%0 Journal Article %J Nature %D 2007 %T Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. %A Birney, Ewan %A Stamatoyannopoulos, John A %A Dutta, Anindya %A Guigó, Roderic %A Gingeras, Thomas R %A Margulies, Elliott H %A Weng, Zhiping %A Snyder, Michael %A Dermitzakis, Emmanouil T %A Thurman, Robert E %A Kuehn, Michael S %A Taylor, Christopher M %A Neph, Shane %A Koch, Christoph M %A Asthana, Saurabh %A Malhotra, Ankit %A Adzhubei, Ivan %A Greenbaum, Jason A %A Andrews, Robert M %A Flicek, Paul %A Boyle, Patrick J %A Cao, Hua %A Carter, Nigel P %A Clelland, Gayle K %A Davis, Sean %A Day, Nathan %A Dhami, Pawandeep %A Dillon, Shane C %A Dorschner, Michael O %A Fiegler, Heike %A Giresi, Paul G %A Goldy, Jeff %A Hawrylycz, Michael %A Haydock, Andrew %A Humbert, Richard %A James, Keith D %A Johnson, Brett E %A Johnson, Ericka M %A Frum, Tristan T %A Rosenzweig, Elizabeth R %A Karnani, Neerja %A Lee, Kirsten %A Lefebvre, Gregory C %A Navas, Patrick A %A Neri, Fidencio %A Parker, Stephen C J %A Sabo, Peter J %A Sandstrom, Richard %A Shafer, Anthony %A Vetrie, David %A Weaver, Molly %A Wilcox, Sarah %A Yu, Man %A Collins, Francis S %A Dekker, Job %A Lieb, Jason D %A Tullius, Thomas D %A Crawford, Gregory E %A Sunyaev, Shamil %A Noble, William S %A Dunham, Ian %A Denoeud, France %A Reymond, Alexandre %A Kapranov, Philipp %A Rozowsky, Joel %A Zheng, Deyou %A Castelo, Robert %A Frankish, Adam %A Harrow, Jennifer %A Ghosh, Srinka %A Sandelin, Albin %A Hofacker, Ivo L %A Baertsch, Robert %A Keefe, Damian %A Dike, Sujit %A Cheng, Jill %A Hirsch, Heather A %A Sekinger, Edward A %A Lagarde, Julien %A Abril, Josep F %A Shahab, Atif %A Flamm, Christoph %A Fried, Claudia %A Hackermüller, Jörg %A Hertel, Jana %A Lindemeyer, Manja %A Missal, Kristin %A Tanzer, Andrea %A Washietl, Stefan %A Korbel, Jan %A Emanuelsson, Olof %A Pedersen, Jakob S %A Holroyd, Nancy %A Taylor, Ruth %A Swarbreck, David %A Matthews, Nicholas %A Dickson, Mark C %A Thomas, Daryl J %A Weirauch, Matthew T %A Gilbert, James %A Drenkow, Jorg %A Bell, Ian %A Zhao, XiaoDong %A Srinivasan, K G %A Sung, Wing-Kin %A Ooi, Hong Sain %A Chiu, Kuo Ping %A Foissac, Sylvain %A Alioto, Tyler %A Brent, Michael %A Pachter, Lior %A Tress, Michael L %A Valencia, Alfonso %A Choo, Siew Woh %A Choo, Chiou Yu %A Ucla, Catherine %A Manzano, Caroline %A Wyss, Carine %A Cheung, Evelyn %A Clark, Taane G %A Brown, James B %A Ganesh, Madhavan %A Patel, Sandeep %A Tammana, Hari %A Chrast, Jacqueline %A Henrichsen, Charlotte N %A Kai, Chikatoshi %A Kawai, Jun %A Nagalakshmi, Ugrappa %A Wu, Jiaqian %A Lian, Zheng %A Lian, Jin %A Newburger, Peter %A Zhang, Xueqing %A Bickel, Peter %A Mattick, John S %A Carninci, Piero %A Hayashizaki, Yoshihide %A Weissman, Sherman %A Hubbard, Tim %A Myers, Richard M %A Rogers, Jane %A Stadler, Peter F %A Lowe, Todd M %A Wei, Chia-Lin %A Ruan, Yijun %A Struhl, Kevin %A Gerstein, Mark %A Antonarakis, Stylianos E %A Fu, Yutao %A Green, Eric D %A Karaöz, Ulaş %A Siepel, Adam %A Taylor, James %A Liefer, Laura A %A Wetterstrand, Kris A %A Good, Peter J %A Feingold, Elise A %A Guyer, Mark S %A Cooper, Gregory M %A Asimenos, George %A Dewey, Colin N %A Hou, Minmei %A Nikolaev, Sergey %A Montoya-Burgos, Juan I %A Löytynoja, Ari %A Whelan, Simon %A Pardi, Fabio %A Massingham, Tim %A Huang, Haiyan %A Zhang, Nancy