Human genome connectivity code links disease-associated SNPs, microRNAs and pyknons

被引：11

作者：

Glinsky, Gennadi V. ^{[1
,2
]}

机构：

[1] Ordway Res Inst Inc, Ctr Med Sci, Ordway Canc Ctr, Albany Med Coll,Dept Pathol & Lab Med,Translat &, Albany, NY 12208 USA

[2] Ordway Res Inst Inc, Ctr Med Sci, Ordway Canc Ctr, Albany Med Coll,Div Urol,Dept Surg, Albany, NY 12208 USA

来源：

CELL CYCLE | 2009年 / 8卷 / 06期

关键词：

pyknons; human genome; templints; genome template design sequences; microRNAs; SNP variations; common human disorders; SYSTEMIC-LUPUS-ERYTHEMATOSUS; WIDE ASSOCIATION; COLORECTAL-CANCER; RHEUMATOID-ARTHRITIS; CONFER SUSCEPTIBILITY; GENETIC-VARIANTS; NUCLEAR IMPORT; MAPS MIRMAPS; RISK; LOCI;

D O I：

10.4161/cc.8.6.7937

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes. Here we report identification of ubiquitous template design sequences (templum intentio series, templints) of human genomes common for disease-associated SNPs, microRNAs and pyknons. We demonstrate that genome-unique SNP-coding sequences associated with multiple common human disorders appear assembled from series of ubiquitous short octamer sequences shared by 5'-UTR pyknons and microRNAs. Our analysis suggests that units of genetic information encoded in the linear sequences of the 3.6 billion bases of human genome are condensed in similar to 200,000 bases (0.006%) of 5'-UTR pyknons which are represented by hundreds of copies in a genome and utilized to build genome-unique sequences. Allele-specific sequence variations link disease-associated SNPs to distinct sets of pyknons and microRNAs, suggesting that increased susceptibility to multiple common human disorders is associated with global alterations of genome- wide regulatory templates affecting the biogenesis and functions of non-coding RNAs.

引用

页码：925 / 930

页数：6

共 37 条

[1] Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility [J].

Barton, Anne ;

Thomson, Wendy ;

Ke, Xiayi ;

Eyre, Steve ;

Hinks, Anne ;

Bowes, John ;

Gibbons, Laura ;

Plant, Darren ;

Wilson, Anthony G. ;

Marinou, Ioanna ;

Morgan, Ann ;

Emery, Paul ;

Steer, Sophia ;

Hocking, Lynne ;

Reid, David M. ;

Wordsworth, Paul ;

Harrison, Pille ;

Worthington, Jane .

HUMAN MOLECULAR GENETICS, 2008, 17 (15) :2274-2279

[2] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

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 .

NATURE, 2007, 447 (7146) :799-816

[3] A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk [J].

Broderick, Peter ;

Carvajal-Carmona, Luis ;

Pittman, Alan M. ;

Webb, Emily ;

Howarth, Kimberley ;

Rowan, Andrew ;

Lubbe, Steven ;

Spain, Sarah ;

Sullivan, Kate ;

Fielding, Sarah ;

Jaeger, Emma ;

Vijayakrishnan, Jayaram ;

Kemp, Zoe ;

Gorman, Maggie ;

Chandler, Ian ;

Papaemmanuil, Elli ;

Penegar, Steven ;

Wood, Wendy ;

Sellick, Gabrielle ;

Qureshi, Mobshra ;

Teixeira, Ana ;

Domingo, Enric ;

Barclay, Ella ;

Martin, Lynn ;

Sieber, Oliver ;

Kerr, David ;

Gray, Richard ;

Peto, Julian ;

Cazier, Jean-Baptiste ;

Tomlinson, Ian ;

Houlston, Richard S. .

NATURE GENETICS, 2007, 39 (11) :1315-1317

[4] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[5] A common coding variant in CASP8 is associated with breast cancer risk [J].

