Search

Your search keyword '"McDowell, Jennifer C"' showing total 23 results
Start Over Author "McDowell, Jennifer C"
23 results on '"McDowell, Jennifer C"'

1. Genetic effects on liver chromatin accessibility identify disease regulatory variants

Author

Barnabas, Beatrice B., Black, Sean, Bouffard, Gerard G., Brooks, Shelise Y., Coleman, Holly, Dekhtyar, Lyudmila, Han, Joel, Ho, Shi-ling, Kim, Juyun, Legaspi, Richelle, Maduro, Quino L., Masiello, Catherine A., McDowell, Jennifer C., Montemayor, Casandra, Mullikin, James C., Park, Morgan, Riebow, Nancy L., Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Sirintorn, Thomas, James W., Thomas, Pamela J., Vemulapalli, Meghana, Young, Alice C., Currin, Kevin W., Erdos, Michael R., Narisu, Narisu, Rai, Vivek, Vadlamudi, Swarooparani, Perrin, Hannah J., Idol, Jacqueline R., Yan, Tingfen, Albanus, Ricardo D’Oliveira, Broadaway, K. Alaine, Etheridge, Amy S., Bonnycastle, Lori L., Orchard, Peter, Didion, John P., Chaudhry, Amarjit S., Innocenti, Federico, Schuetz, Erin G., Scott, Laura J., Parker, Stephen C.J., Collins, Francis S., and Mohlke, Karen L.

Published
2021
Full Text
View/download PDF

2. Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Author

Barnabas, Beatrice B., Bouffard, Gerard G., Brooks, Shelise Y., Coleman, Holly, Dekhtyar, Lyudmila, Guan, Xiaobin, Han, Joel, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino L., Masiello, Catherine A., McDowell, Jennifer C., Montemayor, Casandra, Park, Morgan, Riebow, Nancy L., Schandler, Karen, Scharer, Chanthra, Schmidt, Brian, Sison, Christina, Stantripop, Sirintorn, Thomas, James W., Thomas, Pamela J., Vemulapalli, Meghana, Young, Alice C., Sapp, Julie C., Johnston, Jennifer J., Driscoll, Kate, Heidlebaugh, Alexis R., Miren Sagardia, Ane, Dogbe, D. Nadine, Umstead, Kendall L., Turbitt, Erin, Alevizos, Ilias, Baron, Jeffrey, Bönnemann, Carsten, Brooks, Brian, Donkervoort, Sandra, Jee, Youn Hee, Linehan, W. Marston, McMahon, Francis J., Moss, Joel, Mullikin, James C., Nielsen, Deborah, Pelayo, Eileen, Remaley, Alan T., Siegel, Richard, Su, Helen, Zarate, Carlos, Manolio, Teri A., Biesecker, Barbara B., and Biesecker, Leslie G.

Published
2018
Full Text
View/download PDF

3. Roving methyltransferases generate a mosaic epigenetic landscape and influence evolution in Bacteroides fragilis group.

Author

Tisza, Michael J., Smith, Derek D. N., Clark, Andrew E., Youn, Jung-Ho, Barnabas, Beatrice B., Black, Sean, Bouffard, Gerard G., Brooks, Shelise Y., Crawford, Juyun, Marfani, Holly, Dekhtyar, Lyudmila, Han, Joel, Ho, Shi-Ling, Legaspi, Richelle, Maduro, Quino L., Masiello, Catherine A., McDowell, Jennifer C., Montemayor, Casandra, Mullikin, James C., and Park, Morgan

Subjects
BACTEROIDES fragilis, METHYLTRANSFERASES, BACTERIAL genomes, ANAEROBIC infections, EPIGENETICS, EPIGENOMICS, CATECHOL-O-methyltransferase, DNA methyltransferases
Abstract

