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161.
Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles 总被引:21,自引:0,他引:21
Seal S Thompson D Renwick A Elliott A Kelly P Barfoot R Chagtai T Jayatilake H Ahmed M Spanova K North B McGuffog L Evans DG Eccles D;Breast Cancer Susceptibility Collaboration 《Nature genetics》2006,38(11):1239-1241
We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers. 相似文献
162.
163.
Cohausz O Blenn C Malanga M Althaus FR 《Cellular and molecular life sciences : CMLS》2008,65(4):644-655
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor
(AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR
molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we
determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG),
the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2
and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems
to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
Received 7 November 2007; received after revision 19 December 2007; accepted 21 December 2007
O. Cohausz, C. Blenn: These two authors contributed equally to this work. 相似文献
164.
Oddi S Fezza F Pasquariello N De Simone C Rapino C Dainese E Finazzi-Agrò A Maccarrone M 《Cellular and molecular life sciences : CMLS》2008,65(5):840-850
Anandamide is a lipid messenger that carries out a wide variety of biological functions. It has been suggested that anandamide
accumulation involves binding to a saturable cellular component. To identify the structure(s) involved in this process, we
analyzed the intracellular distribution of both biotinylated and radiolabeled anandamide, providing direct evidence that lipid
droplets, also known as adiposomes, constitute a dynamic reservoir for the sequestration of anandamide. In addition, confocal
microscopy and biochemical studies revealed that the anandamide-hydrolase is also spatially associated with lipid droplets,
and that cells with a larger adiposome compartment have an enhanced catabolism of anandamide. Overall, these findings suggest
that adiposomes may have a critical role in accumulating anandamide, possibly by connecting plasma membrane to internal organelles
along the metabolic route of this endocannabinoid.
S. Oddi, F. Fezza: These authors contributed equally to the study. 相似文献
165.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
166.
Stacey SN Gudbjartsson DF Sulem P Bergthorsson JT Kumar R Thorleifsson G Sigurdsson A Jakobsdottir M Sigurgeirsson B Benediktsdottir KR Thorisdottir K Ragnarsson R Scherer D Rudnai P Gurzau E Koppova K Höiom V Botella-Estrada R Soriano V Juberías P Grasa M Carapeto FJ Tabuenca P Gilaberte Y Gudmundsson J Thorlacius S Helgason A Thorlacius T Jonasdottir A Blondal T Gudjonsson SA Jonsson GF Saemundsdottir J Kristjansson K Bjornsdottir G Sveinsdottir SG Mouy M Geller F Nagore E Mayordomo JI 《Nature genetics》2008,40(11):1313-1318
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. 相似文献
167.
Olfactory receptors typically exhibit poor plasma membrane localization and functionality when heterologously expressed in
most cell types. It has therefore proven difficult to effectively study olfactory receptor pharmacology and signaling mechanisms
using traditional cell culture systems. Over the past few years, a variety of distinct proteins have been reported to interact
with olfactory receptors and facilitate olfactory receptor trafficking to the plasma membrane in heterologous cells. Advances
in this area have shed significant light on the fundamental factors governing the cell-specific control of olfactory receptor
trafficking. 相似文献
168.
A. F. Vanin L. M. Bevers A. Slama-Schwok E. E. van Faassen 《Cellular and molecular life sciences : CMLS》2008,65(24):4066-4069
Announcement
Announcement 相似文献169.
Cardiolipin, the heart of mitochondrial metabolism 总被引:5,自引:0,他引:5
Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is
synthesized from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. After primary synthesis, the mature acyl chain
composition of cardiolipin is achieved by at least two remodeling mechanisms. In the mitochondrial membrane cardiolipin plays
an important role in energy metabolism, mainly by providing stability for the individual enzymes and enzyme complexes involved
in energy production. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process and in
mitochondrial membrane dynamics. Cardiolipin alterations have been described in various pathological conditions. Patients
suffering from Barth syndrome have an altered cardiolipin homeostasis caused by a primary deficiency in cardiolipin remodeling.
Alterations in cardiolipin content or composition have also been reported in more frequent diseases such as diabetes and heart
failure. In this review we provide an overview of cardiolipin metabolism, function and its role in different pathological
states.
Received 16 January 2008; received after revision 26 February 2008; accepted 26 March 2008 相似文献
170.
Uppal S Diggle CP Carr IM Fishwick CW Ahmed M Ibrahim GH Helliwell PS Latos-Bieleńska A Phillips SE Markham AF Bennett CP Bonthron DT 《Nature genetics》2008,40(6):789-793
Digital clubbing, recognized by Hippocrates in the fifth century BC, is the outward hallmark of pulmonary hypertrophic osteoarthropathy, a clinical constellation that develops secondary to various acquired diseases, especially intrathoracic neoplasm. The pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood, but a clinically indistinguishable primary (idiopathic) form of hypertrophic osteoarthropathy (PHO) is recognized. This familial disorder can cause diagnostic confusion, as well as significant disability. By autozygosity methods, we mapped PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation. Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations. These findings not only suggest therapies for PHO, but also imply that clubbing secondary to other pathologies may be prostaglandin mediated. Testing for HPGD mutations and biochemical testing for HPGD deficiency in patients with unexplained clubbing might help to obviate extensive searches for occult pathology. 相似文献