#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2013 - 3

Human Spermatogenic Failure Purges Deleterious Mutation Load from the Autosomes and Both Sex Chromosomes, including the Gene

English version České info

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04–1.16], p<2×10−3), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p<1×10−3), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2×10−5). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.

Vyšlo v časopise: Human Spermatogenic Failure Purges Deleterious Mutation Load from the Autosomes and Both Sex Chromosomes, including the Gene. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003349
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003349

Souhrn

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04–1.16], p<2×10−3), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p<1×10−3), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2×10−5). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.

Zdroje

1. KrauszC (2011) Male infertility: pathogenesis and clinical diagnosis. Best practice & research Clinical endocrinology & metabolism 25 : 271–285.

2. SchultzN, HamraFK, GarbersDL (2003) A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc Natl Acad Sci U S A 100 : 12201–12206.

3. TiepoloL, ZuffardiO (1976) Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 34 : 119–124.

4. LanfrancoF, KamischkeA, ZitzmannM, NieschlagE (2004) Klinefelter's syndrome. Lancet 364 : 273–283.

5. YatsenkoAN, YatsenkoSA, WeedinJW, LawrenceAE, PatelA, et al. (2010) Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men. The Journal of urology 183 : 1636–1642.

6. KoscinskiI, ElinatiE, FossardC, RedinC, MullerJ, et al. (2011) DPY19L2 deletion as a major cause of globozoospermia. American journal of human genetics 88 : 344–350.

7. SykiotisGP, PitteloudN, SeminaraSB, KaiserUB, CrowleyWFJr (2010) Deciphering genetic disease in the genomic era: the model of GnRH deficiency. Science translational medicine 2 : 32rv32.

8. LeePA, HoukCP, AhmedSF, HughesIA (2006) Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics 118: e488–500.

9. StankiewiczP, LupskiJR (2010) Structural variation in the human genome and its role in disease. Annu Rev Med 61 : 437–455.

10. SebatJ, LakshmiB, MalhotraD, TrogeJ, Lese-MartinC, et al. (2007) Strong association of de novo copy number mutations with autism. Science 316 : 445–449.

11. TamGW, RedonR, CarterNP, GrantSG (2009) The role of DNA copy number variation in schizophrenia. Biol Psychiatry 66 : 1005–1012.

12. WilsonGM, FlibotteS, ChopraV, MelnykBL, HonerWG, et al. (2006) DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling. Hum Mol Genet 15 : 743–749.

13. MeffordHC, MuhleH, OstertagP, von SpiczakS, BuysseK, et al. (2010) Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet 6: e1000962 doi:10.1371/journal.pgen.1000962

14. PtacekT, LiX, KelleyJM, EdbergJC (2008) Copy number variants in genetic susceptibility and severity of systemic lupus erythematosus. Cytogenet Genome Res 123 : 142–147.

15. SchaschlH, AitmanTJ, VyseTJ (2009) Copy number variation in the human genome and its implication in autoimmunity. Clin Exp Immunol 156 : 12–16.

16. JeonJP, ShimSM, NamHY, RyuGM, HongEJ, et al. (2010) Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus. BMC Genomics 11 : 426.

17. PollexRL, HegeleRA (2007) Copy number variation in the human genome and its implications for cardiovascular disease. Circulation 115 : 3130–3138.

18. TchatchouS, BurwinkelB (2008) Chromosome copy number variation and breast cancer risk. Cytogenet Genome Res 123 : 183–187.

19. FrankB, BermejoJL, HemminkiK, SutterC, WappenschmidtB, et al. (2007) Copy number variant in the candidate tumor suppressor gene MTUS1 and familial breast cancer risk. Carcinogenesis 28 : 1442–1445.

20. BraudeI, VukovicB, PrasadM, MarranoP, TurleyS, et al. (2006) Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia. BMC Genomics 7 : 138.

21. LaFramboiseT, WeirBA, ZhaoX, BeroukhimR, LiC, et al. (2005) Allele-specific amplification in cancer revealed by SNP array analysis. PLoS Comput Biol 1: e65 doi:10.1371/journal.pcbi.0010065

22. HansenS, EichlerEE, FullertonSM, CarrellD (2010) SPANX gene variation in fertile and infertile males. Syst Biol Reprod Med 55 : 18–26.

