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排序方式: 共有66条查询结果,搜索用时 31 毫秒
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Bond J Roberts E Springell K Lizarraga SB Lizarraga S Scott S Higgins J Hampshire DJ Morrison EE Leal GF Silva EO Costa SM Baralle D Raponi M Karbani G Rashid Y Jafri H Bennett C Corry P Walsh CA Woods CG 《Nature genetics》2005,37(4):353-355
Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain. 相似文献
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P. A. Barrett Elizabeth Beveridge D. Bull I. C. Caldwell P. J. Islip R. A. Neal N. C. Woods 《Cellular and molecular life sciences : CMLS》1982,38(3):338-339
Summary The biological properties of a novel compound 353C with high activity againstTrypanosoma cruzi, are described. The compound was about 10 times and 20 times more effective than either benznidazole or nifurtimox respectively, in producing radical cure in mice. 353C had a long half-life and showed anti-trypanosomal properties when given to mice at weekly intervals. 相似文献
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Yokoyama S Woods SL Boyle GM Aoude LG MacGregor S Zismann V Gartside M Cust AE Haq R Harland M Taylor JC Duffy DL Holohan K Dutton-Regester K Palmer JM Bonazzi V Stark MS Symmons J Law MH Schmidt C Lanagan C O'Connor L Holland EA Schmid H Maskiell JA Jetann J Ferguson M Jenkins MA Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Whiteman DC Pharoah PD Easton DF Dunning AM Newton-Bishop JA Montgomery GW Martin NG Mann GJ Bishop DT Tsao H Trent JM Fisher DE Hayward NK Brown KM 《Nature》2011,480(7375):99-103
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Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome 总被引:5,自引:0,他引:5
Katsanis N Beales PL Woods MO Lewis RA Green JS Parfrey PS Ansley SJ Davidson WS Lupski JR 《Nature genetics》2000,26(1):67-70
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism and renal malformations, with secondary features that include diabetes mellitus, endocrinological dysfunction and behavioural abnormalities. Despite an initial expectation of genetic homogeneity due to relative clinical uniformity, five BBS loci have been reported, with evidence for additional loci in the human genome; however, no genes for BBS have yet been identified. We performed a genome screen with BBS families from Newfoundland that were excluded from BBS1-5 and identified linkage with D20S189. Fine-mapping reduced the critical interval to 1.9 cM between D20S851 and D20S189, encompassing a chaperonin-like gene. Mutations in this gene were recently reported to be associated with McKusick-Kaufman syndrome (MKKS; ref. 8). Given both the mapping position and clinical similarities of these two syndromes, we screened MKKS and identified mutations in five Newfoundland and two European-American BBS pedigrees. Most are frameshift alleles that are likely to result in a non-functional protein. Our data suggest that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, is responsible for the clinical manifestations of BBS. 相似文献
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Smith UM Consugar M Tee LJ McKee BM Maina EN Whelan S Morgan NV Goranson E Gissen P Lilliquist S Aligianis IA Ward CJ Pasha S Punyashthiti R Malik Sharif S Batman PA Bennett CP Woods CG McKeown C Bucourt M Miller CA Cox P Algazali L Trembath RC Torres VE Attie-Bitach T Kelly DA Maher ER Gattone VH Harris PC Johnson CA 《Nature genetics》2006,38(2):191-196
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin. 相似文献
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Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing 总被引:1,自引:0,他引:1
Stark MS Woods SL Gartside MG Bonazzi VF Dutton-Regester K Aoude LG Chow D Sereduk C Niemi NM Tang N Ellis JJ Reid J Zismann V Tyagi S Muzny D Newsham I Wu Y Palmer JM Pollak T Youngkin D Brooks BR Lanagan C Schmidt CW Kobe B MacKeigan JP Yin H Brown KM Gibbs R Trent J Hayward NK 《Nature genetics》2012,44(2):165-169
We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 I780F and MAP3K9 W333* variants had reduced kinase activity. Overexpression of MAP3K5 or MAP3K9 mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma. 相似文献
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Nicholas AK Khurshid M Désir J Carvalho OP Cox JJ Thornton G Kausar R Ansar M Ahmad W Verloes A Passemard S Misson JP Lindsay S Gergely F Dobyns WB Roberts E Abramowicz M Woods CG 《Nature genetics》2010,42(11):1010-1014
Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain. We identified WDR62 as the second most common cause of MCPH after finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7 proteins. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain. 相似文献