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Sample records for gene fto affects

  1. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats.

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    Yi-Chun Loraine Tung

    Full Text Available Sequence variants in the first intron of FTO are strongly associated with human obesity and human carriers of the risk alleles show evidence for increased appetite and food intake. Mice globally lacking Fto display a complex phenotype characterised by both increased energy expenditure and increased food intake. The site of action of FTO on energy balance is unclear. Fasting reduces levels of Fto mRNA in the arcuate nucleus (ARC of the hypothalamus, a site where Fto expression is particularly high. In this study, we have extended this nutritional link by demonstrating that consumption of a high fat diet (45% results in a 2.5 fold increase in Arc Fto expression. We have further explored the role of hypothalamic Fto in the control of food intake by using stereotactic injections coupled with AAV technology to bi-directionally modulate Fto expression. An over expression of Fto protein by 2.5-fold in the ARC results in a 14% decrease in average daily food intake in the first week. In contrast, knocking down Arc Fto expression by 40% increases food intake by 16%. mRNA levels of Agrp, Pomc and Npy, ARC-expressed genes classically associated with the control of food intake, were not affected by the manipulation of Fto expression. However, over expression of Fto resulted in a 4-fold increase in the mRNA levels of Stat3, a signalling molecule critical for leptin receptor signalling, suggesting a possible candidate for the mediation of Fto's actions. These data provide further support for the notion that FTO itself can influence key components of energy balance, and is therefore a strong candidate for the mediation of the robust association between FTO intronic variants and adiposity. Importantly, this provide the first indication that selective alteration of FTO levels in the hypothalamus can influence food intake, a finding consistent with the reported effects of FTO alleles on appetite and food intake in man.

  2. Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1.

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    Boender, Arjen J; van Rozen, Andrea J; Adan, Roger A H

    2012-12-01

    Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of cancer. Variation in common measures of obesity (e.g., BMI, waist/hip ratio) is largely explained by heritability. The advent of genome-wide association studies (GWAS) has made it possible to identify several genetic variants that associate with measures of obesity, but how exactly these genetic variants contribute to overweight has remained largely unresolved. One first hint is given by the fact that many of the associated variants reside in or near genes that act in the central nervous system, which implicates neuronal signaling in the etiology of obesity. Although the brain controls both energy intake and expenditure, it has more capacity to regulate energy intake rather than energy expenditure. In environments where food is abundant, this renders the body prone to weight increases. To gain more insight into the neurobiological mechanisms involved, we set out to investigate the effect of dietary exposure on the expression levels of obesity-associated genes in the ventro-medial hypothalamus (VMH)/arcuate nucleus (ARC) and the substantia nigra (SN)/ventral tegmental area (VTA), two brain regions that are implicated in feeding behavior. We show that the expression of Etv5, Faim2, Fto, Negr1 but not Sh2b1 is affected by nutritional state in these two areas, thereby providing insight into the relationship between nutritional state and expression levels of obesity-associated genes in two brain areas relevant to feeding.

  3. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

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    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  4. An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

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    Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Ence-Eriksson, Fia; Castillo, Sandra; Larsen, Anna L; Bylund, Simon B A; Hogenkamp, Pleunie S; Olivo, Gaia; Bandstein, Marcus; Titova, Olga E; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-05-01

    Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

  5. The obesity-associated Fto gene is a transcriptional coactivator.

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    Wu, Qiong; Saunders, Rudel A; Szkudlarek-Mikho, Maria; Serna, Ivana de la; Chin, Khew-Voon

    2010-10-22

    The fat mass and obesity associated, FTO, gene has been shown to be associated with obesity in human in several genome-wide association scans. In vitro studies suggest that Fto may function as a single-stranded DNA demethylase. In addition, homologous recombination-targeted knockout of Fto in mice resulted in growth retardation, loss of white adipose tissue, and increase energy metabolism and systemic sympathetic activation. Despite these intense investigations, the exact function of Fto remains unclear. We show here that Fto is a transcriptional coactivator that enhances the transactivation potential of the CCAAT/enhancer binding proteins (C/EBPs) from unmethylated as well as methylation-inhibited gene promoters. Fto also exhibits nuclease activity. We showed further that Fto enhances the binding C/EBP to unmethylated and methylated DNA. The coactivator role of FTO in modulating the transcriptional regulation of adipogenesis by C/EBPs is consistent with the temporal progressive loss of adipose tissue in the Fto-deficient mice, thus suggesting a role for Fto in the epigenetic regulation of the development and maintenance of fat tissue. How FTO reactivates transcription from methyl-repressed gene needs to be further investigated.

  6. Fto immunoreactivity is widespread in the rodent brain and abundant in feeding-related sites, but the number of Fto-positive cells is not affected by changes in energy balance.

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    Olszewski, Pawel K; Radomska, Katarzyna J; Ghimire, Kedar; Klockars, Anica; Ingman, Caroline; Olszewska, Agnieszka M; Fredriksson, Robert; Levine, Allen S; Schiöth, Helgi B

    2011-05-03

    A single nucleotide polymorphism in the FTO gene is associated with obesity in humans. Evidence gathered in animals mainly relates energy homeostasis to the central FTO mRNA levels, but our knowledge of the Fto protein distribution and regulation is limited. Fto, a demethylase and transcriptional coactivator, is thought to regulate expression of other genes. Herein, we examined Fto immunoreactivity (IR) in the mouse and rat brain with emphasis on sites governing energy balance. We also studied whether energy status affects central Fto IR. We report that Fto IR, limited to nuclear profiles, is widespread in the brain, in- and outside feeding circuits; it shows a very similar distribution in feeding-related sites in mice and rats. Several areas regulating energy homeostasis display enhanced intensity of Fto staining: the arcuate, paraventricular, supraoptic, dorsomedial, ventromedial nuclei, and dorsal vagal complex. Some regions mediating feeding reward, including the bed nucleus of the stria terminalis, have ample Fto IR. We found that differences in energy status between rats fed ad libitum, deprived or refed following deprivation, did not affect the number of Fto-positive nuclei in 10 sites governing consumption for energy or reward. We conclude that Fto IR, widespread in the rodent brain, is particularly abundant in feeding circuits, but the number of Fto-positive neurons is unaffected by changes in energy balance. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Fat mass and obesity associated gene (FTO expression is regulated negatively by the transcription factor Foxa2.

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    Jianjin Guo

    Full Text Available Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. To investigate the transcriptional regulation of FTO expression, we created 5'-deletion constructs of the FTO promoter to determine which transcription factors are most relevant to FTO expression. The presence of an activation region at -201/+34 was confirmed by luciferase activity analysis. A potential Foxa2 (called HNF-3β binding site and an upstream stimulatory factor (USF-binding site was identified in the -100 bp fragment upstream of the transcription start site (TSS. Furthermore, using mutagenesis, we identified the Foxa2 binding sequence (-26/-14 as a negative regulatory element to the activity of the human FTO promoter. The USF binding site did not affect the FTO promoter activity. Chromatin immunoprecipitation (ChIP assays were performed to confirm Foxa2 binding to the FTO promoter. Overexpression of Foxa2 in HEK 293 cells significantly down-regulated FTO promoter activity and expression. Conversely, knockdown of Foxa2 by siRNA significantly up-regulated FTO expression. These findings suggest that Foxa2 negatively regulates the basal transcription and expression of the human FTO gene.

  8. FTO gene unrelated to overweight in Chinese Han population

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    2008-01-01

    @@ After reviewing genetic data on nearly 4,000 Europeans, British researchers announced their discoveries in early 2007: they had found a common variant in a gene known as FTO was significantly associated with obesity.

  9. An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning.

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    Sevgi, Meltem; Rigoux, Lionel; Kühn, Anne B; Mauer, Jan; Schilbach, Leonhard; Hess, Martin E; Gruendler, Theo O J; Ullsperger, Markus; Stephan, Klaas Enno; Brüning, Jens C; Tittgemeyer, Marc

    2015-09-09

    Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity. Copyright © 2015 the authors 0270-6474/15/3512584-09$15.00/0.

  10. Expression studies of the obesity candidate gene FTO in pig

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    Madsen, Majbritt Busk; Birck, Malene Muusfeldt; Fredholm, Merete

    2010-01-01

    Obesity is an increasing problem worldwide and research on candidate genes in good animal models is highly needed. The pig is an excellent model as its metabolism, organ size, and eating habits resemble that of humans. The present study is focused on the characterization of the fat mass and obesity...... associated gene (FTO) in pig. This gene has recently been associated with increased body mass index in several human populations. To establish information on the expression profile of FTO in the pig we performed quantitative PCR in a panel of adult pig tissues and in tissues sampled at different...... and cerebellum). Additionally, in order to see the involvement of the FTO gene in obesity, the changes in expression level were investigated in a nutritional study in brain of Gottingen minipigs under a high cholesterol diet. Significantly higher (P

  11. FTO gene: a new target for obesity treatment%FTO基因:肥胖治疗的新靶标

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    杨凤娇; 王培; 缪朝玉

    2011-01-01

    大量的实验和临床研究已经证实,FTO 基因是第一个确认的肥胖易感基因.对全球各人种的大型流行病学调查发现,FTO基因的变异与成人及儿童的肥胖指数密切相关.实验已证明FTO可以影响摄食及能量的消耗.FTO和肥胖的发病机制的关系已经成为肥胖研究领域的热点,并被视为肥胖治疗的新靶标.目前,随着研究工作的进一步深入,FTO的功能有望进一步被发现及确认.%Massive experiments and clinical researches confirmed that fat mass and obesity associated gene (FTO) is the first obesity related gene. To the large-scale epidemiology investigation in various races, the FTO gene's variation is closely related to the adult and children's obesity index. It is proved that FTO may affect food intake and energy consumption. The research of the relationship between FTO and the obesity pathogenesis become a hot spot in the area of obesity, and FTO is a new target of obesity treatment. The function of FTO will be discovered and confirmed further.

  12. Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

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    Rask-Andersen Mathias

    2011-11-01

    Full Text Available Abstract Background The Fat mass and obesity gene (FTO has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI. However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. Results We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2, cAMP-dependent protein kinase catalytic subunit beta (Prkacb, Brain derived neurotrophic factor (Bdnf, neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2, Signal transducer and activator of transcription 3 (Stat3, and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. Conclusions Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ.

  13. FTO gene variants are associated with growth and carcass traits in cattle.

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    Jevsinek Skok, D; Kunej, T; Kovac, M; Malovrh, S; Potocnik, K; Petric, N; Zgur, S; Dovc, P; Horvat, S

    2016-04-01

    An important aim in animal breeding is the improvement of growth and meat quality traits. Previous studies have demonstrated that genetic variants in the fat mass and obesity associated (FTO) gene have a relatively large effect on human obesity as well as on body composition in rodents and, more recently, in livestock. Here, we examined the effects of the FTO gene variants on growth and carcass traits in the Slovenian population of Simmental (SS) and Brown (SB) cattle. To validate and identify new polymorphisms, we used sequencing, PCR-RFLP analysis and TaqMan assays in the SS breed and FTO gene variants data from the Illumina BovineSNP50 v1 array for the SB breed. Sequencing of the eight samples of progeny-tested SS sires detected 108 single nucleotide polymorphisms (SNPs) in the bovine FTO gene. Statistical analyses between growth and carcass traits and 34 FTO polymorphisms revealed significant association of FTO variants with lean meat percentage in both breeds. Additionally, FTO SNPs analyzed in SS cattle were associated with fat percentage, bone weight and live weight at slaughter. The FTO gene can thus be regarded as a candidate gene for the marker-assisted selection programs in our and possibly other populations of cattle. Future studies in cattle might reveal novel roles for the FTO gene in shaping carcass traits in livestock species as well as body composition control in other mammals.

  14. Negative regulation of hepatic fat mass and obesity associated (Fto) gene expression by insulin.

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    Mizuno, Tooru M; Lew, Pei San; Luo, Yanming; Leckstrom, Arnold

    2017-02-01

    To investigate the role of glucose and insulin in the regulation of hepatic fat mass and obesity associated (Fto) gene expression and the role of hepatic Fto in the regulation of gluconeogenic gene expression. To determine the effect of hyperglycemia on hepatic Fto expression, levels of Fto mRNA in liver were compared between normoglycemic/normoinsulinemic, hypereglycemic/hyperinsulinemic, and hyperglycemic/hypoinsulinemic mice. To determine the direct effect of insulin on Fto expression, levels of Fto, glucose-6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (Pepck) mRNA levels were compared between control and insulin-treated mouse liver tissues cultured ex vivo and immortalized mouse hepatocytes AML12. To determine the role of Fto in the regulation of gluconeogenic gene expression, we examined the effect of enhanced Fto expression on G6pase and Pepck mRNA levels in AML12 cells. Fto mRNA levels were significantly reduced in hyperglycemic/hyperinsulinemic mice compared to normoglycemic/normoinsulinemic mice, while they were indistinguishable between hyperglycemic/hypoinsulinemic mice and normoglycemic/normoinsulinemic mice. Insulin treatment reduced Fto, G6pase, and Pepck mRNA levels compared to control vehicle treatment in both ex vivo cultured mouse liver tissues and AML12 cells. Enhanced Fto expression significantly increased G6pase and Pepck mRNA level in AML12 cells. Our findings support the hypothesis that hepatic Fto participates in the maintenance of glucose homeostasis possibly by mediating the inhibitory effect of glucose and insulin on gluconeogenic gene expression in liver. It is further suggested that impairments in nutritional and hormonal regulation of hepatic Fto expression may lead to impairments in glycemic control in diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The role of the fat mass and obesity associated gene (FTO in breast cancer risk

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    Agarwal Surbhi

    2011-04-01

    Full Text Available Abstract Background Obesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk. Methods We performed a case-control study of 354 breast cancer cases and 364 controls. This study was conducted at Northwestern University. We examined the role of single nucleotide polymorphisms (SNPs of intron 1 of FTO in breast cancer risk. We genotyped cases and controls for four SNPs: rs7206790, rs8047395, rs9939609 and rs1477196. We also evaluated tissue expression of FTO in normal and malignant breast tissue. Results We found that all SNPs were significantly associated with breast cancer risk with rs1477196 showing the strongest association. We showed that FTO is expressed both in normal and malignant breast tissue. We found that FTO genotypes provided powerful classifiers to predict breast cancer risk and a model with epistatic interactions further improved the prediction accuracy with a receiver operating characteristic (ROC curves of 0.68. Conclusion In conclusion we have shown a significant expression of FTO in malignant and normal breast tissue and that FTO SNPs in intron 1 are significantly associated with breast cancer risk. Furthermore, these FTO SNPs are powerful classifiers in predicting breast cancer risk.

  16. The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro

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    Yang Jiao

    2016-02-01

    Full Text Available The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adipocyte size reduction in vivo. To investigate the potential role of Fto gene on the proliferation and differentiation of pre-adipocytes, we generated Fto-knockdown and overexpressed 3T3-L1 cells. Using numerous proliferation assays our results suggest that Fto knockdown leads to suppression of proliferation, lower mitochondrial membrane potential, less cellular ATP, and decreased and smaller intracellular lipid droplets compared with controls (p < 0.05. Western blot analysis demonstrated that Fto knockdown can significantly suppress peroxisome proliferator-activated receptor gamma (PPARγ and glucose transporter type 4 (GLUT4 expression and inhibit Akt phosphorylation. By contrast, overexpression of Fto had the opposing effect on proliferation, mitochondrial membrane potential, ATP generation, in vitro differentiation, Akt phosphorylation, and PPARγ and GLUT4 expression. Moreover, we demonstrated that Wortmannin, a phosphoinositide 3-kinase (PI3K inhibitor, could inhibit phospho-Akt in Fto overexpressed 3T3-L1 cells. Taken together, the results suggest that Fto regulates the proliferation and differentiation of 3T3-L1 cells via multiple mechanisms, including PPARγ and PI3K/Akt signaling.

  17. Chicken FTO gene: tissue-specific expression, brain distribution, breed difference and effect of fasting.

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    Wang, Yufeng; Rao, Kaiqing; Yuan, Lixia; Everaert, Nadia; Buyse, Johan; Grossmann, Roland; Zhao, Ruqian

    2012-11-01

    Fat mass and obesity-associated (FTO) gene is widely expressed in central and peripheral tissues of mammals, and exhibits a range of functions, especially in energy balance. However, basic knowledge of FTO in the chicken is lacking. Therefore, we studied the tissue distribution, age and breed dependent changes, brain localization, as well as the impact of fasting on FTO mRNA expression in the chicken. FTO mRNA was expressed in all the tissues studied, and generally, with high expression in hypothalamus, liver, visceral fat and cerebellum. However it exhibited breed-specific patterns: in broilers, the highest expression was seen in the liver, while in layers, hypothalamus and cerebellum showed relatively higher FTO mRNA expression. One-week-old broilers expressed markedly higher FTO mRNA in liver compared with the layers of the same age (Pbreed difference was reversed in visceral fat and cerebellum (PBreed-specific expression of FTO mRNA was shown in PVN, but not in VMN, with higher abundance in broilers compared to layers. The decrease in FTO mRNA levels after 24h of fasting was seen only in VMN of layer chickens. These results may provide some intriguing hints for further investigation of FTO function in the chicken. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. FTO gene polymorphisms and obesity risk: a meta-analysis

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    Li Xiaobo

    2011-06-01

    Full Text Available Abstract Background The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO; however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion. Methods We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR and their 95% confidence intervals (CI were estimated using per-allele comparison. Summary ORs were estimated using a random effects model. Results We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36, rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53, rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38, rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68, and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62. Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%. Conclusions This meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.

  19. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

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    Fiona McMurray

    Full Text Available The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.

  20. The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese

    Institute of Scientific and Technical Information of China (English)

    WANG Tong; ZHANG Li-li; ZHANG Yun; SUN Xiao-fang; ZHANG Qian; HUANG Yi; XIAO Xin-hua; WANG Duen-mei; DIAO Cheng-ming; ZHANG Feng; XU Ling-ling; ZHANG Yong-biao; LI Wen-hui

    2010-01-01

    Background Genome-wide association studies for type 2 diabetes mellitus (T2DM) identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han Chinese.Methods We tested 41 FTO single nucleotide polymorphisms (SNPs) for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects (108 cases and 128 controls), grouped according to the International Diabetes Federation (IDF) criteria.Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance (P=0.026) under a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64, 95% CI 1.11-2.42; P=0.014). The common distributions of this polymorphism among Chinese-with a minor allele frequency (MAF) of 36% in the control group versus 48% in the MetS group-greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity-(or T2DM-) associated FTO SNPs were less common in Han Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS.Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.

  1. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

    2012-08-24

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  2. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Y.D. Apalasamy

    2012-12-01

    Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  3. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants.

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    Laura Johnson

    Full Text Available BACKGROUND: Dietary energy density (DED does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609 variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants. METHODS AND FINDINGS: We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC. Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g was calculated excluding drinks. Children were genotyped for the FTO (rs9939609 variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (beta = 0.005, p = 0.51, suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35+/-0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16+/-0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity. CONCLUSIONS: This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.

  4. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants.

    Science.gov (United States)

    Johnson, Laura; van Jaarsveld, Cornelia H M; Emmett, Pauline M; Rogers, Imogen S; Ness, Andy R; Hattersley, Andrew T; Timpson, Nicholas J; Smith, George Davey; Jebb, Susan A

    2009-01-01

    Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants. We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (beta = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35+/-0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16+/-0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity. This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.