Three types of DNA methyl modifications have been detected in bacterial genomes, and mechanistic studies have demonstrated roles for DNA methylation in physiological functions ranging from phage defense to transcriptional control of virulence and host-pathogen interactions. Despite the ubiquity of methyltransferases and the immense variety of possible methylation patterns, epigenomic diversity remains unexplored for most bacterial species. Members of the Bacteroides fragilis group (BFG) reside in the human gastrointestinal tract as key players in symbiotic communities but also can establish anaerobic infections that are increasingly multi-drug resistant. In this work, we utilize long-read sequencing technologies to perform pangenomic (n = 383) and panepigenomic (n = 268) analysis of clinical BFG isolates cultured from infections seen at the NIH Clinical Center over four decades. Our analysis reveals that single BFG species harbor hundreds of DNA methylation motifs, with most individual motif combinations occurring uniquely in single isolates, implying immense unsampled methylation diversity within BFG epigenomes. Mining of BFG genomes identified more than 6000 methyltransferase genes, approximately 1000 of which were associated with intact prophages. Network analysis revealed substantial gene flow among disparate phage genomes, implying a role for genetic exchange between BFG phages as one of the ultimate sources driving BFG epigenome diversity. Here, Tisza, Dekker, and colleagues perform large scale analysis of genome methylation in the gut commensal and pathogen, Bacteroides fragilis group, revealing immense methyl motif diversity and evidence of widespread methyltransferase exchange among phages. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

5. Genetic effects on liver chromatin accessibility identify disease regulatory variants

Author

Currin, Kevin W., primary, Erdos, Michael R., additional, Narisu, Narisu, additional, Rai, Vivek, additional, Vadlamudi, Swarooparani, additional, Perrin, Hannah J., additional, Idol, Jacqueline R., additional, Yan, Tingfen, additional, Albanus, Ricardo D’Oliveira, additional, Broadaway, K. Alaine, additional, Etheridge, Amy S., additional, Bonnycastle, Lori L., additional, Orchard, Peter, additional, Didion, John P., additional, Chaudhry, Amarjit S., additional, Innocenti, Federico, additional, Schuetz, Erin G., additional, Scott, Laura J., additional, Parker, Stephen C.J., additional, Collins, Francis S., additional, Mohlke, Karen L., additional, Barnabas, Beatrice B., additional, Black, Sean, additional, Bouffard, Gerard G., additional, Brooks, Shelise Y., additional, Coleman, Holly, additional, Dekhtyar, Lyudmila, additional, Han, Joel, additional, Ho, Shi-ling, additional, Kim, Juyun, additional, Legaspi, Richelle, additional, Maduro, Quino L., additional, Masiello, Catherine A., additional, McDowell, Jennifer C., additional, Montemayor, Casandra, additional, Mullikin, James C., additional, Park, Morgan, additional, Riebow, Nancy L., additional, Schandler, Karen, additional, Schmidt, Brian, additional, Sison, Christina, additional, Stantripop, Sirintorn, additional, Thomas, James W., additional, Thomas, Pamela J., additional, Vemulapalli, Meghana, additional, and Young, Alice C., additional