R %A Holmes, Ian %A Mullikin, James C %A Ureta-Vidal, Abel %A Paten, Benedict %A Seringhaus, Michael %A Church, Deanna %A Rosenbloom, Kate %A Kent, W James %A Stone, Eric A %A Batzoglou, Serafim %A Goldman, Nick %A Hardison, Ross C %A Haussler, David %A Miller, Webb %A Sidow, Arend %A Trinklein, Nathan D %A Zhang, Zhengdong D %A Barrera, Leah %A Stuart, Rhona %A King, David C %A Ameur, Adam %A Enroth, Stefan %A Bieda, Mark C %A Kim, Jonghwan %A Bhinge, Akshay A %A Jiang, Nan %A Liu, Jun %A Yao, Fei %A Vega, Vinsensius B %A Lee, Charlie W H %A Ng, Patrick %A Shahab, Atif %A Yang, Annie %A Moqtaderi, Zarmik %A Zhu, Zhou %A Xu, Xiaoqin %A Squazzo, Sharon %A Oberley, Matthew J %A Inman, David %A Singer, Michael A %A Richmond, Todd A %A Munn, Kyle J %A Rada-Iglesias, Alvaro %A Wallerman, Ola %A Komorowski, Jan %A Fowler, Joanna C %A Couttet, Phillippe %A Bruce, Alexander W %A Dovey, Oliver M %A Ellis, Peter D %A Langford, Cordelia F %A Nix, David A %A Euskirchen, Ghia %A Hartman, Stephen %A Urban, Alexander E %A Kraus, Peter %A Van Calcar, Sara %A Heintzman, Nate %A Kim, Tae Hoon %A Wang, Kun %A Qu, Chunxu %A Hon, Gary %A Luna, Rosa %A Glass, Christopher K %A Rosenfeld, M Geoff %A Aldred, Shelley Force %A Cooper, Sara J %A Halees, Anason %A Lin, Jane M %A Shulha, Hennady P %A Zhang, Xiaoling %A Xu, Mousheng %A Haidar, Jaafar N S %A Yu, Yong %A Ruan, Yijun %A Iyer, Vishwanath R %A Green, Roland D %A Wadelius, Claes %A Farnham, Peggy J %A Ren, Bing %A Harte, Rachel A %A Hinrichs, Angie S %A Trumbower, Heather %A Clawson, Hiram %A Hillman-Jackson, Jennifer %A Zweig, Ann S %A Smith, Kayla %A Thakkapallayil, Archana %A Barber, Galt %A Kuhn, Robert M %A Karolchik, Donna %A Armengol, Lluis %A Bird, Christine P %A de Bakker, Paul I W %A Kern, Andrew D %A Lopez-Bigas, Nuria %A Martin, Joel D %A Stranger, Barbara E %A Woodroffe, Abigail %A Davydov, Eugene %A Dimas, Antigone %A Eyras, Eduardo %A Hallgrímsdóttir, Ingileif B %A Huppert, Julian %A Zody, Michael C %A Abecasis, Gonçalo R %A Estivill, Xavier %A Bouffard, Gerard G %A Guan, Xiaobin %A Hansen, Nancy F %A Idol, Jacquelyn R %A Maduro, Valerie V B %A Maskeri, Baishali %A McDowell, Jennifer C %A Park, Morgan %A Thomas, Pamela J %A Young, Alice C %A Blakesley, Robert W %A Muzny, Donna M %A Sodergren, Erica %A Wheeler, David A %A Worley, Kim C %A Jiang, Huaiyang %A Weinstock, George M %A Gibbs, Richard A %A Graves, Tina %A Fulton, Robert %A Mardis, Elaine R %A Wilson, Richard K %A Clamp, Michele %A Cuff, James %A Gnerre, Sante %A Jaffe, David B %A Chang, Jean L %A Lindblad-Toh, Kerstin %A Lander, Eric S %A Koriabine, Maxim %A Nefedov, Mikhail %A Osoegawa, Kazutoyo %A Yoshinaga, Yuko %A Zhu, Baoli %A De Jong, Pieter J %K Chromatin %K Chromatin Immunoprecipitation %K Conserved Sequence %K DNA Replication %K Evolution, Molecular %K Exons %K Genetic Variation %K Genome, Human %K Genomics %K Heterozygote %K Histones %K Humans %K Pilot Projects %K Protein Binding %K Regulatory Sequences, Nucleic Acid %K RNA, Messenger %K RNA, Untranslated %K Transcription Factors %K Transcription Initiation Site %K Transcription, Genetic %X

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

