Genetic compensation: A phenomenon in search of mechanisms

PLoS Genetics

Volumn 13, Issue 7, 2017, Pages

  El Brolosy, Mohamed A ^a   Stainier, Didier Y R ^a  

^a MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ARGONAUTE PROTEIN; MICRORNA; RNA BINDING PROTEIN; EGFL7 PROTEIN, ZEBRAFISH; MUTANT PROTEIN; ZEBRAFISH PROTEIN;

5' UNTRANSLATED REGION; ADAPTATION; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA DAMAGE RESPONSE; DOUBLE STRANDED DNA BREAK; EXTRACELLULAR MATRIX; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE SILENCING; GENETIC ANALYSIS; HUMAN; LOSS OF FUNCTION MUTATION; NONHUMAN; OPEN READING FRAME; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; REVIEW; TRANSCRIPTION REGULATION; UPREGULATION; ANIMAL; ANIMAL MODEL; ARABIDOPSIS; BIOSYNTHESIS; DROSOPHILA; GENE INACTIVATION; GENETIC TRANSCRIPTION; GENETICS; MOUSE; ZEBRA FISH;

ANIMALS; ARABIDOPSIS; DOSAGE COMPENSATION, GENETIC; DROSOPHILA; GENE KNOCKDOWN TECHNIQUES; GENE KNOCKOUT TECHNIQUES; MICE; MODELS, ANIMAL; MUTANT PROTEINS; TRANSCRIPTION, GENETIC; ZEBRAFISH; ZEBRAFISH PROTEINS;

EID: 85026662935     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1006780     Document Type: Review

References (156)

1. Mather K, Genetical control of stability in development. Heredity. 1953;7(3):297–336.
2. Waddington CH, Canalization of Development and Genetic Assimilation of Acquired Characters. Nature. 1959;183(4676):1654–5. 13666847
3. Muller HJ, editor Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics; 1932.
4. Mukherjee AS, Beermann W, Synthesis of ribonucleic acid by the X-chromosomes of Drosophila melanogaster and the problem of dosage compensation. Nature. 1965;207(998):785–6. Epub 1965/08/14. 5885936.
5. Barr ML, Bertram EG, A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature. 1949;163(4148):676. Epub 1949/04/30. 18120749.
6. Heard E, Disteche CM, Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes & development. 2006;20(14):1848–67. Epub 2006/07/19. doi: 10.1101/gad.1422906 16847345.
7. Lyon MF, Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961;190:372–3. Epub 1961/04/22. 13764598.
8. Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, et al. Functional profiling of the Saccharomyces cerevisiae genome. Nature. 2002;418(6896):387–91. Epub 2002/07/26. doi: 10.1038/nature00935 12140549.
9. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes. Cell. 2013;154(2):452–64. Epub 2013/07/23. doi: 10.1016/j.cell.2013.06.022 23870131; PubMed Central PMCID: PMCPmc3717207.
10. Kok FO, Shin M, Ni CW, Gupta A, Grosse AS, van Impel A, et al. Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. Developmental cell. 2015;32(1):97–108. Epub 2014/12/24. doi: 10.1016/j.devcel.2014.11.018 25533206; PubMed Central PMCID: PMCPmc4487878.
11. Bouche N, Bouchez D, Arabidopsis gene knockout: phenotypes wanted. Current opinion in plant biology. 2001;4(2):111–7. Epub 2001/03/03. 11228432.
12. Wang Y, Schnegelsberg PN, Dausman J, Jaenisch R, Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin. Nature. 1996;379(6568):823–5. Epub 1996/02/29. doi: 10.1038/379823a0 8587605.
13. von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G, van der Ploeg LH, et al. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiology of aging. 1997;18(6):661–9. Epub 1998/02/14. 9461064.
14. Santamaria D, Barriere C, Cerqueira A, Hunt S, Tardy C, Newton K, et al. Cdk1 is sufficient to drive the mammalian cell cycle. Nature. 2007;448(7155):811–5. Epub 2007/08/19. doi: 10.1038/nature06046 17700700.
15. Cadigan KM, Grossniklaus U, Gehring WJ, Functional redundancy: the respective roles of the two sloppy paired genes in Drosophila segmentation. Proceedings of the National Academy of Sciences of the United States of America. 1994;91(14):6324–8. Epub 1994/07/05. 8022780; PubMed Central PMCID: PMCPmc44194.
16. González-Gaitán M, Rothe M, Wimmer EA, Taubert H, Jäckle H, Redundant functions of the genes knirps and knirps-related for the establishment of anterior Drosophila head structures. Proceedings of the National Academy of Sciences of the United States of America. 1994;91(18):8567–71. PMC44647. 8078924
17. Hoffmann FM, Drosophila abl and genetic redundancy in signal transduction. Trends in genetics: TIG. 1991;7(11–12):351–5. Epub 1991/11/01. 1820686.
18. Cohen R, Yokoi T, Holland JP, Pepper AE, Holland MJ, Transcription of the constitutively expressed yeast enolase gene ENO1 is mediated by positive and negative cis-acting regulatory sequences. Molecular and cellular biology. 1987;7(8):2753–61. Epub 1987/08/01. 3313003; PubMed Central PMCID: PMCPmc367892.