Published
2021
Full Text
View/download PDF

6. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. James, Stone, Eric A., Batzoglou, Serafim, Goldman, Nick, Hardison, Ross C., Haussler, David, Miller, Webb, Sidow, Arend, Trinklein, Nathan D., Zhang, Zhengdong D., Barrera, Leah, Stuart, Rhona, King, David C., Ameur, Adam, Enroth, Stefan, Bieda, Mark C., Kim, Jonghwan, Bhinge, Akshay A., Jiang, Nan, Liu, Jun, Yao, Fei, Vega, Vinsensius B., Lee, Charlie W.H., Ng, Patrick, Yang, Annie, Moqtaderi, Zarmik, Zhu, Zhou, Xu, Xiaoqin, Squazzo, Sharon, Oberley, Matthew J., Inman, David, Singer, Michael A., Richmond, Todd A., Munn, Kyle J., Rada-Iglesias, Alvaro, Wallerman, Ola, Komorowski, Jan, Fowler, Joanna C., Couttet, Phillippe, Bruce, Alexander W., Dovey, Oliver M., Ellis, Peter D., Langford, Cordelia F., Nix, David A., Euskirchen, Ghia, Hartman, Stephen, Urban, Alexander E., Kraus, Peter, Van Calcar, Sara, Heintzman, Nate, Hoon Kim, Tae, Wang, Kun, Qu, Chunxu, Hon, Gary, Luna, Rosa, Glass, Christopher K., Rosenfeld, M. Geoff, Aldred, Shelley Force, Cooper, Sara J., Halees, Anason, Lin, Jane M., Shulha, Hennady P., Zhang, Xiaoling, Xu, Mousheng, Haidar, Jaafar N. S., Yu, Yong, Birney*, Ewan, Iyer, Vishwanath R., Green, Roland D., Wadelius, Claes, Farnham, Peggy J., Ren, Bing, Harte, Rachel A., Hinrichs, Angie S., Trumbower, Heather, Clawson, Hiram, Hillman-Jackson, Jennifer, Zweig, Ann S., Smith, Kayla, Thakkapallayil, Archana, Barber, Galt, Kuhn, Robert M., Karolchik, Donna, Armengol, Lluis, Bird, Christine P., de Bakker, Paul I. W., Kern, Andrew D., Lopez-Bigas, Nuria, Martin, Joel D., Stranger, Barbara E., Woodroffe, Abigail, Davydov, Eugene, Dimas, Antigone, Eyras, Eduardo, Hallgrimsdottir, Ingileif B., Huppert, Julian, Zody, Michael C., Abecasis, Goncalo R., Estivill, Xavier, Bouffard, Gerard G., Guan, Xiaobin, Hansen, Nancy F., Idol, Jacquelyn R., Maduro, Valerie V.B., Maskeri, Baishali, McDowell, Jennifer C., Park, Morgan, Thomas, Pamela J., Young, Alice C., Blakesley, Robert W., Baylor College of Medicine, Human Genome Sequencing Center, Muzny, Donna M., Sodergren, Erica, Wheeler, David A., Worley, Kim C., Jiang, Huaiyang, Weinstock, George M., Gibbs, Richard A., Graves, Tina, Fulton, Robert, Mardis, Elaine R., Wilson, Richard K., Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B., Chang, Jean L., Lindblad-Toh, Kerstin, Lander, Eric S., Koriabine, Maxim, Nefedov, Mikhail, Osoegawa, Kazutoyo, Yoshinaga, Yuko, Zhu, Baoli, and de Jong, Pieter J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
Full Text
View/download PDF

8. Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates

Author

Stantripop Sirintorn, Schandler Karen, Ho Shi-Ling, Haghighi Payam, Coleman Holly, Barnabas Beatrice B, Brooks Shelise Y, Maskeri Baishali, McDowell Jennifer C, Gupta Jyoti, Hansen Nancy F, Blakesley Robert W, Vogt Jennifer L, Thomas Pamela J, Bouffard Gerard G, and Green Eric D

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The approaches for shotgun-based sequencing of vertebrate genomes are now well-established, and have resulted in the generation of numerous draft whole-genome sequence assemblies. In contrast, the process of refining those assemblies to improve contiguity and increase accuracy (known as 'sequence finishing') remains tedious, labor-intensive, and expensive. As a result, the vast majority of vertebrate genome sequences generated to date remain at a draft stage. Results To date, our genome sequencing efforts have focused on comparative studies of targeted genomic regions, requiring sequence finishing of large blocks of orthologous sequence (average size 0.5-2 Mb) from various subsets of 75 vertebrates. This experience has provided a unique opportunity to compare the relative effort required to finish shotgun-generated genome sequence assemblies from different species, which we report here. Importantly, we found that the sequence assemblies generated for the same orthologous regions from various vertebrates show substantial variation with respect to misassemblies and, in particular, the frequency and characteristics of sequence gaps. As a consequence, the work required to finish different species' sequences varied greatly. Application of the same standardized methods for finishing provided a novel opportunity to "assay" characteristics of genome sequences among many vertebrate species. It is important to note that many of the problems we have encountered during sequence finishing reflect unique architectural features of a particular vertebrate's genome, which in some cases may have important functional and/or evolutionary implications. Finally, based on our analyses, we have been able to improve our procedures to overcome some of these problems and to increase the overall efficiency of the sequence-finishing process, although significant challenges still remain. Conclusion Our findings have important implications for the eventual finishing of the draft whole-genome sequences that have now been generated for a large number of vertebrates.