Cox, Angela ;

Dunning, Alison M. ;

Garcia-Closas, Montserrat ;

Balasubramanian, Sabapathy ;

Reed, Malcolm W. R. ;

Pooley, Karen A. ;

Scollen, Serena ;

Baynes, Caroline ;

Ponder, Bruce A. J. ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Brinton, Louise ;

Peplonska, Beata ;

Southey, Melissa C. ;

Hopper, John L. ;

McCredie, Margaret R. E. ;

Giles, Graham G. ;

Fletcher, Olivia ;

Johnson, Nichola ;

dos Santos Silva, Isabel ;

Gibson, Lorna ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Torres, Diana ;

Hamann, Ute ;

Justenhoven, Christina ;

Brauch, Hiltrud ;

Chang-Claude, Jenny ;

Kropp, Silke ;

Risch, Angela ;

Wang-Gohrke, Shan ;

Schuermann, Peter ;

Bogdanova, Natalia ;

Doerk, Thilo ;

Fagerholm, Rainer ;

Aaltonen, Kirsimari ;

Blomqvist, Carl ;

Nevanlinna, Heli ;

Seal, Sheila ;

Renwick, Anthony ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Sangrajrang, Suleeporn ;

Hughes, David ;

Odefrey, Fabrice ;

Brennan, Paul ;

Spurdle, Amanda B. ;

Chenevix-Trench, Georgia ;

Beesley, Jonathan .

NATURE GENETICS, 2007, 39 (03) :352-358

[6] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[7] Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease [J].

Fisher, Sheila A. ;

Tremelling, Mark ;

Anderson, Carl A. ;

Gwilliam, Rhian ;

Bumpstead, Suzannah ;

Prescott, Natalie J. ;

Nimmo, Elaine R. ;

Massey, Dunecan ;

Berzuini, Carlo ;

Johnson, Christopher ;

Barrett, Jeffrey C. ;

Cummings, Fraser R. ;

Drummond, Hazel ;

Lees, Charlie W. ;

Onnie, Clive M. ;

Hanson, Catherine E. ;

Blaszczyk, Katarzyna ;

Inouye, Mike ;

Ewels, Philip ;

Ravindrarajah, Radhi ;

Keniry, Andrew ;

Hunt, Sarah ;

Carter, Martyn ;

Watkins, Nick ;

Ouwehand, Willem ;

Lewis, Cathryn M. ;

Cardon, Lon ;

Lobo, Alan ;

Forbes, Alastair ;

Sanderson, Jeremy ;

Jewell, Derek P. ;

Mansfield, John C. ;

Deloukas, Panos ;

Mathew, Christopher G. ;

Parkes, Miles ;

Satsangi, Jack .

NATURE GENETICS, 2008, 40 (06) :710-712

[8] SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically accessible therapy reversing transcriptional aberrations of nuclear import and inflammasome pathways [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (22) :3564-3576

[9] An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (16) :2570-2583

[10] Phenotype-defining functions of multiple non-coding RNA pathways [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (11) :1630-1639

← 1 2 3 4 →

共 37 条

[1] Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility [J].

Barton, Anne ;

Thomson, Wendy ;

Ke, Xiayi ;

Eyre, Steve ;

Hinks, Anne ;

Bowes, John ;

Gibbons, Laura ;

Plant, Darren ;

Wilson, Anthony G. ;

Marinou, Ioanna ;

Morgan, Ann ;

Emery, Paul ;

Steer, Sophia ;

Hocking, Lynne ;

Reid, David M. ;

Wordsworth, Paul ;

Harrison, Pille ;

Worthington, Jane .

HUMAN MOLECULAR GENETICS, 2008, 17 (15) :2274-2279

[2] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

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 .

NATURE, 2007, 447 (7146) :799-816

[3] A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk [J].

