#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2013 - 1

Mutation of the Diamond-Blackfan Anemia Gene in Mouse Results in Morphological and Neuroanatomical Phenotypes

English version České info

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7Mtu and Rps7Zma) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes.

Vyšlo v časopise: Mutation of the Diamond-Blackfan Anemia Gene in Mouse Results in Morphological and Neuroanatomical Phenotypes. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003094
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003094

Souhrn

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7Mtu and Rps7Zma) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes.

Zdroje

1. UechiT, TanakaT, KenmochiN (2001) A complete map of the human ribosomal protein genes: assignment of 80 genes to the cytogenetic map and implications for human disorders. Genomics 72 : 223–230 doi:10.1006/geno.2000.6470.

2. BoisvertF-M, van KoningsbruggenS, NavascuésJ, LamondAI (2007) The multifunctional nucleolus. Nat Rev Mol Cell Biol 8 : 574–585 doi:10.1038/nrm2184.

3. MarygoldSJ, RooteJ, ReuterG, LambertssonA, AshburnerM, et al. (2007) The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome Biol 8: R216 doi:10.1186/gb-2007-8-10-r216.

4. UechiT, NakajimaY, NakaoA, ToriharaH, ChakrabortyA, et al. (2006) Ribosomal protein gene knockdown causes developmental defects in zebrafish. PLoS ONE 1: e37 doi:10.1371/journal.pone.0000037.

5. McgowanKA, LiJZ, ParkCY, BeaudryV, TaborHK, et al. (2008) Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nat Genet 40 : 963–970 doi:10.1038/ng.188.

6. OliverER, SaundersTL, TarléSA, GlaserT (2004) Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131 : 3907–3920 doi:10.1242/dev.01268.

7. TerzianT, DumbleM, ArbabF, ThallerC, DonehowerLA, et al. (2011) Rpl27a mutation in the sooty foot ataxia mouse phenocopies high p53 mouse models. J Pathol 224 : 540–552 doi:10.1002/path.2891.

8. FarrarJE, NaterM, CaywoodE, McDevittMA, KowalskiJ, et al. (2008) Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood 112 : 1582–1592 doi:10.1182/blood-2008-02-140012.

9. GazdaHT, GrabowskaA, Merida-LongLB, LatawiecE, SchneiderHE, et al. (2006) Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet 79 : 1110–1118 doi:10.1086/510020.

10. DohertyL, SheenMR, VlachosA, ChoesmelV, O'DonohueM-F, et al. (2010) Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet 86 : 222–228 doi:10.1016/j.ajhg.2009.12.015.

11. GazdaHT, SheenMR, VlachosA, ChoesmelV, O'DonohueM-F, et al. (2008) Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet 83 : 769–780 doi:10.1016/j.ajhg.2008.11.004.

12. GazdaHT, PretiM, SheenMR, O'DonohueM-F, VlachosA, et al. (2012) Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia. Hum Mutat doi:10.1002/humu.22081.

13. CmejlaR, CmejlovaJ, HandrkovaH, PetrakJ, PospisilovaD (2007) Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat 28 : 1178–1182 doi:10.1002/humu.20608.

14. DraptchinskaiaN, GustavssonP, AnderssonB, PetterssonM, WilligTN, et al. (1999) The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 21 : 169–175 doi:10.1038/5951.

15. NolanPM, PetersJ, StrivensM, RogersD, HaganJ, et al. (2000) A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet 25 : 440–443 doi:10.1038/78140.

16. BoganiD, WarrN, ElmsP, DaviesJ, Tymowska-LalanneZ, et al. (2004) New semidominant mutations that affect mouse development. Genesis 40 : 109–117 doi:10.1002/gene.20071.

17. MateraI, Watkins-ChowDE, LoftusSK, HouL, IncaoA, et al. (2008) A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy. Hum Mol Genet 17 : 2118–2131 doi:10.1093/hmg/ddn110.

18. ThomasPD, KejariwalA, GuoN, MiH, CampbellMJ, et al. (2006) Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools. Nucleic Acids Res 34: W645–W650.

19. KumarP, HenikoffS, NgPC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4 : 1073–1081 doi:10.1038/nprot.2009.86.

20. RablJ, LeibundgutM, AtaideSF, HaagA, BanN (2011) Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1. Science 331 : 730–736 doi:10.1126/science.1198308.

21. Ben-ShemA, Garreau de LoubresseN, MelnikovS, JennerL, YusupovaG, et al. (2011) The structure of the eukaryotic ribosome at 3.0 Å resolution. Science 334 : 1524–1529 doi:10.1126/science.1212642.

