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排序方式: 共有556条查询结果,搜索用时 26 毫秒
21.
Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
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Kalay E Yigit G Aslan Y Brown KE Pohl E Bicknell LS Kayserili H Li Y Tüysüz B Nürnberg G Kiess W Koegl M Baessmann I Buruk K Toraman B Kayipmaz S Kul S Ikbal M Turner DJ Taylor MS Aerts J Scott C Milstein K Dollfus H Wieczorek D Brunner HG Hurles M Jackson AP Rauch A Nürnberg P Karagüzel A Wollnik B 《Nature genetics》2011,43(1):23-26
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. 相似文献
24.
Garcia-Gonzalo FR Corbit KC Sirerol-Piquer MS Ramaswami G Otto EA Noriega TR Seol AD Robinson JF Bennett CL Josifova DJ García-Verdugo JM Katsanis N Hildebrandt F Reiter JF 《Nature genetics》2011,43(8):776-784
Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies. 相似文献
25.
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters 总被引:5,自引:0,他引:5
26.
The genome of the extremophile crucifer Thellungiella parvula 总被引:1,自引:0,他引:1
Dassanayake M Oh DH Haas JS Hernandez A Hong H Ali S Yun DJ Bressan RA Zhu JK Bohnert HJ Cheeseman JM 《Nature genetics》2011,43(9):913-918
Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a number of tandem duplications that, by the nature of the duplicated genes, suggest a possible basis for T. parvula's extremophile lifestyle. Our results provide essential background for developing genomically influenced testable hypotheses for the evolution of environmental stress tolerance. 相似文献
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A rare penetrant mutation in CFH confers high risk of age-related macular degeneration 总被引:1,自引:0,他引:1
29.
Giardine B Borg J Higgs DR Peterson KR Philipsen S Maglott D Singleton BK Anstee DJ Basak AN Clark B Costa FC Faustino P Fedosyuk H Felice AE Francina A Galanello R Gallivan MV Georgitsi M Gibbons RJ Giordano PC Harteveld CL Hoyer JD Jarvis M Joly P Kanavakis E Kollia P Menzel S Miller W Moradkhani K Old J Papachatzopoulou A Papadakis MN Papadopoulos P Pavlovic S Perseu L Radmilovic M Riemer C Satta S Schrijver I Stojiljkovic M Thein SL Traeger-Synodinos J Tully R Wada T Waye JS Wiemann C 《Nature genetics》2011,43(4):295-301
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases. 相似文献
30.
Crossan GP van der Weyden L Rosado IV Langevin F Gaillard PH McIntyre RE;Sanger Mouse Genetics Project Gallagher F Kettunen MI Lewis DY Brindle K Arends MJ Adams DJ Patel KJ 《Nature genetics》2011,43(2):147-152
The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway. 相似文献