Broderick, Peter ;

Carvajal-Carmona, Luis ;

Pittman, Alan M. ;

Webb, Emily ;

Howarth, Kimberley ;

Rowan, Andrew ;

Lubbe, Steven ;

Spain, Sarah ;

Sullivan, Kate ;

Fielding, Sarah ;

Jaeger, Emma ;

Vijayakrishnan, Jayaram ;

Kemp, Zoe ;

Gorman, Maggie ;

Chandler, Ian ;

Papaemmanuil, Elli ;

Penegar, Steven ;

Wood, Wendy ;

Sellick, Gabrielle ;

Qureshi, Mobshra ;

Teixeira, Ana ;

Domingo, Enric ;

Barclay, Ella ;

Martin, Lynn ;

Sieber, Oliver ;

Kerr, David ;

Gray, Richard ;

Peto, Julian ;

Cazier, Jean-Baptiste ;

Tomlinson, Ian ;

Houlston, Richard S. .

NATURE GENETICS, 2007, 39 (11) :1315-1317

[4] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[5] A common coding variant in CASP8 is associated with breast cancer risk [J].

Cox, Angela ;

Dunning, Alison M. ;

Garcia-Closas, Montserrat ;

Balasubramanian, Sabapathy ;

Reed, Malcolm W. R. ;

Pooley, Karen A. ;

Scollen, Serena ;

Baynes, Caroline ;

Ponder, Bruce A. J. ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Brinton, Louise ;

Peplonska, Beata ;

Southey, Melissa C. ;

Hopper, John L. ;

McCredie, Margaret R. E. ;

Giles, Graham G. ;

Fletcher, Olivia ;

Johnson, Nichola ;

dos Santos Silva, Isabel ;

Gibson, Lorna ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Torres, Diana ;

Hamann, Ute ;

Justenhoven, Christina ;

Brauch, Hiltrud ;

Chang-Claude, Jenny ;

Kropp, Silke ;

Risch, Angela ;

Wang-Gohrke, Shan ;

Schuermann, Peter ;

Bogdanova, Natalia ;

Doerk, Thilo ;

Fagerholm, Rainer ;

Aaltonen, Kirsimari ;

Blomqvist, Carl ;

Nevanlinna, Heli ;

Seal, Sheila ;

Renwick, Anthony ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Sangrajrang, Suleeporn ;

Hughes, David ;

Odefrey, Fabrice ;

Brennan, Paul ;

Spurdle, Amanda B. ;

Chenevix-Trench, Georgia ;

Beesley, Jonathan .

NATURE GENETICS, 2007, 39 (03) :352-358

[6] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[7] Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease [J].

Fisher, Sheila A. ;

Tremelling, Mark ;

Anderson, Carl A. ;

Gwilliam, Rhian ;

Bumpstead, Suzannah ;

Prescott, Natalie J. ;

Nimmo, Elaine R. ;

Massey, Dunecan ;

Berzuini, Carlo ;

Johnson, Christopher ;

Barrett, Jeffrey C. ;

Cummings, Fraser R. ;

Drummond, Hazel ;

Lees, Charlie W. ;

Onnie, Clive M. ;

Hanson, Catherine E. ;

Blaszczyk, Katarzyna ;

Inouye, Mike ;

Ewels, Philip ;

Ravindrarajah, Radhi ;

Keniry, Andrew ;

Hunt, Sarah ;

Carter, Martyn ;

Watkins, Nick ;

Ouwehand, Willem ;

Lewis, Cathryn M. ;

Cardon, Lon ;

Lobo, Alan ;

Forbes, Alastair ;

Sanderson, Jeremy ;

Jewell, Derek P. ;

Mansfield, John C. ;

Deloukas, Panos ;

Mathew, Christopher G. ;

Parkes, Miles ;

Satsangi, Jack .

NATURE GENETICS, 2008, 40 (06) :710-712

[8] SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically accessible therapy reversing transcriptional aberrations of nuclear import and inflammasome pathways [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (22) :3564-3576

[9] An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (16) :2570-2583

[10] Phenotype-defining functions of multiple non-coding RNA pathways [J].

Glinsky, Gennadi V. .

CELL CYCLE, 2008, 7 (11) :1630-1639

← 1 2 3 4 →