  5. Association between polymorphism in the FTO gene and growth and carcass traits in pig crosses

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    Dvořáková Věra

    2012-04-01

    Full Text Available Abstract Background Independent studies have shown that several single nucleotide polymorphisms (SNP in the human FTO (fat mass and obesity associated gene are associated with obesity. SNP have also been identified in the pig FTO gene, among which some are associated with selected fat-deposition traits in F2 crosses and commercial populations. In this study, using both commercial pig populations and an experimental Meishan × Pietrain F2 population, we have investigated the association between one FTO SNP and several growth and carcass traits. Association analyses were performed with the FTO polymorphism either alone or in combination with polymorphisms in flanking loci. Methods SNP (FM244720:g.400C>G in exon 3 of porcine FTO was genotyped by PCR-RFLP and tested for associations with some growth, carcass and fat-related traits. Proportions of genetic variance of four pig chromosome 6 genes (FTO, RYR1, LIPE and TGFB1 on selected traits were evaluated using single- and multi-locus models. Results Linkage analysis placed FTO on the p arm of pig chromosome 6, approximately 22 cM from RYR1. In the commercial populations, allele C of the FTO SNP was significantly associated with back fat depth and allele G with muscling traits. In the Meishan × Pietrain F2 pigs, heterozygotes with allele C from the Pietrain sows and allele G from the Meishan boar were more significantly associated with fat-related traits compared to homozygotes with allele G from the Pietrain and allele G from the Meishan breed. In single- and multi-locus models, genes RYR1, TGFB1 and FTO showed high associations. The contribution in genetic variance from the polymorphism in the FTO gene was highest for back fat depth, meat area on the musculus longissimus lumborum et thoracis tissues and metabolite glucose-6-phosphate dehydrogenase. Conclusions Our results show that in pig, FTO influences back fat depth in the commercial populations, while in the Meishan × Pietrain F2 pigs with a

  6. The 'Fat Mass and Obesity Related' (FTO) gene: Mechanisms of Impact on Obesity and Energy Balance.

    Science.gov (United States)

    Speakman, John R

    2015-03-01

    A cluster of single nucleotide polymorphisms (SNPs) in the first intron of the fat mass and obesity related (FTO) gene were the first common variants discovered to be associated with body mass index and body fatness. This review summarises what has been later discovered about the biology of FTO drawing together information from both human and animal studies. Subsequent work showed that the 'at risk' alleles of these SNPs are associated with greater food intake and increased hunger/lowered satiety, but are not associated with altered resting energy expenditure or low physical activity in humans. FTO is an FE (II) and 2-oxoglutarate dependent DNA/RNA methylase. Contrasting the impact of the SNPs on energy balance in humans, knocking out or reducing activity of the Fto gene in the mouse resulted in lowered adiposity, elevated energy expenditure with no impact on food intake (but the impact on expenditure is disputed). In contrast, overexpression of the gene in mice led to elevated food intake and adiposity, with no impact on expenditure. In rodents, the Fto gene is widely expressed in the brain including hypothalamic nuclei linked to food intake regulation. Since its activity is 2-oxoglutarate dependent it could potentially act as a sensor of citrate acid cycle flux, but this function has been dismissed, and instead it has been suggested to be much more likely to act as an amino acid sensor, linking circulating AAs to the mammalian target of rapamycin complex 1. This may be fundamental to its role in development but the link to obesity is less clear. It has been recently suggested that although the obesity related SNPs reside in the first intron of FTO, they may not only impact FTO but mediate their obesity effects via nearby genes (notably RPGRIP1L and IRX3).

  7. Fat phenotype, associated factors and rs9939609 polymorphism of the FTO gene

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    William Alves Lima

    2010-02-01

    Full Text Available The purpose of this work was to review the main results of studies that have analysed the relationship between the rs9939609 single nucleotide polymorphism (SNP of the FTO gene and the manifestation of overweight/obesity with its associated co-morbidity, and to discuss the interaction of this polymorphism with the other factors which cause obesity. The search was performed using the MEDLINE, Highwire, Science Direct and SciELO databases, applying the following key words: FTO rs9939609, obesity genetic, gene associated obesity, FTO contributes obesity. Inclusion criteria were: original articles where the search was performed in humans and including the rs9939609. Articles that analysed the FTO gene associated with preinstalled hormonal diseases were excluded. Of the several SNP associated with the FTO gene, rs9939609 has been the most researched (studied. This SNP comprises the A and T alleles, with the A homozygote being most susceptible to the development of overweight/obesity in all age ranges, especially in the caucasian population. In this situation, the control of environmental factors (alimentation and physical activity can prevent the excessive build up of fats. Obesity is related to the development of non-transmissible chronic illnesses. Association of rs9939609 polymorphism with the lipidic profile and glycemia were observed. The practicing of physical exercise and feeding habits seem to be the main contributors in the development of overweight/obesity and its resulting co-morbidity.

  8. Common Variant of FTO Gene, rs9939609, and Obesity in Pakistani Females

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    Adeela Shahid

    2013-01-01

    Full Text Available Numerous studies confirmed the association of FTO (fat mass and obesity associated gene common variant, rs9939609, with obesity in European populations. However, studies in Asian populations revealed conflicting results. We examined the association of rs9939609 variant of FTO gene with obesity and obesity-related anthropometric and metabolic parameters in Pakistani population. Body weight, height, waist circumference, hip circumference, and blood pressure (BP were measured. BMI and waist-to-hip ratio (WHR were calculated. Levels of fasting blood glucose (FBG, insulin, leptin, and leptin receptors were measured by enzyme linked immunosorbent assay (ELISA, and homeostasis model assessment of insulin resistance (HOMA-IR was calculated. The results showed association of FTO gene, rs9939609, with obesity in females (>18 years of age. FTO minor allele increased the risk of obesity by 2.8 times (95% CI = 1.3–6.0 in females. This allele showed association with body weight, BMI, waist circumference, hip circumference, WHR, BP, plasma FBG levels, HOMA-IR, plasma insulin levels, and plasma leptin levels. In conclusion, FTO gene, rs9939609, is associated with BMI and risk of obesity in adult Pakistani females. Association of rs9939609 variant with higher FBG, plasma insulin, and leptin levels indicates that this polymorphism may disturb the metabolism in adult females and predispose them to obesity and type 2 diabetes. However, the above-mentioned findings were not seen in children or males.

  9. Nutrition modulates Fto and Irx3 gene transcript levels, but does not alter their DNA methylation profiles in rat white adipose tissues.

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    Nowacka-Woszuk, Joanna; Pruszynska-Oszmalek, Ewa; Szydlowski, Maciej; Szczerbal, Izabela

    2017-02-05

    The fat mass and obesity associated (Fto) and iroquois homeobox 3 (Irx3) genes have been recognised as important obesity-related genes. Studies on the expression of these genes in the fat tissue of human and mouse have produced inconsistent results, while similar data on rat are limited. Environmental factors such as diet, should be considered as potential modulators of gene transcript levels through epigenetic mechanisms including DNA methylation. The aim of this study was to evaluate transcription levels and DNA methylation profiles of rat Fto and Irx3 genes in two white adipose tissue depots in response to high-fat and high-protein diets. The relative transcript levels of Fto and Irx3 were shown to be tissue-specific with higher levels detected in subcutaneous fat tissue than in abdominal fat tissue. Moreover, negative correlations between the transcripts of both genes were observed for subcutaneous fat tissue. The identified interactions (e.g. diet×duration of diet regimen) indicated that the diet had an impact on the transcript level; however, this effect was dependent on the duration of the diet regimen. The high-fat diet led to upregulation of Fto and Irx3 linearly with time across the two tissues. DNA methylation of the regulatory regions of the studied genes was very low and not related with the tissue, diet, or duration of diet regimen. Our study revealed that diet was an important factor modulating transcription of Fto and Irx3, but its affect depended on its duration. In contrast, the DNA methylation profiles of Fto and Irx3 were not altered by nutrition, which may indicate that the feeding type, when applied postnatally, did not affect DNA methylation of these genes.

  10. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.

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    Xue Gao

    Full Text Available FTO (fat mass and obesity associated was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.

  11. Common variations in the FTO gene and obesity in Thais: a family-based study.

    Science.gov (United States)

    Chuenta, Wanida; Phonrat, Benjaluck; Tungtrongchitr, Anchalee; Limwongse, Chanin; Chongviriyaphan, Nalinee; Santiprabhob, Jeerunda; Tungtrongchitr, Rungsunn

    2015-03-01

    Several studies have revealed the association between single nucleotide polymorphisms (SNPs) in the first intron of fat mass and obesity-associated (FTO) gene and obesity. To date, more than 100 SNPs in the FTO gene have been identified in various populations. Nevertheless, this association has not yet been confirmed in Thai populations. The aim of this study was to investigate whether FTO variants are associated with obesity in Thais. We analyzed ten variants in the FTO gene (rs9939609, rs9926289, rs8050136, rs9930501, rs9930506, rs9940646, rs9940128, rs1421085, rs17817449, and rs8043757) in 12 families (83 persons); composed of 12 proband cases and 71 associated family members. All participants were genotyped using polymerase chain reaction (PCR) method and DNA sequencing assay. We found significant associations between three SNPs located in the first intron of FTO gene (rs1421085, rs17817449, and rs8043757) and obesity. The odds ratios were 2.82 (95% CI, 1.16-6.90, p=0.02) for rs1421085 and rs17817449, and 3.15 (95% CI, 1.28-7.76, p=0.01) for rs8043757. Strong linkage disequilibrium among ten SNPs was observed (D'>0.8). Haplotype analysis (combination of rs1421085 (T/C), rs17817449 (T/G), and rs8043757 (A/T)) showed that the CGT haplotype is associated with an increased risk of obesity (OR, 2.42; 95% CI, 1.18-4.97; p=0.018) when compared to the reference haplotype (TTA). The SNPs rs1421085, rs17817449 and rs8043757 in the first intron of the FTO gene are associated with increasing risk of obesity in Thais. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Association analysis of FTO gene polymorphisms with obesity in Greek adults.

    Science.gov (United States)

    Goutzelas, Yiannis; Kotsa, Kalliopi; Vasilopoulos, Yiannis; Tsekmekidou, Xanthippi; Stamatis, Costas; Yovos, John G; Sarafidou, Theologia; Mamuris, Zissis

    2017-05-20

    Nowadays, obesity is the greatest scourge worldwide, particularly for the developed countries and is a huge burden for the public health. Over the past decade, GWAS have revealed a number of genes associated with obesity. The fat mass and obesity associated (FTO) gene was the first one associated with obesity in a significant number of populations and recent meta-analysis studies confirm this association. FTO is a N-methyladenosine demethylase and in addition to the genetic association, its biological role in the regulation of body weight has been documented. Due to lack of replication regarding FTO association with obesity in the Greek adult population, we analyzed three SNPs, i.e. rs9939609, rs9930506 and rs3751812 in a cohort of 203 adults, comprising of 95 obese, 58 overweight and 50 control individuals. Analysis has shown a significant association for FTO (rs9930506; A/G) 'G' allele with obesity and a difference by 3.2 BMI units between the two homozygotes (AA versus GG). This association, which was detected for the first time in this population, suggests that FTO rs9930506 is a predisposition marker to obesity in the Greek adults, but the results should be taken cautiously due to the limitation of the relatively small sample size of the subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. FTO gene variant modulates the neural correlates of visual food perception.

    Science.gov (United States)

    Kühn, Anne B; Feis, Delia-Lisa; Schilbach, Leonhard; Kracht, Lutz; Hess, Martin E; Mauer, Jan; Brüning, Jens C; Tittgemeyer, Marc

    2016-03-01

    Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive. Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Tissue- and breed-specific expression of the chicken fat mass- and obesity-associated gene (FTO).

    Science.gov (United States)

    Song, C; Song, W T; Shu, J T; Tao, Z Y; Zhu, W Q; Di, C; Li, H F

    2015-09-08

    The fat mass- and obesity-associated gene (FTO) is involved in energy metabolism, but little is known about the chicken FTO gene. The objective of the current study was to detect chicken FTO expression patterns in the hypothalamus, liver, and skeletal muscle during development, and analyze the effects of age and breed on FTO expression. Real-time quantitative polymerase chain reaction results revealed that chicken FTO mRNA was expressed in all of the tissues tested. Chicken FTO exhibited tissue- and breed-specific patterns in the recessive White Plymouth Rock chicken and the Qingyuan partridge chicken. The highest FTO expression level was in the hypothalami of 1-week-old chicks. FTO mRNA was expressed more in the breast muscles and livers of recessive White Plymouth Rock chickens than those of Qingyuan partridge chickens at 1 and 8 weeks of age. These results indicate that FTO probably plays a significant role in energy metabolism at 1 week old, when chicks have undergone metabolic adaptations from yolk dependence to the utilization of exogenous feed.

  15. FTO gene variation and measures of body mass in an African population

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    Hattersley Andrew T

    2009-03-01

    Full Text Available Abstract Background Variation in the fat mass and obesity associated (FTO gene has been reproducibly associated with body mass index (BMI and obesity in populations of White European origin. Data from Asians and African-Americans is less conclusive. Methods We assessed the effect of 16 FTO polymorphisms on body mass in a large population of predominantly lean Gambians (Nmax 2208 participating in a long-term surveillance program providing contemporary and early-life anthropometric measurements. Results Sixteen FTO tagSNPs screened here, including several associated with BMI in Europeans, were not associated with birth weight (BWT, early weight gain in 1–2 year olds, BMI in adults (≥ 18 y, or weight-for-height (WFH z-score across all ages. No association was seen between genotype and WFH z-score or other measures of body mass. The confidence limits indicate that the effect size for WFH z-score never exceeded 0.17 units per allele copy for any SNP (excluding the three SNPs with allele Conclusion To our knowledge this is the first study of FTO gene variation in a well-characterised African population. Our results suggest that FTO gene variation does not influence measures of body mass in Gambians living a traditional lifestyle, or has a smaller effect than that detected in Europeans. These findings are not directly comparable to results from previous studies in African-Americans due to differences in study design and analysis. It is also possible that any effect of FTO genotype on body mass is of limited relevance in a lean population where little excess food is available, compared to similar ethnic populations where food supply is plentiful.

  16. Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.

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    Hernández-Caballero, Marta Elena; Sierra-Ramírez, José Alfredo

    2015-03-01

    The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

  17. Association of the fat mass and obesity-associated (FTO) gene variant (rs9939609) with dietary intake in the Finnish Diabetes Prevention Study.

    Science.gov (United States)

    Lappalainen, Tiina; Lindström, Jaana; Paananen, Jussi; Eriksson, Johan G; Karhunen, Leila; Tuomilehto, Jaakko; Uusitupa, Matti

    2012-11-28

    A cluster of variants in the fat mass and obesity-associated (FTO) gene are associated with the common form of obesity. Well-documented dietary data are required for identifying how the genetic risk can be modified by dietary factors. The objective of the present study was to investigate the associations between the FTO risk allele (rs9939609) and dietary intake, and to evaluate how dietary intake affects the association between FTO and BMI in the Finnish Diabetes Prevention Study during a mean follow-up of 3·2 years. A total of 479 (BMI >25 kg/m2) men and women were genotyped for rs9939609. The participants completed a 3 d food record at baseline and before every annual study visit. The average intakes at baseline and during the years 1, 2 and 3 were calculated. At baseline, the FTO variant rs9939609 was not associated with the mean values of total energy intake, macronutrients or fibre. At baseline, a higher BMI by the FTO risk genotype was detected especially in those who reported a diet high in fat with mean BMI of 30·6 (sd 4·1), 31·3 (sd 4·6) and 34·5 (sd 6·2) kg/m2 for TT, TA and AA carriers, respectively (P =0·005). Higher BMI was also observed in those who had a diet low in carbohydrates (P =0·028) and fibre (P =0·015). However, in the analyses adjusted for total energy intake, age and sex, significant interactions between FTO and dietary intakes were not found. These findings suggest that the association between the FTO genotype and obesity is influenced by the components of dietary intake, and the current dietary recommendations are particularly beneficial for those who are genetically susceptible for obesity.

  18. FTO gene: association to weight regain after lifestyle intervention in overweight children.

    Science.gov (United States)

    Reinehr, Thomas; Wolters, Barbara; Roth, Christian L; Hinney, Anke

    2014-01-01

    Polymorphisms in intron 1 of the 'fat mass and obesity-associated' (FTO) gene are associated with weight status. We hypothesized that the risk allele at a polymorphism in intron 1 of FTO is associated with weight regain after end of lifestyle intervention. We longitudinally analyzed the changes of weight status as BMI-SDS in 346 unrelated overweight children (mean age 10.6 ± 2.6 years, 45% male, mean BMI-SDS 2.39 ± 0.49) both at the end of a 1-year lifestyle intervention and 1 year after the end of this intervention. We genotyped the obesity risk SNP rs9939609 at FTO by ARMS-PCR. The children reduced their BMI-SDS (-0.29 ± 0.33; p weight regain 1 year after end of the intervention in multiple linear regression analyses adjusted for age, sex, pubertal stage, and baseline BMI-SDS (Bonferroni corrected p = 0.002). The obesity risk allele at a polymorphism in intron 1 of FTO was associated with weight regain 1 year after a 1-year lifestyle intervention. © 2014 S. Karger AG, Basel.

  19. Does the FTO Gene Interact with the Socio‐Economic Status on the Obesity Development Among Young European Children?

    DEFF Research Database (Denmark)

    Foraita, Ronja; Günther, Frauke; Gwozdz, Wencke

    activity and fitness habits, and parental SES to estimate the main effects of the latter three variables and a FTO polymorphism on obesity. Further, a multiple group SEM is used to explore whether an interaction effect between the single nucleotide polymorphism rs9939609 within the FTO gene and SES exists...... developed countries. The aim of this study is to investigate whether the FTO gene interacts with the socio‐economic status (SES) on childhood obesity in a subsample of the IDEFICS cohort (N=4406). A structural equation model (SEM) is applied with the latent constructs obesity, dietary habits, physical...

  20. Association between rs9930506 polymorphism of the fat mass & obesity-associated (FTO) gene & onset of obesity in Polish adults.

    Science.gov (United States)

    Wrzosek, Malgorzata; Zakrzewska, Anna; Ruczko, Lech; Jabłonowska-Lietz, Beata; Nowicka, Grażyna

    2016-03-01

    The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults. The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism. It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes. This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

  1. An FTO Gene Variant Moderates the Association between Parental Restriction and Child BMI.

    Directory of Open Access Journals (Sweden)

    Alison Tovar

    Full Text Available This study aimed to explore whether a common variant in the FTO gene moderates the relationship between parental restriction and child BMI.This study reports on baseline data from 178 parent-child (ages 9-10 years dyads. Parents completed the Child Feeding Questionnaire and reported on socio-demographic characteristics. Each child's height, weight and FTO rs9939609 genotype was assessed. Ordinary least squares regression was used to fit the child's BMI-percentile on parental restriction and the child's FTO genotype, adjusted for covariates. A likelihood ratio test was used to compare a model with and without a multiplicative interaction term between restriction and genotype.Most participants (93.3% were white, non-Hispanic. Twenty-three percent of children were overweight/obese and FTO genotype was associated with weight status. Mean parental restriction was statistically higher among overweight/obese vs. normal weight children: 3.3 (SD 0.8 vs. 2.8 (SD 1.0; t-test p-value = 0.002. Parental restriction was positively associated with child BMI-percentile and BMI-z only among children with two copies of the high-risk FTO allele (p for interaction = 0.02, where each one-point increase in parental restriction was associated with a 14.7 increase in the child's BMI-percentile or a 0.56-point increase in the child's BMI z-score.For only the children with two high-risk alleles, parental restriction was positively associated with child BMI-percentile.

  2. Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

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    Rivera, Margarita; Locke, Adam E; Corre, Tanguy; Czamara, Darina; Wolf, Christiane; Ching-Lopez, Ana; Milaneschi, Yuri; Kloiber, Stefan; Cohen-Woods, Sara; Rucker, James; Aitchison, Katherine J; Bergmann, Sven; Boomsma, Dorret I; Craddock, Nick; Gill, Michael; Holsboer, Florian; Hottenga, Jouke-Jan; Korszun, Ania; Kutalik, Zoltan; Lucae, Susanne; Maier, Wolfgang; Mors, Ole; Müller-Myhsok, Bertram; Owen, Michael J; Penninx, Brenda W J H; Preisig, Martin; Rice, John; Rietschel, Marcella; Tozzi, Federica; Uher, Rudolf; Vollenweider, Peter; Waeber, Gerard; Willemsen, Gonneke; Craig, Ian W; Farmer, Anne E; Lewis, Cathryn M; Breen, Gerome; McGuffin, Peter

    2017-08-01

    BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10(-4)) and with the Han/Eskin random effects method (P = 1.4 × 10(-7)) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10(-8)). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression. © The Royal College of Psychiatrists 2017.