%B Nature %V 447 %P 799-816 %8 2007 Jun 14 %G eng %N 7146 %1 https://www.ncbi.nlm.nih.gov/pubmed/17571346?dopt=Abstract %R 10.1038/nature05874 %0 Journal Article %J Nature %D 2004 %T Genome sequence of the Brown Norway rat yields insights into mammalian evolution. %A Gibbs, Richard A %A Weinstock, George M %A Metzker, Michael L %A Muzny, Donna M %A Sodergren, Erica J %A Scherer, Steven %A Scott, Graham %A Steffen, David %A Worley, Kim C %A Burch, Paula E %A Okwuonu, Geoffrey %A Hines, Sandra %A Lewis, Lora %A DeRamo, Christine %A Delgado, Oliver %A Dugan-Rocha, Shannon %A Miner, George %A Morgan, Margaret %A Hawes, Alicia %A Gill, Rachel %A Holt, Robert A %A Adams, Mark D %A Amanatides, Peter G %A Baden-Tillson, Holly %A Barnstead, Mary %A Chin, Soo %A Evans, Cheryl A %A Ferriera, Steve %A Fosler, Carl %A Glodek, Anna %A Gu, Zhiping %A Jennings, Don %A Kraft, Cheryl L %A Nguyen, Trixie %A Pfannkoch, Cynthia M %A Sitter, Cynthia %A Sutton, Granger G %A Venter, J Craig %A Woodage, Trevor %A Smith, Douglas %A Lee, Hong-Mei %A Gustafson, Erik %A Cahill, Patrick %A Kana, Arnold %A Doucette-Stamm, Lynn %A Weinstock, Keith %A Fechtel, Kim %A Weiss, Robert B %A Dunn, Diane M %A Green, Eric D %A Blakesley, Robert W %A Bouffard, Gerard G %A De Jong, Pieter J %A Osoegawa, Kazutoyo %A Zhu, Baoli %A Marra, Marco %A Schein, Jacqueline %A Bosdet, Ian %A Fjell, Chris %A Jones, Steven %A Krzywinski, Martin %A Mathewson, Carrie %A Siddiqui, Asim %A Wye, Natasja %A McPherson, John %A Zhao, Shaying %A Fraser, Claire M %A Shetty, Jyoti %A Shatsman, Sofiya %A Geer, Keita %A Chen, Yixin %A Abramzon, Sofyia %A Nierman, William C %A Havlak, Paul H %A Chen, Rui %A Durbin, K James %A Simons, Rain %A Ren, Yanru %A Song, Xing-Zhi %A Li, Bingshan %A Liu, Yue %A Qin, Xiang %A Cawley, Simon %A Worley, Kim C %A Cooney, A J %A D'Souza, Lisa M %A Martin, Kirt %A Wu, Jia Qian %A Gonzalez-Garay, Manuel L %A Jackson, Andrew R %A Kalafus, Kenneth J %A McLeod, Michael P %A Milosavljevic, Aleksandar %A Virk, Davinder %A Volkov, Andrei %A Wheeler, David A %A Zhang, Zhengdong %A Bailey, Jeffrey A %A Eichler, Evan E %A Tuzun, Eray %A Birney, Ewan %A Mongin, Emmanuel %A Ureta-Vidal, Abel %A Woodwark, Cara %A Zdobnov, Evgeny %A Bork, Peer %A Suyama, Mikita %A Torrents, David %A Alexandersson, Marina %A Trask, Barbara J %A Young, Janet M %A Huang, Hui %A Wang, Huajun %A Xing, Heming %A Daniels, Sue %A Gietzen, Darryl %A Schmidt, Jeanette %A Stevens, Kristian %A Vitt, Ursula %A Wingrove, Jim %A Camara, Francisco %A Mar Albà, M %A Abril, Josep F %A Guigó, Roderic %A Smit, Arian %A Dubchak, Inna %A Rubin, Edward M %A Couronne, Olivier %A Poliakov, Alexander %A Hübner, Norbert %A Ganten, Detlev %A Goesele, Claudia %A Hummel, Oliver %A Kreitler, Thomas %A Lee, Young-Ae %A Monti, Jan %A Schulz, Herbert %A Zimdahl, Heike %A Himmelbauer, Heinz %A Lehrach, Hans %A Jacob, Howard J %A Bromberg, Susan %A Gullings-Handley, Jo %A Jensen-Seaman, Michael I %A Kwitek, Anne E %A Lazar, Jozef %A Pasko, Dean %A Tonellato, Peter J %A Twigger, Simon %A Ponting, Chris P %A Duarte, Jose M %A Rice, Stephen %A Goodstadt, Leo %A Beatson, Scott A %A Emes, Richard D %A Winter, Eitan E %A Webber, Caleb %A Brandt, Petra %A Nyakatura, Gerald %A Adetobi, Margaret %A Chiaromonte, Francesca %A Elnitski, Laura %A Eswara, Pallavi %A Hardison, Ross C %A Hou, Minmei %A Kolbe, Diana %A Makova, Kateryna %A Miller, Webb %A Nekrutenko, Anton %A Riemer, Cathy %A Schwartz, Scott %A Taylor, James %A Yang, Shan %A Zhang, Yi %A Lindpaintner, Klaus %A Andrews, T Dan %A Caccamo, Mario %A Clamp, Michele %A Clarke, Laura %A Curwen, Valerie %A Durbin, Richard %A Eyras, Eduardo %A Searle, Stephen M %A Cooper, Gregory M %A Batzoglou, Serafim %A Brudno, Michael %A Sidow, Arend %A Stone, Eric A %A Venter, J Craig %A Payseur, Bret A %A Bourque, Guillaume %A López-Otín, Carlos %A Puente, Xose S %A Chakrabarti, Kushal %A Chatterji, Sourav %A Dewey, Colin %A Pachter, Lior %A Bray, Nicolas %A Yap, Von Bing %A Caspi, Anat %A Tesler, Glenn %A Pevzner, Pavel A %A Haussler, David %A Roskin, Krishna M %A Baertsch, Robert %A Clawson, Hiram %A Furey, Terrence S %A Hinrichs, Angie S %A Karolchik, Donna %A Kent, William J %A Rosenbloom, Kate R %A Trumbower, Heather %A Weirauch, Matt %A Cooper, David N %A Stenson, Peter D %A Ma, Bin %A Brent, Michael %A Arumugam, Manimozhiyan %A Shteynberg, David %A Copley, Richard R %A Taylor, Martin S %A Riethman, Harold %A Mudunuri, Uma %A Peterson, Jane %A Guyer, Mark %A Felsenfeld, Adam %A Old, Susan %A Mockrin, Stephen %A Collins, Francis %K Animals %K Base Composition %K Centromere %K Chromosomes, Mammalian %K CpG Islands %K DNA Transposable Elements %K DNA, Mitochondrial %K Evolution, Molecular %K Gene Duplication %K Genome %K Genomics %K Humans %K Introns %K Male %K Mice %K Models, Molecular %K Mutagenesis %K Polymorphism, Single Nucleotide %K Rats %K Rats, Inbred BN %K Regulatory Sequences, Nucleic Acid %K Retroelements %K RNA Splice Sites %K RNA, Untranslated %K Sequence Analysis, DNA %K Telomere %X

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.

%B Nature %V 428 %P 493-521 %8 2004 Apr 01 %G eng %N 6982 %1 https://www.ncbi.nlm.nih.gov/pubmed/15057822?dopt=Abstract %R 10.1038/nature02426 %0 Journal Article %J Genome Res %D 2004 %T Integrated and sequence-ordered BAC- and YAC-based physical maps for the rat genome. %A Krzywinski, Martin %A Wallis, John %A Gösele, Claudia %A Bosdet, Ian %A Chiu, Readman %A Graves, Tina %A Hummel, Oliver %A Layman, Dan %A Mathewson, Carrie %A Wye, Natasja %A Zhu, Baoli %A Albracht, Derek %A Asano, Jennifer %A Barber, Sarah %A Brown-John, Mabel %A Chan, Susanna %A Chand, Steve %A Cloutier, Alison %A Davito, Jonathon %A Fjell, Chris %A Gaige, Tony %A Ganten, Detlev %A Girn, Noreen %A Guggenheimer, Kurtis %A Himmelbauer, Heinz %A Kreitler, Thomas %A Leach, Stephen %A Lee, Darlene %A Lehrach, Hans %A Mayo, Michael %A Mead, Kelly %A Olson, Teika %A Pandoh, Pawan %A Prabhu, Anna-Liisa %A Shin, Heesun %A Tänzer, Simone %A Thompson, Jason %A Tsai, Miranda %A Walker, Jason %A Yang, George %A Sekhon, Mandeep %A Hillier, LaDeana %A Zimdahl, Heike %A Marziali, Andre %A Osoegawa, Kazutoyo %A Zhao, Shaying %A Siddiqui, Asim %A De Jong, Pieter J %A Warren, Wes %A Mardis, Elaine %A McPherson, John D %A Wilson, Richard %A Hübner, Norbert %A Jones, Steven %A Marra, Marco %A Schein, Jacqueline %K Animals %K Automation %K Chromosomes %K Chromosomes, Artificial, Bacterial %K Chromosomes, Artificial, Yeast %K Cloning, Molecular %K Computational Biology %K Contig Mapping %K DNA Fingerprinting %K Genetic Markers %K Genome %K Physical Chromosome Mapping %K Polymerase Chain Reaction %K Rats %K Sequence Analysis, DNA %X