19. Nedvetzki S, Gonen E, Assayag N, Reich R, Williams RO, Thurmond RL, et al. RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: a different interpretation of redundancy. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(52):18081–6. Epub 2004/12/15. doi: 10.1073/pnas.0407378102 15596723; PubMed Central PMCID: PMCPMC539795.
20. Tautz D, Redundancies, development and the flow of information. BioEssays: news and reviews in molecular, cellular and developmental biology. 1992;14(4):263–6. Epub 1992/04/01. doi: 10.1002/bies.950140410 1596275.
21. Barabasi AL, Oltvai ZN, Network biology: understanding the cell's functional organization. Nat Rev Genet. 2004;5(2):101–13. Epub 2004/01/22. doi: 10.1038/nrg1272 14735121.
22. Davidson E, Levin M, Gene regulatory networks. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(14):4935. doi: 10.1073/pnas.0502024102 15809445
23. Teng X, Dayhoff-Brannigan M, Cheng WC, Gilbert CE, Sing CN, Diny NL, et al. Genome-wide consequences of deleting any single gene. Molecular cell. 2013;52(4):485–94. Epub 2013/11/12. doi: 10.1016/j.molcel.2013.09.026 24211263; PubMed Central PMCID: PMCPmc3975072.
24. Chen P, Wang D, Chen H, Zhou Z, He X, The non-essentiality of essential genes in yeast provides therapeutic insights into a human disease. Genome research. 2016. Epub 2016/07/22. doi: 10.1101/gr.205955.116 27440870.
25. Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S, Kruger M, et al. Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature. 2015;524(7564):230–3. Epub 2015/07/15. doi: 10.1038/nature14580 26168398.
26. Hall EA, Keighren M, Ford MJ, Davey T, Jarman AP, Smith LB, et al. Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct ciliary phenotypes. PLoS Genet. 2013;9(12):e1003928. Epub 2014/01/15. doi: 10.1371/journal.pgen.1003928 24415959; PubMed Central PMCID: PMCPMC3887133.
27. Tondeleir D, Lambrechts A, Muller M, Jonckheere V, Doll T, Vandamme D, et al. Cells lacking beta-actin are genetically reprogrammed and maintain conditional migratory capacity. Molecular & cellular proteomics: MCP. 2012;11(8):255–71. Epub 2012/03/27. 10.1074/mcp.M111.015099. 22448045; PubMed Central PMCID: PMCPMC3412960.
28. Gao Y, Zhang Y, Zhang D, Dai X, Estelle M, Zhao Y, Auxin binding protein 1 (ABP1) is not required for either auxin signaling or Arabidopsis development. Proceedings of the National Academy of Sciences. 2015;112(7):2275–80. doi: 10.1073/pnas.1500365112 25646447
29. Chen X, Grandont L, Li H, Hauschild R, Paque S, Abuzeineh A, et al. Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules. Nature. 2014;516(7529):90–3. Epub 2014/11/20. doi: 10.1038/nature13889 25409144; PubMed Central PMCID: PMCPmc4257754.
30. Braun N, Wyrzykowska J, Muller P, David K, Couch D, Perrot-Rechenmann C, et al. Conditional repression of AUXIN BINDING PROTEIN1 reveals that it coordinates cell division and cell expansion during postembryonic shoot development in Arabidopsis and tobacco. The Plant cell. 2008;20(10):2746–62. Epub 2008/10/28. doi: 10.1105/tpc.108.059048 18952781; PubMed Central PMCID: PMCPmc2590743.
31. Young R, Passet B, Vilotte M, Cribiu EP, Beringue V, Le Provost F, et al. The prion or the related Shadoo protein is required for early mouse embryogenesis. FEBS letters. 2009;583(19):3296–300. Epub 2009/09/22. doi: 10.1016/j.febslet.2009.09.027 19766638.
32. De Souza AT, Dai X, Spencer AG, Reppen T, Menzie A, Roesch PL, et al. Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice. Nucleic acids research. 2006;34(16):4486–94. Epub 2006/09/02. doi: 10.1093/nar/gkl609 16945951; PubMed Central PMCID: PMCPmc1636368.
33. Daude N, Wohlgemuth S, Brown R, Pitstick R, Gapeshina H, Yang J, et al. Knockout of the prion protein (PrP)-like Sprn gene does not produce embryonic lethality in combination with PrP(C)-deficiency. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(23):9035–40. Epub 2012/05/24. doi: 10.1073/pnas.1202130109 22619325; PubMed Central PMCID: PMCPmc3384183.
34. McJunkin K, Mazurek A, Premsrirut PK, Zuber J, Dow LE, Simon J, et al. Reversible suppression of an essential gene in adult mice using transgenic RNA interference. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(17):7113–8. Epub 2011/04/13. doi: 10.1073/pnas.1104097108 21482754; PubMed Central PMCID: PMCPmc3084121.
35. Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, et al. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014;159(1):200–14. Epub 2014/09/27. doi: 10.1016/j.cell.2014.09.002 25259927; PubMed Central PMCID: PMCPmc4298142.
36. Law SH, Sargent TD, The serine-threonine protein kinase PAK4 is dispensable in zebrafish: identification of a morpholino-generated pseudophenotype. PLoS ONE. 2014;9(6):e100268. Epub 2014/06/20. doi: 10.1371/journal.pone.0100268 24945275; PubMed Central PMCID: PMCPMC4063752.