23. JorgezCJ, WeedinJW, SahinA, Tannour-LouetM, HanS, et al. (2011) Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions. J Clin Endocrinol Metab 96: E674–679.

24. TuttelmannF, SimoniM, KlieschS, LedigS, DworniczakB, et al. (2011) Copy number variants in patients with severe oligozoospermia and sertoli-cell-only syndrome. PLoS ONE 6: e19426 doi:10.1371/journal.pone.0019426

25. StouffsK, VandermaelenD, MassartA, MentenB, VergultS, et al. (2012) Array comparative genomic hybridization in male infertility. Human reproduction 27 : 921–929.

26. KuCS, NaidooN, TeoSM, PawitanY (2011) Regions of homozygosity and their impact on complex diseases and traits. Human genetics 129 : 1–15.

27. KellerMC, SimonsonMA, RipkeS, NealeBM, GejmanPV, et al. (2012) Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS Genet 8: e1002656 doi:10.1371/journal.pgen.1002656

28. NallsMA, GuerreiroRJ, Simon-SanchezJ, BrasJT, TraynorBJ, et al. (2009) Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer's disease. Neurogenetics 10 : 183–190.

29. Enciso-MoraV, HoskingFJ, HoulstonRS (2010) Risk of breast and prostate cancer is not associated with increased homozygosity in outbred populations. European journal of human genetics: EJHG 18 : 909–914.

30. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 : 661–678.

31. WangPJ, McCarreyJR, YangF, PageDC (2001) An abundance of X-linked genes expressed in spermatogonia. Nature genetics 27 : 422–426.

32. StankiewiczP, LupskiJR (2002) Genome architecture, rearrangements and genomic disorders. Trends Genet 18 : 74–82.

33. LugtenbergD, Zangrande-VieiraL, KirchhoffM, WhibleyAC, OudakkerAR, et al. (2010) Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation. American journal of medical genetics Part A 152A: 638–645.

34. SkaletskyH, Kuroda-KawaguchiT, MinxPJ, CordumHS, HillierL, et al. (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423 : 825–837.

35. ConradDF, PintoD, RedonR, FeukL, GokcumenO, et al. (2010) Origins and functional impact of copy number variation in the human genome. Nature 464 : 704–712.

36. SmithCA, RoeszlerKN, OhnesorgT, CumminsDM, FarliePG, et al. (2009) The avian Z-linked gene DMRT1 is required for male sex determination in the chicken. Nature 461 : 267–271.

37. MurphyMW, SarverAL, RiceD, HatziK, YeK, et al. (2010) Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis. Proceedings of the National Academy of Sciences of the United States of America 107 : 13360–13365.

38. RaymondCS, ParkerED, KettlewellJR, BrownLG, PageDC, et al. (1999) A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum Mol Genet 8 : 989–996.

39. Tannour-LouetM, HanS, CorbettST, LouetJF, YatsenkoS, et al. (2010) Identification of de novo copy number variants associated with human disorders of sexual development. PLoS ONE 5: e15392 doi:10.1371/journal.pone.0015392

40. BarbaroM, BalsamoA, AnderlidBM, MyhreAG, GennariM, et al. (2009) Characterization of deletions at 9p affecting the candidate regions for sex reversal and deletion 9p syndrome by MLPA. Eur J Hum Genet 17 : 1439–1447.

41. HuZ, XiaY, GuoX, DaiJ, LiH, et al. (2012) A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nature genetics 44 : 183–186.

42. ItsaraA, CooperGM, BakerC, GirirajanS, LiJ, et al. (2009) Population analysis of large copy number variants and hotspots of human genetic disease. American journal of human genetics 84 : 148–161.

43. ShaikhTH, GaiX, PerinJC, GlessnerJT, XieH, et al. (2009) High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications. Genome research 19 : 1682–1690.

44. MiholaO, TrachtulecZ, VlcekC, SchimentiJC, ForejtJ (2009) A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323 : 373–375.

45. MatzukMM, LambDJ (2008) The biology of infertility: research advances and clinical challenges. Nat Med 14 : 1197–1213.

46. CooperGM, CoeBP, GirirajanS, RosenfeldJA, VuTH, et al. (2011) A copy number variation morbidity map of developmental delay. Nature genetics 43 : 838–846.