As part of the effort to sequence the genome of Rattus norvegicus, we constructed a physical map comprised of fingerprinted bacterial artificial chromosome (BAC) clones from the CHORI-230 BAC library. These BAC clones provide approximately 13-fold redundant coverage of the genome and have been assembled into 376 fingerprint contigs. A yeast artificial chromosome (YAC) map was also constructed and aligned with the BAC map via fingerprinted BAC and P1 artificial chromosome clones (PACs) sharing interspersed repetitive sequence markers with the YAC-based physical map. We have annotated 95% of the fingerprint map clones in contigs with coordinates on the version 3.1 rat genome sequence assembly, using BAC-end sequences and in silico mapping methods. These coordinates have allowed anchoring 358 of the 376 fingerprint map contigs onto the sequence assembly. Of these, 324 contigs are anchored to rat genome sequences localized to chromosomes, and 34 contigs are anchored to unlocalized portions of the rat sequence assembly. The remaining 18 contigs, containing 54 clones, still require placement. The fingerprint map is a high-resolution integrative data resource that provides genome-ordered associations among BAC, YAC, and PAC clones and the assembled sequence of the rat genome.

%B Genome Res %V 14 %P 766-79 %8 2004 Apr %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/15060021?dopt=Abstract %R 10.1101/gr.2336604 %0 Journal Article %J Nature %D 2004 %T A physical map of the chicken genome. %A Wallis, John W %A Aerts, Jan %A Groenen, Martien A M %A Crooijmans, Richard P M A %A Layman, Dan %A Graves, Tina A %A Scheer, Debra E %A Kremitzki, Colin %A Fedele, Mary J %A Mudd, Nancy K %A Cardenas, Marco %A Higginbotham, Jamey %A Carter, Jason %A McGrane, Rebecca %A Gaige, Tony %A Mead, Kelly %A Walker, Jason %A Albracht, Derek %A Davito, Jonathan %A Yang, Shiaw-Pyng %A Leong, Shin %A Chinwalla, Asif %A Sekhon, Mandeep %A Wylie, Kristine %A Dodgson, Jerry %A Romanov, Michael N %A Cheng, Hans %A De Jong, Pieter J %A Osoegawa, Kazutoyo %A Nefedov, Mikhail %A Zhang, Hongbin %A McPherson, John D %A Krzywinski, Martin %A Schein, Jacquie %A Hillier, LaDeana %A Mardis, Elaine R %A Wilson, Richard K %A Warren, Wesley C %K Animals %K Chickens %K Chromosomes, Artificial, Bacterial %K Cloning, Molecular %K Contig Mapping %K DNA Fingerprinting %K Genetic Linkage %K Genome %K Genomics %K Physical Chromosome Mapping %K Sequence Tagged Sites %X

Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones. In an accompanying paper we describe the draft genome sequence of the chicken, Gallus gallus, the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes.

%B Nature %V 432 %P 761-4 %8 2004 Dec 09 %G eng %N 7018 %1 https://www.ncbi.nlm.nih.gov/pubmed/15592415?dopt=Abstract %R 10.1038/nature03030 %0 Journal Article %J J Exp Zool B Mol Dev Evol %D 2003 %T A proposal to sequence the amphioxus genome submitted to the Joint Genome Institute of the US Department of Energy. %A Gibson-Brown, Jeremy J %A Osoegawa, Kazutoyo %A McPherson, John D %A Waterston, Robert H %A De Jong, Pieter J %A Rokhsar, Daniel S %A Holland, Linda Z %K Animals %K Chordata, Nonvertebrate %K Genome %K Research Design %K Sequence Analysis, DNA %K United States %B J Exp Zool B Mol Dev Evol %V 300 %P 5-22 %8 2003 Dec 15 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/14984031?dopt=Abstract %R 10.1002/jez.b.42