22. RostB, YachdavG, LiuJ (2004) The PredictProtein server. Nucleic Acids Res 32: W321–W326 doi:10.1093/nar/gkh377.

23. AngeliniM, CannataS, MercaldoV, GibelloL, SantoroC, et al. (2007) Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome. Hum Mol Genet 16 : 1720–1727 doi:10.1093/hmg/ddm120.

24. RobledoS, IdolRA, CrimminsDL, LadensonJH, MasonPJ, et al. (2008) The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA 14 : 1918–1929 doi:10.1261/rna.1132008.

25. O'DonohueM-F, ChoesmelV, FaubladierM, FichantG, GleizesP-E (2010) Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J Cell Biol 190 : 853–866 doi:10.1083/jcb.201005117.

26. BowmanLH, RabinB, SchlessingerD (1981) Multiple ribosomal RNA cleavage pathways in mammalian cells. Nucleic Acids Res 9 : 4951–4966.

27. DianzaniI, LoreniF (2008) Diamond-Blackfan anemia: a ribosomal puzzle. Haematologica 93 : 1601–1604 doi:10.3324/haematol.2008.000513.

28. SocolovskyM, NamH, FlemingMD, HaaseVH, BrugnaraC, et al. (2001) Ineffective erythropoiesis in Stat5a(−/−)5b(−/−) mice due to decreased survival of early erythroblasts. Blood 98 : 3261–3273.

29. ZhangJ, SocolovskyM, GrossAW, LodishHF (2003) Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry-based novel culture system. Blood 102 : 3938–3946 doi:10.1182/blood-2003-05-1479.

30. PotterfSB, MollaaghababaR, HouL, Southard-SmithEM, HornyakTJ, et al. (2001) Analysis of SOX10 function in neural crest-derived melanocyte development: SOX10-dependent transcriptional control of dopachrome tautomerase. Dev Biol 237 : 245–257 doi:10.1006/dbio.2001.0372.

31. DeaconRMJ, RawlinsJNP (2006) T-maze alternation in the rodent. Nat Protoc 1 : 7–12 doi:10.1038/nprot.2006.2.

32. ChakrabortyA, UechiT, HigaS, ToriharaH, KenmochiN (2009) Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response. PLoS ONE 4: e4152 doi:10.1371/journal.pone.0004152.

33. GazdaHT, KhoAT, SanoudouD, ZauchaJM, KohaneIS, et al. (2006) Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells 24 : 2034–2044 doi:10.1634/stemcells.2005-0554.

34. MatssonH, DaveyEJ, DraptchinskaiaN, HamaguchiI, OokaA, et al. (2004) Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation. Mol Cell Biol 24 : 4032–4037.

35. BarkićM, CrnomarkovićS, GrabusićK, BogetićI, PanićL, et al. (2009) The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival. Mol Cell Biol 29 : 2489–2504 doi:10.1128/MCB.01588-08.

36. ToriharaH, UechiT, ChakrabortyA, ShinyaM, SakaiN, et al. (2011) Erythropoiesis failure due to RPS19 deficiency is independent of an activated Tp53 response in a zebrafish model of Diamond-Blackfan anaemia. Br J Haematol 152 : 648–654 doi:10.1111/j.1365-2141.2010.08535.x.

37. SulicS, PanićL, BarkićM, MercepM, UzelacM, et al. (2005) Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response. Genes Dev 19 : 3070–3082 doi:10.1101/gad.359305.

38. WildT, HorvathP, WylerE, WidmannB, BadertscherL, et al. (2010) A protein inventory of human ribosome biogenesis reveals an essential function of exportin 5 in 60S subunit export. PLoS Biol 8: e1000522 doi:10.1371/journal.pbio.1000522.

39. SynetosD, DabevaMD, WarnerJR (1992) The yeast ribosomal protein S7 and its genes. J Biol Chem 267 : 3008–3013.

40. SteffenKK, McCormickMA, PhamKM, MacKayVL, DelaneyJR, et al. (2012) Ribosome Deficiency Protects Against ER Stress in Saccharomyces cerevisiae. Genetics 191 : 107–118 doi:10.1534/genetics.111.136549.

41. BernsteinKA, GallagherJEG, MitchellBM, GrannemanS, BasergaSJ (2004) The Small-Subunit Processome Is a Ribosome Assembly Intermediate. Eukaryotic Cell 3 : 1619–1626 doi:10.1128/EC.3.6.1619-1626.2004.