  3. An obesity-associated FTO gene variant and increased energy intake in children.

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    Cecil, Joanne E; Tavendale, Roger; Watt, Peter; Hetherington, Marion M; Palmer, Colin N A

    2008-12-11

    Variation in the fat mass and obesity-associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown. We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for FTO variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the FTO variant with adiposity, energy expenditure, and food intake. In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to obesity in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82). The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. 2008 Massachusetts Medical Society

  4. Impact of metabolic regulators on the expression of the obesity associated genes FTO and NAMPT in human preadipocytes and adipocytes.

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    Daniela Friebe

    Full Text Available BACKGROUND: FTO and NAMPT/PBEF/visfatin are thought to play a role in obesity but their transcriptional regulation in adipocytes is not fully understood. In this study, we evaluated the transcriptional regulation of FTO and NAMPT in preadipocytes and adipocytes by metabolic regulators. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed FTO mRNA expression during human adipocyte differentiation of Simpson-Golabi-Behmel syndrome (SGBS cells and primary subcutaneous preadipocytes in vitro and evaluated the effect of the metabolic regulators glucose, insulin, dexamethasone, IGF-1 and isoproterenol on FTO and NAMPT mRNA expression in SGBS preadipocytes and adipocytes. FTO mRNA levels were not significantly modulated during adipocyte differentiation. Also, metabolic regulators had no impact on FTO expression in preadipocytes or adipocytes. In SGBS preadipocytes NAMPT expression was more than 3fold induced by dexamethasone and isoproterenol and 1.6fold by dexamethasone in adipocytes. Complete glucose restriction caused an increase in NAMPT mRNA expression by more than 5fold and 1.4fold in SGBS preadipocytes and adipocytes, respectively. CONCLUSION: FTO mRNA expression is not significantly affected by differentiation or metabolic regulators in human adipocytes. The stimulation of NAMPT expression by dexamethasone, isoproterenol and complete glucose restriction may indicate a regulation of NAMPT by metabolic stress, which was more pronounced in preadipocytes compared to mature adipocytes.

  5. Impact of Metabolic Regulators on the Expression of the Obesity Associated Genes FTO and NAMPT in Human Preadipocytes and Adipocytes

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    Schönberg, Maria; Bernhard, Falk; Büttner, Petra; Landgraf, Kathrin; Kiess, Wieland; Körner, Antje

    2011-01-01

    Background FTO and NAMPT/PBEF/visfatin are thought to play a role in obesity but their transcriptional regulation in adipocytes is not fully understood. In this study, we evaluated the transcriptional regulation of FTO and NAMPT in preadipocytes and adipocytes by metabolic regulators. Methodology and Principal Findings We assessed FTO mRNA expression during human adipocyte differentiation of Simpson-Golabi-Behmel syndrome (SGBS) cells and primary subcutaneous preadipocytes in vitro and evaluated the effect of the metabolic regulators glucose, insulin, dexamethasone, IGF-1 and isoproterenol on FTO and NAMPT mRNA expression in SGBS preadipocytes and adipocytes. FTO mRNA levels were not significantly modulated during adipocyte differentiation. Also, metabolic regulators had no impact on FTO expression in preadipocytes or adipocytes. In SGBS preadipocytes NAMPT expression was more than 3fold induced by dexamethasone and isoproterenol and 1.6fold by dexamethasone in adipocytes. Complete glucose restriction caused an increase in NAMPT mRNA expression by more than 5fold and 1.4fold in SGBS preadipocytes and adipocytes, respectively. Conclusion FTO mRNA expression is not significantly affected by differentiation or metabolic regulators in human adipocytes. The stimulation of NAMPT expression by dexamethasone, isoproterenol and complete glucose restriction may indicate a regulation of NAMPT by metabolic stress, which was more pronounced in preadipocytes compared to mature adipocytes. PMID:21687707

  6. Common variant rs9939609 in gene FTO confers risk to polycystic ovary syndrome.

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    Tao Li

    Full Text Available BACKGROUND: Fat mass and obesity-associated gene (FTO has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size. METHOD: This study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese. RESULTS: The less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03, was further confirmed in the replication study (P = 1.86E-09. Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06. To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups-obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55, as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28. CONCLUSION: Variant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases.

  7. Interactions between the FTO and GNB3 genes contribute to varied clinical phenotypes in hypertension.

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    Rahul Kumar

    Full Text Available BACKGROUND: The genes FTO and GNB3 are implicated in essential hypertension but their interaction remains to be explored. This study investigates the role of interaction between the two genes in the pathophysiology of essential hypertension. METHODS/PRINCIPAL FINDINGS: In a case-control study comprising 750 controls and 550 patients, interaction between the polymorphisms of FTO and GNB3 was examined using multifactor dimensionality reduction (MDR. The influence of interaction on clinical phenotypes like systolic and diastolic blood pressure, mean arterial pressure and body mass index was also investigated. The 3-locus MDR model comprising FTO rs8050136C/A and GNB3 rs1129649T/C and rs5443C/T emerged as the best disease conferring model. Moreover, the interacted-genotypes having either 1, 2, 3, 4 or 5 risk alleles correlated with linearly increasing odds ratios of 1.91 (P = 0.027; 3.93 (P = 2.08E-06; 4.51 (P = 7.63E-07; 7.44 (P = 3.66E-08 and 11.57 (P = 1.18E-05, respectively, when compared with interacted-genotypes devoid of risk alleles. Furthermore, interactions among haplotypes of FTO (H1-9 and GNB3 (Ha-d differed by >1.5-fold for protective-haplotypes, CTGGC+TC [H2+Ha] and CTGAC+TC [H4+Ha] (OR = 0.39, P = 0.003; OR = 0.22, P = 6.86E-05, respectively and risk-haplotypes, AAAGC+CT [H3+Hc] and AAAGC+TT [H3+Hd] (OR = 2.91, P = 9.98E-06; OR = 2.50, P = 0.004, respectively compared to individual haplotypes. Moreover, the effectiveness of gene-gene interaction was further corroborated with a 1.29-, 1.25- and 1.38-fold higher SBP, MAP and BMI, respectively, in patients having risk interacted-haplotype H3+Hc and 2.48-fold higher SBP having risk interacted-haplotype H3+Hd compared to individual haplotypes. CONCLUSION: Interactions between genetic variants of FTO and GNB3 influence clinical parameters to augment hypertension.

  8. FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs

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    Zhao Hongyu

    2008-01-01

    Full Text Available Abstract Background FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs in FTO with body mass index (BMI and obesity, particularly rs1421085, rs17817449, and rs9939609. Methods We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI2 and had never been overweight during their lifetimes. Results We detected highly significant associations of obesity with alleles in all three SNPs (p -9. The strongest association was with rs1421085 (p = 3.04 × 10-10, OR = 1.75, CI = 1.47–2.08. A subset of 99 cases had extremely discordant sisters with BMI2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10-4. Conclusion These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.

  9. Indications for potential parent-of-origin effects within the FTO gene.

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    Xuanshi Liu

    Full Text Available Genome-Wide Association Studies (GWAS were successfully applied to discover associations with obesity. However, the GWAS design is usually based on unrelated individuals and inheritance information on the parental origin of the alleles is missing. Taking into account parent-of-origin may provide further insights into the genetic mechanisms contributing to obesity. We hypothesized that there may be variants within the robustly replicated fat mass and obesity associated (FTO gene that may confer different risk for obesity depending on transmission from mother or father. Genome-wide genotypes and pedigree information from the Sorbs population were used. Phased genotypes among 525 individuals were generated by AlphaImpute. Subsequently, 22 SNPs within FTO introns 1 to 3 were selected and parent-of-origin specific association analyses were performed using PLINK. Interestingly, we identified several SNPs conferring different genetic effects (P≤0.05 depending on parental origin--among them, rs1861868, rs1121980 and rs9939973 (all in intron 1. To confirm our findings, we investigated the selected variants in 705 German trios comprising an (extremely obese child or adolescent and both parents. Again, we observed evidence for POE effects in intron 2 and 3 (P≤0.05 as indicated by the parental asymmetry test. Our results suggest that the obesity risk transmitted by several FTO variants may depend on the parental origin of the allele. Larger family-based studies are warranted to replicate our findings.

  10. Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration.

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    Prats-Puig, A; Grau-Cabrera, P; Riera-Pérez, E; Cortés-Marina, R; Fortea, E; Soriano-Rodríguez, P; de Zegher, F; Ibánez, L; Bassols, J; López-Bermejo, A

    2013-02-01

    Shorter sleep duration predisposes to obesity, but the mechanisms whereby sleep deprivation affects body weight are poorly understood. We tested whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3. Body mass index (BMI), waist circumference, visceral fat (abdominal ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297 asymptomatic children (151 boys, 146 girls; age range 5-9 years; BMI s.d. score range -2.0-4.0). Associations between sleep duration and the abovementioned outcomes were tested for three common single-nucleotide polymorphisms (SNPs), namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as for their combination. TT homozygotes (but not A(*) carriers) for the FTO SNP, exhibited nominal associations between decreasing sleep duration and increasing BMI, waist circumference, visceral fat and HOMA-IR (all Psleep and, respectively, BMI (Psleep less per night was associated with an increase in BMI of 1.0 s.d. (95% confidence interval 0.5-1.6 s.d.) and with 8.0 cm (95% confidence interval 3.6-12.2 cm) more waist circumference in genetically susceptible children. By age 7, common variations in FTO, TMEM18 and NRXN3 influence the vulnerability to metabolic complications of sleep deprivation. Further genetic studies are warranted to replicate these findings in other populations.

  11. Polymorphisms in FTO and MAF Genes and Birth Weight, BMI, Ponderal Index, Weight Gain in a Large Cohort of Infants with a Birth Weight below 1500 Grams.

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    Sebastian Haller

    Full Text Available The FTO gene, located on chromosome 16q12.2, and the MAF gene, located on chromosome 16q22-23, were identified as genes harboring common variants with an impact on obesity predisposition. We studied the association of common variants with birth weight, gain of body weight, body mass index (BMI, Ponderal index and relevant neonatal outcomes in a large German cohort of infants with a birth weight below 1500 grams.The single nucleotide polymorphisms rs9939609 (FTO gene and rs1424233 (MAF gene were genotyped using allelic discrimination assays in a prospective multicenter cohort study conducted in 15 neonatal intensive care units in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols.1946 infants were successfully genotyped at FTO and 2149 infants at MAF. Allele frequencies were not significantly different from other European cohorts. The polymorphisms were in Hardy-Weinberg equilibrium. The polymorphisms did not show associations with birth weight, BMI and Ponderal Index at discharge, and weight gain, neither testing for a dominant, additive nor for a recessive model.Since an association of the polymorphisms with weight gain has been demonstrated in multiple populations, the lack of association in a population of preterm infants with regular tube feeding after birth and highly controlled feeding volumes provides evidence for the hypothesis that these polymorphisms affect food intake behavior and hunger rather than metabolism and energy consumption.

  12. Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia.

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    Vanni Caruso

    Full Text Available BACKGROUND: Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs of the fat mass and obesity associated (FTO gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO. METHODS: Female Sprague Dawley rats were exposed to chow or high fat diet (HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1, some litters were adjusted to 3 pups (vs. 12 control to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured. RESULTS: At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05; body weight approached significance (P = 0.07. Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding. SIGNIFICANCE: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human

  13. 肥胖基因FTO的研究进展%Current progress on FTO gene

    Institute of Scientific and Technical Information of China (English)

    王辉; 孟雁

    2010-01-01

    Whole-genome association analysis makes Fro gene (fat mass and obesity associated gene) become the first candidate gene for obesity among general population.It is highly expressed in hypo-thalamus and is involved in the control of energy balance.FTO gene with single nucleotide polymorphism vari-ation is correlated with the choice of dietary intake which may influence body weight that result in obesity.In addition,it is also associated with type 2 diabetes, and has correlation with other genes.%全基因组关联分析使得FTO(fat mass and obesity associated)基因成为第一个普通人群肥胖候选基因,其在下丘脑核丰富表达,参与能量平衡的控制.FTO基因的不同单核苷酸多态性可影响饮食的摄取,从而影响人的体重,参与肥胖的发生.此外,FTO基因还与2型糖尿病等疾病密切相关,与其他基因发挥协同作用.

  14. Hypothalamic FTO is associated with the regulation of energy intake not feeding reward

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    Radomska Katarzyna J

    2009-10-01

    Full Text Available Abstract Background Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal. Results Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin. Conclusion We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.

  15. [Association of polymorphic variants of FTO and MC4R genes with obesity in a Tatar population].

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    Kochetova, O V; Korytina, G F; Akhmadishina, L Z; Semenov, E E; Viktorova, T V

    2015-02-01

    Obesity is a chronic relapsing disease that leads to numerous ailments and requires lifelong treatment. Genetic predisposition is one of the mostly discussed aspects of obesity development, and genome-wide association studies have provided evidence that several variants of the FTO and MC4R genes are significantly associated with obesity. In this study the association of FTO (rs9939609, rs7202116, and rs9930506) and MC4R (rs12970134 and rs17782313) genes' SNPs with obesity in Tatar women has been analyzed. In the investigation 340 women with obesity (Body Mass Index (BMI) ≥ 30 kg/m2) and 330 women from a control group (BMI up to 24.9 kg/m2) took part. The FTO rs9939609 (p = 0.0002) and rs9930506 (p = 0.0005) SNPs were shown to be associated with obesity risk following an additive model, while the MC4R rs12970134 (p = 0.0076) and rs1778231 (p = 0.021) SNPs were associated by a recessive model. We also showed an association of quantitative parameters (age, weight, and BMI) with two the FTO rs9939609 and rs9930506 SNPs and the association of age and the MC4R rs12970134 SNP. Our study demonstrates the role of genetic variability in FTO and MC4R genes in obesity development in Tatar women from Russia.

  16. Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity.

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    Zhaojing Zheng

    Full Text Available OBJECTIVE: To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity. METHODS: Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls. RESULTS: A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05. However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05. None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05. One variant (L293R that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups. CONCLUSION: The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort.

  17. Screening for Coding Variants in FTO and SH2B1 Genes in Chinese Patients with Obesity

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    Huang, Xiaodong; Yang, Peirong; Li, Juan; Ding, Yu; Yao, Ru-en; Geng, Juan; Shen, Yongnian; Shen, Yiping; Fu, Qihua; Yu, Yongguo

    2013-01-01

    Objective To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity. Methods Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls. Results A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05). However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05). None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05). One variant (L293R) that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups. Conclusion The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort. PMID:23825611

  18. Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk.

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    da Cunha, Patrícia Amorim; de Carlos Back, Lia Kubelka; Sereia, Aline Fernanda Rodrigues; Kubelka, Clara; Ribeiro, Maria Cecíia Menks; Fernandes, Bráulio Leal; de Souza, Ilíada Rainha

    2013-12-01

    Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.

  19. Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children

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    Liu Ailing

    2010-09-01

    Full Text Available Abstract Background Fat-mass and obesity-associated (FTO gene is a gene located in chromosome region 16q12.2. Genetic variants in FTO are associated with the obesity phenotype in European and Hispanic populations. However, this association still remains controversial in Asian population. We aimed to test the association of FTO genetic variants with obesity and obesity-related metabolic traits among children living in Beijing, China. Methods We genotyped FTO variants rs9939609 in 670 children (332 girls and 338 boys aged 8-11 years living in Beijing, and analyzed its association with obesity and obesity-related metabolic traits. Overweight and obesity were defined by age- and sex-specific BMI reference for Chinese children. Obesity-related metabolic traits included fasting plasma glucose, lipid profiles, leptin, ghrelin, adiponectin and blood pressures. Results The frequency of rs9939609 A allele was 12.2%, which was 21.9% for the heterozygote and 1.2% for the homozygote of the A allele. The obesity prevalence among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs. 22.6%, P = 0.004. Compared to the carrier of TT genotype, the likelihood of obesity was 1.79 (95% confidence interval (95% CI 1.20-2.67, P = 0.004 for the carrier of AA/AT genotype, after adjustment of sex, age and puberty stages. The BMI Z-score of children with AA/AT genotype were significantly higher than that of their counterparts with the TT genotype (1.1 ± 0.1 vs. 0.8 ± 0.1, P = 0.02. The concentration of triglyceride was 1.03 ± 0.52 mmol/L among TT carrier and 1.13 ± 0.68 mmol/L among AA/AT carrier (P = 0.045. While, the concentrations of adiponectin were 18.0 ± 0.4 μg/ml among carriers of TT and 16.2 ± 0.7 μg/ml among subjects with AA/AT genotype (P = 0.03. The level of glucose marginally increased in the AA/AT genotype subjects (4.67 ± 0.40 mmol/L vs. 4.60 ± 0.35 mmol/L, P = 0.08. The evidence of association

  20. Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

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    Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. To investigate whether MC4R and FTO associations ...

  1. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity?

    DEFF Research Database (Denmark)

    Zimmermann, E; Ängquist, L H; Mirza, S S

    2015-01-01

    Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has s...

  2. Association of the FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms with maternal body weight during pregnancy.

    Science.gov (United States)

    Martins, Maisa Cruz; Trujillo, Janet; Farias, Dayana Rodrigues; Struchiner, Claudio Jose; Kac, Gilberto

    2016-01-01

    The fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with the risk for obesity, but few studies have examined the association of the obesity risk alleles with gestational outcomes. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) of the FTO (rs9939609) and MC4R (rs17782313) genes with changes in maternal body weight during pregnancy. A sample of 136 pregnant women were followed in a prospective cohort at 5 to 13, 20 to 26, and 30 to 36 wk gestation and 30 to 45 d postpartum. SNPs were analyzed by real-time polymerase chain reaction. Associations between polymorphisms and the outcomes were investigated through longitudinal linear mixed-effects models, multiple linear regression models, and Poisson regression models. An SNP in the FTO (rs9939609) gene but not in the MC4R (rs17782313) gene was significantly associated with prepregnancy body mass index (BMI) ≥25 kg/m(2) (relative riskFTO = 2.1; 95% confidence interval [CI], 1.4-3.1). SNPs were not statistically associated with excessive gestational weight gain (GWG) or postpartum weight retention (PPWR). For the FTO (rs9939609) gene, women with the AA genotype were heavier in the body weight trajectory of pregnancy, but not when their weight had been adjusted for prepregnancy BMI (βFTO = 0.5 kg; 95% CI, -1.9 to 3). These women started pregnancy heavier but gained less weight (FTO*gestational age = -0.1; 95% CI, -0.2 to 0.03) compared with those who had at least one T allele. The FTO (rs9939609) AA genotype is positively associated with prepregnancy excessive weight. We found no evidence of a significant effect of the MC4R (rs17782313) or the FTO (rs9939609) gene polymorphisms on the GWG and PPWR. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. FTO gene variant and risk of overweight and obesity among children and adolescents: a systematic review and meta-analysis.

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    Chibo Liu

    Full Text Available OBJECTIVE: The fat mass and obesity associated gene (FTO polymorphisms have been implicated in the susceptibility of overweight/obesity in children and adolescents. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of FTO gene polymorphisms with overweight/obesity risk among children and adolescents. METHODS: PubMed and Embase were used to search for eligible published literatures. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using random- or fixed-effect models. RESULTS: A total of 21 articles containing 23 studies (11208cases and 35015controls were included in our analysis. The results indicated that variant in FTO gene was significantly associated with increased risk of overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44; P<0.001. The overall pooled ORs for risk obesity and overweight were 1.34 (95%CI: 1.21-1.48 and 1.35 (95%CI: 1.25-1.47, respectively. Subgroup analyses also showed similar trends in most subgroups of adjustment for covariates and unadjustment, different ethnicities (Caucasians, Asians, and Amerindians, and each of three investigated polymorphisms (rs9939609, rs1421085, and rs1558902. CONCLUSIONS: The present meta-analysis suggested a positive association between FTO gene polymorphism and overweight/obesity risk among children and adolescents. Further prospective studies should be recommended to confirm the observed association, and underlying mechanism should be investigated to clarify the association of FTO gene polymorphism with overweight/obesity.