Published
2010
Full Text
View/download PDF

9. A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation.

Author

Pei, Wuhong, Xu, Lisha, Chen, Zelin, Slevin, Claire C., Pettie, Kade P., Wincovitch, Stephen, NISC Comparative Sequencing Program, Barnabas, Beatrice B., Black, Sean, Bouffard, Gerard G., Brooks, Shelise Y., Coleman, Holly, Dekhtyar, Lyudmila, Guan, Xiaobin, Han, Joel, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino L., Masiello, Catherine A., and McDowell, Jennifer C.

Subjects
SPINAL muscular atrophy, REGENERATION (Biology), CELL proliferation, RNA sequencing, HAIR cells
Abstract

Spinal muscular atrophy (SMA) is the most common genetic disease in children. SMA is generally caused by mutations in the gene SMN1. The survival of motor neurons (SMN) complex consists of SMN1, Gemins (2–8), and Strap/Unrip. We previously demonstrated smn1 and gemin5 inhibited tissue regeneration in zebrafish. Here we investigated each individual SMN complex member and identified gemin3 as another regeneration-essential gene. These three genes are likely pan-regenerative, since they affect the regeneration of hair cells, liver, and caudal fin. RNA-Seq analysis reveals that smn1, gemin3, and gemin5 are linked to a common set of genetic pathways, including the tp53 and ErbB pathways. Additional studies indicated all three genes facilitate regeneration by inhibiting the ErbB pathway, thereby allowing cell proliferation in the injured neuromasts. This study provides a new understanding of the SMN complex and a potential etiology for SMA and potentially other rare unidentified genetic diseases with similar symptoms. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

10. Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Author

Sapp, Julie C., primary, Johnston, Jennifer J., additional, Driscoll, Kate, additional, Heidlebaugh, Alexis R., additional, Miren Sagardia, Ane, additional, Dogbe, D. Nadine, additional, Umstead, Kendall L., additional, Turbitt, Erin, additional, Alevizos, Ilias, additional, Baron, Jeffrey, additional, Bönnemann, Carsten, additional, Brooks, Brian, additional, Donkervoort, Sandra, additional, Jee, Youn Hee, additional, Linehan, W. Marston, additional, McMahon, Francis J., additional, Moss, Joel, additional, Mullikin, James C., additional, Nielsen, Deborah, additional, Pelayo, Eileen, additional, Remaley, Alan T., additional, Siegel, Richard, additional, Su, Helen, additional, Zarate, Carlos, additional, Manolio, Teri A., additional, Biesecker, Barbara B., additional, Biesecker, Leslie G., additional, Barnabas, Beatrice B., additional, Bouffard, Gerard G., additional, Brooks, Shelise Y., additional, Coleman, Holly, additional, Dekhtyar, Lyudmila, additional, Guan, Xiaobin, additional, Han, Joel, additional, Ho, Shi-ling, additional, Legaspi, Richelle, additional, Maduro, Quino L., additional, Masiello, Catherine A., additional, McDowell, Jennifer C., additional, Montemayor, Casandra, additional, Park, Morgan, additional, Riebow, Nancy L., additional, Schandler, Karen, additional, Scharer, Chanthra, additional, Schmidt, Brian, additional, Sison, Christina, additional, Stantripop, Sirintorn, additional, Thomas, James W., additional, Thomas, Pamela J., additional, Vemulapalli, Meghana, additional, and Young, Alice C., additional

Published
2018
Full Text
View/download PDF

11. An intermediate grade of finished genomic sequence suitable for comparative analyses

Author

Blakesley, Robert W., Vogt, Jennifer L., Shi-Ling Ho, Maskeri, Baishali, Hansen, Nancy F., Walker, Michelle A., Karlins, Eric M., Young, Alice C., Mullikin, James C., Masiello, Catherine A., Maduro, Quino L., Benjamin, Beatrice, Thomas, Pamela J., McDowell, Jennifer C., Green, Eric D., Guan, Xiaobin, Stantrippo, Sirintorn, Brooks, Shelise Y., Bouffard, Gerard G., Tsurgeon, Cyrus, and Gupta, Jyoti

Subjects
Nucleotide sequence -- Research, Genetic research, Health
Abstract

The generation and quality of an intermediate grade of finished genomic sequence, which is tailored for use in multispecies sequence comparisons is described. The results demonstrate that comparative-grade sequence finishing represents a practical and affordable option for sequence refinement en route to comparative analyses.

