Search

Your search keyword '"Blakesley, Robert W"' showing total 49 results
Start Over Author "Blakesley, Robert W"
49 results on '"Blakesley, Robert W"'

3. 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

6. pDUAL: a transposon-based cosmid cloning vector for generating nested deletions and DNA sequencing templates in vivo

Author

Gan Wang, Blakesley, Robert W., Berg, Douglas E., and Berg, Claire M.

Subjects
Transposons -- Genetic aspects, Genetic vectors -- Usage, Science and technology
Abstract

A transposon gamma delta-containing cosmid cloning vector, pDUAL, which can be used in isolated rested deletions in large-scale and small-scale DNA sequencing, was built. pDUAL, previously termed pJANUS, uses the capacity of gamma delta to produce deletion that stretch from a tip of the transposon into nearby DNA, when the gamma delta transposes to fuse regions in the same DNA molecule.

Published
1993

7. Genomic organization, evolution, and expression of photoprotein and opsin genes in Mnemiopsis leidyi: a new view of ctenophore photocytes

Author

Schnitzler Christine E, Pang Kevin, Powers Meghan L, Reitzel Adam M, Ryan Joseph F, Simmons David, Tada Takashi, Park Morgan, Gupta Jyoti, Brooks Shelise Y, Blakesley Robert W, Yokoyama Shozo, Haddock Steven HD, Martindale Mark Q, and Baxevanis Andreas D

Subjects
Bioluminescence, ctenophore, Mnemiopsis leidyi, opsin, photocyte, photoprotein, photoreception, phototransduction, Biology (General), QH301-705.5
Abstract

Abstract Background Calcium-activated photoproteins are luciferase variants found in photocyte cells of bioluminescent jellyfish (Phylum Cnidaria) and comb jellies (Phylum Ctenophora). The complete genomic sequence from the ctenophore Mnemiopsis leidyi, a representative of the earliest branch of animals that emit light, provided an opportunity to examine the genome of an organism that uses this class of luciferase for bioluminescence and to look for genes involved in light reception. To determine when photoprotein genes first arose, we examined the genomic sequence from other early-branching taxa. We combined our genomic survey with gene trees, developmental expression patterns, and functional protein assays of photoproteins and opsins to provide a comprehensive view of light production and light reception in Mnemiopsis. Results The Mnemiopsis genome has 10 full-length photoprotein genes situated within two genomic clusters with high sequence conservation that are maintained due to strong purifying selection and concerted evolution. Photoprotein-like genes were also identified in the genomes of the non-luminescent sponge Amphimedon queenslandica and the non-luminescent cnidarian Nematostella vectensis, and phylogenomic analysis demonstrated that photoprotein genes arose at the base of all animals. Photoprotein gene expression in Mnemiopsis embryos begins during gastrulation in migrating precursors to photocytes and persists throughout development in the canals where photocytes reside. We identified three putative opsin genes in the Mnemiopsis genome and show that they do not group with well-known bilaterian opsin subfamilies. Interestingly, photoprotein transcripts are co-expressed with two of the putative opsins in developing photocytes. Opsin expression is also seen in the apical sensory organ. We present evidence that one opsin functions as a photopigment in vitro, absorbing light at wavelengths that overlap with peak photoprotein light emission, raising the hypothesis that light production and light reception may be functionally connected in ctenophore photocytes. We also present genomic evidence of a complete ciliary phototransduction cascade in Mnemiopsis. Conclusions This study elucidates the genomic organization, evolutionary history, and developmental expression of photoprotein and opsin genes in the ctenophore Mnemiopsis leidyi, introduces a novel dual role for ctenophore photocytes in both bioluminescence and phototransduction, and raises the possibility that light production and light reception are linked in this early-branching non-bilaterian animal.