  4. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.

    Science.gov (United States)

    Ho, April J; Stein, Jason L; Hua, Xue; Lee, Suh; Hibar, Derrek P; Leow, Alex D; Dinov, Ivo D; Toga, Arthur W; Saykin, Andrew J; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J; Craig, David W; Gerber, Jill D; Allen, April N; Corneveaux, Jason J; Stephan, Dietrich A; DeCarli, Charles S; DeChairo, Bryan M; Potkin, Steven G; Jack, Clifford R; Weiner, Michael W; Raji, Cyrus A; Lopez, Oscar L; Becker, James T; Carmichael, Owen T; Thompson, Paul M

    2010-05-04

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes-these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

  5. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

    Science.gov (United States)

    Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

    2010-01-01

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

  6. Variation in sequence and expression of the avian FTO, and association with glucose metabolism, body weight, fatness and body composition in chickens.

    Science.gov (United States)

    Jia, X; Nie, Q; Lamont, S J; Zhang, X

    2012-08-01

    The fat mass and obesity-associated gene (FTO), a crucial gene that affects human obesity and metabolism, has been widely studied in mammals but remains poorly characterized in birds. We aimed to identify variant FTO transcripts in domestic avian species, and to characterize the expression and biological functions of FTO in chickens. Variant FTO transcripts and their expression in birds were investigated using RACE and real-time quantitative reverse transcriptase-PCR technology. The effects of FTO on glucose metabolism, growth and body composition were determined by fasting and various diet treatments, as well as association analysis in a F₂ resource population. The function of cFTO1 was further studied by overexpression in chick embryo fibroblast (CEF) cells. Variant FTO transcripts were identified in chicken (cFTO1 to cFTO4), duck (dFTO1, dFTO2 and dFTO4) and goose (gFTO1, gFTO2 and gFTO5). In the chicken, the complete transcript (cFTO1) was predominantly expressed in the leg muscle, pituitary, hypothalamus and cerebellum. Fasting increased both cFTO1 and PGC1α gene expression in the cerebrum, liver, breast muscle and subcutaneous fat, but decreased expression in the pituitary and anterior hypothalamus. In all tested tissues in chickens, a high-glucose diet markedly increased cFTO1 and PGC1α expression. Feeding a high-fat diet increased both cFTO1 and PGC1α expression, except in the pituitary. Overexpression of cFTO1 in CEF cells significantly increased the expression of PGC1α (2.5-fold), STAT3 (2.2-fold) and HL (1.5-fold), a cluster of genes related to energy metabolism. A total of 65 single nucleotide polymorphisms (SNPs) were identified in chicken FTO, and 18 tested SNPs were significantly associated with traits of body weight, body composition and fatness. These data collectively indicate that FTO is related to glucose metabolism, body weight, fatness and body composition in birds, thus expanding knowledge of FTO function to non-mammalian species.

  7. Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity

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    Włodzimierz Łuczyński

    2014-01-01

    Full Text Available The objective was to compare the impact of clinical and genetic factors on body mass index (BMI in children with type 1 diabetes (T1DM without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (P=0.0003, poor metabolic control (P=0.0001, and carriage of the A allele of the FTO rs9939609 gene (P=0.02. Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161.

  8. Association between fat mass- and obesity-associated (FTO gene polymorphism and polycystic ovary syndrome: a meta-analysis.

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    Xianli Cai

    Full Text Available AIMS: Many studies have investigated the relationship between FTO gene polymorphism and polycystic ovary syndrome (PCOS susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association. METHODS: Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR with 95% confidence interval (CI using the random- or fix- effects model. RESULTS: A total of 5 studies (4778 cases and 4272 controls were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy was marginally associated with PCOS risk after adjustment for body mass index (BMI (OR = 1.26; 95%CI: 1.02-1.55. However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians (OR = 1.43, 95%CI = 1.30-1.59 but not in Caucasians (OR = 1.04, 95%CI = 0.85-1.29. CONCLUSIONS: Our present meta-analysis indicated that FTO rs9939609 polymorphism (or its proxy might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity.

  9. Risk of obesity and metabolic syndrome associated with FTO gene variants discloses clinically relevant gender difference among Turks.

    Science.gov (United States)

    Guclu-Geyik, Filiz; Onat, Altan; Yuzbasıogulları, Ayse Berna; Coban, Neslihan; Can, Gunay; Lehtimäki, Terho; Erginel-Unaltuna, Nihan

    2016-06-01

    Gene variations in the fat mass- and obesity-associated gene (FTO) have shown controversial associations with obesity and metabolic syndrome (MetS) in several populations. We explored the association of FTO gene with obesity, MetS, and insulin-related parameters separately in men and women. Two SNPs in the FTO, gene rs9939609 and rs1421085, were genotyped by the Taqman System in 1967 adults (mean age of the whole group 50.1 ± 12.0; 48.4 % male). A random sample of the Turkish Adult Risk Factor cohort was cross-sectionally analyzed. Both SNPs exhibited strong linkage disequilibrium (r(2) = 0.85) and minor alleles were associated with risk of obesity in women and of MetS in men. Carriers of the rs1421085 C-allele exhibited higher body mass index (BMI) in each gender. Adjusted fasting insulin and HOMA index were significantly higher in C-allele carriers in men alone. Logistic regression analysis demonstrated significantly increased likelihood for obesity in female C-risk allele carriers (OR 1.61; 95 % CI 1.19-2.18), after adjustment for age, smoking status, alcohol usage, physical activity grade and presence of diabetes mellitus. Male C-allele carriers were at increased risk for MetS (OR 1.44; 95 % CI 1.07-1.95), adjusted for age, smoking status, alcohol consumption, and physical activity. Further adjustment for BMI attenuated the MetS risk, indicating interaction between C-allele, gender and BMI. The FTO gene in Turkish adults contributes independently to obesity in women and-by interacting with BMI-to MetS and insulin resistance in men.

  10. The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chibo Liu

    Full Text Available OBJECTIVE: Genome-wide association studies have shown that variance in the fat mass- and obesity- associated gene (FTO is associated with risk of obesity in Europeans and Asians. Since obesity is associated with an increased risk of cardiovascular disease (CVD, several studies have investigated the association between variant in the FTO gene and CVD risk, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of rs9939609 variant (or its proxies [r (2>0.90] in the FTO gene with CVD risk. METHODS: Published literature from PubMed and Embase was retrieved. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random- effects model. RESULTS: A total of 10 studies (comprising 19,153 CVD cases and 103,720 controls were included in the meta-analysis. The results indicated that the rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18, 95% confidence interval = 1.07-1.30, p = 0.001 [Z test], I (2 = 80.6%, p<0.001 [heterogeneity], and there was an insignificant change after adjustment for body mass index (BMI and other conventional CVD risk factors (odds ratio = 1.16, 95% confidence interval = 1.05-1.27, p = 0.003 [Z test], I (2 = 75.4%, p<0.001 [heterogeneity]. CONCLUSIONS: The present meta-analysis confirmed the significant association of the rs9939609 variant in the FTO gene with CVD risk, which was independent of BMI and other conventional CVD risk factors.

  11. The bigger picture of FTO – the first GWAS-identified obesity gene

    Science.gov (United States)

    Loos, Ruth J.F.; Yeo, Giles S.H.

    2014-01-01

    In 2007, SNPs that cluster in the first intron of FTO showed highly significant association in the first two genome-wide association studies for obesity traits of which the minor allele increases body mass index (BMI) by 0.39 kg/m2 (or 1,130 g in body weight) and risk of obesity by 1.20 fold. Subsequent studies convincingly confirmed this association across populations of diverse ancestry and throughout the life course, with the largest effect seen in young adulthood. The effect of FTO SNPs on obesity traits in African and Asian ancestry populations is similar or somewhat smaller than in European ancestry populations, but the BMI-increasing allele is substantially less prevalent in non-European ancestry populations. FTO SNPs do not influence physical activity levels, yet, in physically active individuals, FTO’s effect on obesity susceptibility is attenuated by ~30%. Growing evidence from epidemiological and functional studies suggests that FTO confers an increased risk of obesity through subtle changes in food intake and preference. In addition, recent emerging data now points to a role for FTO in the sensing of nutrients and the regulation of translation and growth. In this review, we explore the genetic epidemiology of FTO and discuss how its complex biology might link to the regulation of body weight. PMID:24247219

  12. Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity.

    Science.gov (United States)

    Berentzen, T; Kring, S I I; Holst, C; Zimmermann, E; Jess, T; Hansen, T; Pedersen, O; Toubro, S; Astrup, A; Sørensen, T I A

    2008-07-01

    A common variant in the first intron of FTO (rs9939609, T/A) is associated with fatness in Caucasians. FTO may regulate energy homeostasis through the hypothalamus, and we hypothesized that AA-genotypes of rs9939609 FTO have lower energy expenditure and/or a lower level of physical activity. The study population included all obese young men (body mass index > or = 31 kg/m(2)) at the mandatory draft board examinations in the Copenhagen area from 1943 to 1977 and a randomly selected control group from this population. Subgroups of 234 obese and 323 controls were examined in 1998-2000 (median age 48 yr). Fat mass (FM), lean body mass (LBM), leisure-time physical activity (LTPA), maximum oxygen uptake (VO(2)max), resting energy expenditure (REE), and glucose-induced thermogenesis (GIT) were measured. The FTO rs9939609 variant was genotyped. A recessive transmission mode fit the data best. Logistic regression was used to assess the odds ratios of the AA-genotype in relation to LTPA, VO(2)max, REE, and GIT. The AA-genotype of FTO rs9939609 had higher REE in the age-adjusted model, but the association was eliminated when adjusting for FM and LBM. The AA-genotype was not associated with LTPA, VO(2)max, or GIT. This was not influenced by adjustment for age, FM, or LBM. The AA-genotype had increased FM, even with adjustment for age, LBM, REE, GIT, VO(2)max, and LTPA. Results were similar for FTO rs8050136 and rs7193144. Homozygous carriers of the A-allele of rs9939609 FTO do not have lower REE, GIT, VO(2)max, or LTPA but higher FM, irrespective of LBM, REE, GIT, VO(2)max, and LTPA.

  13. Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer.

    Science.gov (United States)

    Yang, Baiyu; Thrift, Aaron P; Figueiredo, Jane C; Jenkins, Mark A; Schumacher, Fredrick R; Conti, David V; Lin, Yi; Win, Aung Ko; Limburg, Paul J; Berndt, Sonja I; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hoffmeister, Michael; Hudson, Thomas J; Marchand, Loïc Le; Newcomb, Polly A; Slattery, Martha L; White, Emily; Peters, Ulrike; Casey, Graham; Campbell, Peter T

    2016-10-01

    Obesity is a convincing risk factor for colorectal cancer. Genetic variants in or near FTO and MC4R are consistently associated with body mass index and other body size measures, but whether they are also associated with colorectal cancer risk is unclear. In the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100kb upstream and 300kb downstream from each respective locus with risk of colorectal cancer in data from the Colon Cancer Family Registry (CCFR: 1960 cases; 1777 controls). Next, all SNPs that were nominally statistically significant (pCancer Consortium (GECCO: 9716 cases; 9844 controls). In the discovery stage, 43 FTO variants and 18 MC4R variants were associated with colorectal cancer risk (pobesity-related genes FTO and MC4R are associated with risk of colorectal cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.

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    Kathryn G Ewens

    Full Text Available Polycystic ovary syndrome (PCOS is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT. These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1 was found to have a nominally significant association with PCOS (χ(2 = 6.11, P = 0.013, but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.

  15. Milk: an epigenetic amplifier of FTO-mediated transcription? Implications for Western diseases.

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    Melnik, Bodo C

    2015-12-21

    Single-nucleotide polymorphisms within intron 1 of the FTO (fat mass and obesity-associated) gene are associated with enhanced FTO expression, increased body weight, obesity and type 2 diabetes mellitus (T2DM). The N (6) -methyladenosine (m(6)A) demethylase FTO plays a pivotal regulatory role for postnatal growth and energy expenditure. The purpose of this review is to provide translational evidence that links milk signaling with FTO-activated transcription of the milk recipient. FTO-dependent demethylation of m(6)A regulates mRNA splicing required for adipogenesis, increases the stability of mRNAs, and affects microRNA (miRNA) expression and miRNA biosynthesis. FTO senses branched-chain amino acids (BCAAs) and activates the nutrient sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), which plays a key role in translation. Milk provides abundant BCAAs and glutamine, critical components increasing FTO expression. CpG hypomethylation in the first intron of FTO has recently been associated with T2DM. CpG methylation is generally associated with gene silencing. In contrast, CpG demethylation generally increases transcription. DNA de novo methylation of CpG sites is facilitated by DNA methyltransferases (DNMT) 3A and 3B, whereas DNA maintenance methylation is controlled by DNMT1. MiRNA-29s target all DNMTs and thus reduce DNA CpG methylation. Cow´s milk provides substantial amounts of exosomal miRNA-29s that reach the systemic circulation and target mRNAs of the milk recipient. Via DNMT suppression, milk exosomal miRNA-29s may reduce the magnitude of FTO methylation, thereby epigenetically increasing FTO expression in the milk consumer. High lactation performance with increased milk yield has recently been associated with excessive miRNA-29 expression of dairy cow mammary epithelial cells (DCMECs). Notably, the galactopoietic hormone prolactin upregulates the transcription factor STAT3, which induces miRNA-29 expression. In a retrovirus-like manner

  16. The role of macronutrient intake in reducing the risk of obesity and overweight among carriers of different polymorphisms of FTO gene. A review

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    Przeliorz-Pyszczek, Anna; Regulska-Ilow, Bożena

    Obesity is a growing problem worldwide. The risk of the excessive body weight occurrence is a multifactorial issue. Environmental factors, lifestyle habits, diet, physical activity level, as well as genetic predisposition can increase obesity risk. One of the genes studied – the FTO gene - plays a crucial role in obesity occurrence. Individuals who carry risk alleles of specific single nucleotide polymorphisms (SNP) have a greater risk of being overweight. Recent studies revealed that specific macronutrient diet composition can influence differently on the FTO expression. The aim of this article is to review the recent literature on the topic of the FTO gene, its influence on overweight and obesity prevalence and the role of diet in modifying its impact on the risk of the excessive body weight occurrence. There are not many studies focusing on the dietary intervention influence on the FTO gene expression. As far as it has been researched it seems that the proper dietary habits can modify the FTO gene risk allele influence on obesity susceptibility.

  17. Impact of variation at the FTO locus on milk fat yield in Holstein dairy cattle.

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    Lea G Zielke

    Full Text Available This study explores the biological role of the Fat Mass and Obesity associated (FTO gene locus on milk composition in German Holstein cattle. Since FTO controls energy homeostasis and expenditure and the FTO locus has repeatedly shown association with obesity in human studies, we tested FTO as a candidate gene in particular for milk fat yield, which represents a high amount of energy secreted during lactation. The study was performed on 2,402 bulls and 860 cows where dense milk composition data were available. Genetic information was taken from a 2 Mb region around FTO. Five SNPs and two haplotype blocks in a 725 kb region covering FTO and the neighboring genes RPGRIP1L, U6ATAC, and 5 S rRNA were associated with milk fat yield and also affected protein yield in the same direction. Interestingly, higher frequency SNP alleles and haplotypes within the FTO gene increased milk fat and protein yields by up to 2.8 and 2.2 kg per lactation, respectively, while the most frequent haplotype in the upstream block covering exon 1 of FTO to exon 15 of RPGRIP1L had opposite effects with lower fat and milk yield. Both haplotype blocks were also significant in cows. The loci accounted for about 1% of the corresponding trait variance in the population. The association signals not only provided evidence for at least two causative mutations in the FTO locus with a functional effect on milk but also milk protein yield. The pleiotropic effects suggest a biological function on the usage of energy resources and the control of energy balance rather than directly affecting fat and protein synthesis. The identified effect of the obesity gene locus on milk energy content suggests an impact on infant nutrition by breast feeding in humans.

  18. FTO gene polymorphisms (rs9939609 and rs17817449) as predictors of Type 2 Diabetes Mellitus in obese Iraqi population.

    Science.gov (United States)

    Younus, Laith A; Algenabi, Abdul Hussein A; Abdul-Zhara, Mohammed S; Hussein, Majid K

    2017-09-05

    The variation of the SNPs in FTO (fat mass and obesity associated) gene are improved to be associated with obesity and type 2 diabetes (T2DM) in some ethnic groups for example in European while, this consistency is controversial in Asians and there were few studies in Iraqi population about the effect of this gene on the development of T2DM in obese patients. Therefore, the objective of this study is to investigate the impact of the two common FTO gene variants in the development of T2DM in obese Iraqi patients. A case-control study in which the FTO gene variants rs9939609 and rs17817449 were genotyping in a total of 800 individuals, 400 T2DM obese patients (patients group) and 400 healthy control obese volunteers (control group) to explore the relation of these SNPs with T2DM in obese Iraqi population. The patients group was enrolled from diabetic clinic in Al Najaf al Ashraf based on WHO guidelines of T2DM. From whole blood the DNA was extraction and genotyped by using ScaI and AlwNI enzymes respectively in the PCR-RFLP technique. Multinomial logistic regression was applied to compare the proportions of genotypes and alleles. The odd's ratio, t-test P value at 95% confidence interval were measured before and after adjustment of BMI, age and sex adjustment. The genetic power, Hardy Weinberg equilibrium and haplotype analysis were tested in the present study. It was observed that the presence of T allele in the two SNPs rs9939609 and rs17817449 in the FTO gene polymorphisms was associated with increased risk for the development of T2DM in Iraqi obese individuals. The minor allele (T) in rs9939609 was significantly higher (P=0.0001) in T2DM (31.25%) when compared with that of the control obese group (20%). The Homozygous genotype (TT) significantly (OR=3.25, CI 95% 1.87-5.64, P=0.000) increased the risk of T2DM by three folds with respect to those of wild type (AA) after adjustment for age, sex and BMI, furthermore, it was significantly increased the risk in the

  19. Genetic variation in the fat mass and obesity-associated gene (FTO in association with food preferences in healthy adults

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    Louise Brunkwall

    2013-04-01

    Full Text Available Background: Earlier studies have indicated that the fat mass and obesity-associated gene (FTO is not only associated with BMI and weight but also with appetite and dietary intake. Objectives: We investigated if the FTO rs9939609 associates with food preferences in healthy adults with no cancer, cardiovascular disease, or diabetes. Additionally, we challenged the question if the associations are modified by obesity status (BMI ≤25 or >25 kg/m2. Design: The analyses are made with 22,799 individuals from the Swedish population-based Malmö Diet and Cancer Cohort Study, who were born between 1923 and 1945. To investigate food preference, 27 food groups conducted from a modified diet history method including a 7-day registration of cooked meals and cold beverages were used in the analyses. Bonferroni correction was used to correct for multiple testing, resulting in a cut-off value for significance level of p<0.002. Results: We observed that the obesity susceptible A-allele carriers reported a higher consumption of biscuits and pastry but lower consumption of soft drinks (P for trend <0.0001 for both as compared to TT genotype carriers. In contrast to our hypothesis, the results did not significantly differ depending on obesity status except for consumption of juice, where only the overweight individuals with A-allele had a higher consumption as compared to TT carriers (P for interaction=0.04. Conclusion: Our results indicate that the FTO A-allele may associate with certain food preference and in particular with certain energy-dense foods.