47. HuangN, LeeI, MarcotteEM, HurlesME (2010) Characterising and predicting haploinsufficiency in the human genome. PLoS Genet 6: e1001154 doi:10.1371/journal.pgen.1001154

48. BrowningSR, BrowningBL (2010) High-resolution detection of identity by descent in unrelated individuals. American journal of human genetics 86 : 526–539.

49. KantarciS, RaggeNK, ThomasNS, RobinsonDO, NoonanKM, et al. (2008) Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy. American journal of medical genetics Part A 146A: 1842–1847.

50. KellerMC, VisscherPM, GoddardME (2011) Quantification of inbreeding due to distant ancestors and its detection using dense single nucleotide polymorphism data. Genetics 189 : 237–249.

51. LedigS, HiortO, WunschL, WieackerP (2012) Partial deletion of DMRT1 causes 46,XY ovotesticular disorder of sexual development. European journal of endocrinology/European Federation of Endocrine Societies 167 : 119–124.

52. LedigS, HiortO, SchererG, HoffmannM, WolffG, et al. (2010) Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal dysgenesis: evaluation of array CGH as diagnostic tool and search for new candidate loci. Human reproduction 25 : 2637–2646.

53. MachevN, SautN, LongepiedG, TerriouP, NavarroA, et al. (2004) Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility. Journal of medical genetics 41 : 814–825.

54. GiachiniC, LafaceI, GuarducciE, BalerciaG, FortiG, et al. (2008) Partial AZFc deletions and duplications: clinical correlates in the Italian population. Human genetics 124 : 399–410.

55. LinYW, HsuLC, KuoPL, HuangWJ, ChiangHS, et al. (2007) Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. Human mutation 28 : 486–494.

56. LuC, ZhangF, YangH, XuM, DuG, et al. (2011) Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated risk of spermatogenic impairment in Han Chinese population. Human molecular genetics 20 : 4411–4421.

57. ReppingS, van DaalenSK, BrownLG, KorverCM, LangeJ, et al. (2006) High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nature genetics 38 : 463–467.

58. KrauszC, GiachiniC, Lo GiaccoD, DaguinF, ChianeseC, et al. (2012) High resolution X chromosome-specific array-CGH detects new CNVs in infertile males. PLoS ONE 7: e44887 doi:10.1371/journal.pone.0044887

59. DaviesMJ, MooreVM, WillsonKJ, Van EssenP, PriestK, et al. (2012) Reproductive technologies and the risk of birth defects. The New England journal of medicine 366 : 1803–1813.

60. HoppsCV, MielnikA, GoldsteinM, PalermoGD, RosenwaksZ, et al. (2003) Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Human reproduction 18 : 1660–1665.

61. Pique-RegiR, OrtegaA, AsgharzadehS (2009) Joint estimation of copy number variation and reference intensities on multiple DNA arrays using GADA. Bioinformatics 25 : 1223–1230.

62. WangK, LiM, HadleyD, LiuR, GlessnerJ, et al. (2007) PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome research 17 : 1665–1674.

63. ColellaS, YauC, TaylorJM, MirzaG, ButlerH, et al. (2007) QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic acids research 35 : 2013–2025.

64. KornJM, KuruvillaFG, McCarrollSA, WysokerA, NemeshJ, et al. (2008) Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nature genetics 40 : 1253–1260.

65. PurcellS, NealeB, Todd-BrownK, ThomasL, FerreiraMA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. American journal of human genetics 81 : 559–575.

66. FirthHV, RichardsSM, BevanAP, ClaytonS, CorpasM, et al. (2009) DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. American journal of human genetics 84 : 524–533.

67. SandersSJ, Ercan-SencicekAG, HusV, LuoR, MurthaMT, et al. (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70 : 863–885.

68. MalhotraD, McCarthyS, MichaelsonJJ, VacicV, BurdickKE, et al. (2011) High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 72 : 951–963.

69. PriceAL, PattersonNJ, PlengeRM, WeinblattME, ShadickNA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature genetics 38 : 904–909.

