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11.
Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome 总被引:6,自引:0,他引:6
Windpassinger C Auer-Grumbach M Irobi J Patel H Petek E Hörl G Malli R Reed JA Dierick I Verpoorten N Warner TT Proukakis C Van den Bergh P Verellen C Van Maldergem L Merlini L De Jonghe P Timmerman V Crosby AH Wagner K 《Nature genetics》2004,36(3):271-276
Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs. Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12-q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration. 相似文献
12.
RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta 总被引:18,自引:0,他引:18
Takayanagi H Kim S Matsuo K Suzuki H Suzuki T Sato K Yokochi T Oda H Nakamura K Ida N Wagner EF Taniguchi T 《Nature》2002,416(6882):744-749
13.
A radiation hybrid map of mouse genes 总被引:13,自引:0,他引:13
Hudson TJ Church DM Greenaway S Nguyen H Cook A Steen RG Van Etten WJ Castle AB Strivens MA Trickett P Heuston C Davison C Southwell A Hardisty R Varela-Carver A Haynes AR Rodriguez-Tome P Doi H Ko MS Pontius J Schriml L Wagner L Maglott D Brown SD Lander ES Schuler G Denny P 《Nature genetics》2001,29(2):201-205
A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome. 相似文献
14.
Involvement of chemokine receptors in breast cancer metastasis 总被引:344,自引:0,他引:344
Müller A Homey B Soto H Ge N Catron D Buchanan ME McClanahan T Murphy E Yuan W Wagner SN Barrera JL Mohar A Verástegui E Zlotnik A 《Nature》2001,410(6824):50-56
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells. 相似文献
15.
Kawai J Shinagawa A Shibata K Yoshino M Itoh M Ishii Y Arakawa T Hara A Fukunishi Y Konno H Adachi J Fukuda S Aizawa K Izawa M Nishi K Kiyosawa H Kondo S Yamanaka I Saito T Okazaki Y Gojobori T Bono H Kasukawa T Saito R Kadota K Matsuda H Ashburner M Batalov S Casavant T Fleischmann W Gaasterland T Gissi C King B Kochiwa H Kuehl P Lewis S Matsuo Y Nikaido I Pesole G Quackenbush J Schriml LM Staubli F Suzuki R Tomita M Wagner L Washio T Sakai K Okido T Furuno M Aono H Baldarelli R Barsh G 《Nature》2001,409(6821):685-690
The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones. 相似文献
16.
Convergent evolution of gene circuits 总被引:9,自引:0,他引:9
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In order to elucidate the role of the hypophysis in the regulation of cholesterol 7alpha-hydroxylase activity, male and female rats hypophysectomized on day 50 of life were treated with different hypophyseal hormones and tested on day 85 of life. Only a crude extract from human hypophysis and ovine prolactin was able to enhance the enzyme activity, thereby restoring the level of intact controls. 相似文献
20.
Many rangelands in the southwestern United States provide quality habitat for Northern Bobwhites ( Colinus virginianus ). These same habitats are frequently managed for livestock production and thus are subjected to various brush management practices that are meant to enhance forage production. Bobwhites rely on woody cover for food, thermal and loafing cover, and protection from avian predators. Implementing brush management practices that reflect bobwhite requirements is important for managing usable space and viable populations. We described the structural vegetative characteristics associated with bobwhite locations and random locations on native rangelands in the upper Rolling Plains of Texas that are dominated by honey mesquite ( Prosopis glandulosa ) and managed with aerial herbicide and prescribed fire. We also used binary logistic regression to model habitat selection; the initial model was built using 67% of the data ( n = 179 used-random paired points) and then validated using the remaining 33% of the data ( n = 88 used-random paired points). Locations used by bobwhites had significantly larger mean values of percent brush canopy cover, visual obstruction, and angle of obstruction than did random locations; random locations had a greater mean value of percent bare ground than locations used by bobwhites. The resulting logistic regression model contained only the angle of obstruction; the model had an 80% probability of correctly classifying used and random locations based on the area under the receiver operating curve (ROC). The model maintained a high classification probability when applied to the smaller validation data set, with an area under the ROC of 0.78. 相似文献