapping genes can now be studied using simple epidemiologic methods. PMID:15185398

  5. Genome-Wide Analysis of Copy Number Variation Identifies Candidate Gene Loci Associated with the Progression of Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Zain, Shamsul Mohd; Mohamed, Rosmawati; Cooper, David N.; Razali, Rozaimi; Rampal, Sanjay; Mahadeva, Sanjiv; Chan, Wah-Kheong; Anwar, Arif; Rosli, Nurul Shielawati Mohamed; Mahfudz, Anis Shafina; Cheah, Phaik-Leng; Basu, Roma Choudhury; Mohamed, Zahurin

    2014-01-01

    Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in ‘second hit’ hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH. PMID:24743702

  6. Genome-wide Association Study of Chicken Plumage Pigmentation.

    PubMed

    Park, Mi Na; Choi, Jin Ae; Lee, Kyung-Tai; Lee, Hyun-Jeong; Choi, Bong-Hwan; Kim, Heebal; Kim, Tae-Hun; Cho, Seoae; Lee, Taeheon

    2013-11-01

    To increase plumage color uniformity and understand the genetic background of Korean chickens, we performed a genome-wide association study of different plumage color in Korean native chickens. We analyzed 60K SNP chips on 279 chickens with GEMMA methods for GWAS and estimated the genetic heritability for plumage color. The estimated heritability suggests that plumage coloration is a polygenic trait. We found new loci associated with feather pigmentation at the genome-wide level and from the results infer that there are additional genetic effect for plumage color. The results will be used for selecting and breeding chicken for plumage color uniformity. PMID:25049737

  7. Population Genetics, Evolutionary Genomics, and Genome-Wide Studies of Malaria: A View across the International Centers of Excellence for Malaria Research

    PubMed Central

    Carlton, Jane M.; Volkman, Sarah K.; Uplekar, Swapna; Hupalo, Daniel N.; Alves, João Marcelo Pereira; Cui, Liwang; Donnelly, Martin; Roos, David S.; Harb, Omar S.; Acosta, Monica; Read, Andrew; Ribolla, Paulo E. M.; Singh, Om P.; Valecha, Neena; Wassmer, Samuel C.; Ferreira, Marcelo; Escalante, Ananias A.

    2015-01-01

    The study of the three protagonists in malaria—the Plasmodium parasite, the Anopheles mosquito, and the human host—is key to developing methods to control and eventually eliminate the disease. Genomic technologies, including the recent development of next-generation sequencing, enable interrogation of this triangle to an unprecedented level of scrutiny, and promise exciting progress toward real-time epidemiology studies and the study of evolutionary adaptation. We discuss the use of genomics by the International Centers of Excellence for Malaria Research, a network of field sites and laboratories in malaria-endemic countries that undertake cutting-edge research, training, and technology transfer in malarious countries of the world. PMID:26259940

  8. Case Study Evaluations: A Decade of Progress?

    ERIC Educational Resources Information Center

    Yin, Robert K.

    1997-01-01

    In the last 10 years, there has been increased use of case study methodology, with accompanying refinement and improvement of the methods. Case studies have become legitimate research methods in evaluation, but it is too soon to say whether improvements in methodology are really resulting in improvements in the case studies conducted. (SLD)

  9. EPA releases progress report on hydraulic fracturing study

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-01-01

    The U.S. Environmental Protection Agency (EPA) provided a 21 December progress report on its ongoing national study about the potential impacts of hydraulic fracturing on drinking water resources. The agency said that a draft of the congressionally requested study will be released in 2014 for public and peer review and that its progress report does not draw conclusions about the potential impacts of hydraulic fracturing, often referred to as fracking.

  10. Development and characterization of genomics resources for leafy spurge: A model perennial weed for functional genomics studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High throughput genomics approaches to study weed biology have so far been limited to a small number of research groups within the weed science community. In most cases, these groups have relied on heterologous approaches, since resources needed for functional genomics studies within desired species...

  11. Longitudinal whole genome analysis of pre and post drug treatment Mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.

    PubMed

    Datta, Gargi; Nieto, Luisa M; Davidson, Rebecca M; Mehaffy, Carolina; Pederson, Caroline; Dobos, Karen M; Strong, Michael

    2016-05-01

    Tuberculosis (TB) is one of the leading causes of death due to an infectious disease in the world. Understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant TB cases. We have analyzed three pairs of Mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. In the rifampicin resistant strain, we confirmed a mutation in rpoB (S450L) that is known to confer resistance to rifampicin. We discovered a novel L101R mutation in the katG gene of an isoniazid resistant strain, which may directly contribute to isoniazid resistance due to the proximity of the mutation to the katG isoniazid-activating site. Another isoniazid resistant strain had a rare mutation in the start codon of katG. We also identified a number of mutations in each longitudinal pair, such as toxin-antitoxin mutations that may influence the progression towards resistance or may play a role in compensatory fitness. These findings improve our knowledge of drug resistance progression during therapy and provide a methodology to monitor longitudinal strains using whole genome sequencing, polymorphism comparison, and functional annotation. PMID:27156618

  12. A super powerful method for genome wide association study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-Wide Association Studies shed light on the identification of genes underlying human diseases and agriculturally important traits. This potential has been shadowed by false positive findings. The Mixed Linear Model (MLM) method is flexible enough to simultaneously incorporate population struct...

  13. Listeria Genomics

    NASA Astrophysics Data System (ADS)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

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

  14. Studies in genetic discrimination. Final progress report

    SciTech Connect

    Not Available

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  15. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.

    PubMed

    McDonald, Karin R; Guise, Amanda J; Pourbozorgi-Langroudi, Parham; Cristea, Ileana M; Zakian, Virginia A; Capra, John A; Sabouri, Nasim

    2016-09-01

    Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry. Of the 621 high confidence Pfh1-binding sites in wild type cells, about 40% were sites of fork slowing (as marked by high DNA polymerase occupancy) and/or DNA damage (as marked by high levels of phosphorylated H2A). The replication and integrity of tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and nucleosome depleted regions were particularly Pfh1-dependent. The association of Pfh1 with genomic integrity at highly transcribed genes was S phase dependent, and thus unlikely to be an artifact of high transcription rates. Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase. Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites. These data

  16. Recent Progress in Presolar Grain Studies

    PubMed Central

    Amari, Sachiko

    2014-01-01

    Presolar grains are stardust that condensed in stellar outflows or stellar ejecta, and was incorporated in meteorites. They remain mostly intact throughout the journey from stars to the earth, keeping information of their birthplaces. Studies of presolar grains, which started in 1987, have produced a wealth of information about nucleosynthesis in stars, mixing in stellar ejecta, and temporal variations of isotopic and elemental abundances in the Galaxy. Recent instrumental advancements in secondary ion mass spectrometry (SIMS) brought about the identification of presolar silicate grains. Isotopic and mineralogical investigations of sub-μm grains have been performed using a combination of SIMS, transmission electron microscopy (TEM) and focused ion beam (FIB) techniques. Two instruments have been developed to study even smaller grains (∼50 nm) and measure isotopes and elements of lower abundances than those in previous studies. PMID:26819886

  17. Recent Progress in Presolar Grain Studies.

    PubMed

    Amari, Sachiko

    2014-01-01

    Presolar grains are stardust that condensed in stellar outflows or stellar ejecta, and was incorporated in meteorites. They remain mostly intact throughout the journey from stars to the earth, keeping information of their birthplaces. Studies of presolar grains, which started in 1987, have produced a wealth of information about nucleosynthesis in stars, mixing in stellar ejecta, and temporal variations of isotopic and elemental abundances in the Galaxy. Recent instrumental advancements in secondary ion mass spectrometry (SIMS) brought about the identification of presolar silicate grains. Isotopic and mineralogical investigations of sub-μm grains have been performed using a combination of SIMS, transmission electron microscopy (TEM) and focused ion beam (FIB) techniques. Two instruments have been developed to study even smaller grains (∼50 nm) and measure isotopes and elements of lower abundances than those in previous studies. PMID:26819886

  18. Coordination: Southeast Continental Shelf studies. Progress report

    SciTech Connect

    Menzel, D.W.

    1981-02-01

    An overview of the Oceanograhic Program of Skidaway Institute of Oceanograhy is presented. Included are the current five year plan for studies of the Southeast Continental Shelf, a summary of research accomplishments, proposed research for 1981-1982, current status of the Savannah Navigational Light Tower, and a list of publications. (ACR)

  19. The Human Genome Project and Mental Retardation: An Educational Program. Final Progress Report

    SciTech Connect

    Davis, Sharon

    1999-05-03

    The Arc, a national organization on mental retardation, conducted an educational program for members, many of whom have a family member with a genetic condition causing mental retardation. The project informed members about the Human Genome scientific efforts, conducted training regarding ethical, legal and social implications and involved members in issue discussions. Short reports and fact sheets on genetic and ELSI topics were disseminated to 2,200 of the Arc's leaders across the country and to other interested individuals. Materials produced by the project can e found on the Arc's web site, TheArc.org.