70. PriceAL, TandonA, PattersonN, BarnesKC, RafaelsN, et al. (2009) Sensitive detection of chromosomal segments of distinct ancestry in admixed populations. PLoS Genet 5: e1000519 doi:10.1371/journal.pgen.1000519

Štítky
Genetika Reprodukčná medicína
Článek Power and Predictive Accuracy of Polygenic Risk Scores
Článek Rare Copy Number Variants Are a Common Cause of Short Stature
Článek Coordination of Flower Maturation by a Regulatory Circuit of Three MicroRNAs
Článek Ubiquitous Polygenicity of Human Complex Traits: Genome-Wide Analysis of 49 Traits in Koreans
Článek Genomic Evidence for Island Population Conversion Resolves Conflicting Theories of Polar Bear Evolution
Článek Mechanistic Insight into the Pathology of Polyalanine Expansion Disorders Revealed by a Mouse Model for X Linked Hypopituitarism
Článek Genome-Wide Association Study and Gene Expression Analysis Identifies as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis
Článek Problem Solved: An Interview with Sir Edwin Southern
Článek Long Interspersed Element–1 (LINE-1): Passenger or Driver in Human Neoplasms?
Článek Mouse HFM1/Mer3 Is Required for Crossover Formation and Complete Synapsis of Homologous Chromosomes during Meiosis
Článek Alternative Splicing and Subfunctionalization Generates Functional Diversity in Fungal Proteomes
Článek A WRKY Transcription Factor Recruits the SYG1-Like Protein SHB1 to Activate Gene Expression and Seed Cavity Enlargement
Článek Microhomology-Mediated Mechanisms Underlie Non-Recurrent Disease-Causing Microdeletions of the Gene or Its Regulatory Domain
Článek Ancient Evolutionary Trade-Offs between Yeast Ploidy States
Článek Differential Evolutionary Fate of an Ancestral Primate Endogenous Retrovirus Envelope Gene, the EnvV , Captured for a Function in Placentation
Článek A Feed-Forward Loop Coupling Extracellular BMP Transport and Morphogenesis in Wing
Článek The Tomato Yellow Leaf Curl Virus Resistance Genes and Are Allelic and Code for DFDGD-Class RNA–Dependent RNA Polymerases
Článek The U-Box E3 Ubiquitin Ligase TUD1 Functions with a Heterotrimeric G α Subunit to Regulate Brassinosteroid-Mediated Growth in Rice
Článek Role of the DSC1 Channel in Regulating Neuronal Excitability in : Extending Nervous System Stability under Stress
Článek –Independent Phenotypic Switching in and a Dual Role for Wor1 in Regulating Switching and Filamentation
Článek Pax6 Regulates Gene Expression in the Vertebrate Lens through miR-204
Článek Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression
Článek Genetic Architecture of Skin and Eye Color in an African-European Admixed Population
Článek Fine Characterisation of a Recombination Hotspot at the Locus and Resolution of the Paradoxical Excess of Duplications over Deletions in the General Population
Článek Estrogen Mediated-Activation of miR-191/425 Cluster Modulates Tumorigenicity of Breast Cancer Cells Depending on Estrogen Receptor Status
Článek Complex Patterns of Genomic Admixture within Southern Africa
Článek Yap- and Cdc42-Dependent Nephrogenesis and Morphogenesis during Mouse Kidney Development
Článek Molecular Networks of Human Muscle Adaptation to Exercise and Age
Článek Alp/Enigma Family Proteins Cooperate in Z-Disc Formation and Myofibril Assembly
Článek Polycomb Group Gene Regulates Rice () Seed Development and Grain Filling via a Mechanism Distinct from
Článek RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in
Článek Distinct Molecular Strategies for Hox-Mediated Limb Suppression in : From Cooperativity to Dispensability/Antagonism in TALE Partnership
Článek A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan
Článek TDP2–Dependent Non-Homologous End-Joining Protects against Topoisomerase II–Induced DNA Breaks and Genome Instability in Cells and
Článek Recurrent Rearrangement during Adaptive Evolution in an Interspecific Yeast Hybrid Suggests a Model for Rapid Introgression
Článek Genome-Wide Association Study in Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
Článek Coincident Resection at Both Ends of Random, γ–Induced Double-Strand Breaks Requires MRX (MRN), Sae2 (Ctp1), and Mre11-Nuclease
Článek Identification of a -Specific Modifier Locus at 6p24 Related to Breast Cancer Risk