37. Evers B, Jastrzebski K, Heijmans JP, Grernrum W, Beijersbergen RL, Bernards R, CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes. Nature biotechnology. 2016;34(6):631–3. Epub 2016/04/26. doi: 10.1038/nbt.3536 27111720.
38. Karakas B, Weeraratna AT, Abukhdeir AM, Konishi H, Gustin JP, Vitolo MI, et al. P21 gene knock down does not identify genetic effectors seen with gene knock out. Cancer biology & therapy. 2007;6(7):1025–30. Epub 2007/07/06. 17611398; PubMed Central PMCID: PMCPmc2667557.
39. Morgens DW, Deans RM, Li A, Bassik MC, Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes. Nature biotechnology. 2016;34(6):634–6. Epub 2016/05/10. doi: 10.1038/nbt.3567 27159373; PubMed Central PMCID: PMCPmc4900911.
40. Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C, Farber SA, et al. p53 activation by knockdown technologies. PLoS Genet. 2007;3(5):e78. Epub 2007/05/29. doi: 10.1371/journal.pgen.0030078 17530925; PubMed Central PMCID: PMCPmc1877875.
41. Baek ST, Kerjan G, Bielas SL, Lee JE, Fenstermaker AG, Novarino G, et al. Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous microRNA dysregulation. Neuron. 2014;82(6):1255–62. Epub 2014/06/20. doi: 10.1016/j.neuron.2014.04.036 24945770; PubMed Central PMCID: PMCPmc4086250.
42. Olejniczak M, Galka P, Krzyzosiak WJ, Sequence-non-specific effects of RNA interference triggers and microRNA regulators. Nucleic acids research. 2010;38(1):1–16. Epub 2009/10/22. doi: 10.1093/nar/gkp829 19843612; PubMed Central PMCID: PMCPmc2800214.
43. Olejniczak M, Urbanek MO, Jaworska E, Witucki L, Szczesniak MW, Makalowska I, et al. Sequence-non-specific effects generated by various types of RNA interference triggers. Biochimica et biophysica acta. 2016;1859(2):306–14. Epub 2015/11/28. doi: 10.1016/j.bbagrm.2015.11.005 26612823.
44. Jackson AL, Linsley PS, Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nature reviews Drug discovery. 2010;9(1):57–67. Epub 2010/01/01. doi: 10.1038/nrd3010 20043028.
45. Housden BE, Muhar M, Gemberling M, Gersbach CA, Stainier DY, Seydoux G, et al. Loss-of-function genetic tools for animal models: cross-species and cross-platform differences. Nat Rev Genet. 2017;18(1):24–40. Epub 2016/11/01. doi: 10.1038/nrg.2016.118 27795562; PubMed Central PMCID: PMCPMC5206767.
46. O'Leary MN, Schreiber KH, Zhang Y, Duc AC, Rao S, Hale JS, et al. The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLoS Genet. 2013;9(8):e1003708. Epub 2013/08/31. doi: 10.1371/journal.pgen.1003708 23990801; PubMed Central PMCID: PMCPmc3750023.
47. Mulligan GJ, Wong J, Jacks T, p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and pRB. Molecular and cellular biology. 1998;18(1):206–20. Epub 1998/01/07. 9418868; PubMed Central PMCID: PMCPmc121478.
48. Jackson JG, Pereira-Smith OM, Primary and compensatory roles for RB family members at cell cycle gene promoters that are deacetylated and downregulated in doxorubicin-induced senescence of breast cancer cells. Molecular and cellular biology. 2006;26(7):2501–10. Epub 2006/03/16. doi: 10.1128/MCB.26.7.2501-2510.2006 16537896; PubMed Central PMCID: PMCPmc1430319.
49. Jurkin J, Zupkovitz G, Lagger S, Grausenburger R, Hagelkruys A, Kenner L, et al. Distinct and redundant functions of histone deacetylases HDAC1 and HDAC2 in proliferation and tumorigenesis. Cell Cycle. 2011;10(3):406–12. Epub 2011/01/29. doi: 10.4161/cc.10.3.14712 21270520; PubMed Central PMCID: PMCPMC3115015.
50. Hagelkruys A, Lagger S, Krahmer J, Leopoldi A, Artaker M, Pusch O, et al. A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog. Development (Cambridge, England). 2014;141(3):604–16. Epub 2014/01/23. doi: 10.1242/dev.100487 24449838; PubMed Central PMCID: PMCPmc4773893.
51. Lagger G, O'Carroll D, Rembold M, Khier H, Tischler J, Weitzer G, et al. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. The EMBO journal. 2002;21(11):2672–81. Epub 2002/05/29. doi: 10.1093/emboj/21.11.2672 12032080; PubMed Central PMCID: PMCPMC126040.
52. Dawlaty MM, Ganz K, Powell BE, Hu YC, Markoulaki S, Cheng AW, et al. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell stem cell. 2011;9(2):166–75. Epub 2011/08/06. doi: 10.1016/j.stem.2011.07.010 21816367; PubMed Central PMCID: PMCPMC3154739.
53. Freudenberg JM, Ghosh S, Lackford BL, Yellaboina S, Zheng X, Li R, et al. Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity. Nucleic acids research. 2012;40(8):3364–77. Epub 2012/01/03. doi: 10.1093/nar/gkr1253 22210859; PubMed Central PMCID: PMCPMC3333871.