  20. Elucidation and pharmacological targeting of novel molecular drivers of follicular lymphoma progression | Office of Cancer Genomics

    Cancer.gov

    Follicular lymphoma (FL), the most common indolent subtype of non-Hodgkin's lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, in 20-60% of FL patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of FL transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases.

  1. ICPP water inventory study progress report

    SciTech Connect

    Richards, B.T.

    1993-05-01

    Recent data from the Idaho Chemical Processing Plant (ICPP) indicate that water is entering the sumps located in the bottom of Tank Firm Vaults in quantities that exceed expected levels. In addition, perched water body(s) exist beneath the northern portion of the ICPP. Questions have been raised concerning the origin of water entering the Tank Farm sumps and the recharge sources for the perched water bodies. Therefore, in an effort to determine the source of water, a project has been initiated to identify the source of water for Tank Farm sumps and the perched water bodies. In addition, an accurate water balance for the ICPP will be developed. The purpose of this report is to present the specific results and conclusions for the ICPP water balance portion of the study. In addition, the status of the other activities being conducted as part of study, along with the associated action plans, is provided.

  2. Progress report on nuclear spectroscopic studies

    SciTech Connect

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1994-02-18

    The Nuclear Physics group at the University of Tennessee, Knoxville (UTK) is involved in several aspects of heavy-ion physics including both nuclear structure and reaction mechanisms. While the main emphasis is on experimental problems, the authors have maintained a strong collaboration with several theorists in order to best pursue the physics of their measurements. During the last year they have had several experiments at the ATLAS at Argonne National Laboratory, the GAMMASPHERE at the LBL 88 Cyclotron, and with the NORDBALL at the Niels Bohr Institute Tandem. Also, they continue to be very active in the WA93/98 collaboration studying ultra-relativistic heavy ion physics utilizing the SPS accelerator at CERN in Geneva, Switzerland and in the PHENIX Collaboration at the RHIC accelerator under construction at Brookhaven National Laboratory. During the last year their experimental work has been in three broad areas: (1) the structure of nuclei at high angular momentum, (2) the structure of nuclei far from stability, and (3) ultra-relativistic heavy-ion physics. The results of studies in these particular areas are described in this document. These studies concentrate on the structure of nuclear matter in extreme conditions of rotational motion, imbalance of neutrons and protons, or very high temperature and density. Another area of research is heavy-ion-induced transfer reactions, which utilize the transfer of nucleons to states with high angular momentum to learn about their structure and to understand the transfer of particles, energy, and angular momentum in collisions between heavy ions.

  3. [Laser enhanced chemical reaction studies]. [Progress report

    SciTech Connect

    Not Available

    1992-04-01

    Experimental studies of dynamic molecular processes are described with particular emphasis on the use of a powerful infrared diode laser probe technique developed in our laboratory. This technique allows us to determine the final states of CO{sub 2} (and other molecules) produced by collisions, photofragmentation, or chemical reactions with a spectral resolution of 0.0003 cm{sup {minus}1} and a time resolution of 10{sup {minus}7} sec. Such high spectral resolution provides a detailed picture of the vibrational and rotational states of molecules produced by these dynamic events. We have used this experimental method to probe collisions between hot hydrogen/deuterium atoms and CO{sub 2}, between O({sup 1}D) atoms and CO{sub 2}, to study the final states of DC1 molecules produced as a result of the reactions of hot Cl atoms, and to investigate the dynamics of the reaction between OH and CO molecules. Advances in our techniques over the past two years have allowed us to identify and study more than 200 final rotational states in ten different vibrational levels of CO{sub 2} encompassing all 3 normal modes, many overtones, and combination states of the molecule. We have extended the technique to probe a variety of new molecules such as OCS, N{sub 2}O, DCl, and CS{sub 2}. All of this work is aimed at providing experimental tests for polyatomic molecule potential energy surfaces, chemical transition states in complex systems, and theories of reaction dynamic in molecules with more than 3 atoms.

  4. Improving livestock for agriculture - technological progress from random transgenesis to precision genome editing heralds a new era.

    PubMed

    Laible, Götz; Wei, Jingwei; Wagner, Stefan

    2015-01-01

    Humans have a long history in shaping the genetic makeup of livestock to optimize production and meet growing human demands for food and other animal products. Until recently, this has only been possible through traditional breeding and selection, which is a painstakingly slow process of accumulating incremental gains over a long period. The development of transgenic livestock technology offers a more direct approach with the possibility for making genetic improvements with greater impact and within a single generation. However, initially the technology was hampered by technical difficulties and limitations, which have now largely been overcome by progressive improvements over the past 30 years. Particularly, the advent of genome editing in combination with homologous recombination has added a new level of efficiency and precision that holds much promise for the genetic improvement of livestock using the increasing knowledge of the phenotypic impact of genetic sequence variants. So far not a single line of transgenic livestock has gained approval for commercialization. The step change to genome-edited livestock with precise sequence changes may accelerate the path to market, provided applications of this new technology for agriculture can deliver, in addition to economic incentives for producers, also compelling benefits for animals, consumers, and the environment. PMID:25515661

  5. Human genome research and the public interest: Progress notes from an American Science Policy Experiment

    SciTech Connect

    Juengst, E.T. )

    1994-01-01

    This essay reviews the efforts of the US Human Genome Project to anticipate and address the ethical, legal, and social implications of new advances in human genetics. Since 1990, approximately $10 million has been awarded by the National Institutes of Health and the DOE, in support of 65 research, education, and public discussion projects. These projects address four major areas of need: (1) the need for both client-centered assessments of new genetic services and for improved knowledge of the psychosocial and ethnocultural factors that shape clients' clinical genetic experiences; (2) the need for clear professional policies regarding human-subject research, clinical practical standards, and public health goals in human genetics; (3) the need for social policy protection against unfair access to and use of personal genetic information; (4) the need for improved public and professional understanding and discussion of these issues. The Human Genome Project's goal is to have defined, by 1995, policy options and programs capable of addressing these needs. 47 refs.

  6. Progress report on nuclear spectroscopic studies

    SciTech Connect

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.

    1996-01-16

    The experimental program in nuclear physics at the University of Tennessee, Knoxville, is led by Professors Carrol Bingham, Lee Riedinger, and Soren Sorenseni who respectively lead the studies of the exotic decay modes of nuclei far from stability, the program of high-spin research, and our effort in relativistic heavy-ion physics. Over the years, this broad program of research has been successful partially because of the shared University resources applied to this group effort. The proximity of the Oak Ridge National Laboratory has allowed us to build extremely strong programs of joint research, and in addition to play an important leadership role in the Joint Institute for Heavy Ion Research (JIHIR). Our experimental program is also very closely linked with those at other national laboratories: Argonne (collaborations involving the Fragment Mass Analyzer (FMA) and {gamma}-ray arrays), Brookhaven (the RHIC and Phenix projects), and Berkeley (GAMMASPHERE). We have worked closely with a variety of university groups in the last three years, especially those in the UNISOR and now UNIRIB collaborations. And, in all aspects of our program, we have maintained close collaborations with theorists, both to inspire the most exciting experiments to perform and to extract the pertinent physics from the results. The specific areas discussed in this report are: properties of high-spin states; study of low-energy levels of nuclei far from stability; and high energy heavy-ion physics.

  7. Insights into kidney diseases from genome-wide association studies.

    PubMed

    Wuttke, Matthias; Köttgen, Anna

    2016-09-01

    Over the past decade, genome-wide association studies (GWAS) have considerably improved our understanding of the genetic basis of kidney function and disease. Population-based studies, used to investigate traits that define chronic kidney disease (CKD), have identified >50 genomic regions in which common genetic variants associate with estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Case-control studies, used to study specific CKD aetiologies, have yielded risk loci for specific kidney diseases such as IgA nephropathy and membranous nephropathy. In this Review, we summarize important findings from GWAS and clinical and experimental follow-up studies. We also compare risk allele frequency, effect sizes, and specificity in GWAS of CKD-defining traits and GWAS of specific CKD aetiologies and the implications for study design. Genomic regions identified in GWAS of CKD-defining traits can contain causal genes for monogenic kidney diseases. Population-based research on kidney function traits can therefore generate insights into more severe forms of kidney diseases. Experimental follow-up studies have begun to identify causal genes and variants, which are potential therapeutic targets, and suggest mechanisms underlying the high allele frequency of causal variants. GWAS are thus a useful approach to advance knowledge in nephrology. PMID:27477491

  8. Automated quality control for genome wide association studies

    PubMed Central

    Ellingson, Sally R.; Fardo, David W.

