-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Mutations in Result in Ocular Coloboma, Microcornea and Cataracts
Coloboma is a hole or gap in one or more of the structures of the eye. Coloboma occurs when the eye is not formed properly during prenatal development. It is often associated with additional eye abnormalities and can result in significant loss of vision. Identification of the genetic causes of coloboma provides more information about how the eye develops. We used whole exome sequencing in an affected family to identify mutations in a new gene associated with dominant coloboma in humans, MAB21L2. We used genome editing to disrupt the mab21l2 gene in zebrafish, which led to similar eye conditions in affected fish, providing additional evidence for the role of this gene in eye development. The function of MAB21L2 is largely unknown; further study of the pathways affected by MAB21L2 deficiency and study of the zebrafish generated by this project will provide more information about the role of this gene in eye development.
Vyšlo v časopise: Mutations in Result in Ocular Coloboma, Microcornea and Cataracts. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1005002
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005002Souhrn
Coloboma is a hole or gap in one or more of the structures of the eye. Coloboma occurs when the eye is not formed properly during prenatal development. It is often associated with additional eye abnormalities and can result in significant loss of vision. Identification of the genetic causes of coloboma provides more information about how the eye develops. We used whole exome sequencing in an affected family to identify mutations in a new gene associated with dominant coloboma in humans, MAB21L2. We used genome editing to disrupt the mab21l2 gene in zebrafish, which led to similar eye conditions in affected fish, providing additional evidence for the role of this gene in eye development. The function of MAB21L2 is largely unknown; further study of the pathways affected by MAB21L2 deficiency and study of the zebrafish generated by this project will provide more information about the role of this gene in eye development.
Zdroje
1. Morrison D., FitzPatrick D., Hanson I., Williamson K., van Heyningen V., et al. (2002). National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: Investigation of genetic aetiology. J. Med. Genet. 39, 16–22. 11826019
2. Hornby S.J., Adolph S., Gilbert C.E., Dandona L., Foster A. (2000). Visual acuity in children with coloboma: Clinical features and a new phenotypic classification system. Ophthalmology 107, 511–520. 10711890
3. Skalicky S.E., White A.J., Grigg J.R., Martin F., Smith J., et al. (2013) Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum. JAMA Ophthalmol., 131, 12, 1517–1524. doi: 10.1001/jamaophthalmol.2013.5305 24177921
4. Nakamura K.M., Diehl N.N., Mohney B.G. (2011) Incidence, ocular findings, and systemic associations of ocular coloboma: a population-based study. Arch Ophthalmol. 129(1), 69–74. doi: 10.1001/archophthalmol.2010.320 21220631
5. Toker E., Elcioglu N., Ozcan E., Yenice O., Ogut M. (2003). Colobomatous macrophthalmia with microcornea syndrome: report of a new pedigree. Am J Med Genet A. 121A, 25–30. 12900897
6. Schneider A., Bardakjian T., Reis L.M., Tyler R.C., Semina E.V. (2009). Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. Am. J. Med. Genet. A 149A, 2706–2715. doi: 10.1002/ajmg.a.33098 19921648
7. Schilter K.F., Schneider A., Bardakjian T., Soucy J.F., Tyler R.C., et al. (2011). OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype. Clin. Genet. 79,158–168. doi: 10.1111/j.1399-0004.2010.01450.x 20486942
8. Sanyanusin P., Schimmenti L.A., McNoe L.A., Ward T.A., Pierpont M.E., et al. (1995). Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat. Genet. 9, 358–64. 7795640