54. Wang J, Wang Q, Cui Y, Liu ZY, Zhao W, Wang CL, et al. Knockdown of cyclin D1 inhibits proliferation, induces apoptosis, and attenuates the invasive capacity of human glioblastoma cells. Journal of neuro-oncology. 2012;106(3):473–84. Epub 2011/09/14. doi: 10.1007/s11060-011-0692-4 21912938.
55. Radulovich N, Pham N- A, Strumpf D, Leung L, Xie W, Jurisica I, et al. Differential roles of cyclin D1 and D3 in pancreatic ductal adenocarcinoma. Molecular Cancer. 2010;9(1):1–15. doi: 10.1186/1476-4598-9-24 20113529
56. Becker KA, Ghule PN, Lian JB, Stein JL, van Wijnen AJ, Stein GS, Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells. Journal of cellular physiology. 2010;222(2):456–64. Epub 2009/11/06. doi: 10.1002/jcp.21967 19890848; PubMed Central PMCID: PMCPmc3059841.
57. Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, Yu Q, et al. Requirement for cyclin D3 in lymphocyte development and T cell leukemias. Cancer cell. 2003;4(6):451–61. Epub 2004/01/07. 14706337.
58. Sicinski P, Weinberg RA, A specific role for cyclin D1 in mammary gland development. Journal of mammary gland biology and neoplasia. 1997;2(4):335–42. Epub 2000/08/10. 10935021.
59. Huard JM, Forster CC, Carter ML, Sicinski P, Ross ME, Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development (Cambridge, England). 1999;126(9):1927–35. Epub 1999/04/02. 10101126.
60. Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH, et al. Development of mice expressing a single D-type cyclin. Genes & development. 2002;16(24):3277–89. Epub 2002/12/28. doi: 10.1101/gad.1023602 12502747; PubMed Central PMCID: PMCPmc187507.
61. Lam EW, Glassford J, Banerji L, Thomas NS, Sicinski P, Klaus GG, Cyclin D3 compensates for loss of cyclin D2 in mouse B-lymphocytes activated via the antigen receptor and CD40. The Journal of biological chemistry. 2000;275(5):3479–84. Epub 2000/02/01. 10652342.
62. Yasuhara N, Shibazaki N, Tanaka S, Nagai M, Kamikawa Y, Oe S, et al. Triggering neural differentiation of ES cells by subtype switching of importin-alpha. Nature cell biology. 2007;9(1):72–9. Epub 2006/12/13. doi: 10.1038/ncb1521 17159997.
63. Shmidt T, Hampich F, Ridders M, Schultrich S, Hans VH, Tenner K, et al. Normal brain development in importin-alpha5 deficient-mice. Nature cell biology. 2007;9(12):1337–8; author reply 9. Epub 2007/12/07. doi: 10.1038/ncb1207-1337 18059353.
64. Rajshankar D, Downey GP, McCulloch CA, IL-1β enhances cell adhesion to degraded fibronectin. The FASEB Journal. 2012;26(11):4429–44. doi: 10.1096/fj.12-207381. 22829527
65. Theodosiou M, Widmaier M, Bottcher RT, Rognoni E, Veelders M, Bharadwaj M, et al. Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin. eLife. 2016;5:e10130. Epub 2016/01/29. doi: 10.7554/eLife.10130 26821125; PubMed Central PMCID: PMCPmc4749545.
66. Jost AP, Weiner OD, Probing Yeast Polarity with Acute, Reversible, Optogenetic Inhibition of Protein Function. ACS synthetic biology. 2015;4(10):1077–85. Epub 2015/06/03. doi: 10.1021/acssynbio.5b00053 26035630; PubMed Central PMCID: PMCPmc4609243.
67. Williams JA, Ni HM, Haynes A, Manley S, Li Y, Jaeschke H, et al. Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to Acetaminophen-induced Mitophagy and Liver Injury in Mice. The Journal of biological chemistry. 2015;290(17):10934–46. Epub 2015/03/11. doi: 10.1074/jbc.M114.602284 25752611; PubMed Central PMCID: PMCPMC4409255.
68. Nicchia GP, Srinivas M, Li W, Brosnan CF, Frigeri A, Spray DC, New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and functional relationship with connexin43. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2005;19(12):1674–6. Epub 2005/08/17. doi: 10.1096/fj.04-3281fje 16103109.
69. Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS, Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. J Clin Invest. 1997;100(5):957–62. Epub 1997/09/01. doi: 10.1172/JCI231 9276712; PubMed Central PMCID: PMCPmc508270.
70. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nature medicine. 2000;6(2):159–63. Epub 2000/02/02. doi: 10.1038/72256 10655103.
71. Papadopoulos MC, Manley GT, Krishna S, Verkman AS, Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2004;18(11):1291–3. Epub 2004/06/23. doi: 10.1096/fj.04-1723fje 15208268.
72. Speers C, Zhao SG, Kothari V, Santola A, Liu M, Wilder-Romans K, et al. Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer. Clin Cancer Res. 2016;22(23):5864–75. Epub 2016/11/01. doi: 10.1158/1078-0432.CCR-15-2711 27225691.
73. Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T, Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast cancer research: BCR. 2007;9(1):R17. Epub 2007/02/07. doi: 10.1186/bcr1650 17280616; PubMed Central PMCID: PMCPMC1851384.
74. Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J, Oshima RG, et al. Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo. Cancer Res. 2010;70(21):8863–73. Epub 2010/09/24. doi: 10.1158/0008-5472.CAN-10-1295 20861186; PubMed Central PMCID: PMCPMC3990264.
75. Wang Y, Lee YM, Baitsch L, Huang A, Xiang Y, Tong H, et al. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. eLife. 2014;3:e01763. Epub 2014/05/23. doi: 10.7554/eLife.01763 24844244; PubMed Central PMCID: PMCPMC4059381.
76. Lin A, Giuliano CJ, Sayles NM, Sheltzer JM, CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials. eLife. 2017;6. Epub 2017/03/25. doi: 10.7554/eLife.24179 28337968.
77. Caceres A, Kosik KS, Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. Nature. 1990;343(6257):461–3. Epub 1990/02/01. doi: 10.1038/343461a0 2105469.
78. Caceres A, Potrebic S, Kosik KS, The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons. The Journal of neuroscience: the official journal of the Society for Neuroscience. 1991;11(6):1515–23. Epub 1991/06/01. 1904479.
79. Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, et al. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. 1994;369(6480):488–91. Epub 1994/06/09. doi: 10.1038/369488a0 8202139.
80. Seiberlich V, Bauer NG, Schwarz L, Ffrench-Constant C, Goldbaum O, Richter-Landsberg C, Downregulation of the microtubule associated protein tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes. Glia. 2015;63(9):1621–35. Epub 2015/04/08. doi: 10.1002/glia.22832 25847153.
81. Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC, Metzinger L, et al. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell. 1997;90(4):717–27. Epub 1997/08/22. 9288751.
82. Law DJ, Allen DL, Tidball JG, Talin, vinculin and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosis. Journal of cell science. 1994;107 (Pt 6):1477–83. Epub 1994/06/01. 7962191.
83. Ghahramani Seno MM, Graham IR, Athanasopoulos T, Trollet C, Pohlschmidt M, Crompton MR, et al. RNAi-mediated knockdown of dystrophin expression in adult mice does not lead to overt muscular dystrophy pathology. Human molecular genetics. 2008;17(17):2622–32. Epub 2008/05/31. doi: 10.1093/hmg/ddn162 18511456.
84. Bunnell TM, Burbach BJ, Shimizu Y, Ervasti JM, beta-Actin specifically controls cell growth, migration, and the G-actin pool. Molecular biology of the cell. 2011;22(21):4047–58. Epub 2011/09/09. doi: 10.1091/mbc.E11-06-0582 21900491; PubMed Central PMCID: PMCPMC3204067.
85. Patrinostro X, O'Rourke AR, Chamberlain CM, Moriarity BS, Perrin BJ, Ervasti JM, Relative importance of betacyto- and gammacyto-actin in primary mouse embryonic fibroblasts. Molecular biology of the cell. 2017;28(6):771–82. Epub 2017/01/13. doi: 10.1091/mbc.E16-07-0503 28077619.
86. Dayton TL, Gocheva V, Miller KM, Israelsen WJ, Bhutkar A, Clish CB, et al. Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma. Genes & development. 2016;30(9):1020–33. Epub 2016/04/30. doi: 10.1101/gad.278549.116 27125672; PubMed Central PMCID: PMCPmc4863734.
87. Lunt SY, Muralidhar V, Hosios AM, Israelsen WJ, Gui DY, Newhouse L, et al. Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation. Molecular cell. 2015;57(1):95–107. Epub 2014/12/09. doi: 10.1016/j.molcel.2014.10.027 25482511; PubMed Central PMCID: PMCPmc4289430.
88. Wang RH, Li C, Deng CX, Liver steatosis and increased ChREBP expression in mice carrying a liver specific SIRT1 null mutation under a normal feeding condition. International journal of biological sciences. 2010;6(7):682–90. Epub 2010/11/26. 21103071; PubMed Central PMCID: PMCPmc2990071.
89. Zhou S, Xie Y, Tang J, Huang J, Huang Q, Xu W, et al. FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling. PLoS Genet. 2015;11(6):e1005214. Epub 2015/06/20. doi: 10.1371/journal.pgen.1005214 26091072; PubMed Central PMCID: PMCPmc4474636.
90. Sage J, Miller AL, Perez-Mancera PA, Wysocki JM, Jacks T, Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature. 2003;424(6945):223–8. Epub 2003/07/11. doi: 10.1038/nature01764 12853964.
91. Protin U, Schweighoffer T, Jochum W, Hilberg F, CD44-deficient mice develop normally with changes in subpopulations and recirculation of lymphocyte subsets. Journal of immunology (Baltimore, Md: 1950). 1999;163(9):4917–23. Epub 1999/10/21. 10528194.
92. Schmits R, Filmus J, Gerwin N, Senaldi G, Kiefer F, Kundig T, et al. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity. Blood. 1997;90(6):2217–33. Epub 1997/10/06. 9310473.
93. Shatirishvili M, Burk AS, Franz CM, Pace G, Kastilan T, Breuhahn K, et al. Epidermal-specific deletion of CD44 reveals a function in keratinocytes in response to mechanical stress. Cell death & disease. 2016;7(11):e2461. Epub 2016/11/11. doi: 10.1038/cddis.2016.342 27831556; PubMed Central PMCID: PMCPMC5260879.