Published
2012
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. The completion of the Mammalian Gene Collection (MGC)

Author

Temple, Gary, Gerhard, Daniela, Rasooly, S. Rebekah, Feingold, Elise A., Good, Peter J., Robinson, Cristen, Mandich, Allison, Derge, Jeffrey G., Lewis, Jeanne, Shoaf, Debonny, Collins, Francis S., Wonhee Jang, Wagner, Lukas, Shenmen, Carolyn M., Misquitta, Leonie, Schaefer, Carl F., Buetow, Kenneth H., Bonner, Tom I., Yankie, Linda, Ward, Ming, Phan, Lon, Astashyn, Alex, Brown, Garth, Farrell, Catherine, Hart, Jennifer, Landrum, Melissa, Maidak, Bonnie L., Murphy, Michael, Murphy, Terence, Rajput, Bhanu, Riddick, Lillian, Webb, David, Weber, Janet, Wu, Wendy, Pruitt, Kim D., Maglott, Donna, Siepel, Adam, Brejova, Brona, Diekhans, Mark, Harte, Rachel, Baertsch, Robert, Kent, Jim, Haussler, David, Brent, Michael, Langton, Laura, Comstock, Charles L.G., Stevens, Michael, Chaochun Wei, van Baren, Marijke J., Salehi-Ashtiani, Kourosh, Murray, Ryan R., Ghamsari, Lila, Mello, Elizabeth, Chenwei Lin, Pennacchio, Christa, Schreiber, Kirsten, Shapiro, Nicole, Marsh, Amber, Pardes, Elizabeth, Moore, Troy, Lebeau, Anita, Muratet, Mike, Simmons, Blake, Kloske, David, Sieja, Stephanie, Hudson, James, Sethupathy, Praveen, Brownstein, Michael, Bhat, Narayan, Lazar, Joseph, Jacob, Howard, Gruber, Chris E., Smith, Mark R., McPherson, John, Garcia, Angela M., Gunaratne, Preethi H., Jiaqian Wu, Muzny, Donna, Gibbs, Richard A., Young, Alice C., Bouffard, Gerard G., Blakesley, Robert W., Mullikin, Jim, Green, Eric D., Dickson, Mark C., Rodriguez, Alex C., Grimwood, Jane, Schmutz, Jeremy, Myers, Richard M., Hirst, Martin, Zeng, Thomas, Kane Tse, Moksa, Michelle, Deng, Merinda, Ma, Kevin, Mah, Diana, Pang, Johnson, Taylor, Greg, Chuah, Eric, Deng, Athena, Fichter, Keith, Go, Anne, Lee, Stephanie, Jing Wang, Griffith, Malachi, Morin, Ryan, Moore, Richard A., Mayo, Michael, Munro, Sarah, Wagner, Susan, Jones, Steven J.M., Holt, Robert A., Marra, Marco A., Sun Lu, Shuwei Yang, Hartigan, James, Graf, Marcus, Wagner, Ralf, Letovksy, Stanley, Pulido, Jacqueline C., Robison, Keith, Esposito, Dominic, Hartley, James, Wall, Vanessa E., Hopkins, Ralph F., Osamu Ohara, and Wiemann, Stefan

Subjects
DNA synthesis -- Research, Mammals -- Genetic aspects, Nucleotide sequencing -- Evaluation, Genetic transcription -- Research, Health
Published
2009

10. The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine

Author

Biesecker, Leslie G., Mullikin, James C., Facio, Flavia M., Turner, Clesson, Cherukuri, Praveen F., Blakesley, Robert W., Bouffard, Gerard G., Chines, Peter S., Cruz, Pedro, Hansen, Nancy F., Teer, Jamie K., Maskeri, Baishali, Young, Alice C., Manolio, Teri A., Wilson, Alexander F., Finkel, Toren, Hwang, Paul, Arai, Andrew, Remaley, Alan T., Sachdev, Vandana, Shamburek, Robert, Cannon, Richard O., and Green, Eric D.