    2016-01-01

    This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.

  9. Genomic Comparative Study of Bovine Mastitis Escherichia coli

    PubMed Central

    Kempf, Florent; Slugocki, Cindy; Blum, Shlomo E.; Leitner, Gabriel; Germon, Pierre

    2016-01-01

    Escherichia coli, one of the main causative agents of bovine mastitis, is responsible for significant losses on dairy farms. In order to better understand the pathogenicity of E. coli mastitis, an accurate characterization of E. coli strains isolated from mastitis cases is required. By using phylogenetic analyses and whole genome comparison of 5 currently available mastitis E. coli genome sequences, we searched for genotypic traits specific for mastitis isolates. Our data confirm that there is a bias in the distribution of mastitis isolates in the different phylogenetic groups of the E. coli species, with the majority of strains belonging to phylogenetic groups A and B1. An interesting feature is that clustering of strains based on their accessory genome is very similar to that obtained using the core genome. This finding illustrates the fact that phenotypic properties of strains from different phylogroups are likely to be different. As a consequence, it is possible that different strategies could be used by mastitis isolates of different phylogroups to trigger mastitis. Our results indicate that mastitis E. coli isolates analyzed in this study carry very few of the virulence genes described in other pathogenic E. coli strains. A more detailed analysis of the presence/absence of genes involved in LPS synthesis, iron acquisition and type 6 secretion systems did not uncover specific properties of mastitis isolates. Altogether, these results indicate that mastitis E. coli isolates are rather characterized by a lack of bona fide currently described virulence genes. PMID:26809117

  10. Genome-wide association study identifies five new schizophrenia loci

    PubMed Central

    2012-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9). PMID:21926974

  11. [Strategies of the study on herb genome program].

    PubMed

    Chen, Shi-lin; Sun, Yong-zhen; Xu, Jiang; Luo, Hong-mei; Sun, Chao; He, Liu; Cheng, Xiang-lin; Zhang, Bo-li; Xiao, Pei-gen

    2010-07-01

    Herb Genome Program (HerbGP) includes a series of projects on whole genome sequencing (WGS) and post-genomics research of medicinal plants with unique secondary metabolism pathways or/and those of great medical and pharmaceutical importance. In this paper, we systematically discussed the strategy of HerbGP, from species selection, whole-genome sequencing, assembly and bioinformatics analysis, to postgenomics research. HerbGP will push study on Chinese traditional medicines into the front field of life science, by selecting a series of plants with unique secondary metabolism pathways as models and introducing "omics" methods into the research of these medicinal plants. HerbGP will provide great opportunities for China to be the leader in the basic research field of traditional Chinese medicine. HerbGP shall also have significant impacts on the R&D of natural medicines and the development of medicinal farming by analysis of secondary metabolic pathways and selection of cultivars with good agricultural traits. PMID:20931775

  12. Evaluation of the National Assessment of Educational Progress. Study Reports

    ERIC Educational Resources Information Center

    Buckendahl, Chad W.; Davis, Susan L.; Plake, Barbara S.; Sireci, Stephen G.; Hambleton, Ronald K.; Zenisky, April L.; Wells, Craig S.

    2009-01-01

    The "Evaluation of the National Assessment of Educational Progress: Study Reports" describes the special studies that comprised the design of the evaluation. In the Final Report, the authors presented a practical discussion of the evaluation studies to its primary, intended audience, namely policymakers. On this accompanying CD, readers will find…

  13. A Genome-Wide Association Study of Depressive Symptoms

    PubMed Central

    Cornelis, Marilyn C.; Amin, Najaf; Bakshis, Erin; Baumert, Jens; Ding, Jingzhong; Liu, Yongmei; Marciante, Kristin; Meirelles, Osorio; Nalls, Michael A.; Sun, Yan V.; Vogelzangs, Nicole; Yu, Lei; Bandinelli, Stefania; Benjamin, Emelia J.; Bennett, David A.; Boomsma, Dorret; Cannas, Alessandra; Coker, Laura H.; de Geus, Eco; De Jager, Philip L.; Diez-Roux, Ana V.; Purcell, Shaun; Hu, Frank B.; Rimma, Eric B.; Hunter, David J.; Jensen, Majken K.; Curhan, Gary; Rice, Kenneth; Penman, Alan D.; Rotter, Jerome I.; Sotoodehnia, Nona; Emeny, Rebecca; Eriksson, Johan G.; Evans, Denis A.; Ferrucci, Luigi; Fornage, Myriam; Gudnason, Vilmundur; Hofman, Albert; Illig, Thomas; Kardia, Sharon; Kelly-Hayes, Margaret; Koenen, Karestan; Kraft, Peter; Kuningas, Maris; Massaro, Joseph M.; Melzer, David; Mulas, Antonella; Mulder, Cornelis L.; Murray, Anna; Oostra, Ben A.; Palotie, Aarno; Penninx, Brenda; Petersmann, Astrid; Pilling, Luke C.; Psaty, Bruce; Rawal, Rajesh; Reiman, Eric M.; Schulz, Andrea; Shulman, Joshua M.; Singleton, Andrew B.; Smith, Albert V.; Sutin, Angelina R.; Uitterlinden, André G.; Völzke, Henry; Widen, Elisabeth; Yaffe, Kristine; Zonderman, Alan B.; Cucca, Francesco; Harris, Tamara; Ladwig, Karl-Heinz; Llewellyn, David J.; Räikkönen, Katri; Tanaka, Toshiko

    2013-01-01

    Background Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 × 10−5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 × 10−7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 × 10−3). This 5q21 region reached genome-wide significance (p = 4.78 × 10−8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. PMID:23290196

  14. [Research progress in the third-generation genomic editing technology - CRISPR/Cas9].

    PubMed

    Zhou, Yalan; Zong, Yanan; Kong, Xiangdong

    2016-10-01

    CRISPR/Cas9 technology originated from type II CRISPR/Cas system, which is widely found in bacteria and equips them with acquired immunity against viruses and plasmids. CRISPR-associated protein Cas9 is a RNA-guided endonuclease, which can efficiently introduce double-strand breaks at specific sites and activate homologous recombination and/or non-homologous end joining mechanism for the repair of impaired DNA. Features such as easy-to-use, cost-effectiveness, multiple targeting ability have made it the third-generation genomic engineering tool following ZFNs and TALENs. Here the history of discovery and molecular mechanism of the CRISPR/Cas9 technology are reviewed. The rapid advance in its various applications, especially for the treatment of human genetic disorders, as well as some concomitant problems are discussed. PMID:27577230

  15. New study reveals relatively few mutations in AML genomes - TCGA

    Cancer.gov

    Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

  16. Resources for Functional Genomics Studies in Drosophila melanogaster

    PubMed Central

    Mohr, Stephanie E.; Hu, Yanhui; Kim, Kevin; Housden, Benjamin E.; Perrimon, Norbert

    2014-01-01

    Drosophila melanogaster has become a system of choice for functional genomic studies. Many resources, including online databases and software tools, are now available to support design or identification of relevant fly stocks and reagents or analysis and mining of existing functional genomic, transcriptomic, proteomic, etc. datasets. These include large community collections of fly stocks and plasmid clones, “meta” information sites like FlyBase and FlyMine, and an increasing number of more specialized reagents, databases, and online tools. Here, we introduce key resources useful to plan large-scale functional genomics studies in Drosophila and to analyze, integrate, and mine the results of those studies in ways that facilitate identification of highest-confidence results and generation of new hypotheses. We also discuss ways in which existing resources can be used and might be improved and suggest a few areas of future development that would further support large- and small-scale studies in Drosophila and facilitate use of Drosophila information by the research community more generally. PMID:24653003

  17. Big data challenges in bone research: genome-wide association studies and next-generation sequencing

    PubMed Central

    Alonso, Nerea; Lucas, Gavin; Hysi, Pirro

    2015-01-01

    Genome-wide association studies (GWAS) have been developed as a practical method to identify genetic loci associated with disease by scanning multiple markers across the genome. Significant advances in the genetics of complex diseases have been made owing to advances in genotyping technologies, the progress of projects such as HapMap and 1000G and the emergence of genetics as a collaborative discipline. Because of its great potential to be used in parallel by multiple collaborators, it is important to adhere to strict protocols assuring data quality and analyses. Quality control analyses must be applied to each sample and each single-nucleotide polymorphism (SNP). The software package PLINK is capable of performing the whole range of necessary quality control tests. Genotype imputation has also been developed to substantially increase the power of GWAS methodology. Imputation permits the investigation of associations at genetic markers that are not directly genotyped. Results of individual GWAS reports can be combined through meta-analysis. Finally, next-generation sequencing (NGS) has gained popularity in recent years through its capacity to analyse a much greater number of markers across the genome. Although NGS platforms are capable of examining a higher number of SNPs compared with GWA studies, the results obtained by NGS require careful interpretation, as their biological correlation is incompletely understood. In this article, we will discuss the basic features of such protocols. PMID:25709812