Článek A Novel Function for the Hox Gene in the Male Accessory Gland Regulates the Long-Term Female Post-Mating Response in
Článek Tdp2: A Means to Fixing the Ends
Článek A Novel Role for the RNA–Binding Protein FXR1P in Myoblasts Cell-Cycle Progression by Modulating mRNA Stability
Článek Association Mapping and the Genomic Consequences of Selection in Sunflower
Článek Histone Deacetylase 2 (HDAC2) Regulates Chromosome Segregation and Kinetochore Function via H4K16 Deacetylation during Oocyte Maturation in Mouse
Článek A Novel Mutation in the Upstream Open Reading Frame of the Gene Causes a MEN4 Phenotype
Článek Ataxin1L Is a Regulator of HSC Function Highlighting the Utility of Cross-Tissue Comparisons for Gene Discovery
Článek A Conserved Upstream Motif Orchestrates Autonomous, Germline-Enriched Expression of piRNAs
Článek Statistical Analysis Reveals Co-Expression Patterns of Many Pairs of Genes in Yeast Are Jointly Regulated by Interacting Loci
Článek Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement
Článek A Role for the Malignant Brain Tumour (MBT) Domain Protein LIN-61 in DNA Double-Strand Break Repair by Homologous Recombination
Článek The Population and Evolutionary Dynamics of Phage and Bacteria with CRISPR–Mediated Immunity
Článek Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB
Článek Surveillance-Activated Defenses Block the ROS–Induced Mitochondrial Unfolded Protein Response
Článek DNA Topoisomerase III Localizes to Centromeres and Affects Centromeric CENP-A Levels in Fission Yeast
Článek Genome-Wide Control of RNA Polymerase II Activity by Cohesin
Článek Divergent Selection Drives Genetic Differentiation in an R2R3-MYB Transcription Factor That Contributes to Incipient Speciation in
Článek NODULE INCEPTION Directly Targets Subunit Genes to Regulate Essential Processes of Root Nodule Development in
Článek Spreading of a Prion Domain from Cell-to-Cell by Vesicular Transport in
Článek Deficiency in Origin Licensing Proteins Impairs Cilia Formation: Implications for the Aetiology of Meier-Gorlin Syndrome
Článek Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice
Článek The Conserved SKN-1/Nrf2 Stress Response Pathway Regulates Synaptic Function in
Článek Functional Genomic Analysis of the Regulatory Network in
Článek Astakine 2—the Dark Knight Linking Melatonin to Circadian Regulation in Crustaceans
Článek CRL2 E3-Ligase Regulates Proliferation and Progression through Meiosis in the Germline
Článek Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in
Článek PRMT4 Is a Novel Coactivator of c-Myb-Dependent Transcription in Haematopoietic Cell Lines
Článek A Copy Number Variant at the Locus Likely Confers Risk for Canine Squamous Cell Carcinoma of the Digit
Článek Evidence of Gene–Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors
Článek HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis
Článek Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained
Článek A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen
Článek The Role of ATM in the Deficiency in Nonhomologous End-Joining near Telomeres in a Human Cancer Cell Line
Článek Dynamic Circadian Protein–Protein Interaction Networks Predict Temporal Organization of Cellular Functions
Článek Nuclear Myosin 1c Facilitates the Chromatin Modifications Required to Activate rRNA Gene Transcription and Cell Cycle Progression
Článek Robust Prediction of Expression Differences among Human Individuals Using Only Genotype Information
Článek A Single Cohesin Complex Performs Mitotic and Meiotic Functions in the Protist
Článek The Role of the Arabidopsis Exosome in siRNA–Independent Silencing of Heterochromatic Loci
Článek Elevated Expression of the Integrin-Associated Protein PINCH Suppresses the Defects of Muscle Hypercontraction Mutants
Článek Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest
Článek Genome-Wide Testing of Putative Functional Exonic Variants in Relationship with Breast and Prostate Cancer Risk in a Multiethnic Population
Článek Heteroduplex DNA Position Defines the Roles of the Sgs1, Srs2, and Mph1 Helicases in Promoting Distinct Recombination Outcomes
Článok vyšiel v časopise

PLOS Genetics

2013 Číslo 3
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#