Subjects
Nucleotide sequence -- Analysis, Human genome -- Research, Medical genetics -- Research, Health
Published
2009

11. A diversity profile of the human skin microbiota

Author

Grice, Elizabeth A., Kong, Heidi H., Renaud, Gabriel, Young, Alice C., Bouffard, Gerard G., Blakesley, Robert W., Wolfsberg, Tyra G., Turner, Maria L., and Segre, Julia A.

Subjects
Ribosomal RNA -- Research, Microbiota (Symbiotic organisms) -- Research, Health
Abstract

A study was conducted to analyze 16S rRNA gene survey of the resident skin microbiota of the antecubital fossae (inner elbow) region from healthy humans. The results would provide insight into the role of skin microbiota in health and disease and metagenomic projects and address the complex physiological interactions between the skin and the microbes.

Published
2008

12. Sequencing and analysis of 10,967 full-length cDNA clones from Xenopus laevis and Xenopus tropicalis reveals post-tetraploidization transcriptome remodeling

Author

Morin, Ryan D., Chang, Elbert, Petrescu, Anca, Liao, Nancy, Griffith, Malachi, Jones, Steven J.M., Holt, Robert A., Kirkpatrick, Robert, Butterfield, Yaron S., Young, Alice C., Stott, Jeffrey, Barber, Sarah, Pennacchio, Christa Prange, Myers, Richard M., Green, Eric D., Wagner, Lukas, Gerhard, Daniela S., Marra, Marco A., Babakaiff, Ryan, Dickson, Mark C., Matsuo, Corey, Wong, David, Yang, George S., Blakesley, Robert W., Zeeberg, Barry R., Narasimhan, Sudarshan, Weinstein, John N., Smailus, Duan E, Wetherby, Keith D., Kwong, Peggy N., Grimwood, Jane, Brinkley, Charles P., III, Tsai, Miranda, Featherstone, Ruth, Chand, Steve, Siddiqui, Asim S., Wonhee Jang, Ed Lee, Klein, Steven L., Brown-John, Mabel, Reddix-Dugue, Natalie D., Mayo, Michael, Schmutz, Jeremy, Beland, Jaclyn, Park, Morgan, Gibson, Susan, Olson, Teika, and Bouffard, Gerard G.

Subjects
Xenopus -- Genetic aspects, Xenopus -- Physiological aspects, Nucleotide sequencing -- Analysis, Cloning -- Usage, Chromosome mapping -- Usage, Health
Abstract

Around 10,967 full ORF verified cDNA clones from Xenopus laevis and 2918 from Xenopus tropicalis are presented as a community resource. It was found that the paralogs that are lost since the tetraploidization events are enriched for several molecular functions, but have found no such enrichment in the extant paralogs.

Published
2006

13. 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

14. 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

15. 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

16. 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

17. Personalized genomic medicine: Lessons from the exome

Author

Solomon, Benjamin D., Pineda-Alvarez, Daniel E., Hadley, Donald W., NISC Comparative Sequencing Program, Teer, Jamie K., Cherukuri, Praveen F., Hansen, Nancy F., Cruz, Pedro, Young, Alice C., Blakesley, Robert W., Lanpher, Brendan, Mayfield Gibson, Stephanie, Sincan, Murat, Chandrasekharappa, Settara C., and Mullikin, James C.

Published
2011
Full Text
View/download PDF

22. Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

Author

Bentley, Amy R., primary, Chen, Guanjie, additional, Shriner, Daniel, additional, Doumatey, Ayo P., additional, Zhou, Jie, additional, Huang, Hanxia, additional, Mullikin, James C., additional, Blakesley, Robert W., additional, Hansen, Nancy F., additional, Bouffard, Gerard G., additional, Cherukuri, Praveen F., additional, Maskeri, Baishali, additional, Young, Alice C., additional, Adeyemo, Adebowale, additional, and Rotimi, Charles N., additional

