排序方式: 共有16条查询结果,搜索用时 35 毫秒
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The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts 总被引:7,自引:0,他引:7
Drosophila neuroblasts are a model system for studying asymmetric cell division: they divide unequally to produce an apical neuroblast and a basal ganglion mother cell that differ in size, mitotic activity and developmental potential. During neuroblast mitosis, an apical protein complex orients the mitotic spindle and targets determinants of cell fate to the basal cortex, but the mechanism of each process is unknown. Here we show that the tumour-suppressor genes lethal giant larvae (lgl) and discs large (dlg) regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts. Dlg protein is apically enriched and is required for maintaining cortical localization of Lgl protein. Basal protein targeting requires microfilament and myosin function, yet the lgl phenotype is strongly suppressed by reducing levels of myosin II. We conclude that Dlg and Lgl promote, and myosin II inhibits, actomyosin-dependent basal protein targeting in neuroblasts. 相似文献
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Ching TT Maunakea AK Jun P Hong C Zardo G Pinkel D Albertson DG Fridlyand J Mao JH Shchors K Weiss WA Costello JF 《Nature genetics》2005,37(6):645-651
CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats. 相似文献
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Ishkanian AS Malloff CA Watson SK DeLeeuw RJ Chi B Coe BP Snijders A Albertson DG Pinkel D Marra MA Ling V MacAulay C Lam WL 《Nature genetics》2004,36(3):299-303
We constructed a tiling resolution array consisting of 32,433 overlapping BAC clones covering the entire human genome. This increases our ability to identify genetic alterations and their boundaries throughout the genome in a single comparative genomic hybridization (CGH) experiment. At this tiling resolution, we identified minute DNA alterations not previously reported. These alterations include microamplifications and deletions containing oncogenes, tumor-suppressor genes and new genes that may be associated with multiple tumor types. Our findings show the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers. Our submegabase resolution tiling set for array CGH (SMRT array) allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease. 相似文献
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Radisky DC Levy DD Littlepage LE Liu H Nelson CM Fata JE Leake D Godden EL Albertson DG Nieto MA Werb Z Bissell MJ 《Nature》2005,436(7047):123-127
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Tuzun E Sharp AJ Bailey JA Kaul R Morrison VA Pertz LM Haugen E Hayden H Albertson D Pinkel D Olson MV Eichler EE 《Nature genetics》2005,37(7):727-732
Inversions, deletions and insertions are important mediators of disease and disease susceptibility. We systematically compared the human genome reference sequence with a second genome (represented by fosmid paired-end sequences) to detect intermediate-sized structural variants >8 kb in length. We identified 297 sites of structural variation: 139 insertions, 102 deletions and 56 inversion breakpoints. Using combined literature, sequence and experimental analyses, we validated 112 of the structural variants, including several that are of biomedical relevance. These data provide a fine-scale structural variation map of the human genome and the requisite sequence precision for subsequent genetic studies of human disease. 相似文献
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Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene 总被引:21,自引:0,他引:21
Albertson DG Ylstra B Segraves R Collins C Dairkee SH Kowbel D Kuo WL Gray JW Pinkel D 《Nature genetics》2000,25(2):144-146
We show here that quantitative measurement of DNA copy number across amplified regions using array comparative genomic hybridization (CGH) may facilitate oncogene identification by providing precise information on the locations of both amplicon boundaries and amplification maxima. Using this analytical capability, we resolved two regions of amplification within an approximately 2-Mb region of recurrent aberration at 20q13.2 in breast cancer. The putative oncogene ZNF217 (ref. 5) mapped to one peak, and CYP24 (encoding vitamin D 24 hydroxylase), whose overexpression is likely to lead to abrogation of growth control mediated by vitamin D, mapped to the other. 相似文献
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Cheung VG Nowak N Jang W Kirsch IR Zhao S Chen XN Furey TS Kim UJ Kuo WL Olivier M Conroy J Kasprzyk A Massa H Yonescu R Sait S Thoreen C Snijders A Lemyre E Bailey JA Bruzel A Burrill WD Clegg SM Collins S Dhami P Friedman C Han CS Herrick S Lee J Ligon AH Lowry S Morley M Narasimhan S Osoegawa K Peng Z Plajzer-Frick I Quade BJ Scott D Sirotkin K Thorpe AA Gray JW Hudson J Pinkel D Ried T Rowen L Shen-Ong GL Strausberg RL Birney E Callen DF Cheng JF Cox DR Doggett NA Carter NP Eichler EE 《Nature》2001,409(6822):953-958
We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer. 相似文献
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