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排序方式: 共有287条查询结果,搜索用时 15 毫秒
91.
Ross MT Grafham DV Coffey AJ Scherer S McLay K Muzny D Platzer M Howell GR Burrows C Bird CP Frankish A Lovell FL Howe KL Ashurst JL Fulton RS Sudbrak R Wen G Jones MC Hurles ME Andrews TD Scott CE Searle S Ramser J Whittaker A Deadman R Carter NP Hunt SE Chen R Cree A Gunaratne P Havlak P Hodgson A Metzker ML Richards S Scott G Steffen D Sodergren E Wheeler DA Worley KC Ainscough R Ambrose KD Ansari-Lari MA Aradhya S Ashwell RI Babbage AK Bagguley CL Ballabio A Banerjee R Barker GE Barlow KF 《Nature》2005,434(7031):325-337
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. 相似文献
92.
Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin 总被引:14,自引:0,他引:14
Otto EA Loeys B Khanna H Hellemans J Sudbrak R Fan S Muerb U O'Toole JF Helou J Attanasio M Utsch B Sayer JA Lillo C Jimeno D Coucke P De Paepe A Reinhardt R Klages S Tsuda M Kawakami I Kusakabe T Omran H Imm A Tippens M Raymond PA Hill J Beales P He S Kispert A Margolis B Williams DS Swaroop A Hildebrandt F 《Nature genetics》2005,37(3):282-288
Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children. Identification of four genes mutated in NPHP subtypes 1-4 (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10-20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN. 相似文献
93.
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
94.
Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors 总被引:14,自引:0,他引:14
Ostendorff HP Peirano RI Peters MA Schlüter A Bossenz M Scheffner M Bach I 《Nature》2002,416(6876):99-103
95.
Constância M Hemberger M Hughes J Dean W Ferguson-Smith A Fundele R Stewart F Kelsey G Fowden A Sibley C Reik W 《Nature》2002,417(6892):945-948
96.
97.
Ferrón SR Charalambous M Radford E McEwen K Wildner H Hind E Morante-Redolat JM Laborda J Guillemot F Bauer SR Fariñas I Ferguson-Smith AC 《Nature》2011,475(7356):381-385
The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome. Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. Notably, we find that there is a requirement for Dlk1 to be expressed from both maternally and paternally inherited chromosomes. Selective absence of Dlk1 imprinting in both NSCs and niche astrocytes is associated with postnatal acquisition of DNA methylation at the germ-line-derived imprinting control region. The results emphasize molecular relationships between NSCs and the niche astrocyte cells of the microenvironment, identifying a signalling system encoded by a single gene that functions coordinately in both cell types. The modulation of genomic imprinting in a stem-cell environment adds a new level of epigenetic regulation to the establishment and maintenance of the niche, raising wider questions about the adaptability, function and evolution of imprinting in specific developmental contexts. 相似文献
98.
Vascular endothelial growth factors (VEGFs) and their high-affinity tyrosine kinase VEGF receptors (VEGFRs) are key regulators of both angiogenesis and neurogenesis. The current issue of CMLS discusses recent literature and work implementing these signals in nervous system development, maintenance and disease pathology. 相似文献
99.
100.
Kévin Baranger Yannick Marchalant Amandine E. Bonnet Nadine Crouzin Alex Carrete Jean-Michel Paumier Nathalie A. Py Anne Bernard Charlotte Bauer Eliane Charrat Katrin Moschke Mothoharu Seiki Michel Vignes Stefan F. Lichtenthaler Frédéric Checler Michel Khrestchatisky Santiago Rivera 《Cellular and molecular life sciences : CMLS》2016,73(1):217-236