Published
2014
Full Text
View/download PDF

23. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

Author

Pierson, Tyler Mark, Adams, David, Bonn, Florian, Martinelli, Paola, Cherukuri, Praveen F., Teer, Jamie K., Hansen, Nancy F., Cruz, Pedro, Mullikin, James C., Blakesley, Robert W., Golas, Gretchen, Kwan, Justin, Sandler, Anthony, Fajardo, Karin Fuentes, Markello, Thomas, Tifft, Cynthia, Blackstone, Craig, Rugarli, Elena I., Langer, Thomas, Gahl, William A., Toro, Camilo, Pierson, Tyler Mark, Adams, David, Bonn, Florian, Martinelli, Paola, Cherukuri, Praveen F., Teer, Jamie K., Hansen, Nancy F., Cruz, Pedro, Mullikin, James C., Blakesley, Robert W., Golas, Gretchen, Kwan, Justin, Sandler, Anthony, Fajardo, Karin Fuentes, Markello, Thomas, Tifft, Cynthia, Blackstone, Craig, Rugarli, Elena I., Langer, Thomas, Gahl, William A., and Toro, Camilo

Abstract

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other mitochondrial'' features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.

Published
2011

24. Correction: Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

Author

Pierson, Tyler Mark, primary, Adams, David, additional, Bonn, Florian, additional, Martinelli, Paola, additional, Cherukuri, Praveen F., additional, Teer, Jamie K., additional, Hansen, Nancy F., additional, Cruz, Pedro, additional, Mullikin, James C., additional, Blakesley, Robert W., additional, Golas, Gretchen, additional, Kwan, Justin, additional, Sandler, Anthony, additional, Fuentes Fajardo, Karin, additional, Markello, Thomas, additional, Tifft, Cynthia, additional, Blackstone, Craig, additional, Rugarli, Elena I., additional, Langer, Thomas, additional, Gahl, William A., additional, and Toro, Camilo, additional

Published
2013
Full Text
View/download PDF

25. 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

26. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

Author

Pierson, Tyler Mark, primary, Adams, David, additional, Bonn, Florian, additional, Martinelli, Paola, additional, Cherukuri, Praveen F., additional, Teer, Jamie K., additional, Hansen, Nancy F., additional, Cruz, Pedro, additional, Mullikin for the NISC Comparative Sequencing Program, James C., additional, Blakesley, Robert W., additional, Golas, Gretchen, additional, Kwan, Justin, additional, Sandler, Anthony, additional, Fuentes Fajardo, Karin, additional, Markello, Thomas, additional, Tifft, Cynthia, additional, Blackstone, Craig, additional, Rugarli, Elena I., additional, Langer, Thomas, additional, Gahl, William A., additional, and Toro, Camilo, additional

Published
2011
Full Text
View/download PDF

27. Erratum: Corrigendum: TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum

Author

Davis, Erica E, primary, Zhang, Qi, additional, Liu, Qin, additional, Diplas, Bill H, additional, Davey, Lisa M, additional, Hartley, Jane, additional, Stoetzel, Corinne, additional, Szymanska, Katarzyna, additional, Ramaswami, Gokul, additional, Logan, Clare V, additional, Muzny, Donna M, additional, Young, Alice C, additional, Wheeler, David A, additional, Cruz, Pedro, additional, Morgan, Margaret, additional, Lewis, Lora R, additional, Cherukuri, Praveen, additional, Maskeri, Baishali, additional, Hansen, Nancy F, additional, Mullikin, James C, additional, Blakesley, Robert W, additional, Bouffard, Gerard G, additional, Gyapay, Gabor, additional, Rieger, Susanne, additional, Tönshoff, Burkhard, additional, Kern, Ilse, additional, Soliman, Neveen A, additional, Neuhaus, Thomas J, additional, Swoboda, Kathryn J, additional, Kayserili, Hulya, additional, Gallagher, Tomas E, additional, Lewis, Richard A, additional, Bergmann, Carsten, additional, Otto, Edgar A, additional, Saunier, Sophie, additional, Scambler, Peter J, additional, Beales, Philip L, additional, Gleeson, Joseph G, additional, Maher, Eamonn R, additional, Attié-Bitach, Tania, additional, Dollfus, Hélène, additional, Johnson, Colin A, additional, Green, Eric D, additional, Gibbs, Richard A, additional, Hildebrandt, Friedhelm, additional, Pierce, Eric A, additional, and Katsanis, Nicholas, additional

Published
2011
Full Text
View/download PDF

28. 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

29. Cycle Sequencing.

Author

Walker, John M., Graham, Colin A., Hill, Alison J. M., and Blakesley, Robert W.