  20. FTO Gene Associates and Interacts with Obesity Risk, Physical Activity, Energy Intake, and Time Spent Sitting: Pilot Study in a Nigerian Population

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    Bolaji Fatai Oyeyemi

    2017-01-01

    Full Text Available Fat mass and obesity-associated (FTO gene influences obesity but studies have shown that environmental/lifestyle variables like physical activity (PA, time spent sitting (TSS, and energy intake might mediate the effect. However, this is poorly understood in Nigeria due to scarce studies. We demystified association and interaction between FTO rs9939609, obesity, PA, TSS, and energy intake in Nigeria. FTO gene variant was genotyped by restriction fragment length polymorphism and gene sequencing analysis in 103 people with obesity and 98 controls. Anthropometrics and environmental variables were measured using standard procedures. Significant associations were found between FTO rs9939609 with obesity and environmental/lifestyle variables before and after adjusting for age. Carriers of allele A have significantly higher odds of being overweight/obese using BMI [0.191 (0.102–0.361, p<0.001] but this was attenuated by PA (p[interaction]=0.029; odds of being overweight reduced from 0.625 (0.181–2.159 to 0.082 (0.009–0.736 for low and high PA, respectively. Mediation analysis of total indirect effect also confirmed this by showing a simultaneous mediating role of total PA, energy intake, and TSS in the relationship between FTO and BMI (unstandardized-coefficient = 1.68; 95% CI: 1.26–2.22. This study shows a relationship between FTO and obesity phenotype and environmental/lifestyle factors might be an important modulator/mediator in the association.

  1. A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery.

    Science.gov (United States)

    Rodrigues, Gisele K; Resende, Cristina M M; Durso, Danielle F; Rodrigues, Lorena A A; Silva, José Luiz P; Reis, Rodrigo C; Pereira, Solange S; Ferreira, Daniela C; Franco, Gloria R; Alvarez-Leite, Jacqueline

    2015-01-01

    The rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is involved in obesity. Few studies have been conducted on patients who underwent bariatric surgery. The aim of this study was to evaluate the influence of FTO SNPs on body weight, body composition, and weight regain during a 60-mo follow-up period after bariatric surgery. The rs9939609 was genotyped in 146 individuals using a real-time polymerase chain reaction TaqMan assay. Data for lifestyle, comorbidities, body weight, body mass index (BMI), excess weight loss (EWL), and body composition were obtained before and 6, 12, 18, 24, 36, 48, and 60 mo after surgery. Data were analyzed by comparing two groups of patients according to rs9939609 FTO gene polymorphism. Mixed-regression models were constructed to evaluate the dynamics of body weight, BMI, and EWL over time in female patients. No differences were observed between the groups during the first 24 mo after surgery. After 36, 48, and 60 mo, body weight, fat mass, and BMI were higher, whereas fat-free mass and EWL were lower in the FTO-SNP patient group. Weight regain was more frequent and occurred sooner in the FTO-SNP group. There is a different evolution of weight loss in obese carriers of the FTO gene variant rs9939609 after bariatric surgery. However, this pattern was evident at only 2 y postbariatric surgery, inducing a lower proportion of surgery success and a greater and earlier weight regain. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.

    Science.gov (United States)

    Frayling, Timothy M; Timpson, Nicholas J; Weedon, Michael N; Zeggini, Eleftheria; Freathy, Rachel M; Lindgren, Cecilia M; Perry, John R B; Elliott, Katherine S; Lango, Hana; Rayner, Nigel W; Shields, Beverley; Harries, Lorna W; Barrett, Jeffrey C; Ellard, Sian; Groves, Christopher J; Knight, Bridget; Patch, Ann-Marie; Ness, Andrew R; Ebrahim, Shah; Lawlor, Debbie A; Ring, Susan M; Ben-Shlomo, Yoav; Jarvelin, Marjo-Riitta; Sovio, Ulla; Bennett, Amanda J; Melzer, David; Ferrucci, Luigi; Loos, Ruth J F; Barroso, Inês; Wareham, Nicholas J; Karpe, Fredrik; Owen, Katharine R; Cardon, Lon R; Walker, Mark; Hitman, Graham A; Palmer, Colin N A; Doney, Alex S F; Morris, Andrew D; Smith, George Davey; Hattersley, Andrew T; McCarthy, Mark I

    2007-05-11

    Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.

  3. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults

    NARCIS (Netherlands)

    Zimmermann, E.; Angquist, L. H.; Mirza, S. S.; Zhao, J. H.; Chasman, D. I.; Fischer, K.; Qi, Q.; Smith, A. V.; Thinggaard, M.; Jarczok, M. N.; Nalls, M. A.; Trompet, S.; Timpson, N. J.; Schmidt, B.; Jackson, A. U.; Lyytikainen, L. P.; Verweij, N.; Mueller-Nurasyid, M.; Vikstrom, M.; Marques-Vidal, P.; Wong, A.; Meidtner, K.; Middelberg, R. P.; Strawbridge, R. J.; Christiansen, L.; Kyvik, K. O.; Hamsten, A.; Jaaskelainen, T.; Tjonneland, A.; Eriksson, J. G.; Whitfield, J. B.; Boeing, H.; Hardy, R.; Vollenweider, P.; Leander, K.; Peters, A.; van der Harst, P.; Kumari, M.; Lehtimaki, T.; Meirhaeghe, A.; Tuomilehto, J.; Joeckel, K. -H.; Ben-Shlomo, Y.; Sattar, N.; Baumeister, S. E.; Smith, G. Davey; Casas, J. P.; Houston, D. K.; Maerz, W.; Christensen, K.; Gudnason, V.; Hu, F. B.; Metspalu, A.; Ridker, P. M.; Wareham, N. J.; Loos, R. J. F.; Tiemeier, H.; Sonestedt, E.; Sorensen, T. I. A.

    Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has

  4. Complete re-sequencing of a 2Mb topological domain encompassing the FTO/IRXB genes identifies a novel obesity-associated region upstream of IRX5

    DEFF Research Database (Denmark)

    Hunt, Lilian E; Noyvert, Boris; Bhaw-Rosun, Leena

    2015-01-01

    implicated in the aetiology of obesity. METHODS: Here, we sequence a 2 Mb region encompassing the FTO, RPGRIP1L and IRXB cluster genes in 284 individuals from a well-characterised study group of Danish men containing extremely overweight young adults and controls. We further replicate our findings both...

  5. [Regional features of obesity-associated gene polymorphism (rs9939609 FTO gene and gene Trp64Arg ADRB3) in Russian population].

    Science.gov (United States)

    Baturin, A K; Sorokina, E Iu; Pogozheva, A V; Peskova, E V; Makurina, O N; Tutel'ian, V A

    2014-01-01

    Recent studies have shown a significant association with obesity polymorphisms: rs9939609 gene due to fat mass and obesity FTO in European and some Asian and African American populations Trp64Arg ADRB3 gene in several European populations. Association of variants rs9939609 and Trp64Arg obesity was studied in 1244 the inhabitants of Moscow and Sverdlovsk regions. Genotyping was performed using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphic sites. The frequency of the mutant allele of the FTO gene in the population of Moscow and Sverdlovsk region was 45.1%, with the TT genotype was detected in 30.2% of cases, AT--49.5%, AA--20.3%. Women had the presence of the mutant allele more likely than men (48.4 vs. 42.5%). People with obesity were more genotypes AA (26.3%) and AT (52.8%) compared to the surveyed with a BMI of less than 30 kg/m2 (respectively 18.1 and 50.7%). A significantly higher incidence of risk allele A was found in individuals with obesity (52.6 and 43.4%). The presence of the mutant allele of the gene ADRB3 among the population of Moscow and Sverdlovsk regions was noted in 7.4% of cases. While 15.5% of patients had a heterozygous genotype Trp64Arg ADRB3, that is consistent with international research. The frequency of the risk allele and genotype Arg64 Trp64Arg in women (9.3 and 18.5%) was significantly higher than men (6.2 and 12.2%). The presence of the mutant allele and genotype Trp64Arg ADRB3 (respectively, 9.1 and 18.1%) were significantly more marked in the examined obese compared with those with a body mass index less than 30 kg/m2 (7.4 and 14.9%), but these differences were not statistically significant. The results of these studies suggest that genetic variants of the FTO gene rs9939609 genotype and Trp64Arg ADRB3 contribute to the development of obesity among residents of Moscow and Sverdlovsk Region of Russia. The risk of obesity increases in the case of combined polymorphisms in

  6. The study of the rs9939609 FTO gene polymorphism in association with obesity and the management of obesity in a Romanian cohort.

    Science.gov (United States)

    Ursu, R I; Badiu, C; Cucu, N; Ursu, G F; Craciunescu, I; Severin, E

    2015-01-01

    The incidence of obesity especially in Romanian population is presently escalating as a major nutrition and health problem. Clinicians aided by scientists are engaged in research approaches that include heredity aspects linked with behavior, education, applied nutrition studies and clinical therapies in order to prevent, control and reverse obesity. The common goal is to identify areas of basic and clinical research to understand aspects of human biology that may be considered as obesogenic. Regarding these approaches, recent discoveries in genetics, epigenetics and functional genomics, based on advancing technologies, are tools employed to prevent and treat obesity. The purpose of this article is to present the current knowledge of key components of the FTO gene role in the obesogenic system that links genetic, epigenetic and environmental, lifestyle/ diet nutritional and behavioral components and to describe the results obtained by genotyping and interviewing relevant selected groups of Romanian population. FTO rs9939609 genotyping was performed on a Romanian study group of 53 subjects (30 obese, 23 normal). Results have been analyzed in association with obesity parameters and comorbidities in order to identify this polymorphism's effect on body mass in our Caucasian cohort. At the same time, personal history of the subjects in correlation with the FTO genotypes provided important information on the FTO gene's influence on the feeding behavior and food selection of these individuals. In conclusion, the FTO rs9939609 polymorphism has been identified as a common gene variant in our Romanian Caucasian cohort, proving a high association with all the parameters of obesity and obesity comorbidities. The adherence to a Mediterranean diet is benefic for subjects with genetic predisposition for this disorder as long as it is kept for a long period of time along with sustained physical exercise. Association studies are an extremely important tool in understanding the

  7. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO variants in patients with polycystic ovary syndrome (PCOS

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    Kimmig Rainer

    2010-01-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS, a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM on metabolic and PCOS-specific traits in patients with PCOS. Methods We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria using single nucleotide polymorphisms (SNPs in or in proximity to the fat mass and obesity associated gene (FTO, insulin-induced gene-2 (INSIG2, transcription factor 7-like 2 gene (TCF7L2 and melanocortin 4 receptor gene (MC4R. To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4. Results The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously. Conclusion The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.

  8. The rs9939609 gene variant in FTO modified the metabolic response of weight loss after a 3-month intervention with a hypocaloric diet.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Conde, Rosa; Izaola, Olatz; Gonzalez Sagrado, Manuel; Castrodeza Sanz, Javier

    2013-01-01

    Common polymorphisms in the fat mass and obesity associated gene (FTO) have been linked to obesity in some populations. Nevertheless, the role of FTO variants on body weight response after dietary intervention remains equivocal. We decided to analyze the effects of the rs9939609 FTO gene polymorphism on body weight changes and metabolic parameters after 3 months of a hypocaloric diet. Before and after 3 months on a low-fat hypocaloric diet, a white population of 106 subjects with obesity was analyzed. Of the study subjects, 35 (33%) had the genotype TT and 71 (67%) had the next genotypes; TA (46 study subjects, 43.4%) or AA (25 study subjects, 23.6%). After dietary treatment and in TT group, weight, waist circumference, total cholesterol, LDL-cholesterol, insulin, and homeostasis model assessment decreases were less than subjects carrying the A allele [-3.1 (3.6) vs -2.4 (4.1) kg: P weight loss in A carriers of FTO rs9939609 polymorphism than in TT genotype study subjects.

  9. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

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    Struan F A Grant

    Full Text Available Recently an association was demonstrated between the single nucleotide polymorphism (SNP, rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA. Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile, 2,270 Caucasian controls (BMI<95th percentile, 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2 = 1 in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR of 1.27 (95% CI 1.08-1.47; P = 0.0022. Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49 and of 1.31 (95% CI 1.050-1.643; P = 0.017 respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.

  10. Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness - in Cohorts of Danish Men

    DEFF Research Database (Denmark)

    Zimmermann, E; Kring, SI; Berentzen, TL;

    2009-01-01

    prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system. CONCLUSION: Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar...... to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system....... men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height...

  11. Fatness-associated FTO gene variant increases mortality independent of fatness--in cohorts of Danish men.

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    Esther Zimmermann

    Full Text Available BACKGROUND: The A-allele of the single nucleotide polymorphism (SNP, rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2 and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA. In total 205 men died. Mortality was 42% lower (p = 0.001 with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system. CONCLUSION: Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system.

  12. Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption.

    Science.gov (United States)

    Corella, Dolores; Ortega-Azorín, Carolina; Sorlí, Jose V; Covas, M Isabel; Carrasco, Paula; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Lamuela-Raventos, Rosa; Gómez-Gracia, Enrique; Fiol, Miquel; Pintó, Xavier; Ros, Emilio; Martí, Amelia; Coltell, Oscar; Ordovás, Jose M; Estruch, Ramon

    2012-01-01

    Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (Pobese (OR=1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (Pobesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P=0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P=0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P=0.001). Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.

  13. Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population

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    Zhi Song

    2016-10-01

    Full Text Available Background: Obesity is a well-established risk factor for large artery atherosclerotic (LAA stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. Methods: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313 and FTO (rs8050136 and rs9939609 were genotyped. Results: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609 or MC4R (rs17782313 between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI = 1.55 (1.07-2.23 in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313, hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p Conclusion: Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke.

  14. Genome wide association (GWA study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO variants.

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    Anke Hinney

    Full Text Available BACKGROUND: Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA for early onset (extreme obesity. METHODOLOGY/PRINCIPAL FINDINGS: a GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency > or =10% with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene within one linkage disequilibrium (LD block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13 x 10(-7, corrected p = 0.0494; odds ratio (OR(CT 1.67, 95% confidence interval (CI 1.22-2.27; OR(TT 2.76, 95% CI 1.88-4.03 belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock. For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01. However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. CONCLUSIONS/SIGNIFICANCE: Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only

  15. The FTO gene is associated with an atherogenic lipid profile and myocardial infarction in patients with type 2 diabetes:A Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) Study

    OpenAIRE

    2009-01-01

    Background-Common variation in the fat mass and obesity (FTO)-related gene is associated with increased body fat and susceptibility to type 2 diabetes. We hypothesized that this would also associate with metabolic phenotypes of insulin resistance and increased risk of cardiovascular morbidity and mortality. Methods and Results-FTO rs9939609 genotype was determined in 4897 patients with type 2 diabetes in the prospective Genetics of Diabetes Audit and Research Study in Tayside Scotland study. ...

  16. Milk: an epigenetic amplifier of FTO-mediated transcription? Implications for Western diseases

    OpenAIRE

    Melnik, Bodo C.

    2015-01-01

    Single-nucleotide polymorphisms within intron 1 of the FTO (fat mass and obesity-associated) gene are associated with enhanced FTO expression, increased body weight, obesity and type 2 diabetes mellitus (T2DM). The N 6 -methyladenosine (m6A) demethylase FTO plays a pivotal regulatory role for postnatal growth and energy expenditure. The purpose of this review is to provide translational evidence that links milk signaling with FTO-activated transcription of the milk recipient. FTO-dependent de...

  17. Common SNPs in FTO gene are associated with obesity related anthropometric traits in an island population from the eastern Adriatic coast of Croatia.

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    Ge Zhang

    Full Text Available BACKGROUND: Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population. METHODOLOGY/PRINCIPAL FINDINGS: We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses and two derived measures (BMI and WHR. Using single locus score tests, 15 common SNPs were found to be significantly associated with "body fatness" measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of "body fatness". However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156 could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for "body fatness", two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211 and rs16945088 (P-value = 0.00203. CONCLUSIONS/SIGNIFICANCE: The current study confirmed the association of common variants of FTO gene with "body fatness" measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm

  18. Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study.

    Science.gov (United States)

    Bjørnland, Thea; Langaas, Mette; Grill, Valdemar; Mostad, Ingrid Løvold

    2017-01-01

    Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.

  19. Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Dolores Corella

    Full Text Available BACKGROUND: Fat mass and obesity (FTO and melanocortin-4 receptor (MC4R and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. OBJECTIVE: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA, and to study their association with alcohol and food intake. METHODS: Adherence to Mediterranean diet (AdMedDiet and physical activity (PA were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score as well as statistical and biological gene-lifestyle interactions were analyzed. RESULTS: FTO rs9939609 was associated with higher body mass index (BMI, waist circumference (WC and obesity (P<0.05 for all. A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score were significant and we observed a 7% per-allele increase of being obese (OR=1.07; 95%CI 1.01-1.13. We found relevant statistical interactions (P<0.05 with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P=0.502 than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P=0.021 than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P=0.001. CONCLUSION: Statistical and biological interactions with PA

  20. Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

    Science.gov (United States)

    Covas, M. Isabel; Carrasco, Paula; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Lamuela-Raventos, Rosa; Gómez-Gracia, Enrique; Fiol, Miquel; Pintó, Xavier; Ros, Emilio; Martí, Amelia; Coltell, Oscar; Ordovás, Jose M.; Estruch, Ramon

    2012-01-01

    Background Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. Results FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (Pobese (OR = 1.07; 95%CI 1.01–1.13). We found relevant statistical interactions (Pobesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001). Conclusion Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI. PMID:23284998

  1. Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study

    Indian Academy of Sciences (India)

    TUN-JEN HSIAO; LIN EUGENE

    2016-09-01

    It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether theFTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by theTaqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTO rs9939609 SNP exhibited a significant association with obesity (BMI >=30 kg/m ²) among the subjects ( P=0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subject

  2. Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study.

    Science.gov (United States)

    Hsiao, Tun-Jen; Lin, Eugene

    2016-09-01

    It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether the FTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by the Taqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTO rs9939609 SNP exhibited a significant association with obesity (BMI ≥ 30 kg/m²) among the subjects (P = 0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subjects.

  3. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Holst, Claus; Zimmermann, Esther

    2008-01-01

    A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already i...

  4. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Holst, Claus; Zimmermann, Esther;

    2008-01-01

    A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already...

  5. Estudo de associação entre polimorfismos no gene FTO e composição corporal em idosas brasileiras

    Directory of Open Access Journals (Sweden)

    Cláudia Cruz Lunardi

    2016-03-01

    Full Text Available Estudos de associação genética (GWAS sugerem uma importante contribuição do gene candidato FTO na composição corporal em diferentes populações e variada faixa etária. Este estudo teve como objetivo examinar a associação entre os polimorfismos no gene FTO (rs9939609 e rs1861868 e fenótipos de adiposidade em uma amostra de idosas brasileiras não caucasianas. A amostra foi composta por 241 mulheres (66.65± 5.5 anos. Os dados referentes à composição corporal foram mensurados através da absorciometria por raios-x de dupla energia (DXA e a genotipagem dos SNPs foi realizada utilizando o sistema SnaPShot Multiplex System (Applied Biosystems. Não foram encontradas diferenças estatisticamente significativas para as variáveis de composição corporal entre os polimorfismos estudados, mesmo após o ajuste para ancestralidade Africana. Especificamente, índice de massa corporal (p= 0.94 e p= 0.66, percentual de gordura (p= 0.42 e p= 0.93 e massa livre de gordura total (p= 0.75 e p= 0.30, sendo os valores de p referentes aos rs9939609 e rs1861868, respectivamente. Nesta amostra de idosas brasileiras os polimorfismos do gene FTO (rs9939609 e rs1861868 não apresentaram associação com fenótipos de obesidade.

  6. Efeitos de um programa interdisciplinar sobre a circunferência da cintura em escolares com alelo de risco para o polimorfismo rs9939609 no gene (FTO

    Directory of Open Access Journals (Sweden)

    Felipe Ziemann

    2016-10-01

    Full Text Available Objetivo: verificar se escolares portadores e não portadores do alelo de risco para obesidade (A, do polimorfismo rs9939609, no gene FTO (fat mass and obesity associated, apresentam resposta diferente a um programa interdisciplinar com exercício físico, com relação à circunferência da cintura. Método: o polimorfismo no gene FTO rs9939609 foi identificado em 46 escolares, com idades entre 6 e 16 anos, de escolas rurais de Santa Cruz do Sul, RS. Avaliou-se a circunferência da cintura (CC e demais características antropométricas. A intervenção teve como base estratégias de exercícios da Educação Física e alimentação saudável, além de cuidados posturais. Resultados: após o programa de intervenção, observou-se redução significativa da CC, no grupo experimental, somente para os escolares com a presença do alelo A (genótipos AT + AA: p=0,023. Considerações finais: o programa interdisciplinar com exercícios físicos foi efetivo para redução da circunferência da cintura apenas nos escolares com a presença do alelo de risco para a obesidade, do polimorfismo rs9939609, no gene FTO. Sugere-se a realização de estudos experimentais que avaliem também outros polimorfismos, com uma amostra maior de sujeitos.

