排序方式: 共有122条查询结果,搜索用时 15 毫秒
101.
Sara M. Reekmans Thorsten Pflanzner Philip L. S. M. Gordts Simone Isbert Pascale Zimmermann Wim Annaert Sascha Weggen Anton J. M. Roebroek Claus U. Pietrzik 《Cellular and molecular life sciences : CMLS》2010,67(1):135-145
The proximal NPXY and distal NPXYXXL motifs in the intracellular domain of LRP1 play an important role in regulation of the
function of the receptor. The impact of single and double inactivating knock-in mutations of these motifs on receptor maturation,
cell surface expression, and ligand internalization was analyzed in mutant and control wild-type mice and MEFs. Single inactivation
of the proximal NPXY or in combination with inactivation of the distal NPXYXXL motif are both shown to be associated with
an impaired maturation and premature proteasomal degradation of full-length LRP1. Therefore, only a small mature LRP1 pool
is able to reach the cell surface resulting indirectly in severe impairment of ligand internalization. Single inactivation
of the NPXYXXL motif revealed normal maturation, but direct impairment of ligand internalization. In conclusion, the proximal
NPXY motif proves to be essential for early steps in the LRP1 biosynthesis, whereas NPXYXXL appears rather relevant for internalization. 相似文献
102.
Ballif BC Hornor SA Jenkins E Madan-Khetarpal S Surti U Jackson KE Asamoah A Brock PL Gowans GC Conway RL Graham JM Medne L Zackai EH Shaikh TH Geoghegan J Selzer RR Eis PS Bejjani BA Shaffer LG 《Nature genetics》2007,39(9):1071-1073
We have identified a recurrent de novo pericentromeric deletion in 16p11.2-p12.2 in four individuals with developmental disabilities by microarray-based comparative genomic hybridization analysis. The identification of common clinical features in these four individuals along with the characterization of complex segmental duplications flanking the deletion regions suggests that nonallelic homologous recombination mediated these rearrangements and that deletions in 16p11.2-p12.2 constitute a previously undescribed syndrome. 相似文献
103.
Sarparanta J Jonson PH Golzio C Sandell S Luque H Screen M McDonald K Stajich JM Mahjneh I Vihola A Raheem O Penttilä S Lehtinen S Huovinen S Palmio J Tasca G Ricci E Hackman P Hauser M Katsanis N Udd B 《Nature genetics》2012,44(4):450-5, S1-2
Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in vivo showed that the mutations have a dominant toxic effect mediated specifically by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the mutations increase the half-life of DNAJB6, extending this effect to the wild-type protein, and reduce its protective anti-aggregation effect. Further, we show that DNAJB6 interacts with members of the CASA complex, including the myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone function and highlight how mutations in a ubiquitously expressed gene can exert effects in a tissue-, isoform- and cellular compartment-specific manner. 相似文献
104.
Dunlop MG Dobbins SE Farrington SM Jones AM Palles C Whiffin N Tenesa A Spain S Broderick P Ooi LY Domingo E Smillie C Henrion M Frampton M Martin L Grimes G Gorman M Semple C Ma YP Barclay E Prendergast J Cazier JB Olver B Penegar S Lubbe S Chander I Carvajal-Carmona LG Ballereau S Lloyd A Vijayakrishnan J Zgaga L Rudan I Theodoratou E;Colorectal Tumour Gene Identification 《Nature genetics》2012,44(7):770-776
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. 相似文献
105.
Broderick P Chubb D Johnson DC Weinhold N Försti A Lloyd A Olver B Ma YP Dobbins SE Walker BA Davies FE Gregory WA Child JA Ross FM Jackson GH Neben K Jauch A Hoffmann P Mühleisen TW Nöthen MM Moebus S Tomlinson IP Goldschmidt H Hemminki K Morgan GJ Houlston RS 《Nature genetics》2012,44(1):58-61
To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights. 相似文献
106.
Lindström S Vachon CM Li J Varghese J Thompson D Warren R Brown J Leyland J Audley T Wareham NJ Loos RJ Paterson AD Rommens J Waggott D Martin LJ Scott CG Pankratz VS Hankinson SE Hazra A Hunter DJ Hopper JL Southey MC Chanock SJ Silva Idos S Liu J Eriksson L Couch FJ Stone J Apicella C Czene K Kraft P Hall P Easton DF Boyd NF Tamimi RM 《Nature genetics》2011,43(3):185-187
High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer. 相似文献
107.
Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
108.
Gudmundsson J Sulem P Rafnar T Bergthorsson JT Manolescu A Gudbjartsson D Agnarsson BA Sigurdsson A Benediktsdottir KR Blondal T Jakobsdottir M Stacey SN Kostic J Kristinsson KT Birgisdottir B Ghosh S Magnusdottir DN Thorlacius S Thorleifsson G Zheng SL Sun J Chang BL Elmore JB Breyer JP McReynolds KM Bradley KM Yaspan BL Wiklund F Stattin P Lindström S Adami HO McDonnell SK Schaid DJ Cunningham JM Wang L Cerhan JR St Sauver JL Isaacs SD Wiley KE Partin AW Walsh PC Polo S Ruiz-Echarri M 《Nature genetics》2008,40(3):281-283
We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease. 相似文献
109.
Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer
Stacey SN Manolescu A Sulem P Thorlacius S Gudjonsson SA Jonsson GF Jakobsdottir M Bergthorsson JT Gudmundsson J Aben KK Strobbe LJ Swinkels DW van Engelenburg KC Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Saez B Lambea J Godino J Polo E Tres A Picelli S Rantala J Margolin S Jonsson T Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Sveinsdottir SG Alexiusdottir K Saemundsdottir J Sigurdsson A Kostic J Gudmundsson L Kristjansson K Masson G 《Nature genetics》2008,40(6):703-706
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer. 相似文献
110.
Preweaning malnutrition permanently reduced brain size and cellular content but in spite of changes in the adrenocotical stress response no learning deficit was observed. Differential rearing environments did not influence the effects of malnutrition. 相似文献