Abstract

Cycle sequencing is a variant of standard dideoxy, chain terminator DNA sequencing (1-3). The protocol has gained popularity owing to at least three features: simple execution, robust performance, and signal amplification. The main characteristic that defines the cycle sequencing protocol is that the sequencing reactions are incubated in a thermal cycler, with programs similar to those used in polymerase chain reaction (PCR). This method assures efficient, reproducible utilization of even difficult templates by repeated thermal denaturation of the DNA template during the sequencing reactions. In fact, through heat cycling the same template molecules are used repeatedly, resulting in accumulation of sufficient sequencing signal even when a very limited amount of template is used, for example, when sequencing DNA from single bacterial colonies or phage plaques (4,5). It should be made clear, however, that no new template molecules are created as they are in PCR; cycle sequencing products accumulate linearly, not geometrically, in this single-primer DNA synthesis reaction. Cycle sequencing can be performed using a variety of labeling and detection techniques. The following protocol utilizes radioactive end-labeled primer and X-ray film. [ABSTRACT FROM AUTHOR]

Published
2001
Full Text
View/download PDF

31. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae.

Author

Conlan, Sean, Thomas, Pamela J., Deming, Clayton, Park, Morgan, Lau, Anna F., Dekker, John P., Snitkin, Evan S., Clark, Tyson A., Khai Luong, Yi Song, Yu-Chih Tsai, Boitano, Matthew, Dayal, Jyoti, Brooks, Shelise Y., Schmidt, Brian, Young, Alice C., Thomas, James W., Bouffard, Gerard G., Blakesley, Robert W., and Mullikin, James C.

Published
2014
Full Text
View/download PDF

33. Cycle Sequencing.

Author

Walker, John M., Griffin, Hugh G., Griffin, Annette M., and Blakesley, Robert W.

Abstract

Cycle sequencing (1,2) is a simple, yet powerful tool for conveniently sequencing double-stranded DNA (dsDNA). As in other dideoxy sequencing methods (3-5) dsDNA is denatured, a primer is annealed, then a complementary oligonucleotide is synthesized by a DNA poIymerase until extension is terminated by incorporation of a dideoxynucleotide. The difference is that in cycle sequencing this series of events occurs not once, but 20-30 times in succession under the control of a thermal cycler. The result is more, clearer, and stronger sequence from dsDNA for less effort. [ABSTRACT FROM AUTHOR]

Published
1993
Full Text
View/download PDF

36. The Role of DNA Structure in Genetic Regulatio.

Author

Wells, Robert D., Blakesley, Robert W., Hardies, Stephen C., Horn, Glenn T., Larson, Jacquelynn E., Seising, Erik, Burd, John F., Chan, Hardy W., Dodgson, Jerry B., Jensen, Kaj Frank, Nes, Ingolf F., Wartell, Roger M., and von Hippel, Peter H.

Published
1977
Full Text
View/download PDF

41. 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

42. Marek's Disease Herpesvirus-Induced DNA Polymerase

Author

Boezi, John A., Lee, Lucy F., Blakesley, Robert W., Koenig, Mark, and Towle, Howard C.