Published
2004

12. Pericentromeric duplications in the laboratory mouse

Author

Thomas, James W., Schueler, Mary G., Summers, Tyrone J, Blakesley, Robert W., McDowell, Jennifer C., Thomas, Pamela J., Idol, Jacquelyn R., Maduro, Valerie V. B., Lee-Lin, Shih-Queen, Thouchman, Jeffrey W., Bouffard, Gerard G., Beckstrom-Sternberg, Stephen M., and Green, Eric D.

Subjects
Genetic research -- Analysis, Genomes -- Research, Gene mutations -- Physiological aspects, Chromosome mapping -- Genetic aspects, Chromosome replication -- Genetic aspects, Health
Abstract

Research has been conducted on genomic sequence evolution. The mapping and sequencing of mouse chromosome regions and the comparative sequence analysis of the human and mouse genomic regions are reported, and the results demonstrate that duplications associated with mouse chromosomes are recent.

Published
2003

13. Generation and comparative analysis of ~3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7qll.23 implicated in Williams syndrome

Author

DeSilva, Udaya, Elnitski, Laura, Idol, Jacquelyn R., Doyle, Johannah L., Gan, Weiniu; ., Green, Eric D., Miller, Webb, Touchman, Jeffrey W., Thomas, Pamela J., Bouffard, Gerard G., Blakesley, Robert W., McDowell, Jennifer C., Beckstrom-Sternberg, Stephen M., Dietriich, Nicole L, Schwartz, Scott;, and Thomas, James W.

Subjects
Developmental disabilities -- Research, Child development deviations -- Research, Human chromosomes -- Research, Williams syndrome -- Research, Genetic research, Health
Abstract

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a ~1.6-Mb segment of human chromosome 7qll.23. The results from a study in this context provided an important comparative sequence resource to develop mouse models of the disorder.

Published
2002

14. Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates

Author

Blakesley, Robert W, Hansen, Nancy F, Gupta, Jyoti, McDowell, Jennifer C, Maskeri, Baishali, Barnabas, Beatrice B, Brooks, Shelise Y, Coleman, Holly, Haghighi, Payam, Ho, Shi-Ling, Schandler, Karen, Stantripop, Sirintorn, Vogt, Jennifer L, Thomas, Pamela J, Comparative Sequencing Program, NISC, Bouffard, Gerard G, and Green, Eric D

Subjects
Whole genome sequencing, Genetics, Comparative genomics, Chromosomes, Artificial, Bacterial, Genome, lcsh:QH426-470, lcsh:Biotechnology, Chromosome Mapping, Genomics, Computational biology, Genome project, Sequence Analysis, DNA, Biology, DNA sequencing, lcsh:Genetics, lcsh:TP248.13-248.65, Vertebrates, Animals, DNA microarray, Sequence (medicine), Biotechnology, Research Article
Abstract

Background The approaches for shotgun-based sequencing of vertebrate genomes are now well-established, and have resulted in the generation of numerous draft whole-genome sequence assemblies. In contrast, the process of refining those assemblies to improve contiguity and increase accuracy (known as 'sequence finishing') remains tedious, labor-intensive, and expensive. As a result, the vast majority of vertebrate genome sequences generated to date remain at a draft stage. Results To date, our genome sequencing efforts have focused on comparative studies of targeted genomic regions, requiring sequence finishing of large blocks of orthologous sequence (average size 0.5-2 Mb) from various subsets of 75 vertebrates. This experience has provided a unique opportunity to compare the relative effort required to finish shotgun-generated genome sequence assemblies from different species, which we report here. Importantly, we found that the sequence assemblies generated for the same orthologous regions from various vertebrates show substantial variation with respect to misassemblies and, in particular, the frequency and characteristics of sequence gaps. As a consequence, the work required to finish different species' sequences varied greatly. Application of the same standardized methods for finishing provided a novel opportunity to "assay" characteristics of genome sequences among many vertebrate species. It is important to note that many of the problems we have encountered during sequence finishing reflect unique architectural features of a particular vertebrate's genome, which in some cases may have important functional and/or evolutionary implications. Finally, based on our analyses, we have been able to improve our procedures to overcome some of these problems and to increase the overall efficiency of the sequence-finishing process, although significant challenges still remain. Conclusion Our findings have important implications for the eventual finishing of the draft whole-genome sequences that have now been generated for a large number of vertebrates.

Published
2010

15. Hypoxia-induced HIF1 α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.

Author

Loftus, Stacie K., Baxter, Laura L., Cronin, Julia C., Fufa, Temesgen D., Pavan, William J., Barnabas, Beatrice B., Bouffard, Gerard G., Brooks, Shelise Y., Coleman, Holly, Dekhtyar, Lyudmila, Guan, Xiaobin, Han, Joel, Ho, Shi ‐ ling, Legaspi, Richelle, Maduro, Quino L., Masiello, Catherine A., McDowell, Jennifer C., Montemayor, Casandra, Mullikin, James C., and Park, Morgan

Subjects
MELANOMA prognosis, HYPOXIA-inducible factors, MELANOCYTES, CANCER invasiveness, METASTASIS
Abstract

Hypoxia and HIF1 α signaling direct tissue-specific gene responses regulating tumor progression, invasion, and metastasis. By integrating HIF1 α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1 α-dependent/hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1 α Ch IP-Seq analysis identifies 81 HIF1 α direct target genes in melanocytes. The expression levels for 10 of the HIF1 α direct targets - GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 - are significantly correlated with reduced time of disease-free status in melanoma by logistic regression (P -value = 0.0013) and ROC curve analysis ( AUC = 0.826, P-value < 0.0001). This HIF1 α-regulated profile defines a melanocyte-specific response under hypoxia, and demonstrates the role of HIF1 α as an invasive cell state gatekeeper in regulating cellular metabolism, chromatin and transcriptional regulation, vascularization, and invasion. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

16. Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Author

Margulies, Elliott H, Cooper, Gregory M, Asimenos, George, Thomas, Daryl J, Dewey, Colin N, Siepel, Adam, Birney, Ewan, Keefe, Damian, Schwartz, Ariel S, Hou, Minmei, Taylor, James, Nikolaev, Sergey, Montoya-Burgos, Juan I, Löytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Brown, James B, Bickel, Peter, Holmes, Ian, Mullikin, James C, Ureta-Vidal, Abel, Paten, Benedict, Stone, Eric A, Rosenbloom, Kate R, Kent, W James, Bouffard, Gerard G, Guan, Xiaobin, Hansen, Nancy F, Idol, Jacquelyn R, Maduro, Valerie V B, Maskeri, Baishali, McDowell, Jennifer C, Park, Morgan, Thomas, Pamela J, Young, Alice C, Blakesley, Robert W, Muzny, Donna M, Sodergren, Erica, Wheeler, David A, Worley, Kim C, Jiang, Huaiyang, Weinstock, George M, Gibbs, Richard A, Graves, Tina, Fulton, Robert, Mardis, Elaine R, Wilson, Richard K, Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B, Chang, Jean L, Lindblad-Toh, Kerstin, Lander, Eric S, Hinrichs, Angie, Trumbower, Heather, Clawson, Hiram, Zweig, Ann, Kuhn, Robert M, Barber, Galt, Harte, Rachel, Karolchik, Donna, Field, Matthew A, Moore, Richard A, Matthewson, Carrie A, Schein, Jacqueline E, Marra, Marco A, Antonarakis, Stylianos E, Batzoglou, Serafim, Goldman, Nick, Hardison, Ross, Haussler, David, Miller, Webb, Pachter, Lior, Green, Eric D, Sidow, Arend, Margulies, Elliott H, Cooper, Gregory M, Asimenos, George, Thomas, Daryl J, Dewey, Colin N, Siepel, Adam, Birney, Ewan, Keefe, Damian, Schwartz, Ariel S, Hou, Minmei, Taylor, James, Nikolaev, Sergey, Montoya-Burgos, Juan I, Löytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Brown, James B, Bickel, Peter, Holmes, Ian, Mullikin, James C, Ureta-Vidal, Abel, Paten, Benedict, Stone, Eric A, Rosenbloom, Kate R, Kent, W James, Bouffard, Gerard G, Guan, Xiaobin, Hansen, Nancy F, Idol, Jacquelyn R, Maduro, Valerie V B, Maskeri, Baishali, McDowell, Jennifer C, Park, Morgan, Thomas, Pamela J, Young, Alice C, Blakesley, Robert W, Muzny, Donna M, Sodergren, Erica, Wheeler, David A, Worley, Kim C, Jiang, Huaiyang, Weinstock, George M, Gibbs, Richard A, Graves, Tina, Fulton, Robert, Mardis, Elaine R, Wilson, Richard K, Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B, Chang, Jean L, Lindblad-Toh, Kerstin, Lander, Eric S, Hinrichs, Angie, Trumbower, Heather, Clawson, Hiram, Zweig, Ann, Kuhn, Robert M, Barber, Galt, Harte, Rachel, Karolchik, Donna, Field, Matthew A, Moore, Richard A, Matthewson, Carrie A, Schein, Jacqueline E, Marra, Marco A, Antonarakis, Stylianos E, Batzoglou, Serafim, Goldman, Nick, Hardison, Ross, Haussler, David, Miller, Webb, Pachter, Lior, Green, Eric D, and Sidow, Arend

Abstract

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.

Published
2007
Full Text
View/download PDF

17. Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Author

Margulies, Elliott H., primary, Cooper, Gregory M., additional, Asimenos, George, additional, Thomas, Daryl J., additional, Dewey, Colin N., additional, Siepel, Adam, additional, Birney, Ewan, additional, Keefe, Damian, additional, Schwartz, Ariel S., additional, Hou, Minmei, additional, Taylor, James, additional, Nikolaev, Sergey, additional, Montoya-Burgos, Juan I., additional, Löytynoja, Ari, additional, Whelan, Simon, additional, Pardi, Fabio, additional, Massingham, Tim, additional, Brown, James B., additional, Bickel, Peter, additional, Holmes, Ian, additional, Mullikin, James C., additional, Ureta-Vidal, Abel, additional, Paten, Benedict, additional, Stone, Eric A., additional, Rosenbloom, Kate R., additional, Kent, W. James, additional, Bouffard, Gerard G., additional, Guan, Xiaobin, additional, Hansen, Nancy F., additional, Idol, Jacquelyn R., additional, Maduro, Valerie V.B., additional, Maskeri, Baishali, additional, McDowell, Jennifer C., additional, Park, Morgan, additional, Thomas, Pamela J., additional, Young, Alice C., additional, Blakesley, Robert W., additional, Muzny, Donna M., additional, Sodergren, Erica, additional, Wheeler, David A., additional, Worley, Kim C., additional, Jiang, Huaiyang, additional, Weinstock, George M., additional, Gibbs, Richard A., additional, Graves, Tina, additional, Fulton, Robert, additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Clamp, Michele, additional, Cuff, James, additional, Gnerre, Sante, additional, Jaffe, David B., additional, Chang, Jean L., additional, Lindblad-Toh, Kerstin, additional, Lander, Eric S., additional, Hinrichs, Angie, additional, Trumbower, Heather, additional, Clawson, Hiram, additional, Zweig, Ann, additional, Kuhn, Robert M., additional, Barber, Galt, additional, Harte, Rachel, additional, Karolchik, Donna, additional, Field, Matthew A., additional, Moore, Richard A., additional, Matthewson, Carrie A., additional, Schein, Jacqueline E., additional, Marra, Marco A., additional, Antonarakis, Stylianos E., additional, Batzoglou, Serafim, additional, Goldman, Nick, additional, Hardison, Ross, additional, Haussler, David, additional, Miller, Webb, additional, Pachter, Lior, additional, Green, Eric D., additional, and Sidow, Arend, additional

Published
2007
Full Text
View/download PDF

20. Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome.

Author

DeSilva, Udaya, Elnitski, Laura, Idol, Jacquelyn R, Doyle, Johannah L, Gan, Weiniu, Thomas, James W, Schwartz, Scott, Dietrich, Nicole L, Beckstrom-Sternberg, Stephen M, McDowell, Jennifer C, Blakesley, Robert W, Bouffard, Gerard G, Thomas, Pamela J, Touchman, Jeffrey W, Miller, Webb, and Green, Eric D

Abstract

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a approximately 1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (approximately 300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of approximately 3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder.