  18. Social Studies Progress Monitoring and Intervention for Middle School Students

    ERIC Educational Resources Information Center

    Beyers, Sarah J.; Lembke, Erica S.; Curs, Bradley

    2013-01-01

    This study examined the technical adequacy of vocabulary-matching curriculum-based measurement (CBM) to identify and monitor the progress of 148 middle school students in social studies. In addition, the effectiveness of a reading comprehension intervention, Collaborative Strategic Reading (Klingner, Vaughn, Dimino, Schumm, & Bryant, 2001),…

  19. Unclassified renal cell carcinoma: a clinicopathological, comparative genomic hybridization, and whole-genome exon sequencing study

    PubMed Central

    Hu, Zhen-Yan; Pang, Li-Juan; Qi, Yan; Kang, Xue-Ling; Hu, Jian-Ming; Wang, Lianghai; Liu, Kun-Peng; Ren, Yuan; Cui, Mei; Song, Li-Li; Li, Hong-An; Zou, Hong; Li, Feng

    2014-01-01

    Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for only 3-5% of all cases. Studies on the molecular genetics of URCC are limited, and hence, we report on 2 cases of URCC analyzed using comparative genome hybridization (CGH) and the genome-wide human exon GeneChip technique to identify the genomic alterations of URCC. Both URCC patients (mean age, 72 years) presented at an advanced stage and died within 30 months post-surgery. Histologically, the URCCs were composed of undifferentiated, multinucleated, giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC cases had strong p53 protein expression and partial expression of cluster of differentiation-10 and cytokeratin. The CGH profiles showed chromosomal imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12-13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p. Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC tissues, including 32 missense and 8 silent mutations. Functional enrichment analysis revealed that the missense mutation genes were involved in 11 different biological processes and pathways, including cell cycle regulation, lipid localization and transport, neuropeptide signaling, organic ether metabolism, and ATP-binding cassette transporter signaling. Our findings indicate that URCC may be a highly aggressive cancer, and the genetic alterations identified herein may provide clues regarding the tumorigenesis of URCC and serve as a basis for the development of targeted therapies against URCC in the future. PMID:25120763

  20. Common Variants Confer Susceptibility to Barrett's Esophagus: Insights from the First Genome-Wide Association Studies.

    PubMed

    Palles, Claire; Findlay, John M; Tomlinson, Ian

    2016-01-01

    Eight loci have been identified by the two genome-wide association studies of Barrett's esophagus that have been conducted to date. Esophageal adenocarcinoma cases were included in the second study following evidence that predisposing genetic variants for this cancer overlap with those for Barrett's esophagus. Genes with roles in embryonic development of the foregut are adjacent to 6 of the loci identified (FOXF1, BARX1, FOXP1, GDF7, TBX5, and ALDH1A2). An additional locus maps to a gene with known oncogenic potential (CREB-regulated transcription coactivator 1), but expression quantitative trait data implicates yet another gene involved in esophageal development (PBX4). These results strongly support a model whereby dysregulation of genes involved in esophageal and thoracic development increases susceptibility to Barrett's esophagus and esophageal adenocarcinoma, probably by reducing anatomical antireflux mechanisms. An additional signal at 6p21 in the major histocompatibility complex also reinforces evidence that immune and inflammatory response to reflux is involved in the development of both diseases. All of the variants identified are intronic or intergenic rather than coding and are presumed to be or to mark regulatory variants. As with genome-wide association studies of other diseases, the functional variants at each locus are yet to be identified and the genes affected need confirming. In this chapter as well as discussing the biology behind each genome-wide association signal, we review the requirements for successfully conducting genome-wide association studies and discuss how progress in understanding the genetic variants that contribute to Barrett's esophagus/esophageal adenocarcinoma susceptibility compares to other cancers. PMID:27573776

  1. A Pooled Genome-Wide Association Study of Asperger Syndrome

    PubMed Central

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E.; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision. PMID:26176695

  2. Genome-wide association studies in diverse populations

    PubMed Central

    Rosenberg, Noah A; Huang, Lucy; Jewett, Ethan M; Szpiech, Zachary A; Jankovic, Ivana; Boehnke, Michael

    2011-01-01

    Genome-wide association (GWA) studies have identified a large number of single-nucleotide polymorphisms (SNPs) associated with disease phenotypes. As most GWA studies have been performed primarily in populations of European descent, this review examines the issues involved in extending consideration of GWA studies to diverse worldwide populations. Although challenges exist with such issues as imputation, admixture, and replication, investigation of diverse populations in GWA studies has significant potential to advance the project of mapping the genetic determinants of complex diseases for the human population as a whole. PMID:20395969

  3. The application of genome editing in studying hearing loss.

    PubMed

    Zou, Bing; Mittal, Rahul; Grati, M'hamed; Lu, Zhongmin; Shu, Yilai; Tao, Yong; Feng, Youg; Xie, Dinghua; Kong, Weijia; Yang, Shiming; Chen, Zheng-Yi; Liu, Xuezhong

    2015-09-01

    Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss. PMID:25987504

  4. Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure

    SciTech Connect

    Huang Shing; Chueh Pinju; Lin Yunwei; Shih Tungsheng; Chuang Showmei

    2009-12-01

    Titanium dioxide (TiO2) nano-particles (< 100 nm in diameter) have been of interest in a wide range of applications, such as in cosmetics and pharmaceuticals because of their low toxicity. However, recent studies have shown that TiO2 nano-particles (nano-TiO2) induce cytotoxicity and genotoxicity in various lines of cultured cells as well as tumorigenesis in animal models. The biological roles of nano-TiO2 are shown to be controversial and no comprehensive study paradigm has been developed to investigate their molecular mechanisms. In this study, we showed that short-term exposure to nano-TiO2 enhanced cell proliferation, survival, ERK signaling activation and ROS production in cultured fibroblast cells. Moreover, long-term exposure to nano-TiO2 not only increased cell survival and growth on soft agar but also the numbers of multinucleated cells and micronucleus (MN) as suggested in confocal microscopy analysis. Cell cycle phase analysis showed G2/M delay and slower cell division in long-term exposed cells. Most importantly, long-term TiO2 exposure remarkably affected mitotic progression at anaphase and telophase leading to aberrant multipolar spindles and chromatin alignment/segregation. Moreover, PLK1 was demonstrated as the target for nano-TiO2 in the regulation of mitotic progression and exit. Notably, a higher fraction of sub-G1 phase population appeared in TiO2-exposed cells after releasing from G2/M synchronization. Our results demonstrate that long-term exposure to nano-TiO2 disturbs cell cycle progression and duplicated genome segregation, leading to chromosomal instability and cell transformation.

  5. Genome-Scale Studies of Aging: Challenges and Opportunities

    PubMed Central

    McCormick, Mark A; Kennedy, Brian K

    2012-01-01

    Whole-genome studies involving a phenotype of interest are increasingly prevalent, in part due to a dramatic increase in speed at which many high throughput technologies can be performed coupled to simultaneous decreases in cost. This type of genome-scale methodology has been applied to the phenotype of lifespan, as well as to whole-transcriptome changes during the aging process or in mutants affecting aging. The value of high throughput discovery-based science in this field is clearly evident, but will it yield a true systems-level understanding of the aging process? Here we review some of this work to date, focusing on recent findings and the unanswered puzzles to which they point. In this context, we also discuss recent technological advances and some of the likely future directions that they portend. PMID:23633910

  6. Quality control procedures for genome-wide association studies.

    PubMed

    Turner, Stephen; Armstrong, Loren L; Bradford, Yuki; Carlson, Christopher S; Crawford, Dana C; Crenshaw, Andrew T; de Andrade, Mariza; Doheny, Kimberly F; Haines, Jonathan L; Hayes, Geoffrey; Jarvik, Gail; Jiang, Lan; Kullo, Iftikhar J; Li, Rongling; Ling, Hua; Manolio, Teri A; Matsumoto, Martha; McCarty, Catherine A; McDavid, Andrew N; Mirel, Daniel B; Paschall, Justin E; Pugh, Elizabeth W; Rasmussen, Luke V; Wilke, Russell A; Zuvich, Rebecca L; Ritchie, Marylyn D

    2011-01-01

    Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of complex disease. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the electronic MEdical Records and Genomics (eMERGE) network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research. PMID:21234875

  7. Progress in the Laboratory Study of Interstellar Analogs

    NASA Technical Reports Server (NTRS)

    Salama, Farid; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    Recent progress in the laboratory study of cosmic carbon analogs will be discussed. After a brief review of the history of laboratory studies of interstellar carbon molecules and ions, new gas-phase results will be discussed and contrasted to previous studies that used the techniques of matrix isolation spectroscopy. Finally, the impact of these new laboratory studies on the field of astrophysics will be discussed.

