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1.
Béguin P Crambert G Monnet-Tschudi F Uldry M Horisberger JD Garty H Geering K 《The EMBO journal》2002,21(13):3264-3273
Recently, corticosteroid hormone-induced factor (CHIF) and the gamma-subunit, two members of the FXYD family of small proteins, have been identified as regulators of renal Na,K-ATPase. In this study, we have investigated the tissue distribution and the structural and functional properties of FXYD7, another family member which has not yet been characterized. Expressed exclusively in the brain, FXYD7 is a type I membrane protein bearing N-terminal, post-translationally added modifications on threonine residues, most probably O-glycosylations that are important for protein stabilization. Expressed in Xenopus oocytes, FXYD7 can interact with Na,K-ATPase alpha 1-beta 1, alpha 2-beta 1 and alpha 3-beta 1 but not with alpha-beta 2 isozymes, whereas, in brain, it is only associated with alpha 1-beta isozymes. FXYD7 decreases the apparent K(+) affinity of alpha 1-beta 1 and alpha 2-beta 1, but not of alpha 3-beta1 isozymes. These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability. 相似文献
2.
Clara C. Elbers Carolien G. F. de Kovel Yvonne T. van der Schouw Juliaan R. Meijboom Florianne Bauer Diederick E. Grobbee Gosia Trynka Jana V. van Vliet-Ostaptchouk Cisca Wijmenga N. Charlotte Onland-Moret 《PloS one》2009,4(9)
There is a large variation in caloric intake and macronutrient preference between individuals and between ethnic groups, and these food intake patterns show a strong heritability. The transition to new food sources during the agriculture revolution around 11,000 years ago probably created selective pressure and shaped the genome of modern humans. One major player in energy homeostasis is the appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R genes and nutrient intake in a cross-sectional, single-center study of 400 men aged 40 to 80 years, and we examine whether genomic regions containing these genes show signatures of recent selection in 270 HapMap individuals (90 Africans, 90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides. We also show that carriers of these derived alleles, on average, consume meals with a lower glycemic index and glycemic load and have higher alcohol consumption. One of these variants shows the hallmark of recent selection in Europe. Our data suggest that lower carbohydrate intake, consuming meals with a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a survival advantage in Europeans since the agricultural revolution. This advantage could lie in overall health benefits, because lower carbohydrate intake, consuming meals with a low GI and GL, and/or higher alcohol consumption, are known to be associated with a lower risk of chronic diseases. 相似文献
3.
Five density-defined subpopulations of rat thymocytes were separated by isopycnic centrifugation on a discontinuous density Ficoll gradient and compared with respect to their response to Con A stimulation under normal and adenosine deaminase (ADA) deficiency conditions. This study shows that (a) immunocompetent (low-density) thymocytes and splenic T lymphocytes produce T-cell growth factor (TCGF) in response to mitogenic stimulation in normal culture conditions, but are unable to synthesize effective TCGF in the presence of an adenosine deaminase inhibitor and excess substrate (ADA deficiency conditions), and (b) high-density immunoincompetent thymocytes proliferate and differentiate into mature T cells in response to Con A if effective exogenous TCGF is added to the culture medium but are unable to do so under ADA deficiency conditions. 相似文献
4.
Florianne Marandel Grgory Charrier Jean‐Baptiste Lamy Sabrina Le Cam Pascal Lorance Verena M. Trenkel 《Ecology and evolution》2020,10(4):1929-1937
Effective population size (Ne) is a key parameter of population genetics. However, Ne remains challenging to estimate for natural populations as several factors are likely to bias estimates. These factors include sampling design, sequencing method, and data filtering. One issue inherent to the restriction site‐associated DNA sequencing (RADseq) protocol is missing data and SNP selection criteria (e.g., minimum minor allele frequency, number of SNPs). To evaluate the potential impact of SNP selection criteria on Ne estimates (Linkage Disequilibrium method) we used RADseq data for a nonmodel species, the thornback ray. In this data set, the inbreeding coefficient FIS was positively correlated with the amount of missing data, implying data were missing nonrandomly. The precision of Neestimates decreased with the number of SNPs. Mean Ne estimates (averaged across 50 random data sets with2000 SNPs) ranged between 237 and 1784. Increasing the percentage of missing data from 25% to 50% increased Ne estimates between 82% and 120%, while increasing the minor allele frequency (MAF) threshold from 0.01 to 0.1 decreased estimates between 71% and 75%. Considering these effects is important when interpreting RADseq data‐derived estimates of effective population size in empirical studies. 相似文献
5.
van Vliet-Ostaptchouk JV van Haeften TW Landman GW Reiling E Kleefstra N Bilo HJ Klungel OH de Boer A van Diemen CC Wijmenga C Boezen HM Dekker JM van 't Riet E Nijpels G Welschen LM Zavrelova H Bruin EJ Elbers CC Bauer F Onland-Moret NC van der Schouw YT Grobbee DE Spijkerman AM van der A DL Simonis-Bik AM Eekhoff EM Diamant M Kramer MH Boomsma DI de Geus EJ Willemsen G Slagboom PE Hofker MH 't Hart LM 《PloS one》2012,7(3):e32148
Background
Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients.Methodology
The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp.Principal Findings
We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07–1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications.Conclusions
Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism. 相似文献6.
Lanktree MB Guo Y Murtaza M Glessner JT Bailey SD Onland-Moret NC Lettre G Ongen H Rajagopalan R Johnson T Shen H Nelson CP Klopp N Baumert J Padmanabhan S Pankratz N Pankow JS Shah S Taylor K Barnard J Peters BJ Maloney CM Lobmeyer MT Stanton A Zafarmand MH Romaine SP Mehta A van Iperen EP Gong Y Price TS Smith EN Kim CE Li YR Asselbergs FW Atwood LD Bailey KM Bhatt D Bauer F Behr ER Bhangale T Boer JM Boehm BO Bradfield JP Brown M Braund PS Burton PR Carty C Chandrupatla HR Chen W Connell J 《American journal of human genetics》2011,(1):688-18
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. 相似文献
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8.
Richa Saxena Clara C. Elbers Yiran Guo Inga Peter Tom R. Gaunt Jessica L. Mega Matthew B. Lanktree Archana Tare Berta Almoguera Castillo Yun R. Li Toby Johnson Marcel Bruinenberg Diane Gilbert-Diamond Ramakrishnan Rajagopalan Benjamin F. Voight Ashok Balasubramanyam John Barnard Florianne Bauer Brendan J. Keating 《American journal of human genetics》2012,90(4):753
9.
Saxena R Elbers CC Guo Y Peter I Gaunt TR Mega JL Lanktree MB Tare A Castillo BA Li YR Johnson T Bruinenberg M Gilbert-Diamond D Rajagopalan R Voight BF Balasubramanyam A Barnard J Bauer F Baumert J Bhangale T Böhm BO Braund PS Burton PR Chandrupatla HR Clarke R Cooper-DeHoff RM Crook ED Davey-Smith G Day IN de Boer A de Groot MC Drenos F Ferguson J Fox CS Furlong CE Gibson Q Gieger C Gilhuijs-Pederson LA Glessner JT Goel A Gong Y Grant SF Grobbee DE Hastie C Humphries SE Kim CE Kivimaki M 《American journal of human genetics》2012,90(3):410-425
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ~50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ~2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. 相似文献
10.
F. Monnet-Tschudi P. Favrod M. -B. Burnand C. Verdan P. Kučera 《Cell and tissue research》1985,241(1):85-92
Summary Distribution of fibronectin-like immunoreactivity was studied in the area opaca of the young chick embryo (stages 4–6 HH) by use of the immunofluorescence and protein A-coupled to colloidal gold techniques. Fibronectin, associated to the basement membrane, formed a fibrillar network, the pattern of which changed from the centre to the periphery of the area opaca. At the ultrastructural level, differences in fibronectin distribution were found between non-moving and moving cells. The epithelial-like cells presented fibronectin staining exclusively on their basal side. Actively migrating cells (edge and mesodermal cells) showed immunoreactive material localized around their entire surface and within the cytoplasm. The fibronectin distribution is discussed in relation to three important phenomena taking place during the early growth of the area opaca: (i) anchorage and migration of the edge cells, (ii) modification of cell shape in relation to mechanical tension, and (iii) expansion of the area vasculosa. 相似文献