42. Ferreira-CercaS, PöllG, GleizesP-E, TschochnerH, MilkereitP (2005) Roles of Eukaryotic Ribosomal Proteins in Maturation and Transport of Pre-18S rRNA and Ribosome Function. Molecular Cell 20 : 263–275 doi:10.1016/j.molcel.2005.09.005.

43. GoodmanFR (2003) Congenital abnormalities of body patterning: embryology revisited. Lancet 362 : 651–662 doi:10.1016/S0140-6736(03)14187-6.

44. BoganiD, WilloughbyC, DaviesJ, KaurK, MirzaG, et al. (2005) Dissecting the genetic complexity of human 6p deletion syndromes by using a region-specific, phenotype-driven mouse screen. Proc Natl Acad Sci USA 102 : 12477–12482 doi:10.1073/pnas.0500584102.

45. MatssonH, DaveyEJ, FröjmarkAS, MiyakeK, UtsugisawaT, et al. (2006) Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response and biochemical markers for Diamond-Blackfan anemia. Blood Cells Mol Dis 36 : 259–264 doi:10.1016/j.bcmd.2005.12.002.

46. MorganWC (1950) A new tail-short mutation in the mouse whose lethal effects are conditioned by the residual genotypes. J Hered 41 : 208–215.

47. KondrashovN, PusicA, StumpfCR, ShimizuK, HsiehAC, et al. (2011) Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145 : 383–397 doi:10.1016/j.cell.2011.03.028.

48. SouthardJ, EischerE (1977) Belly spot and tail (Bst). Mouse News Letter 56 : 40.

49. AndersonSJ, LauritsenJPH, HartmanMG, FousheeAMD, LefebvreJM, et al. (2007) Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity 26 : 759–772 doi:10.1016/j.immuni.2007.04.012.

50. StadanlickJE, ZhangZ, LeeS-Y, HemannM, BieryM, et al. (2011) Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. J Immunol 187 : 664–675 doi:10.4049/jimmunol.1100029.

51. Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, et al.. (2008) Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Vol. 142. pp. 859–876. doi:10.1111/j.1365-2141.2008.07269.x.

52. TangYP, WadeJ (2010) Sex -⁠ and age-related differences in ribosomal proteins L17 and L37, as well as androgen receptor protein, in the song control system of zebra finches. Neuroscience 171 : 1131–1140 doi:10.1016/j.neuroscience.2010.10.014.

53. FumagalliS, IvanenkovVV, TengT, ThomasG (2012) Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint. Genes Dev 26 : 1028–1040 doi:10.1101/gad.189951.112.

54. DuanJ, BaQ, WangZ, HaoM, LiX, et al. (2011) Knockdown of ribosomal protein S7 causes developmental abnormalities via p53 dependent and independent pathways in zebrafish. The International Journal of Biochemistry & Cell Biology 43 : 1218–1227 doi:10.1016/j.biocel.2011.04.015.

55. WarnerJR, McIntoshKB (2009) How common are extraribosomal functions of ribosomal proteins? Molecular Cell 34 : 3–11 doi:10.1016/j.molcel.2009.03.006.

56. BortoluzziS, d'AlessiF, RomualdiC, DanieliGA (2001) Differential expression of genes coding for ribosomal proteins in different human tissues. Bioinformatics 17 : 1152–1157.

57. BévortM, LeffersH (2000) Down regulation of ribosomal protein mRNAs during neuronal differentiation of human NTERA2 cells. Differentiation 66 : 81–92 doi:10.1046/j.1432-0436.2000.660203.x.

58. TerzianT, TorchiaEC, DaiD, RobinsonSE, MuraoK, et al. (2010) p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation. Pigment Cell & Melanoma Research 23 : 781–794 doi:10.1111/j.1755-148X.2010.00773.x.

59. KapasiP, ChaudhuriS, VyasK, BausD, KomarAA, et al. (2007) L13a Blocks 48S Assembly: Role of a General Initiation Factor in mRNA-Specific Translational Control. Molecular Cell 25 : 113–126 doi:10.1016/j.molcel.2006.11.028.

60. SatoY, YanoS, EwisAA, NakahoriY (2011) SRY interacts with ribosomal proteins S7 and L13a in nuclear speckles. Cell Biology International 35 : 449–452 doi:10.1042/CBI20090201.

61. WilkinsonDG, NietoMA (1993) Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts. Meth Enzymol 225 : 361–373.

62. Phan Dinh TuyF, SaillourY, KappelerC, ChellyJ, FrancisF (2008) Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice. Dev Neurosci 30 : 171–186 doi:10.1159/000109861.