  8. Multiple Hypotheses Testing Procedures in Clinical Trials and Genomic Studies

    PubMed Central

    Pan, Qing

    2013-01-01

    We review and compare multiple hypothesis testing procedures used in clinical trials and those in genomic studies. Clinical trials often employ global tests, which draw an overall conclusion for all the hypotheses, such as SUM test, Two-Step test, Approximate Likelihood Ratio test (ALRT), Intersection-Union Test (IUT), and MAX test. The SUM and Two-Step tests are most powerful under homogeneous treatment effects, while the ALRT and MAX test are robust in cases with non-homogeneous treatment effects. Furthermore, the ALRT is robust to unequal sample sizes in testing different hypotheses. In genomic studies, stepwise procedures are used to draw marker-specific conclusions and control family wise error rate (FWER) or false discovery rate (FDR). FDR refers to the percent of false positives among all significant results and is preferred over FWER in screening high-dimensional genomic markers due to its interpretability. In cases where correlations between test statistics cannot be ignored, Westfall-Young resampling method generates the joint distribution of P-values under the null and maintains their correlation structure. Finally, the GWAS data from a clinical trial searching for SNPs associated with nephropathy among Type 1 diabetic patients are used to illustrate various procedures. PMID:24350232

  9. A Genome-Wide Association Study of Aging

    PubMed Central

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W.; Garcia, Melissa E.; Kaplan, Robert C.; Kumari, Meena; Lunetta, Kathryn L.; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J.; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J.; Biffar, Reiner; Buchman, Aron S.; Boerwinkle, Eric; Couper, David; De Jager, Philip L.; Evans, Denis A.; Harris, Tamara B.; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P.; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J.; Lohman, Kurt K.; Lutsey, Pamela L.; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M.; Reiman, Eric M.; Rotter, Jerome I.; Seshadri, Sudha; Shardell, Michelle D.; Smith, Albert V.; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M. Carola; Bandinelli, Stefania; Baumeister, Sebastian E.; Bennett, David A.; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M.; Newman, Anne B.; Tiemeier, Henning; Franceschini, Nora

    2011-01-01

    Human longevity and healthy aging show moderate heritability (20–50%). We conducted a meta-analysis of genome-wide association studies from nine studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for two outcomes: a) all-cause mortality and b) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found fourteen independent SNPs that predicted risk of death, and eight SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer’s disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity. PMID:21782286

  10. Genome-wide association study of Tourette's syndrome.

    PubMed

    Scharf, J M; Yu, D; Mathews, C A; Neale, B M; Stewart, S E; Fagerness, J A; Evans, P; Gamazon, E; Edlund, C K; Service, S K; Tikhomirov, A; Osiecki, L; Illmann, C; Pluzhnikov, A; Konkashbaev, A; Davis, L K; Han, B; Crane, J; Moorjani, P; Crenshaw, A T; Parkin, M A; Reus, V I; Lowe, T L; Rangel-Lugo, M; Chouinard, S; Dion, Y; Girard, S; Cath, D C; Smit, J H; King, R A; Fernandez, T V; Leckman, J F; Kidd, K K; Kidd, J R; Pakstis, A J; State, M W; Herrera, L D; Romero, R; Fournier, E; Sandor, P; Barr, C L; Phan, N; Gross-Tsur, V; Benarroch, F; Pollak, Y; Budman, C L; Bruun, R D; Erenberg, G; Naarden, A L; Lee, P C; Weiss, N; Kremeyer, B; Berrío, G B; Campbell, D D; Cardona Silgado, J C; Ochoa, W C; Mesa Restrepo, S C; Muller, H; Valencia Duarte, A V; Lyon, G J; Leppert, M; Morgan, J; Weiss, R; Grados, M A; Anderson, K; Davarya, S; Singer, H; Walkup, J; Jankovic, J; Tischfield, J A; Heiman, G A; Gilbert, D L; Hoekstra, P J; Robertson, M M; Kurlan, R; Liu, C; Gibbs, J R; Singleton, A; Hardy, J; Strengman, E; Ophoff, R A; Wagner, M; Moessner, R; Mirel, D B; Posthuma, D; Sabatti, C; Eskin, E; Conti, D V; Knowles, J A; Ruiz-Linares, A; Rouleau, G A; Purcell, S; Heutink, P; Oostra, B A; McMahon, W M; Freimer, N B; Cox, N J; Pauls, D L

    2013-06-01

    Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  11. Genome-wide association study of Tourette Syndrome

    PubMed Central

    Scharf, Jeremiah M.; Yu, Dongmei; Mathews, Carol A.; Neale, Benjamin M.; Stewart, S. Evelyn; Fagerness, Jesen A; Evans, Patrick; Gamazon, Eric; Edlund, Christopher K.; Service, Susan; Tikhomirov, Anna; Osiecki, Lisa; Illmann, Cornelia; Pluzhnikov, Anna; Konkashbaev, Anuar; Davis, Lea K; Han, Buhm; Crane, Jacquelyn; Moorjani, Priya; Crenshaw, Andrew T.; Parkin, Melissa A.; Reus, Victor I.; Lowe, Thomas L.; Rangel-Lugo, Martha; Chouinard, Sylvain; Dion, Yves; Girard, Simon; Cath, Danielle C; Smit, Jan H; King, Robert A.; Fernandez, Thomas; Leckman, James F.; Kidd, Kenneth K.; Kidd, Judith R.; Pakstis, Andrew J.; State, Matthew; Herrera, Luis Diego; Romero, Roxana; Fournier, Eduardo; Sandor, Paul; Barr, Cathy L; Phan, Nam; Gross-Tsur, Varda; Benarroch, Fortu; Pollak, Yehuda; Budman, Cathy L.; Bruun, Ruth D.; Erenberg, Gerald; Naarden, Allan L; Lee, Paul C; Weiss, Nicholas; Kremeyer, Barbara; Berrío, Gabriel Bedoya; Campbell, Desmond; Silgado, Julio C. Cardona; Ochoa, William Cornejo; Restrepo, Sandra C. Mesa; Muller, Heike; Duarte, Ana V. Valencia; Lyon, Gholson J; Leppert, Mark; Morgan, Jubel; Weiss, Robert; Grados, Marco A.; Anderson, Kelley; Davarya, Sarah; Singer, Harvey; Walkup, John; Jankovic, Joseph; Tischfield, Jay A.; Heiman, Gary A.; Gilbert, Donald L.; Hoekstra, Pieter J.; Robertson, Mary M.; Kurlan, Roger; Liu, Chunyu; Gibbs, J. Raphael; Singleton, Andrew; Hardy, John; Strengman, Eric; Ophoff, Roel; Wagner, Michael; Moessner, Rainald; Mirel, Daniel B.; Posthuma, Danielle; Sabatti, Chiara; Eskin, Eleazar; Conti, David V.; Knowles, James A.; Ruiz-Linares, Andres; Rouleau, Guy A.; Purcell, Shaun; Heutink, Peter; Oostra, Ben A.; McMahon, William; Freimer, Nelson; Cox, Nancy J.; Pauls, David L.

    2012-01-01

    Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  12. Genome-wide gene-based association study.

    PubMed

    Yang, Hsin-Chou; Liang, Yu-Jen; Chung, Chia-Min; Chen, Jia-Wei; Pan, Wen-Harn

    2009-01-01

    Genome-wide association studies, which analyzes hundreds of thousands of single-nucleotide polymorphisms to identify disease susceptibility genes, are challenging because the work involves intensive computation and complex modeling. We propose a two-stage genome-wide association scanning procedure, consisting of a single-locus association scan for the first stage and a gene-based association scan for the second stage. Marginal effects of single-nucleotide polymorphisms are examined by using the exact Armitage trend test or logistic regression, and gene effects are examined by using a p-value combination method. Compared with some existing single-locus and multilocus methods, the proposed method has the following merits: 1) convenient for definition of biologically meaningful regions, 2) powerful for detection of minor-effect genes, 3) helpful for alleviation of a multiple-testing problem, and 4) convenient for result interpretation. The method was applied to study Genetic Analysis Workshop 16 Problem 1 rheumatoid arthritis data, and strong association signals were found. The results show that the human major histocompatibility complex region is the most important genomic region associated with rheumatoid arthritis. Moreover, previously reported genes including PTPN22, C5, and IL2RB were confirmed; novel genes including HLA-DRA, BTNL2, C6orf10, NOTCH4, TAP2, and TNXB were identified by our analysis. PMID:20018002

  13. Genome-wide association study of periodontal pathogen colonization.

    PubMed

    Divaris, K; Monda, K L; North, K E; Olshan, A F; Lange, E M; Moss, K; Barros, S P; Beck, J D; Offenbacher, S

    2012-07-01

    Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease. PMID:22699663

  14. Functional Genomics in the Study of Mind-Body Therapies

    PubMed Central

    Niles, Halsey; Mehta, Darshan H.; Corrigan, Alexandra A.; Bhasin, Manoj K.; Denninger, John W.