9. Azuma N., Yamaguchi Y., Handa H., Tadokoro K., Asaka A., et al. (2003). Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am. J. Hum. Genet. 72, 1565–1570. 12721955
10. Vissers L.E., van Ravenswaaij C.M., Admiraal R., Hurst J.A., de Vries B.B., et al. (2004). Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nature Genet., 36, 955–957. 15300250
11. Wang L., He F., Bu J., Zhen Y., Liu X., et al. (2012) ABCB6 mutations cause ocular coloboma. Am.J.Hum.Genet., 90, 1, 40–48. doi: 10.1016/j.ajhg.2011.11.026 22226084
12. Schimmenti L.A., de la Cruz J., Lewis R.A., Karkera J.D., Manligas G.S., et al. (2003). Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia. Am. J. Med. Genet. A 116A, 215–221. 12503095
13. Asai-Coakwell M., French C.R., Berry K.M., Ye M., Koss R., et al. (2007). GDF6, a novel locus for a spectrum of ocular developmental anomalies. Am. J. Hum. Genet. 80, 306–15. 17236135
14. Ye M., Berry-Wynne K.M., Asai-Coakwell M., Sundaresan P., Footz T., et al. (2010). Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. Hum. Mol. Genet. 19,287–98. doi: 10.1093/hmg/ddp496 19864492
15. Casey J., Kawaguchi R., Morrissey M., Sun H., McGettigan P., et al. (2011) First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype. Hum. Mutat. 32, 1417–1426. doi: 10.1002/humu.21590 21901792
16. Fares-Taie L., Gerber S., Chassaing N., Clayton-Smith J., Hanein S., et al. (2013). ALDH1A3 mutations cause recessive anophthalmia and microphthalmia. Am. J. Hum. Genet. 92, 265–270. doi: 10.1016/j.ajhg.2012.12.003 23312594
17. Kelberman D., Islam L., Lakowski J., Bacchelli C., Chanudet E., et al. (2014) Mutation of SALL2 causes recessive ocular coloboma in humans and mice. Hum.Mol.Genet., 23, 10, 2511–2526, doi: 10.1093/hmg/ddt643 24412933
18. Williamson K.A., Rainger J., Floyd J.A., Ansari M., Meynert A., et al (2014). Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects. Am. J. Hum. Genet. 94, 295–302. doi: 10.1016/j.ajhg.2014.01.001 24462371
19. Williamson K.A., FitzPatrick D.R. (2014). The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur. J. Med. Genet. 57, 369–80. doi: 10.1016/j.ejmg.2014.05.002 24859618
20. Kondo Y., Koshimizu E., Megarbane A., Hamanoue H., Okada I., et al. (2013). Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies. Am. J. Med. Genet. A161A, 1543–1546. doi: 10.1002/ajmg.a.35983 23703728
21. Zahrani F., Aldahmesh M.A., Alshammari M.J., Al-Hazzaa S.A., Alkuraya F.S. (2013). Mutations in c12orf57 cause a syndromic form of colobomatous microphthalmia. Am. J. Hum. Genet. 92, 387–391. doi: 10.1016/j.ajhg.2013.01.008 23453665
22. Manzini M.C., Tambunan D.E., Hill R.S., Yu T.W., Maynard T.M., et al (2012) Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome. Am J Hum Genet. 91(3), 541–7. doi: 10.1016/j.ajhg.2012.07.009 22958903
23. Sanjana N.E., Cong L., Zhou Y., Cunniff M.M., Feng G., et al. (2012). A transcription activator-like effector toolbox for genome engineering. Nat. Protoc. 7, 171–192. doi: 10.1038/nprot.2011.431 22222791
24. Hashemi H., Khabazkhoob M., Miraftab M., Emamian M.H., Shariati M., et al. (2012) The distribution of axial length, anterior chamber depth, lens thickness, and vitreous chamber depth in an adult population of Shahroud, Iran. BMC Ophthalmol. 12, 50–57 doi: 10.1186/1471-2415-12-50 22988958
25. Deml, B., Reis, L.M., Maheshwari, M., Griffis, C., Bick, D., et al. (2014). Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia. Clin. Genet. [Epub ahead of print]
26. Davydov E.V., Goode D.L., Sirota M., Cooper G.M., Sidow A., et al. (2010). Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput. Biol. 6, e1001025. doi: 10.1371/journal.pcbi.1001025 21152010
27. Baird S.E., Fitch D.H., Kassem I.A., Emmons S.W. (1991). Pattern formation in the nematode epidermis: determination of the arrangement of peripheral sense organs in the C. elegans male tail. Development 113, 515–526. 1782863