63. HennigJ, NauerthA, FriedburgH (1986) RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 3 : 823–833.

64. Paxinos G, Halliday GM, Watson C, Koutcherov Y, Wang H (2006) Atlas of the Developing Mouse Brain at E17.5, P0 and P6. Academic Press.

Štítky
Genetika Reprodukčná medicína
Článek A Model of High Sugar Diet-Induced Cardiomyopathy
Článek Comparative Genome Structure, Secondary Metabolite, and Effector Coding Capacity across Pathogens
Článek Emerging Function of Fat Mass and Obesity-Associated Protein (Fto)
Článek Positional Cloning Reveals Strain-Dependent Expression of to Alter Susceptibility to Bleomycin-Induced Pulmonary Fibrosis in Mice
Článek Genetics of Ribosomal Proteins: “Curiouser and Curiouser”
Článek Transposable Elements Re-Wire and Fine-Tune the Transcriptome
Článek Function and Regulation of , a Gene Implicated in Autism and Human Evolution
Článek MAML1 Enhances the Transcriptional Activity of Runx2 and Plays a Role in Bone Development
Článek Predicting Mendelian Disease-Causing Non-Synonymous Single Nucleotide Variants in Exome Sequencing Studies
Článek A Systematic Mapping Approach of 16q12.2/ and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study
Článek Transcription of the Major microRNA–Like Small RNAs Relies on RNA Polymerase III
Článek Histone H3K56 Acetylation, Rad52, and Non-DNA Repair Factors Control Double-Strand Break Repair Choice with the Sister Chromatid
Článek Genome-Wide Association Study Identifies a Novel Susceptibility Locus at 12q23.1 for Lung Squamous Cell Carcinoma in Han Chinese
Článek Genetic Disruption of the Copulatory Plug in Mice Leads to Severely Reduced Fertility
Článek The [] Prion Exists as a Dynamic Cloud of Variants
Článek Adult Onset Global Loss of the Gene Alters Body Composition and Metabolism in the Mouse
Článek Fis Protein Insulates the Gene from Uncontrolled Transcription
Článek The Meiotic Nuclear Lamina Regulates Chromosome Dynamics and Promotes Efficient Homologous Recombination in the Mouse
Článek Genome-Wide Haplotype Analysis of Expression Quantitative Trait Loci in Monocytes
Článek TATES: Efficient Multivariate Genotype-Phenotype Analysis for Genome-Wide Association Studies
Článek Structural Basis of a Histone H3 Lysine 4 Demethylase Required for Stem Elongation in Rice
Článek The Ecm11-Gmc2 Complex Promotes Synaptonemal Complex Formation through Assembly of Transverse Filaments in Budding Yeast
Článek MCM8 Is Required for a Pathway of Meiotic Double-Strand Break Repair Independent of DMC1 in
Článek Comparative Genomic Analysis of the Endosymbionts of Herbivorous Insects Reveals Eco-Environmental Adaptations: Biotechnology Applications
Článek Integration of Nodal and BMP Signals in the Heart Requires FoxH1 to Create Left–Right Differences in Cell Migration Rates That Direct Cardiac Asymmetry
Článek Pharmacodynamics, Population Dynamics, and the Evolution of Persistence in
Článek A Hybrid Likelihood Model for Sequence-Based Disease Association Studies
Článek Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity
Článek Multiple Opposing Constraints Govern Chromosome Interactions during Meiosis
Článek Transcriptional Dynamics Elicited by a Short Pulse of Notch Activation Involves Feed-Forward Regulation by Genes
Článek Dynamic Large-Scale Chromosomal Rearrangements Fuel Rapid Adaptation in Yeast Populations
Článek Heterologous Gln/Asn-Rich Proteins Impede the Propagation of Yeast Prions by Altering Chaperone Availability
Článek Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans
Článek An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in
Článek Secondary Metabolism and Development Is Mediated by LlmF Control of VeA Subcellular Localization in
Článek Single-Stranded Annealing Induced by Re-Initiation of Replication Origins Provides a Novel and Efficient Mechanism for Generating Copy Number Expansion via Non-Allelic Homologous Recombination
Článek Tbx2 Controls Lung Growth by Direct Repression of the Cell Cycle Inhibitor Genes and
Článek Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene
Článek A Conserved Helicase Processivity Factor Is Needed for Conjugation and Replication of an Integrative and Conjugative Element
Článek Telomerase-Null Survivor Screening Identifies Novel Telomere Recombination Regulators
Článek Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds
Článek Coordinated Degradation of Replisome Components Ensures Genome Stability upon Replication Stress in the Absence of the Replication Fork Protection Complex