    2014-01-01

    Background Mind-body therapies (MBTs) are used throughout the world in treatment, disease prevention, and health promotion. However, the mechanisms by which MBTs exert their positive effects are not well understood. Investigations into MBTs using functional genomics have revolutionized the understanding of MBT mechanisms and their effects on human physiology. Methods We searched the literature for the effects of MBTs on functional genomics determinants using MEDLINE, supplemented by a manual search of additional journals and a reference list review. Results We reviewed 15 trials that measured global or targeted transcriptomic, epigenomic, or proteomic changes in peripheral blood. Sample sizes ranged from small pilot studies (n=2) to large trials (n=500). While the reliability of individual genes from trial to trial was often inconsistent, genes related to inflammatory response, particularly those involved in the nuclear factor-kappa B (NF-κB) pathway, were consistently downregulated across most studies. Conclusion In general, existing trials focusing on gene expression changes brought about by MBTs have revealed intriguing connections to the immune system through the NF-κB cascade, to telomere maintenance, and to apoptotic regulation. However, these findings are limited to a small number of trials and relatively small sample sizes. More rigorous randomized controlled trials of healthy subjects and specific disease states are warranted. Future research should investigate functional genomics areas both upstream and downstream of MBT-related gene expression changes—from epigenomics to proteomics and metabolomics. PMID:25598735

  15. Genome-wide Association Studies from the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative | Office of Cancer Genomics

    Cancer.gov

    CGEMS identifies common inherited genetic variations associated with a number of cancers, including breast and prostate. Data from these genome-wide association studies (GWAS) are available through the Division of Cancer Epidemiology & Genetics website.

  16. A genome-wide DNA methylation study in colorectal carcinoma

    PubMed Central

    2011-01-01

    Background We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC). Methods We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center. Results We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application. Conclusion Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application. PMID:21699707

  17. Genome-wide association study of schizophrenia in Ashkenazi Jews.

    PubMed

    Goes, Fernando S; McGrath, John; Avramopoulos, Dimitrios; Wolyniec, Paula; Pirooznia, Mehdi; Ruczinski, Ingo; Nestadt, Gerald; Kenny, Eimear E; Vacic, Vladimir; Peters, Inga; Lencz, Todd; Darvasi, Ariel; Mulle, Jennifer G; Warren, Stephen T; Pulver, Ann E

    2015-12-01

    Schizophrenia is a common, clinically heterogeneous disorder associated with lifelong morbidity and early mortality. Several genetic variants associated with schizophrenia have been identified, but the majority of the heritability remains unknown. In this study, we report on a case-control sample of Ashkenazi Jews (AJ), a founder population that may provide additional insights into genetic etiology of schizophrenia. We performed a genome-wide association analysis (GWAS) of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently, we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640 controls, followed by a meta-analysis and polygenic risk scoring using summary results from Psychiatric GWAS Consortium 2 schizophrenia study. The U.S. AJ sample showed strong evidence of polygenic inheritance (pseudo-R(2) ∼9.7%) and a SNP-heritability estimate of 0.39 (P = 0.00046). We found no genome-wide significant associations in the U.S. sample or in the combined US/Israeli AJ meta-analysis of 1505 cases and 2145 controls. The strongest AJ specific associations (P-values in 10(-6) -10(-7) range) were in the 22q 11.2 deletion region and included the genes TBX1, GLN1, and COMT. Supportive evidence (meta P < 1 × 10(-4) ) was also found for several previously identified genome-wide significant findings, including the HLA region, CNTN4, IMMP2L, and GRIN2A. The meta-analysis of the U.S. sample with the PGC2 results provided initial genome-wide significant evidence for six new loci. Among the novel potential susceptibility genes is PEPD, a gene involved in proline metabolism, which is associated with a Mendelian disorder characterized by developmental delay and cognitive deficits. PMID:26198764

  18. Bioinformatics challenges for genome-wide association studies

    PubMed Central

    Moore, Jason H.; Asselbergs, Folkert W.; Williams, Scott M.

    2010-01-01

    Motivation: The sequencing of the human genome has made it possible to identify an informative set of >1 million single nucleotide polymorphisms (SNPs) across the genome that can be used to carry out genome-wide association studies (GWASs). The availability of massive amounts of GWAS data has necessitated the development of new biostatistical methods for quality control, imputation and analysis issues including multiple testing. This work has been successful and has enabled the discovery of new associations that have been replicated in multiple studies. However, it is now recognized that most SNPs discovered via GWAS have small effects on disease susceptibility and thus may not be suitable for improving health care through genetic testing. One likely explanation for the mixed results of GWAS is that the current biostatistical analysis paradigm is by design agnostic or unbiased in that it ignores all prior knowledge about disease pathobiology. Further, the linear modeling framework that is employed in GWAS often considers only one SNP at a time thus ignoring their genomic and environmental context. There is now a shift away from the biostatistical approach toward a more holistic approach that recognizes the complexity of the genotype–phenotype relationship that is characterized by significant heterogeneity and gene–gene and gene–environment interaction. We argue here that bioinformatics has an important role to play in addressing the complexity of the underlying genetic basis of common human diseases. The goal of this review is to identify and discuss those GWAS challenges that will require computational methods. Contact: jason.h.moore@dartmouth.edu PMID:20053841

  19. Genome-Wide Association Studies for Polycystic Ovary Syndrome.

    PubMed

    Liu, Hongbin; Zhao, Han; Chen, Zi-Jiang

    2016-07-01

    Over the past several years, the field of reproductive medicine has witnessed great advances in genome-wide association studies (GWASs) of polycystic ovary syndrome (PCOS), leading to identification of several promising genes involved in hormone action, type 2 diabetes, and cell proliferation. This review summarizes the key findings and discusses their potential implications with regard to genetic mechanisms of PCOS. Limitations of GWAS are evaluated, emphasizing the understanding of the reasons for variability in results between individual studies. Root causes of misinterpretations of GWASs are also addressed. Finally, the impact of GWAS on future directions of multi- and interdisciplinary studies is discussed. PMID:27513023

  20. Genomics of sorghum.

    PubMed

    Paterson, Andrew H

    2008-01-01

    Sorghum (Sorghum bicolor (L.) Moench) is a subject of plant genomics research based on its importance as one of the world's leading cereal crops, a biofuels crop of high and growing importance, a progenitor of one of the world's most noxious weeds, and a botanical model for many tropical grasses with complex genomes. A rich history of genome analysis, culminating in the recent complete sequencing of the genome of a leading inbred, provides a foundation for invigorating progress toward relating sorghum genes to their functions. Further characterization of the genomes other than Saccharinae cereals may shed light on mechanisms, levels, and patterns of evolution of genome size and structure, laying the foundation for further study of sugarcane and other economically important members of the group. PMID:18483564

  1. [Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection].

    PubMed

    Han, Yinglun; Li, Qingwei

    2016-01-01

    The goal of gene therapy is to introduce foreign genes into human target cells in a certain way to correct or compensate diseases caused by defective or abnormal genes. Therefore, gene therapy has great practical significance in studying the treatment of persistent or latent HIV-1 infection. At present, the existing methods of gene therapy have some major defects such as limited target site recognition and high frequency of off-targets. The latest research showed that the clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated nuclease 9 (Cas9) system from bacteria and archaea has been successfully reformed to a targeted genome editing tool. Thus, how to achieve the goal of treating HIV-1 infection by modifying targeted HIV-1 virus genome effectively using the CRISPR/Cas9 system has become a current research focus. Here we review the latest achievements worldwide and briefly introduce applications of the CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection, including CCR5 gene editing, removal of HIV-1 virus and activation of HIV-1 virus, in order to provide reference for the prevention and treatment of HIV-1 infection. PMID:26787519

  2. Optical studies of dynamical processes in disordered systems. Progress report

    SciTech Connect

    Yen, W.M.