28. Finn R.D., Bateman A., Clements J., Coggill P., Eberhardt R.Y., et al. (2014) Pfam: the protein families database. Nucleic Acids Res. 42, D222–D230. doi: 10.1093/nar/gkt1223 24288371
29. Kranzusch P.J., Lee A.S., Berger J.M., Doudna J.A. (2013). Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity. Cell Rep. 3, 1362–1368. doi: 10.1016/j.celrep.2013.05.008 23707061
30. Sun L., Wu J., Du F., Chen X., Chen Z.J. (2013). Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 339, 786–791. doi: 10.1126/science.1232458 23258413
31. Muddyman D., Smee C., Griffin H., Kaye J., the UK10K Project. (2013). Implementing a successful data-management framework: the UK10K managed access model. Genome Med. 5, 100. doi: 10.1186/gm504 24229443
32. Andley U.P., Rhim J.S., Chylack L.T. Jr., Fleming T.P. (1994). Propagation and immortalization of human lens epithelial cells in culture. Invest. Ophthalmol. Vis. Sci. 35, 3094–3102. 8206728
33. Mariani M., Baldessari D., Francisconi S., Viggiano L., Rocchi M., et al. (1999). Two murine and human homologs of mab-21, a cell fate determination gene involved in Caenorhabditis elegans neural development. Hum. Mol. Genet. 8, 2397–2406. 10556287
34. Alvarez-Castelao B., Ruiz-Rivas C., Castaño J.G. (2012) A critical appraisal of quantitative studies of protein degradation in the framework of cellular proteostasis. Biochem Res Int. 2012, 823597, 1–11. doi: 10.1155/2012/823597 23119163
35. Morita K., Chow K.L., Ueno N. (1999). Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family. Development 126, 1337–1347. 10021351
36. Baldessari D., Badaloni A., Longhi R., Zappavigna V., Consalez G.G. (2004). MAB21L2, a vertebrate member of the Male-abnormal 21 family, modulates BMP signaling and interacts with SMAD1. BMC Cell Biol. 5, 48. 15613244
37. Reis L.M., Tyler R.C., Schilter K.F., Abdul-Rahman O., Innis J.W., et al. (2011). BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Hum. Genet. 130, 495–504. doi: 10.1007/s00439-011-0968-y 21340693
38. Wyatt A.W., Osborne R.J., Stewart H., Ragge N.K. (2010). Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies. Hum. Mutat. 31, 781–787. doi: 10.1002/humu.21280 20506283
39. French C.R., Stach T.R., March L.D., Lehmann O.J., Waskiewicz A.J. (2013). Apoptotic and proliferative defects characterize ocular development in a microphthalmic BMP model. Invest. Ophthalmol. Vis. Sci. 54, 4636–4647. doi: 10.1167/iovs.13-11674 23737474
40. Wolf L.V., Yang Y., Wang J., Xie Q., Braunger B., et al. (2009). Identification of pax6-dependent gene regulatory networks in the mouse lens. PLoS One 4, e4159. doi: 10.1371/journal.pone.0004159 19132093
41. Yamada R., Mizutani-Koseki Y., Koseki H., Takahashi N. (2004). Requirement for Mab21l2 during murine retina and ventral body wall. Dev. Biol. 274, 295–307. 15385160
42. Saito Y., Kojima T., Takahashi N. (2012). Mab21l2 is essential for embryonic heart and liver development. PLoS One. 7,e32991. doi: 10.1371/journal.pone.0032991 22412967
43. Wong R.L., Chow K.L. (2002). Depletion of Mab21l1 and Mab21l2 messages in mouse embryo arrests axial turning, and impairs notochord and neural tube differentiation. Teratology. 65, 70–77. 11857508
44. Yamada R., Mizutani-Koseki Y., Hasegawa T., Osumi N., Koseki H., et al. (2003). Cell-autonomous involvement of Mab21l1 is essential for lens placode development. Development. 130, 1759–1770. 12642482
45. Wong Y.M., Chow K.L. (2002). Expression of zebrafish mab21 genes marks the differentiating eye, midbrain and neural tube. Mech Dev. 113, 149–152. 11960703
46. Cederlund M.L., Vendrell V., Morrissey M.E., Yin J., Gaora P.Ó., et al. (2011). mab21l2 transgenics reveal novel expression patterns of mab21l1 and mab21l2, and conserved promoter regulation without sequence conservation. Dev Dyn. 240, 745–754. doi: 10.1002/dvdy.22573 21360786
47. Kennedy B.N., Stearns G.W., Smyth V.A., Ramamurthy V., van Eeden F., et al. (2004). Zebrafish rx3 and mab21l2 are required during eye morphogenesis. Dev Bio. 270, 336–349.