94. Takahashi K, Kaneko I, Changes in nuclease sensitivity of mammalian cells after irradiation with 60Co gamma-rays. International journal of radiation biology and related studies in physics, chemistry, and medicine. 1985;48(3):389–95. Epub 1985/09/01. 3875579.
95. Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, et al. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nature cell biology. 2006;8(8):870–6. Epub 2006/07/25. doi: 10.1038/ncb1446 16862143.
96. Downs JA, Nussenzweig MC, Nussenzweig A, Chromatin dynamics and the preservation of genetic information. Nature. 2007;447(7147):951–8. Epub 2007/06/22. doi: 10.1038/nature05980 17581578.
97. Stuckenholz C, Kageyama Y, Kuroda MI, Guilt by association: non-coding RNAs, chromosome-specific proteins and dosage compensation in Drosophila. Trends in genetics: TIG. 1999;15(11):454–8. Epub 1999/10/26. 10529808.
98. Bowerman B, Eaton BA, Priess JR, skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell. 1992;68(6):1061–75. Epub 1992/03/20. 1547503.
99. Raj A, Rifkin SA, Andersen E, van Oudenaarden A, Variability in gene expression underlies incomplete penetrance. Nature. 2010;463(7283):913–8. Epub 2010/02/19. doi: 10.1038/nature08781 20164922; PubMed Central PMCID: PMCPmc2836165.
100. Chambeyron S, Bickmore WA, Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes & development. 2004;18(10):1119–30. Epub 2004/05/25. doi: 10.1101/gad.292104 15155579; PubMed Central PMCID: PMCPmc415637.
101. Wei Z, Huang D, Gao F, Chang WH, An W, Coetzee GA, et al. Biological implications and regulatory mechanisms of long-range chromosomal interactions. The Journal of biological chemistry. 2013;288(31):22369–77. Epub 2013/06/20. doi: 10.1074/jbc.R113.485292 23779110; PubMed Central PMCID: PMCPMC3829327.
102. Li L, Lyu X, Hou C, Takenaka N, Nguyen HQ, Ong CT, et al. Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing. Molecular cell. 2015;58(2):216–31. Epub 2015/03/31. doi: 10.1016/j.molcel.2015.02.023 25818644; PubMed Central PMCID: PMCPMC4402144.
103. Wei W, Ba Z, Gao M, Wu Y, Ma Y, Amiard S, et al. A role for small RNAs in DNA double-strand break repair. Cell. 2012;149(1):101–12. Epub 2012/03/27. doi: 10.1016/j.cell.2012.03.002 22445173.
104. Francia S, Michelini F, Saxena A, Tang D, de Hoon M, Anelli V, et al. Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature. 2012;488(7410):231–5. Epub 2012/06/23. doi: 10.1038/nature11179 22722852; PubMed Central PMCID: PMCPMC3442236.
105. d'Adda di Fagagna F, A direct role for small non-coding RNAs in DNA damage response. Trends in cell biology. 2014;24(3):171–8. Epub 2013/10/26. doi: 10.1016/j.tcb.2013.09.008 24156824.
106. Franke A, Baker BS, The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila. Molecular cell. 1999;4(1):117–22. Epub 1999/08/13. 10445033.
107. Meller VH, Wu KH, Roman G, Kuroda MI, Davis RL, roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell. 1997;88(4):445–57. Epub 1997/02/21. 9038336.
108. Amrein H, Axel R, Genes expressed in neurons of adult male Drosophila. Cell. 1997;88(4):459–69. Epub 1997/02/21. 9038337.
109. Yang Y, Li T, Vu TH, Ulaner GA, Hu JF, Hoffman AR, The histone code regulating expression of the imprinted mouse Igf2r gene. Endocrinology. 2003;144(12):5658–70. Epub 2003/09/17. doi: 10.1210/en.2003-0798 12975326.
110. Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM, Esteller M, et al. Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. The EMBO journal. 2002;21(23):6560–70. Epub 2002/11/29. 12456662; PubMed Central PMCID: PMCPMC136958. doi: 10.1093/emboj/cdf655
111. Carr MS, Yevtodiyenko A, Schmidt CL, Schmidt JV, Allele-specific histone modifications regulate expression of the Dlk1-Gtl2 imprinted domain. Genomics. 2007;89(2):280–90. Epub 2006/11/28. doi: 10.1016/j.ygeno.2006.10.005 17126526; PubMed Central PMCID: PMCPMC1802099.
112. McEwen KR, Ferguson-Smith AC, Ferguson-Smith AC, Greally JM, Martienssen RA, Genomic Imprinting–A Model for Roles of HistoneModifications in Epigenetic Control. In: Epigenomics. Dordrecht: Springer Netherlands; 2009. p. 235–58.
113. Barreto G, Schafer A, Marhold J, Stach D, Swaminathan SK, Handa V, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007;445(7128):671–5. Epub 2007/02/03. doi: 10.1038/nature05515 17268471.
114. Lykke-Andersen S, Jensen TH, Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat Rev Mol Cell Biol. 2015;16(11):665–77. Epub 2015/09/24. doi: 10.1038/nrm4063 26397022.