Abstract

Infection of duck embryo fibroblasts by Marek's disease herpesvirus (MDHV), strain GA, led to the induction of a novel DNA polymerase. This novel DNA polymerase, designated MDHV-induced DNA polymerase, could be distinguished from the DNA polymerase activities of uninfected duck embryo fibroblasts by its chromatographic behavior on phosphocellulose, by its sedimentation coefficient, and by its catalytic properties. The characteristics of MDHV-induced DNA polymerase which had been purified by phosphocellulose chromatography were investigated. The sedimentation coefficient of the enzyme, as determined by sucrose density gradient centrifugation in the presence of 0.25 M KCl, was 5.9S. From this sedimentation coefficient, the molecular weight of MDHV-induced DNA polymerase was estimated to be 100,000. MDHV-induced DNA polymerase could not effectively use either poly(dA)·oligo(dT)12-18or poly(dC)·oligo(dG)12-18as a template-primer. The DNA polymerases from uninfected duck embryo fibroblasts could use these synthetic template-primers. MDHV-induced DNA polymerase also could not use poly(rA)·oligo(dT)12-18or poly(rC)·oligo(dG)12-18as template-primers or oligo(dT)12-18as a primer, indicating that it was not a polymerase of the type R-DNA polymerase, reverse transcriptase, or a terminal nucleotidyl transferase. In vitro synthesis of DNA by MDHV-induced DNA polymerase was markedly inhibited by the addition of (NH4)2SO4to the reaction mixture.

Published
1974
Full Text
View/download PDF

47. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.

Author

Davis EE, Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, Stoetzel C, Szymanska K, Ramaswami G, Logan CV, Muzny DM, Young AC, Wheeler DA, Cruz P, Morgan M, Lewis LR, Cherukuri P, Maskeri B, Hansen NF, Mullikin JC, Blakesley RW, Bouffard GG, Gyapay G, Rieger S, Tönshoff B, Kern I, Soliman NA, Neuhaus TJ, Swoboda KJ, Kayserili H, Gallagher TE, Lewis RA, Bergmann C, Otto EA, Saunier S, Scambler PJ, Beales PL, Gleeson JG, Maher ER, Attié-Bitach T, Dollfus H, Johnson CA, Green ED, Gibbs RA, Hildebrandt F, Pierce EA, and Katsanis N

Subjects
Animals, Genetic Variation, Humans, Mice, Mutation, Pedigree, Photoreceptor Cells physiology, Zebrafish genetics, Adaptor Proteins, Signal Transducing genetics, Alleles, Ciliary Motility Disorders genetics
Abstract

Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ∼5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders.

Published
2011
Full Text
View/download PDF

48. Genome sequence of the Brown Norway rat yields insights into mammalian evolution.

Author

Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Simons R, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Albà M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hübner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, López-Otín C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, and Collins F

Subjects
Animals, Base Composition, Centromere genetics, Chromosomes, Mammalian genetics, CpG Islands genetics, DNA Transposable Elements genetics, DNA, Mitochondrial genetics, Gene Duplication, Humans, Introns genetics, Male, Mice, Models, Molecular, Mutagenesis, Polymorphism, Single Nucleotide genetics, RNA Splice Sites genetics, RNA, Untranslated genetics, Rats, Regulatory Sequences, Nucleic Acid genetics, Retroelements genetics, Sequence Analysis, DNA, Telomere genetics, Evolution, Molecular, Genome, Genomics, Rats, Inbred BN genetics
Abstract

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

Published
2004
Full Text
View/download PDF

49. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.

Author

Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, and Marra MA

Subjects
Algorithms, Animals, DNA, Complementary analysis, Gene Library, Humans, Mice, Open Reading Frames, DNA, Complementary chemistry, Sequence Analysis, DNA
Abstract

The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence a cDNA clone containing a complete ORF for each human and mouse gene. ESTs were generated from libraries enriched for full-length cDNAs and analyzed to identify candidate full-ORF clones, which then were sequenced to high accuracy. The MGC has currently sequenced and verified the full ORF for a nonredundant set of >9,000 human and >6,000 mouse genes. Candidate full-ORF clones for an additional 7,800 human and 3,500 mouse genes also have been identified. All MGC sequences and clones are available without restriction through public databases and clone distribution networks (see http:mgc.nci.nih.gov).

Published
2002
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results