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排序方式: 共有356条查询结果,搜索用时 15 毫秒
91.
Zanke BW Greenwood CM Rangrej J Kustra R Tenesa A Farrington SM Prendergast J Olschwang S Chiang T Crowdy E Ferretti V Laflamme P Sundararajan S Roumy S Olivier JF Robidoux F Sladek R Montpetit A Campbell P Bezieau S O'Shea AM Zogopoulos G Cotterchio M Newcomb P McLaughlin J Younghusband B Green R Green J Porteous ME Campbell H Blanche H Sahbatou M Tubacher E Bonaiti-Pellié C Buecher B Riboli E Kury S Chanock SJ Potter J Thomas G Gallinger S Hudson TJ Dunlop MG 《Nature genetics》2007,39(8):989-994
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer. 相似文献
92.
Volkman SK Sabeti PC DeCaprio D Neafsey DE Schaffner SF Milner DA Daily JP Sarr O Ndiaye D Ndir O Mboup S Duraisingh MT Lukens A Derr A Stange-Thomann N Waggoner S Onofrio R Ziaugra L Mauceli E Gnerre S Jaffe DB Zainoun J Wiegand RC Birren BW Hartl DL Galagan JE Lander ES Wirth DF 《Nature genetics》2007,39(1):113-119
Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite. 相似文献
93.
Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth 总被引:2,自引:0,他引:2
Douglas J Cilliers D Coleman K Tatton-Brown K Barker K Bernhard B Burn J Huson S Josifova D Lacombe D Malik M Mansour S Reid E Cormier-Daire V Cole T;Childhood Overgrowth Collaboration Rahman N 《Nature genetics》2007,39(8):963-965
17q11 microdeletions that encompass NF1 cause 5%-10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is within the NF1 microdeletion region, in six families characterized by overgrowth, learning disability, dysmorphic features and variable additional features. These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases. 相似文献
94.
DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis 总被引:14,自引:0,他引:14
Lorenz-Depiereux B Bastepe M Benet-Pagès A Amyere M Wagenstaller J Müller-Barth U Badenhoop K Kaiser SM Rittmaster RS Shlossberg AH Olivares JL Loris C Ramos FJ Glorieux F Vikkula M Jüppner H Strom TM 《Nature genetics》2006,38(11):1248-1250
Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression. 相似文献
95.
Yeung TM Chia LA Kosinski CM Kuo CJ 《Cellular and molecular life sciences : CMLS》2011,68(15):2513-2523
The gastrointestinal epithelium is a highly organised tissue that is constantly being renewed. In order to maintain homeostasis,
the balance between intestinal stem cell (ISC) self-renewal and differentiation must be carefully regulated. In this review,
we describe how the intestinal stem cell niche provides a unique environment to regulate self-renewal and differentiation
of ISCs. It has traditionally been believed that the mesenchymal myofibroblasts play an important role in the crosstalk between
ISCs and the niche. However, recent evidence in Drosophila and in vertebrates suggests that epithelial cells also contribute to the niche. We discuss the multiple signalling pathways
that are utilised to regulate stemness within the niche, including members of the Wnt, BMP and Hedgehog pathways, and how
aberrations in these signals lead to disruption of the normal crypt–villus axis. Finally, we also discuss how CDX1 and inhibition
of the Notch pathway are important in specifying enterocyte and goblet cell differentiation respectively. 相似文献
96.
Bass AJ Lawrence MS Brace LE Ramos AH Drier Y Cibulskis K Sougnez C Voet D Saksena G Sivachenko A Jing R Parkin M Pugh T Verhaak RG Stransky N Boutin AT Barretina J Solit DB Vakiani E Shao W Mishina Y Warmuth M Jimenez J Chiang DY Signoretti S Kaelin WG Spardy N Hahn WC Hoshida Y Ogino S Depinho RA Chin L Garraway LA Fuchs CS Baselga J Tabernero J Gabriel S Lander ES Getz G Meyerson M 《Nature genetics》2011,43(10):964-968
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. 相似文献
97.
Charlier C Coppieters W Rollin F Desmecht D Agerholm JS Cambisano N Carta E Dardano S Dive M Fasquelle C Frennet JC Hanset R Hubin X Jorgensen C Karim L Kent M Harvey K Pearce BR Simon P Tama N Nie H Vandeputte S Lien S Longeri M Fredholm M Harvey RJ Georges M 《Nature genetics》2008,40(4):449-454
The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings. 相似文献
98.
In this paper, we describe an image enhancement and interpretation methodology to enhance and recognize surface defects and critical patterns from remote imagery of sewer pipeline inspection. The objective is to provide inspectors and professionals with better tools to allow them to examine the imagery for condition assessment. We present initial results of a collaboration with a robotic company through a case study on computer-assisted processing and interpretation of sewer pipeline inspection imagery. In the mean time, the described enhancement and interpretation methodology can also be applied to sewer pipeline condition assessment in an offline mode, where this methodology can support professionals’ examination of acquired sewer condition imagery. 相似文献
99.
100.
Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. 总被引:19,自引:0,他引:19
We report here the determination and refinement to 1.9 A resolution by X-ray cryo-crystallography the structure of HLA-Aw68. The averaged image from the collection of bound, endogenous peptides clearly shows the atomic structure at the first three and last two amino acids in the peptides but no connected electron density in between. This suggests that bound peptides, held at both ends, take alternative pathways and could be of different lengths by bulging out in the middle. Peptides eluted from HLA-Aw68 include peptides of 9, 10 and 11 amino acids, a direct indication of the length heterogeneity of tightly bound peptides. Peptide sequencing shows relatively conserved 'anchor' residues at position 2 and the carboxy-terminal residue. Conserved binding sites for the peptide N and C termini at the ends of the class I major histocompatibility complex binding groove are apparently dominant in producing the long half-lives of peptide binding and the peptide-dependent stabilization of the class I molecule's structure. 相似文献