  7. The correlation of the expression levels of obesity-associated gene FTO and type 2 diabetes%肥胖相关基因FTO表达水平与2型糖尿病的相关性

    Institute of Scientific and Technical Information of China (English)

    王小红; 杨威; 李珊; 郑丽丽

    2014-01-01

    目的:探讨肥胖相关基因FTO表达水平与2型糖尿病的相关性。方法选取河南地区135例2型糖尿病患者,分为肥胖组(60例)与非肥胖组(75例),郑州大学第一附属医院体检科体检的正常人(51例)作为正常对照组,以RT-PCR法测定FTO mRNA表达水平,ELISA法测定FTO蛋白表达水平,分析FTO表达水平与2型糖尿病患者的相关性。结果2型糖尿病两组的FTO mRNA 及蛋白表达水平高于正常组(P<0.05);FTO 表达水平与收缩压、舒张压、FINS、HOMA-IR、FBG、2 h BG、HbA1c、24 h Alb、TC呈正相关(P<0.05),与HDL-C呈负相关(P<0.05),而与BMI无关(P>0.05);Logistic回归分析显示:BMI、TG、HOMA-IR、FTO 基因及蛋白表达水平是患2型糖尿病的主要危险因素。结论新诊断2型糖尿病患者外周血淋巴细胞FTO基因和血清FTO蛋白高表达,可能是2型糖尿病的早期预测因子之一。%Objective To explore the correlation of the expression levels of the fat mass and obesity-associated gene(FTO) and type 2 diabetes. Methods 135 cases with type 2 diabetes mellitus in Henan province were selected as experimental subjects, divided into obese group(n=60 cases) and non-obese group (n=75 cases), and selected people who were diagnosed as normal person in the department of physical examination as control group (51 cases). Meanwhile the expression level of FTO mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression level of FTO protein was measured by enzyme-linked immunosorbent assay (ELISA), and then, analysing the correlation between the expression level of FTO gene and clinical parameters of type 2 diabetes. Results The expression level of FTO gene in obese and non-obese group of type 2 diabetic patients were higher than normal group (P<0.05); and FTO mRNA and protein expression level were positively correlated with systolic blood pressure, diastolic blood

  8. FTO Obesity Risk Variants Are Linked to Adipocyte IRX3 Expression and BMI of Children - Relevance of FTO Variants to Defend Body Weight in Lean Children?

    Science.gov (United States)

    Landgraf, Kathrin; Scholz, Markus; Kovacs, Peter; Kiess, Wieland; Körner, Antje

    2016-01-01

    Background Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. Conclusion One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children. PMID:27560134

  9. Fat mass and obesity-associated gene (FTO) is linked to higher plasma levels of the hunger hormone ghrelin and lower serum levels of the satiety hormone leptin in older adults.

    Science.gov (United States)

    Benedict, Christian; Axelsson, Tomas; Söderberg, Stefan; Larsson, Anders; Ingelsson, Erik; Lind, Lars; Schiöth, Helgi B

    2014-11-01

    The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. Using cross-sectional data from 985 older people (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]). Linear regression analyses controlling for sex, self-reported physical activity level, fasting plasma glucose, and BMI were used. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005; relative plasma ghrelin difference between CC and AA carriers = ∼ 9%). In contrast, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin difference between CC and AA carriers = ∼ 11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin.

  10. Fat mass and obesity-associated (FTO) gene polymorphisms are associated with physical activity, food intake, eating behaviors, psychological health, and modeled change in body mass index in overweight/obese Caucasian adults.

    Science.gov (United States)

    Harbron, Janetta; van der Merwe, Lize; Zaahl, Monique G; Kotze, Maritha J; Senekal, Marjanne

    2014-08-06

    The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085-rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire), psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory), and eating behavior (Three Factor Eating questionnaire). The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores), a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

  11. Fat Mass and Obesity-Associated (FTO Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

    Directory of Open Access Journals (Sweden)

    Janetta Harbron

    2014-08-01

    Full Text Available The fat mass and obesity-associated (FTO gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire, psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory, and eating behavior (Three Factor Eating questionnaire. The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores, a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

  12. FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.

    Directory of Open Access Journals (Sweden)

    James S McTaggart

    Full Text Available Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16-48 hour fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.

  13. Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Ai Ling; Xie, Hui Jun; Xie, Hong Yan; Liu, Jun; Yin, Jie; Hu, Jin Song; Peng, Cui Ying

    2017-08-21

    Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results. Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2. A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28-1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25-1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38-2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25-1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29-1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08-1.64, P = 0.008) CONCLUSION: This meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.

  14. Dietary intake, FTO genetic variants and adiposity

    DEFF Research Database (Denmark)

    Qi, Qibin; Downer, Mary K; Oskari Kilpeläinen, Tuomas

    2015-01-01

    The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association...

  15. Dietary intake, FTO genetic variants and adiposity

    DEFF Research Database (Denmark)

    Qi, Qibin; Downer, Mary K; Oskari Kilpeläinen, Tuomas;

    2015-01-01

    The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association...

  16. Rs7206790 and rs11644943 in FTO gene are associated with risk of obesity in Chinese school-age population.

    Directory of Open Access Journals (Sweden)

    Yuyang Xu

    Full Text Available To evaluate the associations between candidate FTO single nucleotide polymorphisms (SNPs and obesity, a case-control study was conducted among Chinese school-age children, which included 500 obese cases and 500 matched controls (age, gender and location. We selected 24 candidate FTO tag-SNPs via bio-informatics analysis and performed genotyping using SNPScan technology. Results indicated that rs7206790 and rs11644943 were significantly associated with obesity among school-age children in both additive and recessive models (P<0.05 after adjusting confounders. Comparing rs7206790 CC and CG genotype of carriers, those carrying the GG genotype had an increased risk of obesity (adjusted odds ratio [OR], 3.76; 95% Confidence interval [CI], 1.24-11.43. Carriers of the AA allele of rs11644943 had a lower risk of obesity (adjusted OR, 0.16; 95% CI, 0.04-0.72 compared with those of the T allele (TT and TA. These two SNPs (rs7206790 and rs11644943 were not Linkage Disequilibrium (LD with previous reported obesity-associated SNPs. Under the recessive model adjusted for age and gender and location, rs7206790 GG allele carriers had significantly increased BMIs (P = 0.012, weight (P = 0.012, waist circumferences (WC (P = 0.045 and hip circumferences (HC (P = 0.033. Conversely, rs11644943 AA allele carriers had significantly decreased BMIs (P = 0.006, WC (P = 0.037 and Waist-to-height ratios (WHtR (P = 0.012. A dose-response relationship was found between the number of risk alleles in rs7206790, rs11644943 and rs9939609 and the risk of obesity. The Genetic Risk Score (GRS of the reference group was 3; in comparison, those of 2, 4, and ≥5 had ORs for obesity of 0.24 (95%CI, 0.05-1.13, 1.49 (95%CI, 1.10-2.01, and 5.20 (95%CI, 1.75-15.44, respectively. This study confirmed the role of FTO variation on genetic susceptibility to obesity. We reported two new obesity-related FTO SNPs (rs7206790 and rs11644943 among Chinese school

  17. Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types

    Directory of Open Access Journals (Sweden)

    Seongwon Cha

    2011-01-01

    Full Text Available Sasang constitutional medicine (SCM, a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO and melanocortin 4 receptor (MC4R genes have been associated with increased body mass index (BMI by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m2 and MC4R variants (effect size ≃ 0.64 kg/m2. After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76% than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.

  18. Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types.

    Science.gov (United States)

    Cha, Seongwon; Koo, Imhoi; Park, Byung L; Jeong, Sangkyun; Choi, Sun M; Kim, Kil S; Shin, Hyoung D; Kim, Jong Y

    2011-01-01

    Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m(2)) and MC4R variants (effect size ≃ 0.64 kg/m(2)). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.

  19. A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes.

    Science.gov (United States)

    Razquin, C; Martinez, J A; Martinez-Gonzalez, M A; Bes-Rastrollo, M; Fernández-Crehuet, J; Marti, A

    2010-02-01

    The aim of this study was to analyze the effects of the rs9939609 (T/A) gene variant in fat mass and obesity-associated gene (FTO) on body weight changes after 3 years and its modification by a randomized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk. A substudy of PREDIMED, which is a randomized trial aimed at assessing the effect of the Mediterranean diet (MD) for primary cardiovascular disease prevention. There were three nutritional intervention groups: two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. A total of 776 high cardiovascular risk subjects aged 55-80 years. Anthropometric measurements were recorded at baseline and at 3 years. The participants were genotyped by RT-PCR, followed by allelic discrimination. Homozygous subjects had the highest baseline body weight. The dominant model showed that subjects carrying the A allele had the lowest body weight gain (B=-0.685; P=0.022) after 3 years of nutritional intervention compared with nonmutated subjects (TT genotype) regardless of the nutritional intervention. Moreover, this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups (B=-0.830; P=0.018), but it was not significant among those allocated to the control group (P for interaction=0.649). This study confirmed the association between body weight and the FTO rs9939609 polymorphism. Interestingly, our results showed that, although at baseline the A allele was associated with higher body weight, after 3 years of nutritional intervention with a Mediterranean-style-diet, A-allele carriers had lower body weight gain than wild type subjects. No interaction between nutritional intervention and the polymorphism was found.

  20. A variant in the fat mass and obesity-associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) do not influence dietary intake

    DEFF Research Database (Denmark)

    Hasselbalch, Ann L; Angquist, Lars; Christiansen, Lene

    2010-01-01

    . In a population-based sample of 756 healthy adult twin pairs, we studied associations between FTO rs9939609, near-MC4R rs12970134, rs17700633, and rs17782313 single nucleotide polymorphisms (SNP) and habitual dietary intake. Habitual dietary intake was assessed by a 247-question FFQ. Nontransformed variables...... and variables transformed by natural logarithm were analyzed by linear regression and dichotomized variables were analyzed by logistic regression. FTO SNP rs9939609 was not associated with habitual dietary intake. For the near-MC4R SNP rs12970134 and rs17700633, we found significant positive associations...

  1. Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case–control study in Japan

    OpenAIRE

    Lin, Yingsong; Ueda, Junko; Yagyu, Kiyoko; Ishii, Hiroshi; Ueno, Makoto; Egawa, Naoto; Nakao, Haruhisa; MORI, MITSURU; Matsuo, Keitaro; Kikuchi, Shogo

    2013-01-01

    Background It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. Methods We conducted a hospital-based case–control study in Japan to investigate whether genetic variations in the FTO gene were associated...

  2. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness.

    Directory of Open Access Journals (Sweden)

    Sofia I I Kring

    Full Text Available BACKGROUND: A common single nucleotide polymorphism (SNP of FTO (rs9939609, T/A is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence. METHODOLOGY/PRINCIPAL FINDINGS: Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2 and a randomly selected group (n = 879 from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively. The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype, for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6, OR = 1.20, p = 1.7*10(-7, OR = 1.17, p = 3.4*10(-3, respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7 and OR = 1.21, p = 1.0*10(-3. Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6 and OR = 1.19, p = 5.9*10(-3, sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4 and OR = 1.18, p = 0.011 and intra-abdominal adipose tissue (OR = 1.21, p = 0.005. Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5 and OR = 1.18, p = 0.004 and lower body fat mass (OR = 1.26, p = 0.002 was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02 and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037, but not with any other of the metabolic traits. However

  3. Relación del polimorfismo rs9939609 del gen FTO con factores de riesgo cardiovascular y niveles de adipocitoquinas en pacientes con obesidad mórbida Relation of the rs9939609 gene variant in FTO with cardiovascular risk factor and serum adipokine levels in morbid obese patients

    Directory of Open Access Journals (Sweden)

    D. A. de Luis

    2012-08-01

    Full Text Available Introducción: Algunos polimorfismos del gen asociado con la masa grasa y la obesidad (FTO se han relacionado con la obesidad y parámetros bioquímicos. Nuestro objetivo fue analizar la relación del polimorfismo rs9939609 del gen FTO con el peso corporal, factores de riesgo cardiovascular y los niveles séricos de adipocitoquinas en una muestra de pacientes con obesidad mórbida. Material y métodos: Una muestra de 129 pacientes con obesidad mórbida (IMC > 40 se analizó en un diseño de corte transversal. A todos los pacientes se les determinó el peso, presión arterial, glucemia basal, proteína C reactiva (PCR, insulina, resistencia a la insulina (HOMA-R, colesterol total, LDL-colesterol, HDL-colesterol, triglicéridos y adipocitoquinas (adiponectina leptina, resistina, TNF-alfa, y los niveles de interleucina-6. Se evaluó la masa grasa mediante bioimpedancia tetrapolar y registró prospectivamente la ingesta de nutrientes durante tres días. En todos ellos se genotipo el polimorfismo del gen FTO (rs9939609. Resultados: Cuarenta y un pacientes (31,8% tenían el genotipo TT (grupo genotipo salvaje, 55 pacientes (42,6% el genotipo TA y 33 pacientes (25,6% el genotipo AA. El índice de masa corporal (43,6 (2,6 kg/m² vs. 44,1 (2,9 kg/m²; p Background: Common polymorphisms of the fat mass and obesity associated gene (FTO have been linked to obesity in some populations. The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels in morbid obese patients. Material and methods: A sample of 129 patients with obesity was analyzed in a cross sectional design. Weight, blood pressure, basal glucose, creactive protein (CRP, insulin, insulin resistance (HOMA, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adipocytokines (leptin, adiponectin, resistin, TNF alpha, and interleukin 6 levels were measured. A tetrapolar

  4. Use of SNP Markers Within the Fat Mass and Obesity-associated (FTO Gene to Verify Pedigrees and Determine Haplotypes in Paternal Half-sib Families of Slovenian Simmental Cattle

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    Daša Jevšinek Skok

    2011-10-01

    Full Text Available The objective of this preliminary study was to identify SNP markers within the FTO gene for evaluation of pedigree data accuracy and determination of haplotypes in paternal half-sib families of Slovenian Simmental cattle. Out of 23 polymorphic SNPs identified ten most informative SNPs for genotyping 31 sires and 56 half-sib progeny were used. The ATLAS program was used for paternity testing. Haplotype analysis revealed three haplotype blocks. The effect of SNPs “ex2 T>C” and “int2 indel*>T” was significant on three correlated carcass traits: live weight at slaughter (P= 0.03, carcass weight (P= 0.038, and lean weight (P= 0.048. The FTO gene can thus be regarded as a candidate for the marker assisted selection programs in our and possibly other populations of cattle. Future studies in cattle might also reveal novel roles of the FTO gene in carcass traits on livestock species as well as fatness control in other mammals.

  5. Use of SNP Markers Within the Fat Mass and Obesity-associated (FTO Gene to Verify Pedigrees and Determine Haplotypes in Paternal Half-sib Families of Slovenian Simmental Cattle

    Directory of Open Access Journals (Sweden)

    Daša Jevšinek Skok

    2011-12-01

    Full Text Available The objective of this preliminary study was to identify SNP markers within the FTO gene for evaluation of pedigree data accuracy and determination of haplotypes in paternal half-sib families of Slovenian Simmental cattle. Out of 23 polymorphic SNPs identified ten most informative SNPs for genotyping 31 sires and 56 half-sib progeny were used. The ATLAS program was used for paternity testing. Haplotype analysis revealed three haplotype blocks. The effect of SNPs “ex2 T>C” and “int2 indel*>T” was significant on three correlated carcass traits: live weight at slaughter (P= 0.03, carcass weight (P= 0.038, and lean weight (P= 0.048. The FTO gene can thus be regarded as a candidate for the marker assisted selection programs in our and possibly other populations of cattle. Future studies in cattle might also reveal novel roles of the FTO gene in carcass traits on livestock species as well as fatness control in other mammals.

  6. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    Directory of Open Access Journals (Sweden)

    Daniel P S Osborn

    Full Text Available Common intronic variants in the Human fat mass and obesity-associated gene (FTO are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish and in vitro (Fto(-/- MEFs and HEK293T. Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  7. FTO is a relevant factor for the development of the metabolic syndrome in mice.

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    Kathrin Ikels

    Full Text Available The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob;Fto(-/-. Lep(ob/ob;Fto(-/- mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob;Fto(-/- mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob;Fto(-/-mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

  8. Programming effects of FTO in the development of obesity.

    Science.gov (United States)

    Sebert, S; Salonurmi, T; Keinänen-Kiukaanniemi, S; Savolainen, M; Herzig, K-H; Symonds, M E; Järvelin, M-R

    2014-01-01

    It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to 'non- or epi-genetic' causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

  9. Interaction between FTO gene polymorphism and 1ife style may contribute to obesity in Kazakh schoolchildren%FTO 基因与环境因素交互作用对哈萨克族学龄儿童肥胖的影响

    Institute of Scientific and Technical Information of China (English)

    李敏; 张涛; 沙坎·阿克纳依; 徐佩茹

    2014-01-01

    目的:体脂量和肥胖相关( fat mass and obesity associated , FTO)基因与体质指数增加以及过多能量摄入相关。文中探讨FTO基因多态性与环境因素的交互作用对哈萨克族学龄儿童肥胖的影响。方法从“伊犁哈萨克自治州哈萨克族学龄儿童超重肥胖调查”中选择279名6~13岁小学生,根据中国肥胖问题工作组提出的《中国学龄儿童青少年超重、肥胖筛查体质指数值分类标准》中不同年龄、性别的BMI判定,分为肥胖组(141名)和正常组(138名),进行体格检查、问卷调查以及FTO基因rs9939609多态性检测。结果采用主成分方法进行探索性因子分析,共提取不良饮食习惯、食欲状况、户外活动、挑食情况、活动方式和睡眠时间6个因子。 Logistic回归分析显示,FTO基因rs9939609与食欲状况、户外活动的交互作用归因百分依次为76.49%、79.95%。结论在哈萨克族学龄儿童中,食欲状况、户外活动可能修饰FTO基因与肥胖的关系,但需要进一步前瞻性的干预性研究证实该种影响作用。%Objective The fat mass-and obesity-associated (FTO) gene is related to increased body mass index (BMI) and elevated energy intake .This study explored the contribution of the interaction between FTO gene polymorphism and 1ife style to the risk of obesity in the Kazakh schoolchildren . Methods A total of 279 Kazakh schoolchildren aged 6-13 years were selected from Yili Ka-zakh Child Obesity Study and divided into an obesity group (n=141) and a normal weight group (n=138) based on the BMI cutoffs rec-ommended by the Chinese Working Group on Obesity for Children .The children were subjected to anthropometric measurement , question-naire investigation , and determination of the rs9939609 polymorphism of the FTO gene. Results Six risk factors of obesity were extrac-ted by factor analysis, including harmful eating habits, appetite status, outdoor

  10. The Demethylase Activity of FTO (Fat Mass and Obesity Associated Protein Is Required for Preadipocyte Differentiation.

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    Meizi Zhang

    Full Text Available FTO (fat mass and obesity associated gene was genetically identified to be associated with body mass index (BMI, presumably through functional regulation of energy homeostasis. However, the cellular and molecular mechanisms by which FTO functions remain largely unknown. Using 3T3-L1 preadipocyte as a model to study the role of FTO in adipogenesis, we demonstrated that FTO is functionally required for 3T3-L1 differentiation. FTO knock-down with siRNA inhibited preadipocyte differentiation, whereas ectopic over-expression of FTO enhanced the process. The demethylase activity of FTO is required for differentiation. Level of N6-methyladenosine (m6A is decreased in cells over-expressing FTO. In contrast, overexpression of R96Q, a FTO missense mutant lack of demethylase activity, had no effect on cellular m6A level and impeded differentiation. Treatment with Rosiglitazone, a PPARγ agonist, could overcome the differentiation inhibition imposed by R96Q mutant, suggesting the effect of FTO is mediated through PPARγ.