Článek Nkx6.1 Controls a Gene Regulatory Network Required for Establishing and Maintaining Pancreatic Beta Cell Identity
Článek HIF- and Non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in
Článek Delineating a Conserved Genetic Cassette Promoting Outgrowth of Body Appendages
Článek The Telomere Capping Complex CST Has an Unusual Stoichiometry, Makes Multipartite Interaction with G-Tails, and Unfolds Higher-Order G-Tail Structures
Článek Comprehensive Methylome Characterization of and at Single-Base Resolution
Článek Loci Associated with -Glycosylation of Human Immunoglobulin G Show Pleiotropy with Autoimmune Diseases and Haematological Cancers
Článek Switchgrass Genomic Diversity, Ploidy, and Evolution: Novel Insights from a Network-Based SNP Discovery Protocol
Článek Centromere-Like Regions in the Budding Yeast Genome
Článek Sequencing of Loci from the Elephant Shark Reveals a Family of Genes in Vertebrate Genomes, Forged by Ancient Duplications and Divergences
Článek Mendelian and Non-Mendelian Regulation of Gene Expression in Maize
Článek Mutational Spectrum Drives the Rise of Mutator Bacteria
Článek Human Disease-Associated Genetic Variation Impacts Large Intergenic Non-Coding RNA Expression
Článek The Roles of Whole-Genome and Small-Scale Duplications in the Functional Specialization of Genes
Článek Sex-Specific Signaling in the Blood–Brain Barrier Is Required for Male Courtship in
Článek A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity
Článek Is Required for Leptin-Mediated Depolarization of POMC Neurons in the Hypothalamic Arcuate Nucleus in Mice
Článek Unlocking the Bottleneck in Forward Genetics Using Whole-Genome Sequencing and Identity by Descent to Isolate Causative Mutations
Článek The Role of Autophagy in Genome Stability through Suppression of Abnormal Mitosis under Starvation
Článek MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals
Článek Downregulation and Altered Splicing by in a Mouse Model of Facioscapulohumeral Muscular Dystrophy (FSHD)
Článek NBR1-Mediated Selective Autophagy Targets Insoluble Ubiquitinated Protein Aggregates in Plant Stress Responses
Článek Retroactive Maintains Cuticle Integrity by Promoting the Trafficking of Knickkopf into the Procuticle of
Článek Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network
Článek Genetic and Functional Modularity of Activities in the Specification of Limb-Innervating Motor Neurons
Článek A Population Genetic Model for the Maintenance of R2 Retrotransposons in rRNA Gene Loci
Článek A Quartet of PIF bHLH Factors Provides a Transcriptionally Centered Signaling Hub That Regulates Seedling Morphogenesis through Differential Expression-Patterning of Shared Target Genes in
Článek A Genome-Wide Integrative Genomic Study Localizes Genetic Factors Influencing Antibodies against Epstein-Barr Virus Nuclear Antigen 1 (EBNA-1)
Článek Life, the Universe, and Everything: An Interview with David Haussler
Článek Alternative Oxidase Expression in the Mouse Enables Bypassing Cytochrome Oxidase Blockade and Limits Mitochondrial ROS Overproduction
Článek An Evolutionarily Conserved Synthetic Lethal Interaction Network Identifies FEN1 as a Broad-Spectrum Target for Anticancer Therapeutic Development
Článek The Flowering Repressor Underlies a Novel QTL Interacting with the Genetic Background
Článek Telomerase Is Required for Zebrafish Lifespan
Článek and Diversified Expression of the Gene Family Bolster the Floral Stem Cell Network
Článek Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies
Článek An Insertion in 5′ Flanking Region of Causes Blue Eggshell in the Chicken
Článek Increased Maternal Genome Dosage Bypasses the Requirement of the FIS Polycomb Repressive Complex 2 in Arabidopsis Seed Development
Článek WNK1/HSN2 Mutation in Human Peripheral Neuropathy Deregulates Expression and Posterior Lateral Line Development in Zebrafish ()
Článek Synergistic Interaction of Rnf8 and p53 in the Protection against Genomic Instability and Tumorigenesis
Článek Dot1-Dependent Histone H3K79 Methylation Promotes Activation of the Mek1 Meiotic Checkpoint Effector Kinase by Regulating the Hop1 Adaptor
Článek A Heterogeneous Mixture of F-Series Prostaglandins Promotes Sperm Guidance in the Reproductive Tract
Článek Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin
Článek Directed Evolution of a Model Primordial Enzyme Provides Insights into the Development of the Genetic Code
Článek Genome-Wide Screens for Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures
Článok vyšiel v časopise

PLOS Genetics

2013 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#