48. Viringipurampeer I.A., Ferreira T., DeMaria S., Yoon J.J., Shan X., et al. (2012). Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development. Hum. Mol. Genet. 21, 2357–69. doi: 10.1093/hmg/dds056 22357656
49. Masai I., Lele Z., Yamaguchi M., Komori A., Nishiwaki Y., et al. (2003). N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neuritis. Development. 130, 2479–2494. 12702661
50. Yamaguchi M., Imai F., Tonou-Fujimori N., Masai I. (2010). Mutations in N-cadherin and a Stardust homolog, Nagie oko, affect cell-cycle exit in zebrafish retina. Mech Dev. 127, 247–64. doi: 10.1016/j.mod.2010.03.004 20362667
51. Barbieri A.M., Lupo G., Bulfone A., Andreazzoli M., Mariani M., et al. (1999) A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis. Proc Natl Acad Sci USA, 96(19), 10729–34. 10485894
52. Hallonet M., Hollemann T., Pieler T., Gruss P. (1999) Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system. Genes Dev. 13, 3106–3114. 10601036
53. Take-uchi M., Clarke J.D., Wilson S.W. (2003) Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity. Development. 130, 955–68. 12538521
54. Mui S. H., Kim J. W., Lemke G., Bertuzzi S. (2005). Vax genes ventralize the embryonic eye. Genes Dev. 19, 1249–1259. 15905411
55. Ou J., Bharti K., Nodari A., Bertuzzi S., Arnheiter H. (2013). Vax1/2 genes counteract Mitf-induced respecification of the retinal pigment epithelium. PLoS One. 8, e59247. doi: 10.1371/journal.pone.0059247 23555005
56. Gestri G., Osborne R.J., Wyatt A.W., Gerrelli D., Gribble S., et al. (2009). Reduced TFAP2A function causes variable optic fissure closure and retinal defects and sensitizes eye development to mutations in other morphogenetic regulators. Hum. Genet. 126, 791–803. doi: 10.1007/s00439-009-0730-x 19685247
57. French C.R., Stach T.R., March L.D., Lehmann O.J., Waskiewicz A.J. (2013). Apoptotic and proliferative defects characterize ocular development in a microphthalmic BMP model. Invest Ophthalmol Vis Sci. 54, 4636–47. doi: 10.1167/iovs.13-11674 23737474
58. Asai-Coakwell M., French C.R., Ye M., Garcha K., Bigot K., et al. (2009). Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet. 18,1110–21. doi: 10.1093/hmg/ddp008 19129173
59. Rosenbaum D.M., Degterev A., David J., Rosenbaum P.S., Roth S., et al. (2010). Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model. J. Neurosci. Res. 88, 1569–76. doi: 10.1002/jnr.22314 20025059
60. Grasl-Kraupp B., Ruttkay-Nedecky B., Koudelka H., Bukowska K., Bursch W., et al. (1995). In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21, 1465–8. 7737654
61. Zhang Z.1., Baldini A. (2008) In vivo response to high-resolution variation of Tbx1 mRNA dosage. Hum Mol Genet. 17(1), 150–7. 17916582
62. Rainger J., Pehlivan D., Johansson S., Bengani H., Sanchez-Pulido L., et al. (2014). Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations. Am. J. Hum. Genet. 94, 915–923. doi: 10.1016/j.ajhg.2014.05.005 24906020
63. Liu X., Jian X., Boerwinkle E. (2013). dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum. Mutat. 34, E2393–E2402. doi: 10.1002/humu.22376 23843252
64. Alur R.P., Vijayasarathy C., Brown J.D., Mehtani M., Onojafe I.F., et al. (2010). Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human. PLoS Genet. 6, e1000870. doi: 10.1371/journal.pgen.1000870 20221250
65. Liu Y., Semina E.V. (2012). pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish. PLoS One.7, e30896. doi: 10.1371/journal.pone.0030896 22303467
66. Eimon P.M. (2014). Studying apoptosis in the Zebrafish. Methods Enzymol. 544, 395–431. doi: 10.1016/B978-0-12-417158-9.00016-9 24974299
67. Imai F., Yoshizawa A., Fujimori-Tonou N., Kawakami K., Masai I. (2010). The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish. Development. 137, 3257–3268. doi: 10.1242/dev.053124 20724448