  11. Association of FTO Polymorphisms with Early Age of Obesity in Obese Italian Subjects

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    Federica Sentinelli

    2012-01-01

    Aims of our study are to investigate: (1 the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI and obesity-related parameters in a large cohort (n=752 of Italian obese subjects; (2 the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P<0.043 and rs9930506 (P<0.029 with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2 per G allele. We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population.

  12. No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles

    DEFF Research Database (Denmark)

    Kjeldahl, Karin; Rasmussen, Morten Arendt; Hasselbalch, Ann Louise

    2014-01-01

    In this paper it was investigated if any genotypic footprints from the fat mass and obesity associated (FTO) SNP could be found in 600 MHz 1H CPMG NMR profiles of around 1,000 human plasma samples from healthy Danish twins. The problem was addressed with a combination of univariate and multivariate...

  13. Effects of MC4R, FTO, and NMB gene variants to obesity, physical activity, and eating behavior phenotypes.

    Science.gov (United States)

    Kirac, Deniz; Kasimay Cakir, Ozgur; Avcilar, Tuba; Deyneli, Oguzhan; Kurtel, Hizir; Yazici, Dilek; Kaspar, Elif Cigdem; Celik, Nurgul; Guney, Ahmet Ilter

    2016-10-01

    Obesity is a major contributory factor of morbidity and mortality. It has been suggested that biological systems may be involved in the tendency to be and to remain physically inactive also behaviors such as food and beverage preferences and nutrient intake may at least partially genetically determined. Consequently, besides environment, genetic factors may also contribute to the level of physical activity and eating behaviors thus effect obesity. Therefore the aim of this study is to investigate the effect of various gene mutations on obesity, physical activity levels and eating behavior phenotypes. One hundred patients and 100 controls were enrolled to the study. Physical activity levels were measured with an actical acceloremeter device. Eating behaviors were evaluated using Three-Factor Eating questionnaire (TFEQ). Associations between eating behavior scores and physical characteristics were also evaluated. The information about other obesity risk factors were also collected. Mutations were investigated with PCR, direct sequencing and Real-Time PCR. rs1051168, rs8050146 -2778C > T mutations were found statistically significant in patients, rs1121980 was found statistically significant in controls. 21 mutations were found in MC4R and near MC4R of which 18 of them are novel and 8 of them cause amino acid change. In addition, it was found that, some obesity related factors and questions of TFEQ are associated with various investigated gene mutations. Any relation between gene mutations and physical activity levels were not detected. It is thought that, due to the genotype data and eating behaviors, it may be possible to recommend patients for proper eating patterns to prevent obesity. © 2016 IUBMB Life, 68(10):806-816, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  14. FTO at rs9939609, Food Responsiveness, Emotional Control and Symptoms of ADHD in Preschool Children

    NARCIS (Netherlands)

    F.P. Velders (Fleur); F.R.C. de Wit (Frank); P.W. Jansen (Pauline); V.W.V. Jaddoe (Vincent); A. Hofman (Albert); F.C. Verhulst (Frank); H.W. Tiemeier (Henning)

    2012-01-01

    textabstractThe FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)2) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural

  15. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Qi, Lu; Brage, Soren

    2011-01-01

    Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambi...

  16. A link between FTO, ghrelin, and impaired brain food-cue responsivity.

    Science.gov (United States)

    Karra, Efthimia; O'Daly, Owen G; Choudhury, Agharul I; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T; Scott, William R; Chandarana, Keval; Manning, Sean; Hess, Martin E; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E; Rahman, Sofia; Emmanuel, Julian J; Williams, Steven C R; Rüther, Ulrich U; Brüning, Jens C; Withers, Dominic J; Zelaya, Fernando O; Batterham, Rachel L

    2013-08-01

    Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

  17. Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children

    Science.gov (United States)

    2013-01-01

    Background Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children. Methods The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (Ncases = 514; Ncontrols = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children. Results We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10-3) and decreased fasting serum insulin levels (β = −0.10 μU/mL; P = 1.21 × 10-3), respectively. Conclusion Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels. PMID:23375129

  18. Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children

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    Mejía-Benítez Aurora

    2013-02-01

    Full Text Available Abstract Background Recent genome wide association studies (GWAS and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children. Methods The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (Ncases = 514; Ncontrols = 949. We also assessed effects of these SNPs on the variation of body mass index (BMI, fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children. Results We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3. Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10-3 and decreased fasting serum insulin levels (β = −0.10 μU/mL; P = 1.21 × 10-3, respectively. Conclusion Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.

  19. Fat mass and obesity-associated gene (FTO) is associated to eating disorders susceptibility and moderates the expression of psychopathological traits

    Science.gov (United States)

    Bagnoli, Silvia; Lelli, Lorenzo; Balsamo, Michela; Mancini, Milena; Nacmias, Benedetta; Ricca, Valdo; Sorbi, Sandro; Antonucci, Ivana; Stuppia, Liborio; Stanghellini, Giovanni

    2017-01-01

    Eating Disorders (EDs) show a multifactorial etiopathogenesis including environmental, psychological and biological factors. In the present study, we propose a model of interactions between genetic vulnerability—represented by Fat Mass and Obesity-Associated (FTO) gene—and stable psychopathological traits, such as bodily disorders and emotion dysregulation for EDs patients. The distribution of a polymorphism of the FTO (rs9939609 T>A) was evaluated in a series of 250 EDs patients and in a group of 119 healthy control subjects. Clinical data were collected through a face-to-face interview and several self-reported questionnaires were applied, including the Emotional Eating Scale and the IDentity and EAting disorders (IDEA) questionnaire for bodily disorders and self-identity. The A-allele was associated with an increased vulnerability to EDs (AA+AT genotypes frequency 72.8% in EDs vs. 52.9% in controls). The presence of the A-allele was associated with binge eating behavior, higher emotional eating and higher IDEA scores. Finally, the FTO rs9939609 SNP was found to influence the relationship between these variables, as an association between disorder of corporeality and emotional eating was found only in A-allele carriers. A-allele seems to represent a potential additive risk factor for EDs persons, with bodily disorders to develop emotional eating and binge eating behaviors. PMID:28282466

  20. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D;

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES...... well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.......: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after...

  1. Escolares portadores do alelo a para o polimorfismo rs9939609 do gene FTO apresentam resposta diferente para o índice de massa corporal, após programa de intervenção interdisciplinar?

    Directory of Open Access Journals (Sweden)

    Priscila Tatiana da Silva

    2016-10-01

    Full Text Available Justificativa e Objetivo: Polimorfismos no gene relacionado à massa gorda e obesidade - FTO (fat mass and obesity associated têm sido associados com obesidade pelos seus efeitos na homeostase de energia do indivíduo. Assim, busca-se verificar se escolares portadores do alelo de risco para obesidade (A, do polimorfismo rs9939609, do gene FTO, respondem diferentemente a um programa de intervenção com exercício físico e orientação nutricional, em comparação aos escolares que não possuem este alelo, com relação ao Índice de Massa Corporal (IMC. Métodos: estudo quase-experimental, realizado com 46 escolares, distribuídos, igualmente, em grupos experimental e controle, da zona rural do município de Santa Cruz do Sul-RS. A variante A/T, do polimorfismo rs9939609 do gene FTO, foi genotipada utilizando-se o sistemaTaqManTM, em equipamento automatizado StepOne Plus. O programa interdisciplinar teve duração de 4 meses, sendo realizado 3 vezes por semana, no turno contrário ao das aulas. A duração de cada foi de 1 hora e 30 minutos. Resultados: no grupo experimental, um escolar com genótipo TT que apresentava sobrepeso, passou a ter IMC normal após o programa. Para os genótipos AT + AA, os escolares mantiveram a classificação (obesidade, sendo que um escolar que apresentava sobrepeso, passou a apresentar obesidade, após o término da intervenção. A análise dos valores de IMC, antes e após a intervenção, revelou que não houve diferença significativa, tanto no grupo experimental (p=0,088, quanto no controle (p=0,964. Conclusão: independente do genótipo, os escolares responderam de forma semelhante ao programa interdisciplinar com exercícios físicos e orientação nutricional.

  2. Effect of wet etching process on the morphology and transmittance of fluorine doped tin oxide (FTO)

    Science.gov (United States)

    Triana, S. L.; Kusumandari; Suryana, R.

    2016-11-01

    Wet etching process was performed on the surface of FTO. The FTO coated glasses subtrates with size of 2×2 cm covered by screen were patterned using zinc powder and concentrated hydrochloric acid (1 M). The substrates were then cleaned in ultrasonic baths of special detergent(helmanex) diluted in deionized water and isopropanol in sequence. The screens with various of hole size denotes by T32, T49 and T55 were used in order to create a pattern of surface textured. The atomic force microscopy (AFM) image revealed that wet etching process changes the morphology of FTO. It indicates that texturization occured. Moreover, from the UV-Vis Spectrophotometer measurement, the transmittance of FTO increase after wet etching process. The time of etching and pattern of screen were affect to the morphology and the transmittance of FTO.

  3. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  4. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D;

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  5. Responses to FTO genetic test feedback for obesity in a sample of overweight adults: a qualitative analysis.

    Science.gov (United States)

    Meisel, S F; Wardle, J

    2014-01-01

    Current evidence indicates that genetic testing for obesity risk has limited affective or behavioral impact, but few studies have explored the effects among individuals who self-identify as having weight problems. Here, we report findings from in-depth telephone interviews with seven overweight or obese volunteers who were genotyped for one weight-related gene (FTO), which may offer interesting insights into motivations to seek out genetic testing and immediate reactions to it. All participants had a BMI > 25. The gene test identified one participant as homozygous for the 'higher-risk' variant (AA), three heterozygous (AT), and three homozygous for the 'lower-risk' variant (TT) of FTO. All participants said they took part to find an explanation for their personal struggle with weight control. Those with one or two higher-risk variants experienced relief and saw the result as confirming their private assumption that they were susceptible to weight gain for reasons perceived as 'external' to them. However, at the same time, they described themselves as more motivated to overcome their genetic predisposition. Those with lower-risk variants reported brief disappointment, but then focused on alternative explanations, reinforcing the multifactorial nature of obesity. Despite objectively low 'information value,' all individuals derived some 'personal' benefit from FTO genetic test feedback. However, improving education about the multifactorial nature of complex conditions is important to decrease polarized thinking and associated genetic determinism and stigma to derive the greatest benefits of novel genetic technologies for individuals and their health.

  6. Association of FTO Mutations with Risk and Survival of Breast Cancer in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Xianxu Zeng

    2015-01-01

    Full Text Available Recently, several studies have reported associations between fat mass and obesity-associated (FTO gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, including 537 breast cancer cases and 537 controls. FTO rs1477196 AA genotype had significant decreased breast cancer risk [odds ratio (OR = 0.54, 95% confidence interval (CI: 0.34–0.86] compared to GG genotype, and this association was only found in women with BMI < 24 kg/m2 (OR = 0.41, 95% CI: 0.22–0.76; and rs16953002 AA genotype conferred significant increased breast cancer risk (OR = 1.80, 95% CI: 1.23–2.63 compared to GG genotype. Haplotype analysis showed that FTO TAC haplotype (rs9939609-rs1477196-rs1121980 had significant reduced breast cancer risk (OR = 0.76, 95% CI: 0.62–0.93 compared with TGC haplotype. But we failed to find any association between FTO polymorphisms and breast cancer survival. These findings suggest that variants in FTO gene may influence breast cancer susceptibility.

  7. Inverse association between obesity predisposing FTO genotype and completed suicide.

    Directory of Open Access Journals (Sweden)

    Izabela Chojnicka

    Full Text Available The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, Pcor = 0.006 with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361 and those who were not (OR = 0.80, P = 0.007, N = 469. The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.

  8. Dietary Intake, FTO Genetic Variants, and Adiposity : A Combined Analysis of Over 16,000 Children and Adolescents

    NARCIS (Netherlands)

    Qi, Qibin; Downer, Mary K.; Kilpelaeinen, Tuomas O.; Taal, H. Rob; Barton, Sheila J.; Ntalla, Ioanna; Standl, Marie; Boraska, Vesna; Huikari, Ville; Kiefte-de Jong, Jessica C.; Koerner, Antje; Lakka, Timo A.; Liu, Gaifen; Magnusson, Jessica; Okuda, Masayuki; Raitakari, Olli; Richmond, Rebecca; Scott, Robert A.; Bailey, Mark E. S.; Scheuermann, Kathrin; Holloway, John W.; Inskip, Hazel; Isasi, Carmen R.; Mossavar-Rahmani, Yasmin; Jaddoe, Vincent W. V.; Laitinen, Jaana; Lindi, Virpi; Melen, Erik; Pitsiladis, Yannis; Pitkaenen, Niina; Snieder, Harold; Heinrich, Joachim; Timpson, Nicholas J.; Wang, Tao; Yuji, Hinoda; Zeggini, Eleftheria; Dedoussis, George V.; Kaplan, Robert C.; Wylie-Rosett, Judith; Loos, Ruth J. F.; Hu, Frank B.; Qi, Lu

    The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the association

  9. Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

    NARCIS (Netherlands)

    Q. Qi (Qibin); M.K. Downer (Mary K.); T.O. Kilpeläinen (Tuomas); H.R. Taal (Rob); S.J. Barton (Sheila J.); I. Ntalla (Ioanna); E. Standl (Eberhard); V. Boraska (Vesna); V. Huikari (Ville); J.C. Kiefte-de Jong (Jessica); A. KöRner (Antje); T.A. Lakka (Timo); G. Liu (Gaifen); J. Magnusson (Jessica); M. Okuda (Masayuki); O. Raitakari (Olli); R.C. Richmond (Rebecca C.); R.A. Scott (Robert); M.E.S. Bailey (Mark E.S.); K. Scheuermann (Kathrin); J. Holloway (John); H.M. Inskip (Hazel); C.R. Isasi (Carmen R.); Y. Mossavar-Rahmani (Yasmin); V.W.V. Jaddoe (Vincent W. V.); J. Laitinen (Jaana); V. Lindi (Virpi); E. Melén (Erik); Y. Pitsiladis (Yannis); N. Pitkanen (Niina); H. Snieder (Harold); J. Heinrich (Joachim); N.J. Timpson (Nicholas); T. Wang (Teng); H. Yuji (Hinoda); E. Zeggini (Eleftheria); G.V. Dedoussis (George); R.C. Kaplan (Robert); J. Wylie-Rosett (Judith); R.J.F. Loos (Ruth); F.B. Hu (Frank B.); L. Qi (Lu)

    2015-01-01

    textabstractThe FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the

  10. Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

    NARCIS (Netherlands)

    Q. Qi (Qibin); M.K. Downer (Mary K.); T.O. Kilpeläinen (Tuomas); H.R. Taal (Rob); S.J. Barton (Sheila J.); I. Ntalla (Ioanna); E. Standl (Eberhard); V. Boraska (Vesna); V. Huikari (Ville); J.C. Kiefte-de Jong (Jessica); A. KöRner (Antje); T.A. Lakka (Timo); G. Liu (Gaifen); J. Magnusson (Jessica); M. Okuda (Masayuki); O. Raitakari (Olli); R.C. Richmond (Rebecca C.); R.A. Scott (Robert); M.E.S. Bailey (Mark E.S.); K. Scheuermann (Kathrin); J. Holloway (John); H.M. Inskip (Hazel); C.R. Isasi (Carmen R.); Y. Mossavar-Rahmani (Yasmin); V.W.V. Jaddoe (Vincent W. V.); J. Laitinen (Jaana); V. Lindi (Virpi); E. Melén (Erik); Y. Pitsiladis (Yannis); N. Pitkanen (Niina); H. Snieder (Harold); J. Heinrich (Joachim); N. Timpson (Nicholas); T. Wang (Teng); H. Yuji (Hinoda); E. Zeggini (Eleftheria); G.V. Dedoussis (George); R.C. Kaplan (Robert); J. Wylie-Rosett (Judith); R.J.F. Loos (Ruth J.F.); F.B. Hu (Frank B.); L. Qi (Lu)

    2015-01-01

    textabstractThe FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the as

  11. Dietary Intake, FTO Genetic Variants, and Adiposity : A Combined Analysis of Over 16,000 Children and Adolescents

    NARCIS (Netherlands)

    Qi, Qibin; Downer, Mary K.; Kilpelaeinen, Tuomas O.; Taal, H. Rob; Barton, Sheila J.; Ntalla, Ioanna; Standl, Marie; Boraska, Vesna; Huikari, Ville; Kiefte-de Jong, Jessica C.; Koerner, Antje; Lakka, Timo A.; Liu, Gaifen; Magnusson, Jessica; Okuda, Masayuki; Raitakari, Olli; Richmond, Rebecca; Scott, Robert A.; Bailey, Mark E. S.; Scheuermann, Kathrin; Holloway, John W.; Inskip, Hazel; Isasi, Carmen R.; Mossavar-Rahmani, Yasmin; Jaddoe, Vincent W. V.; Laitinen, Jaana; Lindi, Virpi; Melen, Erik; Pitsiladis, Yannis; Pitkaenen, Niina; Snieder, Harold; Heinrich, Joachim; Timpson, Nicholas J.; Wang, Tao; Yuji, Hinoda; Zeggini, Eleftheria; Dedoussis, George V.; Kaplan, Robert C.; Wylie-Rosett, Judith; Loos, Ruth J. F.; Hu, Frank B.; Qi, Lu

    2015-01-01

    The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the association be

  12. The beneficial effects of early short-term exercise in the offspring of obese mothers are accompanied by alterations in the hypothalamic gene expression of appetite regulators and FTO (fat mass and obesity associated) gene.

    Science.gov (United States)

    Caruso, V; Bahari, H; Morris, M J

    2013-08-01

    Maternal overnutrition is implicated in the development of adult metabolic disease, and has been shown to alter the expression of genes involved in energy homeostasis. In the present study, we aimed to test whether a short period of voluntary exercise, followed by a sedentary period, would regulate hypothalamic markers involved in appetite. Adult female Sprague-Dawley rats were fed either normal chow or high-fat diet (HFD) ad lib. for 5 weeks, mated and continued on their assigned diet during gestation/lactation. At weaning males, were separated into chow or HFD groups; half were exercised (running wheels), whereas the remainder were sedentary. At week 10, wheels were removed and rats remained sedentary for 5 weeks, prior to tissue collection. Maternal obesity increased offspring adiposity at 15 weeks and this was exacerbated by postnatal HFD (P obese mothers if they exercised, and this was maintained even after 5 weeks without exercise. At 15 weeks, fasting plasma insulin, leptin and triglyceride concentrations were significantly reduced by exercise in offspring of lean and obese mothers consuming chow, with little benefit in those consuming HFD. Hypothalamic mRNA expression of pro-opiomelanocortin was increased by exercise but only in offspring of lean mothers. Exercise reduced hypothalamic FTO (fat mass and obesity associated) mRNA in offspring of lean dams regardless of diet. A short period of exercise early in life had lasting beneficial effects on body weight, adiposity and hormone profile of male offspring from obese and lean dams, despite being followed by a period of inactivity. The effects of exercise on hypothalamic appetite regulators were more marked in offspring of lean dams. © 2013 British Society for Neuroendocrinology.

  13. FTO Genotype Interacts with Improvement in Aerobic Fitness on Body Weight Loss During Lifestyle Intervention

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    Corinna Sailer

    2016-06-01

    Full Text Available Objective: Not every participant responds with a comparable body weight loss to lifestyle intervention, despite the same compliance. Genetic factors may explain parts of this difference. Variation in fat mass and obesity-associated gene (FTO is the strongest common genetic determinant of body weight. The aim of the present study was to evaluate the impact of FTO genotype differences in the link between improvement of fitness and reduction of body weight during a lifestyle intervention. Methods: We genotyped 292 healthy subjects for FTO rs8050136. Participants underwent a 9-month lifestyle intervention. Before and after intervention, aerobic fitness was tested by bicycle (VO2max and treadmill spiroergometry (individual anaerobic threshold (IAT, subgroup of N = 192. Results: Participants lost body weight (p FTO genotype (p = 0.5. There was a significant correlation between improvement in VO2max and decrease in body weight (p FTO genotype interacted with this relationship (p = 0.0042 for VO2max, p = 0.0049 for IAT. When stratifying the cohort according to their improvement in VO2max, FTO obesity-risk A-allele carriers in the higher quartiles of improvement in fitness lost significantly less body weight. Conclusions: Our data reveal that genetic variation in FTO impacts on body weight reduction during lifestyle intervention only in subjects with marked improvement in aerobic fitness.