    1994-05-01

    The authors present an abbreviated summary of the progress they have attained in the course of the abbreviated first year of the present three-year grant. The focus of their research continues to be on studies which help them understand various dynamical processes which affect the structure and the optical properties of disordered and amorphous materials. They continue to make significant progress in their attempts to understand the factors which affect, for example, the efficiencies of activated glasses. This report contains a brief description of the work they have carried out during the present grant period and an outline of the initiatives they are presently undertaking or continuing during the second period.

  3. Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis

    PubMed Central

    Cao, Qizhi; Didelot, Xavier; Wu, Zhongbiao; Li, Zongwei; He, Lihua; Li, Yunsheng; Ni, Ming; You, Yuanhai; Lin, Xi; Li, Zhen; Gong, Yanan; Zheng, Minqiao; Zhang, Minli; Liu, Jie; Wang, Weijun; Bo, Xiaochen; Falush, Daniel; Wang, Shengqi; Zhang, Jianzhong

    2015-01-01

    Objective To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. Design We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. Results The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy. PMID:25007814

  4. Biological Sciences Curriculum Study Newsletter Number 56, Progress Report.

    ERIC Educational Resources Information Center

    Clark, George M., Ed.

    This newsletter presents a progress report for the 1973-74 year for the Biological Sciences Curriculum Study (BSCS). The program for the Educable Mentally Handicapped is reviewed and a new series of Animal Behavior films is described. Other articles in the newsletter include information on the Human Sciences Program with emphasis on the…

  5. On Studies of Moral Socialization of Students: Progress and Perplexities

    ERIC Educational Resources Information Center

    Zhang, Renjie

    2008-01-01

    Moral socialization of students consists of five elements: process, subject, agent, content and pattern. This paper discusses the studies of the former three: their progress and perplexities, covering the following puzzles: "Why does the youth socialization take longer time?" "Are there any critical periods in student socialization?" "How do we…

  6. Progressive Macular Hypomelanosis in Korean Patients: A Clinicopathologic Study

    PubMed Central

    Hwang, Seon Wook; Hong, Soon Kwon; Kim, Sang Hyun; Park, Jeong Hoon; Seo, Jong Keun; Sung, Ho Suk

    2009-01-01

    Background Progressive macular hypomelanosis is characterized by ill-defined, non-scaly, hypopigmented macules primarily on the trunk of the body. Although numerous cases of progressive macular hypomelanosis have been reported, there have been no clinicopathologic studies of progressive macular hypomelanosis in Korean patients. Objective In this study we examined the clinical characteristics, histologic findings, and treatment methods for progressive macular hypomelanosis in a Korean population. Methods Between 1996 and 2005, 20 patients presented to the Department of Dermatology at Busan Paik Hospital with acquired, non-scaly, confluent, hypopigmented macules on the trunk, and with no history of inflammation or infection. The medical records, clinical photographs, and pathologic findings for each patient were examined. Results The patients included 5 men and 15 women. The mean age of onset was 21.05±3.47 years. The back was the most common site of involvement. All KOH examinations were negative. A Wood's lamp examination showed hypopigmented lesions compared with the adjacent normal skin. A microscopic examination showed a reduction in the number of melanin granules in the lesions compared with the adjacent normal skin, although S-100 immunohistochemical staining did not reveal significant differences in the number of melanocytes. Among the 20 patients, 7 received topical drug therapy, 6 were treated with narrow-band ultraviolet B phototherapy, 4 received oral minocycline, and 3 did not receive any treatment. Conclusion Most of the patients with progressive macular hypomelanosis had asymptomatic ill-defined, non-scaly, and symmetric hypopigmented macules, especially on the back and abdomen. Histologically, the number of melanocytes did not differ significantly between the hypopigmented macules and the normal perilesional skin. No effective treatment is known for progressive macular hypomelanosis; however, narrow-band ultraviolet B phototherapy may be a useful

  7. A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure

    PubMed Central

    Liu, Xiao-Gang; Liu, Yong-Jun; Liu, Jianfeng; Pei, Yufang; Xiong, Dong-Hai; Shen, Hui; Deng, Hong-Yi; Papasian, Christopher J; Drees, Betty M; Hamilton, James J; Recker, Robert R; Deng, Hong-Wen

    2008-01-01

    Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures. PMID:18597637

  8. [Genome-wide association study for adolescent idiopathic scoliosis].

    PubMed

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS. PMID:27013625

  9. Genome-Wide Association Study of Parity in Bangladeshi Women

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L.; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G.; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10-7 and number of pregnancies at P <10-6. This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10-6. The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10-5 for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  10. Genome-wide association study of parity in Bangladeshi women.

    PubMed

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10(-7) and number of pregnancies at P <10(-6). This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10(-6). The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10(-5) for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  11. Genome-wide association studies in pharmacogenetics research debate

    PubMed Central

    Bailey, Kent R; Cheng, Cheng

    2016-01-01

    Will genome-wide association studies (GWAS) ‘work’ for pharmacogenetics research? This question was the topic of a staged debate, with pro and con sides, aimed to bring out the strengths and weaknesses of GWAS for pharmacogenetics studies. After a full day of seminars at the Fifth Statistical Analysis Workshop of the Pharmacogenetics Research Network, the lively debate was held – appropriately – at Goonies Comedy Club in Rochester (MN, USA). The pro side emphasized that the many GWAS successes for identifying genetic variants associated with disease risk show that it works; that the current genotyping platforms are efficient, with good imputation methods to fill in missing data; that its global assessment is always a success even if no significant associations are detected; and that genetic effects are likely to be large because humans have not evolved in a drug-therapy environment. By contrast, the con side emphasized that we have limited knowledge of the complexity of the genome; limited clinical phenotypes compromise studies; the likely multifactorial nature of drug response clouding the small genetic effects; and limitations of sample size and replication studies in pharmacogenetic studies. Lively and insightful discussions emphasized further research efforts that might benefit GWAS in pharmacogenetics. PMID:20235786

  12. Complete Genome Sequence of Streptomyces ambofaciens DSM 40697, a Paradigm for Genome Plasticity Studies

    PubMed Central

    Thibessard, Annabelle

    2016-01-01

    The sequence of Streptomyces ambofaciens DSM 40697 was completely determined. The genome consists of an 8.1-Mbp linear chromosome with terminal inverted repeats of 210 kb. Genomic islands were identified, one of which corresponds to a new putative integrative and conjugative element (ICE) called pSAM3. PMID:27257195

  13. Complete Genome Sequence of Streptomyces ambofaciens DSM 40697, a Paradigm for Genome Plasticity Studies.

    PubMed

    Thibessard, Annabelle; Leblond, Pierre

    2016-01-01

    The sequence of Streptomyces ambofaciens DSM 40697 was completely determined. The genome consists of an 8.1-Mbp linear chromosome with terminal inverted repeats of 210 kb. Genomic islands were identified, one of which corresponds to a new putative integrative and conjugative element (ICE) called pSAM3. PMID:27257195

  14. Effectiveness study of atropine for progressive myopia in Europeans

    PubMed Central

    Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

    2016-01-01

    Purpose Randomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country. Methods An effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy. Results Mean spherical equivalent at baseline was −6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (−1.0D/year±0.7) diminished substantially during treatment (−0.1D/year±0.7) compared to those who ceased therapy (−0.5D/year±0.6; P=0.03). Conclusions Despite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans. PMID:27101751

  15. Effectiveness study of atropine for progressive myopia in Europeans.

    PubMed

    Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

    2016-07-01

    PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans. PMID:27101751

  16. Voxelwise genome-wide association study (vGWAS)

    PubMed Central

    Stein, Jason L.; Hua, Xue; Lee, Suh; Ho, April J.; Leow, Alex D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; DeChairo, Bryan M.; Potkin, Steven G.; Weiner, Michael W.; Thompson, Paul M.

    2010-01-01

    The structure of the human brain is highly heritable, and is thought to be influenced by many common genetic variants, many of which are currently unknown. Recent advances in neuroimaging and genetics have allowed collection of both highly detailed structural brain scans and genome-wide genotype information. This wealth of information presents a new opportunity to find the genes influencing brain structure. Here we explore the relation between 448,293 single nucleotide polymorphisms in each of 31,622 voxels of the entire brain across 740 elderly subjects (mean age±s.d.: 75.52±6.82 years; 438 male) including subjects with Alzheimer's disease, Mild Cognitive Impairment, and healthy elderly controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used tensor-based morphometry to measure individual differences in brain structure at the voxel level relative to a study-specific template based on healthy elderly subjects. We then conducted a genome-wide association at each voxel to identify genetic variants of interest. By studying only the most associated variant at each voxel, we developed a novel method to address the multiple comparisons problem and computational burden associated with the unprecedented amount of data. No variant survived the strict significance criterion, but several genes worthy of further exploration were identified, including CSMD2 and CADPS2. These genes have high relevance to brain structure. This is the first voxelwise genome wide association study to our knowledge, and offers a novel method to discover genetic influences on brain structure. PMID:20171287

  17. GenomicusPlants: A Web Resource to Study Genome Evolution in Flowering Plants

    PubMed Central

    Louis, Alexandra; Murat, Florent; Salse, Jérôme; Roest Crollius, Hugues

    2015-01-01

    Comparative genomics combined with phylogenetic reconstructions are powerful approaches to study the evolution of genes and genomes. However, the current rapid expansion of the volume of genomic information makes it increasingly difficult to interrogate, integrate and synthesize comparative genome data while taking into account the maximum breadth of information available. GenomicusPlants (http://www.genomicus.biologie.ens.fr/genomicus-plants) is an extension of the Genomicus webserver that addresses this issue by allowing users to explore flowering plant genomes in an intuitive way, across the broadest evolutionary scales. Extant genomes of 26 flowering plants can be analyzed, as well as 23 ancestral reconstructed genomes. Ancestral gene order provides a long-term chronological view of gene order evolution, greatly facilitating comparative genomics and evolutionary studies. Four main interfaces (‘views’) are available where: (i) PhyloView combines phylogenetic trees with comparisons of genomic loci across any number of genomes; (ii) AlignView projects loci of interest against all other genomes to visualize its topological conservation; (iii) MatrixView compares two genomes in a classical dotplot representation; and (iv) Karyoview visualizes chromosome karyotypes ‘painted’ with colours of another genome of interest. All four views are interconnected and benefit from many customizable features. PMID:25432975

  18. [New insight of genome-wide association study (GWAS)].

    PubMed

    Hotta, Kikuko

    2013-02-01

    The number of obese patients is increasing in Japan, due to the westernization of lifestyle. Obesity, especially visceral fat obesity, is important for the development of metabolic syndrome. Genetic factors are important for the development of obesity as well as environmental factors. Importance of genetic factors of fat distribution is also reported. Recent genome-wide association studies (GWASs) have revealed the obesity and fat distribution-related polymorphisms. GWAS will highlight a better understanding of the underlying molecular mechanisms in the regulation of obesity and distribution of body fat. PMID:23631198

  19. Genome-Wide Association Study of Metabolic Syndrome in Koreans

    PubMed Central

    Jeong, Seok Won; Chung, Myungguen; Park, Soo-Jung; Cho, Seong Beom

    2014-01-01

    Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (<5 × 10-8), 8 SNPs with genome-wide suggestive p-values (5 × 10-8 ≤ p < 1 × 10-5), and 2 SNPs of more functional variants with borderline p-values (5 × 10-5 ≤ p < 1 × 10-4). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies. PMID:25705157

  20. Genome-wide association study of periweaning failure-to-thrive syndrome (PFTS) in pigs.

    PubMed

    Zanella, R; Morés, N; Morés, M A Z; Peixoto, J O; Zanella, E L; Ciacci-Zanella, J R; Ibelli, A M G; Gava, D; Cantão, M E; Ledur, M C

    2016-06-25

    Porcine periweaning-failure-to-thrive syndrome (PFTS) is a condition that affects newly weaned piglets. It is characterised by a progressive debilitation leading to death, in the absence of infectious, nutritional, management or environmental factors. In this study, we present the first report of PFTS in South America and the results of a genome-wide association study to identify the genetic markers associated with the appearance of this condition in a crossbred swine population. Four chromosomal regions were associated with PFTS predisposition, one located on SSCX, one on SSC8, and the two other regions on SSC14. Regions on SSC8 and SSC14 harbour important functional candidate genes involved in human depression and might have an important role in PFTS. Our findings contribute to the increasing knowledge about this syndrome, which has been investigated since 2007, and to the identification of the aetiology of this disease. PMID:27162284

  1. Genome-Wide Association Studies of the Human Gut Microbiota.

    PubMed

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  2. Genome-Wide Association Studies of the Human Gut Microbiota

    PubMed Central

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  3. Study Progress on Tissue Culture of Maize Mature Embryo

    NASA Astrophysics Data System (ADS)

    Wang, Hongzhen; Cheng, Jun; Cheng, Yanping; Zhou, Xioafu

    It has been paid more and more attention on maize tissue culture as it is a basic work in maize genetic transformation, especially huge breakthrough has been made in maize tissue culture utilizing mature embryos as explants in the recent years. This paper reviewed the study progress on maize tissue culture and plant regeneration utilizing mature embryos as explants from callus induction, subculture, plant regeneration and browning reduction and so on.

  4. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

  5. Genotype imputation in genome-wide association studies.

    PubMed

    Porcu, Eleonora; Sanna, Serena; Fuchsberger, Christian; Fritsche, Lars G

    2013-07-01

    Imputation is an in silico method that can increase the power of association studies by inferring missing genotypes, harmonizing data sets for meta-analyses, and increasing the overall number of markers available for association testing. This unit provides an introductory overview of the imputation method and describes a two-step imputation approach that consists of the phasing of the study genotypes and the imputation of reference panel genotypes into the study haplotypes. Detailed steps for data preparation and quality control illustrate how to run the computationally intensive two-step imputation with the high-density reference panels of the 1000 Genomes Project, which currently integrates more than 39 million variants. Additionally, the influence of reference panel selection, input marker density, and imputation settings on imputation quality are demonstrated with a simulated data set to give insight into crucial points of successful genotype imputation. PMID:23853078

  6. Genomic Aspects of Research Involving Polyploid Plants

    SciTech Connect

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

    2011-01-01

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

  7. Progress in a genome scan for linkage in schizophrenia in a large Swedish kindred

    SciTech Connect

    Barr, C.L.; Kennedy, J.L.; Pakstis, A.J.

    1994-03-15

    Genetic linkage studies of a kindred from Sweden segregating for schizophrenia have been performed using a genetic model (autosomal dominant, f - 0.72, q - 0.02, phenocopies=0.001) as described in Kennedy et al., 1988. Analyses of the restriction fragment length polymorphism (RFLP), allele-specific oligonucleotides (ASO), and short tandem repeat (STR also called microsatellite) data for 180 polymorphisms (individual probe-enzyme, ASO, or STR systems) at 155 loci have been completed using the MLINK and LIPED programs. Linkage to schizophrenia was excluded, under the given model, at 47 loci; indeterminate lod scores occurred at 108 loci. The total exclusion region across 20 chromosomes is estimated at 330 cM; 211 cM excluded by pairwise analyses and 119 cM previously excluded by multipoint analyses. 37 refs., 2 tabs.

  8. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    SciTech Connect

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  9. Cytokine Gene Polymorphisms and Human Autoimmune Disease in the Era of Genome-Wide Association Studies

    PubMed Central

    2012-01-01

    Cytokine (receptor) genes have traditionally attracted great interest as plausible genetic risk factors for autoimmune disease. Since 2007, the implementation of genome-wide association studies has facilitated the robust identification of allelic variants in more than 35 cytokine loci as susceptibility factors for a wide variety of over 15 autoimmune disorders. In this review, we catalog the gene loci of interleukin, chemokine, and tumor necrosis factor receptor superfamily and ligands that have emerged as autoimmune risk factors. We examine recent progress made in the clarification of the functional mechanisms by which polymorphisms in the genes coding for interleukin-2 receptor alpha (IL2RA), IL7R, and IL23R may alter risk for autoimmune disease, and discuss opposite autoimmune risk alleles found, among others, at the IL10 locus. PMID:22191464

  10. Realizing privacy preserving genome-wide association studies

    PubMed Central

    Simmons, Sean; Berger, Bonnie

    2016-01-01

    Motivation: As genomics moves into the clinic, there has been much interest in using this medical data for research. At the same time the use of such data raises many privacy concerns. These circumstances have led to the development of various methods to perform genome-wide association studies (GWAS) on patient records while ensuring privacy. In particular, there has been growing interest in applying differentially private techniques to this challenge. Unfortunately, up until now all methods for finding high scoring SNPs in a differentially private manner have had major drawbacks in terms of either accuracy or computational efficiency. Results: Here we overcome these limitations with a substantially modified version of the neighbor distance method for performing differentially private GWAS, and thus are able to produce a more viable mechanism. Specifically, we use input perturbation and an adaptive boundary method to overcome accuracy issues. We also design and implement a convex analysis based algorithm to calculate the neighbor distance for each SNP in constant time, overcoming the major computational bottleneck in the neighbor distance method. It is our hope that methods such as ours will pave the way for more widespread use of patient data in biomedical research. Availability and implementation: A python implementation is available at http://groups.csail.mit.edu/cb/DiffPriv/. Contact: bab@csail.mit.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26769317