68. French C.R., Erickson T., French D.V., Pilgrim D.B., Waskiewicz A.J. (2009). Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development. Dev. Biol. 333, 37–47. doi: 10.1016/j.ydbio.2009.06.018 19545559
69. Collery R.F., Link B.A. (2011). Dynamic smad-mediated BMP signaling revealed through transgenic zebrafish. Dev. Dyn. 240, 712–722. doi: 10.1002/dvdy.22567 21337469
70. Greiling T.M., Aose M., Clark J.I. (2010). Cell fate and differentiation of the developing ocular lens. IOVS. 51, 1540–1546.
Štítky
Genetika Reprodukčná medicína
Článek 2014 Reviewer Thank YouČlánek Closing the Gap between Knowledge and Clinical Application: Challenges for Genomic TranslationČlánek Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate CellsČlánek K-homology Nuclear Ribonucleoproteins Regulate Floral Organ Identity and Determinacy in ArabidopsisČlánek A Nitric Oxide Regulated Small RNA Controls Expression of Genes Involved in Redox Homeostasis inČlánek Contribution of the Two Genes Encoding Histone Variant H3.3 to Viability and Fertility in MiceČlánek The Genetic Architecture of the Genome-Wide Transcriptional Response to ER Stress in the Mouse
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2015 Číslo 2- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- 2014 Reviewer Thank You
- Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for and Myocardial Infarction
- African Glucose-6-Phosphate Dehydrogenase Alleles Associated with Protection from Severe Malaria in Heterozygous Females in Tanzania
- Genomics of Divergence along a Continuum of Parapatric Population Differentiation
- microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes
- A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in
- Closing the Gap between Knowledge and Clinical Application: Challenges for Genomic Translation
- Partially Redundant Enhancers Cooperatively Maintain Mammalian Expression Above a Critical Functional Threshold
- Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling
- Mutations in Result in Ocular Coloboma, Microcornea and Cataracts
- A Genome-Wide Hybrid Incompatibility Landscape between and
- Recurrent Evolution of Melanism in South American Felids
- Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
- Tissue Expression Pattern of PMK-2 p38 MAPK Is Established by the miR-58 Family in
- Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes
- Matrix Metalloproteinase 2 Is Required for Ovulation and Corpus Luteum Formation in
- Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks
- RR-1 Cuticular Protein TcCPR4 Is Required for Formation of Pore Canals in Rigid Cuticle
- GC-Content Evolution in Bacterial Genomes: The Biased Gene Conversion Hypothesis Expands
- Proteotoxic Stress Induces Phosphorylation of p62/SQSTM1 by ULK1 to Regulate Selective Autophagic Clearance of Protein Aggregates
- K-homology Nuclear Ribonucleoproteins Regulate Floral Organ Identity and Determinacy in Arabidopsis
- A Nitric Oxide Regulated Small RNA Controls Expression of Genes Involved in Redox Homeostasis in
- HYPER RECOMBINATION1 of the THO/TREX Complex Plays a Role in Controlling Transcription of the Gene in Arabidopsis
- Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan
- Structured Observations Reveal Slow HIV-1 CTL Escape
- An Integrative Multi-scale Analysis of the Dynamic DNA Methylation Landscape in Aging
- Combining Natural Sequence Variation with High Throughput Mutational Data to Reveal Protein Interaction Sites
- Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production
- Regulators of Autophagosome Formation in Muscles