115. Akimitsu N, Messenger RNA Surveillance Systems Monitoring Proper Translation Termination. The Journal of Biochemistry. 2008;143(1):1–8. doi: 10.1093/jb/mvm204 17981821
116. Harigaya Y, Parker R, No-go decay: a quality control mechanism for RNA in translation. Wiley interdisciplinary reviews RNA. 2010;1(1):132–41. Epub 2010/07/01. doi: 10.1002/wrna.17 21956910.
117. Schuermann A, Helker CS, Herzog W, Metallothionein 2 regulates endothelial cell migration through transcriptional regulation of vegfc expression. Angiogenesis. 2015;18(4):463–75. Epub 2015/07/23. doi: 10.1007/s10456-015-9473-6 26198291; PubMed Central PMCID: PMCPmc4596909.
118. Mitchell P, Tollervey D, An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'—>5' degradation. Molecular cell. 2003;11(5):1405–13. Epub 2003/05/29. 12769863.
119. Vance KW, Ponting CP, Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends in genetics: TIG. 2014;30(8):348–55. Epub 2014/06/30. doi: 10.1016/j.tig.2014.06.001 24974018; PubMed Central PMCID: PMCPMC4115187.
120. Ghanbarian H, Wagner N, Michiels JF, Cuzin F, Wagner KD, Rassoulzadegan M, Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation. Scientific reports. 2017;7:41799. Epub 2017/02/07. doi: 10.1038/srep41799 28165496; PubMed Central PMCID: PMCPMC5292948.
121. Wagner KD, Wagner N, Ghanbarian H, Grandjean V, Gounon P, Cuzin F, et al. RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. Developmental cell. 2008;14(6):962–9. Epub 2008/06/10. doi: 10.1016/j.devcel.2008.03.009 18539123.
122. Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, et al. Small dsRNAs induce transcriptional activation in human cells. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(46):17337–42. Epub 2006/11/07. doi: 10.1073/pnas.0607015103 17085592; PubMed Central PMCID: PMCPMC1859931.
123. Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR, Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nature chemical biology. 2007;3(3):166–73. Epub 2007/01/30. doi: 10.1038/nchembio860 17259978.
124. Schwartz JC, Younger ST, Nguyen NB, Hardy DB, Monia BP, Corey DR, et al. Antisense transcripts are targets for activating small RNAs. Nature structural & molecular biology. 2008;15(8):842–8. Epub 2008/07/08. doi: 10.1038/nsmb.1444 18604220; PubMed Central PMCID: PMCPMC2574822.
125. Zhang X, Li H, Burnett JC, Rossi JJ, The role of antisense long noncoding RNA in small RNA-triggered gene activation. RNA. 2014;20(12):1916–28. doi: 10.1261/rna.043968.113. 25344398
126. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, et al. Antisense transcription in the mammalian transcriptome. Science (New York, NY). 2005;309(5740):1564–6. Epub 2005/09/06. doi: 10.1126/science.1112009 16141073.
127. Kiyosawa H, Yamanaka I, Osato N, Kondo S, Riken Ger Group Laboratory for Genome Exploration Research Group RGSCRYIS-cT-kYKJGslmembers Genome Science Laboratory RHWSJet al. Antisense Transcripts With FANTOM2 Clone Set and Their Implications for Gene Regulation. Genome research. 2003;13(6b):1324–34. doi: 10.1101/gr.982903. 12819130
128. Yelin R, Dahary D, Sorek R, Levanon EY, Goldstein O, Shoshan A, et al. Widespread occurrence of antisense transcription in the human genome. Nature biotechnology. 2003;21(4):379–86. Epub 2003/03/18. doi: 10.1038/nbt808 12640466.
129. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. The transcriptional landscape of the mammalian genome. Science (New York, NY). 2005;309(5740):1559–63. Epub 2005/09/06. doi: 10.1126/science.1112014 16141072.
130. Chen J, Sun M, Kent WJ, Huang X, Xie H, Wang W, et al. Over 20% of human transcripts might form sense-antisense pairs. Nucleic acids research. 2004;32(16):4812–20. Epub 2004/09/10. doi: 10.1093/nar/gkh818 15356298; PubMed Central PMCID: PMCPMC519112.
131. Glisovic T, Bachorik JL, Yong J, Dreyfuss G, RNA-binding proteins and post-transcriptional gene regulation. FEBS letters. 2008;582(14):1977–86. Epub 2008/03/18. doi: 10.1016/j.febslet.2008.03.004 18342629; PubMed Central PMCID: PMCPmc2858862.
132. Kuwano Y, Rabinovic A, Srikantan S, Gorospe M, Demple B, Analysis of nitric oxide-stabilized mRNAs in human fibroblasts reveals HuR-dependent heme oxygenase 1 upregulation. Molecular and cellular biology. 2009;29(10):2622–35. Epub 2009/03/18. doi: 10.1128/MCB.01495-08 19289500; PubMed Central PMCID: PMCPmc2682029.
133. Gerber AP, Herschlag D, Brown PO, Extensive association of functionally and cytotopically related mRNAs with Puf family RNA-binding proteins in yeast. PLoS Biol. 2004;2(3):E79. Epub 2004/03/17. doi: 10.1371/journal.pbio.0020079 15024427; PubMed Central PMCID: PMCPMC368173.
134. Keene JD, Tenenbaum SA, Eukaryotic mRNPs may represent posttranscriptional operons. Molecular cell. 2002;9(6):1161–7. Epub 2002/06/28. 12086614.
135. Keene JD, Lager PJ, Post-transcriptional operons and regulons co-ordinating gene expression. Chromosome research: an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology. 2005;13(3):327–37. Epub 2005/05/04. doi: 10.1007/s10577-005-0848-1 15868425.
136. Keene JD, RNA regulons: coordination of post-transcriptional events. Nat Rev Genet. 2007;8(7):533–43. Epub 2007/06/19. doi: 10.1038/nrg2111 17572691.
137. Filipowicz W, Bhattacharyya SN, Sonenberg N, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?Nat Rev Genet. 2008;9(2):102–14. Epub 2008/01/17. doi: 10.1038/nrg2290 18197166.
138. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R, MicroRNA-373 induces expression of genes with complementary promoter sequences. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(5):1608–13. Epub 2008/01/30. doi: 10.1073/pnas.0707594105 18227514; PubMed Central PMCID: PMCPmc2234192.
139. Orom UA, Nielsen FC, Lund AH, MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Molecular cell. 2008;30(4):460–71. Epub 2008/05/24. doi: 10.1016/j.molcel.2008.05.001 18498749.
140. Pasquinelli AE, MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13(4):271–82. Epub 2012/03/14. doi: 10.1038/nrg3162 22411466.
141. Jacobsen A, Silber J, Harinath G, Huse JT, Schultz N, Sander C, Analysis of microRNA-target interactions across diverse cancer types. Nature structural & molecular biology. 2013;20(11):1325–32. Epub 2013/10/08. doi: 10.1038/nsmb.2678 24096364; PubMed Central PMCID: PMCPmc3982325.
142. Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, Leon-Ricardo BX, et al. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell. 2014;159(1):148–62. Epub 2014/09/16. doi: 10.1016/j.cell.2014.08.028 25219674; PubMed Central PMCID: PMCPMC4180118.
143. Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB, Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015;526(7574):591–4. Epub 2015/10/13. doi: 10.1038/nature15377 26458103; PubMed Central PMCID: PMCPMC4851248.
144. Licht K, Jantsch MF, Rapid and dynamic transcriptome regulation by RNA editing and RNA modifications. J Cell Biol. 2016;213(1):15–22. Epub 2016/04/06. doi: 10.1083/jcb.201511041 27044895; PubMed Central PMCID: PMCPMC4828693.
145. Iacono M, Mignone F, Pesole G, uAUG and uORFs in human and rodent 5'untranslated mRNAs. Gene. 2005;349:97–105. Epub 2005/03/22. doi: 10.1016/j.gene.2004.11.041 15777708.
146. Chew GL, Pauli A, Rinn JL, Regev A, Schier AF, Valen E, Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs. Development (Cambridge, England). 2013;140(13):2828–34. Epub 2013/05/24. doi: 10.1242/dev.098343 23698349; PubMed Central PMCID: PMCPmc3678345.
147. Morris DR, Geballe AP, Upstream open reading frames as regulators of mRNA translation. Molecular and cellular biology. 2000;20(23):8635–42. Epub 2000/11/14. 11073965; PubMed Central PMCID: PMCPmc86464.
148. Calvo SE, Pagliarini DJ, Mootha VK, Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(18):7507–12. Epub 2009/04/18. doi: 10.1073/pnas.0810916106 19372376; PubMed Central PMCID: PMCPmc2669787.
149. Hinnebusch AG, Dever TE, Asano K. 9 Mechanism of Translation Initiation in the Yeast Saccharomyces cerevisiae2007.
150. Mueller PP, Hinnebusch AG, Multiple upstream AUG codons mediate translational control of GCN4. Cell. 1986;45(2):201–7. Epub 1986/04/25. 3516411.
151. Chen R, Shi L, Hakenberg J, Naughton B, Sklar P, Zhang J, et al. Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases. Nature biotechnology. 2016;34(5):531–8. Epub 2016/04/12. doi: 10.1038/nbt.3514 27065010.
152. Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Barnes MR, et al. Health and population effects of rare gene knockouts in adult humans with related parents. Science (New York, NY). 2016;352(6284):474–7. Epub 2016/03/05. doi: 10.1126/science.aac8624 26940866; PubMed Central PMCID: PMCPmc4985238.
153. Sulem P, Helgason H, Oddson A, Stefansson H, Gudjonsson SA, Zink F, et al. Identification of a large set of rare complete human knockouts. Nature genetics. 2015;47(5):448–52. Epub 2015/03/26. doi: 10.1038/ng.3243 25807282.
154. Nadeau JH, Modifier genes in mice and humans. Nat Rev Genet. 2001;2(3):165–74. Epub 2001/03/21. doi: 10.1038/35056009 11256068.
155. Raj A, van Oudenaarden A, Nature, nurture, or chance: stochastic gene expression and its consequences. Cell. 2008;135(2):216–26. Epub 2008/10/30. doi: 10.1016/j.cell.2008.09.050 18957198; PubMed Central PMCID: PMCPmc3118044.
156. Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, White JK, et al. High-throughput discovery of novel developmental phenotypes. Nature. 2016;537(7621):508–14. Epub 2016/09/15. doi: 10.1038/nature19356 27626380.