排序方式: 共有44条查询结果,搜索用时 15 毫秒
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Mira MT Alcaïs A Van Thuc N Thai VH Huong NT Ba NN Verner A Hudson TJ Abel L Schurr E 《Nature genetics》2003,33(3):412-415
Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) lod score 4.31; P = 5 x 10(-6)). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D6S1035 and D6S305) showed strong evidence for association with leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively). 相似文献
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Auwerx J Avner P Baldock R Ballabio A Balling R Barbacid M Berns A Bradley A Brown S Carmeliet P Chambon P Cox R Davidson D Davies K Duboule D Forejt J Granucci F Hastie N de Angelis MH Jackson I Kioussis D Kollias G Lathrop M Lendahl U Malumbres M von Melchner H Müller W Partanen J Ricciardi-Castagnoli P Rigby P Rosen B Rosenthal N Skarnes B Stewart AF Thornton J Tocchini-Valentini G Wagner E Wahli W Wurst W 《Nature genetics》2004,36(9):925-927
The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease. 相似文献
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Mira MT Alcaïs A Nguyen VT Moraes MO Di Flumeri C Vu HT Mai CP Nguyen TH Nguyen NB Pham XK Sarno EN Alter A Montpetit A Moraes ME Moraes JR Doré C Gallant CJ Lepage P Verner A Van De Vosse E Hudson TJ Abel L Schurr E 《Nature》2004,427(6975):636-640
Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy. 相似文献
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p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway 总被引:4,自引:0,他引:4
Hui L Bakiri L Mairhorfer A Schweifer N Haslinger C Kenner L Komnenovic V Scheuch H Beug H Wagner EF 《Nature genetics》2007,39(6):741-749
The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional Mapk14 (also known as p38alpha) alleles, we investigated its function in postnatal development and tumorigenesis. When we specifically deleted Mapk14 in the mouse embryo, fetuses developed to term but died shortly after birth, probably owing to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha showed increased proliferation resulting from sustained activation of the c-Jun N-terminal kinase (JNK)-c-Jun pathway. Notably, in chemical-induced liver cancer development, mice with liver-specific deletion of Mapk14 showed enhanced hepatocyte proliferation and tumor development that correlated with upregulation of the JNK-c-Jun pathway. Furthermore, inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient hepatocytes and tumor cells. These results demonstrate a new mechanism whereby p38alpha negatively regulates cell proliferation by antagonizing the JNK-c-Jun pathway in multiple cell types and in liver cancer development. 相似文献
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Enterotypes of the human gut microbiome 总被引:6,自引:0,他引:6
Arumugam M Raes J Pelletier E Le Paslier D Yamada T Mende DR Fernandes GR Tap J Bruls T Batto JM Bertalan M Borruel N Casellas F Fernandez L Gautier L Hansen T Hattori M Hayashi T Kleerebezem M Kurokawa K Leclerc M Levenez F Manichanh C Nielsen HB Nielsen T Pons N Poulain J Qin J Sicheritz-Ponten T Tims S Torrents D Ugarte E Zoetendal EG Wang J Guarner F Pedersen O de Vos WM Brunak S Doré J;MetaHIT Consortium Antolín M Artiguenave F Blottiere HM Almeida M Brechot C Cara C Chervaux C Cultrone A 《Nature》2011,473(7346):174-180
Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers. 相似文献