- Genomic Selection and Association Mapping in Rice (): Effect of Trait Genetic Architecture, Training Population Composition, Marker Number and Statistical Model on Accuracy of Rice Genomic Selection in Elite, Tropical Rice Breeding Lines
- Eye Selector Logic for a Coordinated Cell Cycle Exit
- Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations
- The DNA Polymerase δ Has a Role in the Deposition of Transcriptionally Active Epigenetic Marks, Development and Flowering
- Contribution of the Two Genes Encoding Histone Variant H3.3 to Viability and Fertility in Mice
- Membrane Recognition and Dynamics of the RNA Degradosome
- P-TEFb, the Super Elongation Complex and Mediator Regulate a Subset of Non-paused Genes during Early Embryo Development
- is a Long Non-coding RNA in JNK Signaling in Epithelial Shape Changes during Drosophila Dorsal Closure
- A Pleiotropy-Informed Bayesian False Discovery Rate Adapted to a Shared Control Design Finds New Disease Associations From GWAS Summary Statistics
- Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers
- and Hyperdrive Mechanisms (in Mouse Meiosis)
- Elevated In Vivo Levels of a Single Transcription Factor Directly Convert Satellite Glia into Oligodendrocyte-like Cells
- Systemic Delivery of MicroRNA-101 Potently Inhibits Hepatocellular Carcinoma by Repressing Multiple Targets
- Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in and Implicates Other Immune Related Genes
- Abscission Is Regulated by the ESCRT-III Protein Shrub in Germline Stem Cells
- Temperature Stress Mediates Decanalization and Dominance of Gene Expression in
- Transcriptome Wide Annotation of Eukaryotic RNase III Reactivity and Degradation Signals
- The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway
- Sex-specific -regulatory Variation on the X Chromosome
- Regulation of Toll-like Receptor Signaling by the SF3a mRNA Splicing Complex
- Modeling of the Human Alveolar Rhabdomyosarcoma Chromosome Translocation in Mouse Myoblasts Using CRISPR-Cas9 Nuclease
- Asymmetry of the Budding Yeast Tem1 GTPase at Spindle Poles Is Required for Spindle Positioning But Not for Mitotic Exit
- TIM Binds Importin α1, and Acts as an Adapter to Transport PER to the Nucleus
- Antagonistic Roles for KNOX1 and KNOX2 Genes in Patterning the Land Plant Body Plan Following an Ancient Gene Duplication
- The Genetic Architecture of the Genome-Wide Transcriptional Response to ER Stress in the Mouse
- Fatty Acid Synthase Cooperates with Glyoxalase 1 to Protect against Sugar Toxicity
- Region-Specific Activation of mRNA Translation by Inhibition of Bruno-Mediated Repression
- An Essential Role of the Arginine Vasotocin System in Mate-Guarding Behaviors in Triadic Relationships of Medaka Fish ()
- Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo
- Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis
- Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction
- Recent Selective Sweeps in North American Show Signatures of Soft Sweeps
- Identification and Functional Analysis of Healing Regulators in
- A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2
- Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels
- The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Ovary
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Genomic Selection and Association Mapping in Rice (): Effect of Trait Genetic Architecture, Training Population Composition, Marker Number and Statistical Model on Accuracy of Rice Genomic Selection in Elite, Tropical Rice Breeding Lines
- Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling
- Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks
- Proteotoxic Stress Induces Phosphorylation of p62/SQSTM1 by ULK1 to Regulate Selective Autophagic Clearance of Protein Aggregates
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy