排序方式: 共有55条查询结果,搜索用时 15 毫秒
41.
Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma 总被引:20,自引:0,他引:20
42.
Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family 总被引:23,自引:0,他引:23
Schlingmann KP Weber S Peters M Niemann Nejsum L Vitzthum H Klingel K Kratz M Haddad E Ristoff E Dinour D Syrrou M Nielsen S Sassen M Waldegger S Seyberth HW Konrad M 《Nature genetics》2002,31(2):166-170
Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease. 相似文献
43.
Signalling by means of toll-like receptors (TLRs) is essential for the development of innate and adaptive immune responses. UNC93B1, essential for signalling of TLR3, TLR7 and TLR9 in both humans and mice, physically interacts with these TLRs in the endoplasmic reticulum (ER). Here we show that the function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes. In dendritic cells of 3d mice, which express an UNC93B1 missense mutant (H412R) incapable of TLR binding, neither TLR7 nor TLR9 exits the ER. Furthermore, the trafficking and signalling defects of the nucleotide-sensing TLRs in 3d dendritic cells are corrected by expression of wild-type UNC93B1. However, UNC93B1 is dispensable for ligand recognition and signal initiation by TLRs. To our knowledge, UNC93B1 is the first protein to be identified as a molecule specifically involved in trafficking of nucleotide-sensing TLRs. By inhibiting the interaction between UNC93B1 and TLRs it should be possible to achieve specific regulation of the nucleotide-sensing TLRs without compromising signalling via the cell-surface-disposed TLRs. 相似文献
44.
Ghoussaini M Fletcher O Michailidou K Turnbull C Schmidt MK Dicks E Dennis J Wang Q Humphreys MK Luccarini C Baynes C Conroy D Maranian M Ahmed S Driver K Johnson N Orr N dos Santos Silva I Waisfisz Q Meijers-Heijboer H Uitterlinden AG Rivadeneira F;Netherlands Collaborative Group on Hereditary Breast Ovarian Cancer 《Nature genetics》2012,44(3):312-318
Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ~8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ~70,000 cases and ~68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth. 相似文献
45.
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer 总被引:1,自引:0,他引:1
Reid S Schindler D Hanenberg H Barker K Hanks S Kalb R Neveling K Kelly P Seal S Freund M Wurm M Batish SD Lach FP Yetgin S Neitzel H Ariffin H Tischkowitz M Mathew CG Auerbach AD Rahman N 《Nature genetics》2007,39(2):162-164
PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer. 相似文献
46.
MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer 总被引:8,自引:0,他引:8
Theodorou V Kimm MA Boer M Wessels L Theelen W Jonkers J Hilkens J 《Nature genetics》2007,39(6):759-769
We performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated with mammary cancer and 13 had not previously been linked to cancer in general. Although members of the Wnt and fibroblast growth factors (Fgf) families were frequently tagged, our exhaustive screening for MMTV insertion sites uncovered a new repertoire of candidate breast cancer oncogenes. We validated one of these genes, Rspo3, as an oncogene by overexpression in a p53-deficient mammary epithelial cell line. The human orthologs of the candidate oncogenes were frequently deregulated in human breast cancers and associated with several tumor parameters. Computational analysis of all MMTV-tagged genes uncovered specific gene families not previously associated with cancer and showed a significant overrepresentation of protein domains and signaling pathways mainly associated with development and growth factor signaling. Comparison of all tagged genes in MMTV and Moloney murine leukemia virus-induced malignancies showed that both viruses target mostly different genes that act predominantly in distinct pathways. 相似文献
47.
Morison IM Cramer Bordé EM Cheesman EJ Cheong PL Holyoake AJ Fichelson S Weeks RJ Lo A Davies SM Wilbanks SM Fagerlund RD Ludgate MW da Silva Tatley FM Coker MS Bockett NA Hughes G Pippig DA Smith MP Capron C Ledgerwood EC 《Nature genetics》2008,40(4):387-389
We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis. 相似文献
48.
Melanie Tannenbaum 《科学大观园》2014,(14):35-37
<正>对于那些不熟悉X战警系列的人来说,里面的故事都围绕着一群有超能力的"变种人",他们代表人类演化的下一个阶段。除了电影中的炫目特效和精彩的动作片段外,影片中超能力的涵盖面非常广,从心灵感应到细胞再生应有尽有。最令人注目的特点在于,人们很容易就能理解并代入X战警及其他变种人面对惶恐不堪的普通人时受到的偏见。事实上,X战警系列电影能够在很大程度上帮助我们理解刻板印象的特性,了解它们是如何形成 相似文献
49.
Melanie Tannenbaum 《大众科学.科学研究与实践》2014,(9)
正X战警系列电影能在很大程度上帮助我们理解"刻板印象"的特性,了解它们是如何形成的,在日常生活中又是怎样被唤醒的对于那些不熟悉《X战警》电影系列的人来说,里面的故事都围绕着一群有超能力的"变种人"。影片中超能力的涵盖面非常广,从心灵感应到细胞再生应有尽有。除了电影中的炫目特效和精彩的动作片段外,这个系列最令人注目的特点在于,人们很容易就能理解并代入 相似文献
50.
Braig M Lee S Loddenkemper C Rudolph C Peters AH Schlegelberger B Stein H Dörken B Jenuwein T Schmitt CA 《Nature》2005,436(7051):660-665
Acute induction of oncogenic Ras provokes cellular senescence involving the retinoblastoma (Rb) pathway, but the tumour suppressive potential of senescence in vivo remains elusive. Recently, Rb-mediated silencing of growth-promoting genes by heterochromatin formation associated with methylation of histone H3 lysine 9 (H3K9me) was identified as a critical feature of cellular senescence, which may depend on the histone methyltransferase Suv39h1. Here we show that Emicro-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively. By contrast, most N-Ras-transgenic wild-type ('control') animals develop a non-lymphoid neoplasia significantly later. Proliferation of primary lymphocytes is directly stalled by a Suv39h1-dependent, H3K9me-related senescent growth arrest in response to oncogenic Ras, thereby cancelling lymphomagenesis at an initial step. Suv39h1-deficient lymphoma cells grow rapidly but, unlike p53-deficient cells, remain highly susceptible to adriamycin-induced apoptosis. In contrast, only control, but not Suv39h1-deficient or p53-deficient, lymphomas senesce after drug therapy when apoptosis is blocked. These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras. 相似文献