Published
2002
Full Text
View/download PDF

21. Structural and Functional Cross-Talk between a Distant Enhancer and the ?-Globin Gene Promoter Shows Interdependence of the Two Elements in Chromatin

Author

McDowell, Jennifer C. and Dean, Ann

Abstract

ABSTRACTWe investigated the requirements for enhancer-promoter communication by using the human ß-globin locus control region (LCR) DNase I-hypersensitive site 2 (HS2) enhancer and the ?-globin gene in chromatinized minichromosomes in erythroid cells. Activation of globin genes during development is accompanied by localized alterations of chromatin structure, and CACCC binding factors and GATA-1, which interact with both globin promoters and the LCR, are believed to be critical for globin gene transcription activation. We found that an HS2 element mutated in its GATA motif failed to remodel the ?-globin promoter or activate transcription yet HS2 nuclease accessibility did not change. Accessibility and transcription were reduced at promoters with mutated GATA-1 or CACCC sites. Strikingly, these mutations also resulted in reduced accessibility at HS2. In the absence of a globin gene, HS2 is similarly resistant to nuclease digestion. In contrast to observations in Saccharomyces cerevisiae, HS2-dependent promoter remodeling was diminished when we mutated the TATA box, crippling transcription. This mutation also reduced HS2 accessibility. The results indicate that the ?-globin promoter and HS2 interact both structurally and functionally and that both upstream activators and the basal transcription apparatus contribute to the interaction. Further, at least in this instance, transcription activation and promoter remodeling by a distant enhancer are not separable.

Published
1999
Full Text
View/download PDF

22. Arts in the Garden.

Author

MCDOWELL, JENNIFER C.

Subjects
ARTS, GARDENS, HORTICULTURE, POETS, CHILDREN, SCULPTURE, WATER in art
Abstract

The author offers tips on incorporating arts in gardens during interpretive horticulture programs. She suggests inviting poets to share their works. She also recommends creating mud pies to engage the senses of participants, especially children, in creating sculptures of soil, water and flower cuttings. Other ways are reading a related story and collaborating cultural organizations.

Published
2013

23. Beta-globin locus control region HS2 and HS3 interact structurally and functionally.

Author

Jackson DA, McDowell JC, and Dean A

Subjects
Binding Sites, DNA-Binding Proteins genetics, DNA-Binding Proteins physiology, Gene Expression Regulation, Globins metabolism, Humans, K562 Cells, Kruppel-Like Transcription Factors, Plasmids genetics, RNA genetics, RNA metabolism, Transcription Factors genetics, Transcription Factors physiology, Transcription, Genetic, Transfection, Globins genetics, Regulatory Sequences, Nucleic Acid genetics
Abstract

The overall structure of the DNase I hypersensitive sites (HSs) that comprise the beta-globin locus control region (LCR) is highly conserved among mammals, implying that the HSs have conserved functions. However, it is not well understood how the LCR HSs, either individually or collectively, activate transcription. We analyzed the interactions of HS2, HS3 and HS4 with the human epsilon- and beta-globin genes in chromatinized episomes in fetal/embryonic K562 cells. Only HS2 activates transcription of the epsilon-globin gene, while all three HSs activate the beta-globin gene. HS3 stimulates the beta-globin gene constitutively, but HS2 and HS4 transactivation requires expression of the transcription factor EKLF, which is not present in K562 cells but is required for beta-globin expression in vivo. To begin addressing how the individual HSs may interact with one another in a complex, we linked the beta-globin gene to both the HS2 and HS3. HS2 and HS3 together resulted in synergistic stimulation of beta-globin transcription. Unexpectedly, mutated, inactive forms of HS2 impeded the activation of the beta-globin gene by HS3. Thus, there appear to be distinct interactions among the HSs and between the HSs and the globin genes. These preferential, non-exclusive interactions may underlie an important structural and functional cooperativity among the regulatory sequences of the beta-globin locus in vivo.

Published
2003
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results