  14. LPS-induced inflammation in the chicken is associated with CCAAT/enhancer binding protein beta-mediated fat mass and obesity associated gene down-regulation in the liver but not hypothalamus.

    Science.gov (United States)

    Zhang, Yanhong; Guo, Feng; Ni, Yingdong; Zhao, Ruqian

    2013-12-17

    The fat mass and obesity associated gene (FTO) is widely investigated in humans regarding its important roles in obesity and type 2 diabetes. Studies in mammals demonstrate that FTO is also associated with inflammation markers. However, the association of FTO with inflammation in chickens remains unclear. In this study, male chickens on day 28 posthatching were injected intraperitoneally with lipopolysaccharide (LPS) or saline to investigate whether the FTO gene is involved in LPS-induced inflammation. We detected significant down-regulation of FTO mRNA in the liver (P hypothalamus, 2 and 24 h after LPS challenge. Toll-like receptor (TLR) 2 (P hypothalamus. IL-1β was dramatically up-regulated (P hypothalamus 2 h after LPS challenge, while activation of IL-6 was observed in the liver (P hypothalamus. The 5'-flanking sequence of the chicken FTO gene contains nine predicted binding sites for CCAAT/enhancer binding protein beta (C/EBP beta) and one for signal transducer and activator of transcription 3 (STAT3). Significant elevation of C/EBP beta was detected in the liver (P hypothalamus, 2 h after LPS challenge. Lipopolysaccharide challenge increased the C/EBP beta binding to FTO promoter in the liver (P hypothalamus, is affected by the i.p. injection of LPS, which may be mediated through tissue-specific FTO transcriptional regulation by C/EBP beta and STAT3 interaction.

  15. FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children.

    Directory of Open Access Journals (Sweden)

    Fleur P Velders

    Full Text Available The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg/height (m(2 in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03. Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01 and showed more emotional control (OR 0.64, p = 0.01 compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO.

  16. FTO polymorphisms moderate the association of food reinforcement with energy intake.

    Science.gov (United States)

    Scheid, Jennifer L; Carr, Katelyn A; Lin, Henry; Fletcher, Kelly D; Sucheston, Lara; Singh, Prashant K; Salis, Robbert; Erbe, Richard W; Faith, Myles S; Allison, David B; Epstein, Leonard H

    2014-06-10

    Food reinforcement (RRVfood) is related to increased energy intake, cross-sectionally related to obesity, and prospectively related to weight gain. The fat mass and obesity-associated (FTO) gene is related to elevated body mass index and increased energy intake. The primary purpose of the current study was to determine whether any of 68 FTO single nucleotide polymorphisms (SNPs) or a FTO risk score moderate the association between food reinforcement and energy or macronutrient intake. Energy and macronutrient intake was measured using a laboratory ad libitum snack food consumption task in 237 adults of varying BMI. Controlling for BMI, the relative reinforcing value of reading (RRVreading) and proportion of African ancestry, RRVfood predicted 14.2% of the variance in energy intake, as well as predicted carbohydrate, fat, protein and sugar intake. In individual analyses, six FTO SNPs (rs12921970, rs9936768, rs12446047, rs7199716, rs8049933 and rs11076022, spanning approximately 251kbp) moderated the relationship between RRVfood and energy intake to predict an additional 4.9-7.4% of variance in energy intake. We created an FTO risk score based on 5 FTO SNPs (rs9939609, rs8050136, rs3751812, rs1421085, and rs1121980) that are related to BMI in multiple studies. The FTO risk score did not increase variance accounted for beyond individual FTO SNPs. rs12921970 and rs12446047 served as moderators of the relationship between RRVfood and carbohydrate, fat, protein, and sugar intake. This study shows for the first time that the relationship between RRVfood and energy intake is moderated by FTO SNPs. Research is needed to understand how these processes interact to predict energy and macronutrient intake. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children.

    Science.gov (United States)

    Gilbert-Diamond, D; Emond, J A; Lansigan, R K; Rapuano, K M; Kelley, W M; Heatherton, T F; Sargent, J D

    2017-01-01

    Exposure to food advertisements may cue overeating among children, especially among those genetically predisposed to respond to food cues. We aimed to assess how television food advertisements affect eating in the absence of hunger among children in a randomized trial. We hypothesized that the fat mass and obesity-associated gene (FTO) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements. In this randomized experiment, 200 children aged 9-10 years were served a standardized lunch and then shown a 34-min television show embedded with either food or toy advertisements. Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake. Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype. A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted. About 172 unrelated participants were included in this analysis. Children consumed on average 453 (s.d.=185) kcals during lunch and 482 (s.d.=274) kcals during the experimental exposure. Children who viewed food advertisements consumed an average of 48 kcals (95% confidence interval: 10, 85; P=0.01) more of a recently advertised food than those who viewed toy advertisements. There was a statistically significant interaction between genotype and food advertisement condition (P for interaction=0.02), where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele, even after controlling for body mass index percentile. Food advertisement exposure was associated with greater caloric consumption of a recently advertised food, and this effect was modified by an FTO genotype. Future research is needed to understand the neurological mechanism underlying these associations.

  18. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.

    Directory of Open Access Journals (Sweden)

    Luca Carnevali

    Full Text Available In humans, variants of the fat mass and obesity associated (FTO gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12 and wild-type (n = 8 mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i higher heart rate values during resting and stress conditions, (ii heart rate variability changes (increased LF to HF ratio, (iii larger vulnerability to stress-induced tachyarrhythmias, (iv altered ventricular repolarization, and (v cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.

  19. FTO, RNA epigenetics and epilepsy

    OpenAIRE

    2012-01-01

    Several recent landmark papers describing N6-methyladenosine (m6A) RNA modifications have provided valuable new insights as to the importance of m6A in the RNA transcriptome and in furthering the understanding of RNA epigenetics. One endogenous enzyme responsible for demethylating RNA m6A, FTO, is highly expressed in the CNS and is likely involved in mRNA metabolism, splicing or other nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding transcripts that bind to tar...

  20. Association of FTO and IRX3 genetic variants to obesity risk in north India.

    Science.gov (United States)

    Srivastava, Apurva; Mittal, Balraj; Prakash, Jai; Srivastava, Pranjal; Srivastava, Nimisha; Srivastava, Neena

    2016-09-01

    Obesity is an increasingly important health problem worldwide as well as in developing countries like India. Recent genetic studies suggest that obesity associated FTO and IRX3 are functionally linked and many effects due to genetic variants in FTO gene act through IRX3. To evaluate the association of FTO and IRX3 genetic variants towards obesity risk. North Indian individuals categorised as non-obese (BMI obese (BMI ≥ 30 kg/m(2)) were selected. FTO rs8050136, rs1421085, rs9939609, rs17817449 and IRX3 rs3751723 were genotyped by means of validated Taqman® allelic discrimination to evaluate their association with obesity by means of single locus logistic regression by SPSS ver. 19 and multi-locus linkage and haplotype analysis by SNPStats and gene-gene interaction with Generalised Multifactor Dimensionality Reduction (GMDR) ver.6. In single locus analysis, FTO rs8050136 CA (p = 0.0001; OR (95% CI) = 2.4 (1.7-3.4) and AA (p = 0.0001; OR (95% CI) = 3.1 (1.9-5.2); FTO rs1421085 TA (p = 0.0001; OR (95% CI) = 2.1 (1.4-3.0) and AA (p = 0.0001; OR (95% CI) = 3.0 (1.8-5.0); FTO rs9939609 TC (p = 0.0001; OR (95% CI) = 2.1 (1.5-3.1) and CC (p = 0.0001; OR (95% CI) = 4.2 (2.5-7.3) along with TG (p = 0.001; OR (95% CI) = 2.1 (1.3-3.2) and GG (p = 0.021; OR (95% CI) = 3.8 (1.2-11.8) genotypes of FTO rs17817449 with GT (p = 0.0001; OR (95% CI) = 2.1 (1.5-3.1) and TT (p = 0.012; OR (95% CI) = 3.3 (1.8-3.6) genotypes of IRX3 rs3751723 were significantly associated with obesity. In multi-locus analysis, SNPs of FTO and IRX3 were in strong linkage disequilibrium and in haplotype and GMDR analysis the SNPs were significantly associated with obesity risk (p genetic variants of both FTO and IRX3 genes are in high linkage disequilibrium (LD) and are associated with obesity risk in North Indians.

  1. ROLE OF RS9939609 FTO GENE VARIANT IN WEIGHT LOSS, INSULIN RESISTANCE AND METABOLIC PARAMETERS AFTER A HIGH MONOUNSATURATED VS A HIGH POLYUNSATURATED FAT HYPOCALORIC DIETS.

    Science.gov (United States)

    De Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; Pacheco, D

    2015-07-01

    Introducción: un polimorfismo comun (rs9939609) del gen de la masa grasa y la obesidad (FTO) se ha relacionado con la obesidad. Objetivos: nuestro objetivo fue investigar el papel de este polimorfismo en la resistencia a la insulina, los cambios metabólicos y la pérdida de peso secundarios a una dieta hipocalórica con alto contenido en grasas monoinsaturadas vs. una dieta hipocalórica con alto contenido en grasas poliinsaturadas. Material y métodos: fue estudiada una muestra de 233 sujetos obesos de forma prospectiva. En la visita basal, los pacientes fueron asignados al azar durante tres meses a Dieta M (dieta hipocalórica con alto contenido en grasa monoinsaturada) o dieta P (dieta hipocalórica con alto contenido en grasa poliinsaturada). Resultados: después del tratamiento con las dos dietas y en ambos genotipos, la circunferencia de la cintura, el peso, la masa grasa y la cintura disminuyeron. Se detectaron niveles más bajos de índice de masa corporal (IMC), peso y masa de grasa después de la dieta P en los portadores del alelo A comparados con los sujetos de genotipo TT. Con la dieta P y en los dos genotipos (TT y AT + AA), los niveles de colesterol total (-15,3 + 35,1 mg/ dl vs. -11,6 + 32,1 mg/dl: p > 0,05) y los niveles de colesterol LDL (-11,5 + 34,1 mg/dl vs. -8,5 + 30,1 mg/dl: p > 0,05) disminuyeron. En los portadores del alelo A se detectó una disminución significativa en los niveles de insulina (-2,8 + 2,1 UI/L vs. -1,3 + 8,0 UI/L: p 0.05). Con la dieta M y en los dos genotipos, los niveles de leptina (-8,0 + 17,1 ng/ml vs. -4,9 + 18,7 ng/ml: p > 0,05) disminuyeron. Conclusiones: las mejorías metabólicas secundarias a la pérdida de peso fueron superiores en los portadores del alelo A tras recibir una dieta hipocalórica rica en grasa poliinsaturada.

  2. FTO, RNA epigenetics and epilepsy.

    Science.gov (United States)

    Rowles, Joie; Wong, Morgan; Powers, Ryan; Olsen, Mark

    2012-10-01

    Several recent landmark papers describing N(6) -methyladenosine (m(6) A) RNA modifications have provided valuable new insights as to the importance of m(6) A in the RNA transcriptome and in furthering the understanding of RNA epigenetics. One endogenous enzyme responsible for demethylating RNA m(6) A, FTO, is highly expressed in the CNS and is likely involved in mRNA metabolism, splicing or other nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding transcripts that bind to target mRNAs and inhibit subsequent translation, are highly expressed in the CNS and are associated with several neurological disorders, including epilepsy. miRNAs frequently bind to recognition sequences in the 3'UTR, a region that is also enriched for m(6) A. Certain specific miRNAs are upregulated by neuronal activity and are coupled to epileptogenesis; these miRNAs contain a consensus m(6) A site that if methylated could possibly regulate miRNA processing or function. This commentary highlights aspects from recent papers to propose a functional association between FTO, RNA epigenetics and epilepsy.

  3. FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice.

    Science.gov (United States)

    Chen, Jingqing; Zhou, Xihong; Wu, Weiche; Wang, Xinxia; Wang, Yizhen

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

  4. FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain function, impulsivity and diet.

    Science.gov (United States)

    Chuang, Y-F; Tanaka, T; Beason-Held, L L; An, Y; Terracciano, A; Sutin, A R; Kraut, M; Singleton, A B; Resnick, S M; Thambisetty, M

    2015-02-01

    Although overweight and obesity are associated with poor health outcomes in the elderly, the biological bases of obesity-related behaviors during aging are poorly understood. Common variants in the FTO gene are associated with adiposity in children and younger adults as well as with adverse mental health in older individuals. However, it is unclear whether FTO influences longitudinal trajectories of adiposity and other intermediate phenotypes relevant to mental health during aging. We examined whether a commonly carried obesity-risk variant in the FTO gene (rs1421085 single-nucleotide polymorphism) influences adiposity and is associated with changes in brain function in participants within the Baltimore Longitudinal Study of Aging, one of the longest-running longitudinal aging studies in the United States. Our results show that obesity-related risk allele carriers of FTO gene show dose-dependent increments in body mass index during aging. Moreover, the obesity-related risk allele is associated with reduced medial prefrontal cortical function during aging. Consistent with reduced brain function in regions intrinsic to impulse control and taste responsiveness, risk allele carriers of FTO exhibit dose-dependent increments in both impulsivity and intake of fatty foods. We propose that a common neural mechanism may underlie obesity-associated impulsivity and increased consumption of high-calorie foods during aging.

  5. Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

    NARCIS (Netherlands)

    T.O. Kilpeläinen (Tuomas); L. Qi (Lu); S. Brage (Soren); S.J. Sharp (Stephen); E. Sonestedt (Emily); E.W. Demerath (Ellen); T. Ahmad (Tariq); S. Mora (Samia); M. Kaakinen (Marika); C. Sandholt (Camilla); C. Holzapfel (Christina); C.S. Autenrieth (Christine); E. Hyppönen (Elina); S. Cauchi (Stephane); M. He (Meian); Z. Kutalik (Zoltán); M. Kumari (Meena); A. Stancáková (Alena); K. Meidtner (Karina); B. Balkau (Beverley); J.T. Tan (Jonathan); M. Mangino (Massimo); N.J. Timpson (Nicholas); Y. Song (Yiqing); M.C. Zillikens (Carola); K.A. Jablonski (Kathleen); M. Garcia (Melissa); S. Johansson (Stefan); J.L. Bragg-Gresham (Jennifer L.); Y. Wu (Ying); J.V. van Vliet-Ostaptchouk (Jana); N.C. Onland-Moret (Charlotte); E. Zimmermann (Esther); N.V. Rivera (Natalia); T. Tanaka (Toshiko); H.M. Stringham (Heather); G. Silbernagel (Günther); S. Kanoni (Stavroula); M.F. Feitosa (Mary Furlan); S. Snitker (Soren); J.R. Ruiz (Jonatan); J. Metter (Jeffery); M.T.M. Larrad; M. Atalay (Mustafa); M. Hakanen (Maarit); N. Amin (Najaf); C. Cavalcanti-Proença (Christine); A. Grøntved (Anders); G. Hallmans (Göran); J.O. Jansson; J. Kuusisto (Johanna); M. Kähönen (Mika); P.L. Lutsey (Pamela); J.J. Nolan (John); L. Palla (Luigi); O. Pedersen (Oluf); L. Pérusse (Louis); F. Renström (Frida); R.A. Scott (Robert); D. Shungin (Dmitry); U. Sovio (Ulla); T.H. Tammelin (Tuija); T. Rönnemaa (Tapani); T.A. Lakka (Timo); M. Uusitupa (Matti); M.S. Rios; L. Ferrucci (Luigi); C. Bouchard (Claude); A. Meirhaeghe (Aline); M. Fu (Mao); M. Walker (Mark); I.B. Borecki (Ingrid); G.V. Dedoussis (George); A. Fritsche (Andreas); C. Ohlsson (Claes); M. Boehnke (Michael); S. Bandinelli (Stefania); P. Tikka-Kleemola (Päivi); D.A. Lawlor (Debbie); V. Gudnason (Vilmundur); T.B. Harris (Tamara); T.I.A. Sørensen (Thorkild); K.L. Mohlke (Karen); A. Hofman (Albert); A.G. Uitterlinden (André); J. Tuomilehto (Jaakko); T. Lehtimäki (Terho); O. Raitakari (Olli); B. Isomaa (Bo); P. Njolstad (Pal); J.C. Florez (Jose); S. Liu (Simin); A.R. Ness (Andrew); T.D. Spector (Timothy); E.S. Tai (Shyong); P. Froguel (Philippe); H. Boeing (Heiner); M. Laakso (Markku); M. Marmot (Michael); S.M. Bergmann (Sven); C. Power (Chris); K.-T. Khaw; D.I. Chasman (Daniel); P.M. Ridker (Paul); T. Hansen (Torben); K.L. Monda (Keri); T. Illig (Thomas); M.R. Järvelin; N.J. Wareham (Nick); S. Ebrahim (Shanil); F.B. Hu (Frank); L. Groop (Leif); M. Orho-Melander (Marju); U. Ekelund (Ulf); P.W. Franks (Paul); R.J.F. Loos (Ruth)

    2011-01-01

    textabstractBackground: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or

  6. FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth

    NARCIS (Netherlands)

    Liu, Gaifen; Zhu, Haidong; Lagou, Vasiliki; Gutin, Bernard; Stallmann-Jorgensen, Inger S.; Treiber, Frank A.; Dong, Yanbin; Snieder, Harold

    2010-01-01

    Background: Genome-wide association studies found common variants in the fat mass and obesity-associated (FTO) gene associated with adiposity in Caucasians and Asians but the association was not confirmed in African populations. Association of FTO variants with insulin resistance and energy intake

  7. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk : A Meta-Analysis of 218,166 Adults and 19,268 Children

    NARCIS (Netherlands)

    Kilpelaeinen, Tuomas O.; Qi, Lu; Brage, Soren; Sharp, Stephen J.; Sonestedt, Emily; Demerath, Ellen; Ahmad, Tariq; Mora, Samia; Kaakinen, Marika; Sandholt, Camilla Helene; Holzapfel, Christina; Autenrieth, Christine S.; Hyppoenen, Elina; Cauchi, Stephane; He, Meian; Kutalik, Zoltan; Kumari, Meena; Stancakova, Alena; Meidtner, Karina; Balkau, Beverley; Tan, Jonathan T.; Mangino, Massimo; Timpson, Nicholas J.; Song, Yiqing; Zillikens, M. Carola; Jablonski, Kathleen A.; Garcia, Melissa E.; Johansson, Stefan; Bragg-Gresham, Jennifer L.; Wu, Ying; van Vliet-Ostaptchouk, Jana V.; Onland-Moret, N. Charlotte; Zimmermann, Esther; Rivera, Natalia V.; Tanaka, Toshiko; Stringham, Heather M.; Silbernagel, Guenther; Kanoni, Stavroula; Feitosa, Mary F.; Snitker, Soren; Ruiz, Jonatan R.; Metter, Jeffery; Martinez Larrad, Maria Teresa; Atalay, Mustafa; Hakanen, Maarit; Amin, Najaf; Cavalcanti-Proenca, Christine; Grontved, Anders; Hallmans, Goran; Jansson, John-Olov; Kuusisto, Johanna; Kahonen, Mika; Lutsey, Pamela L.; Nolan, John J.; Palla, Luigi; Pedersen, Oluf; Perusse, Louis; Renstrom, Frida; Scott, Robert A.; Shungin, Dmitry; Sovio, Ulla; Tammelin, Tuija H.; Ronnemaa, Tapani; Lakka, Timo A.; Uusitupa, Matti; Serrano Rios, Manuel; Ferrucci, Luigi; Bouchard, Claude; Meirhaeghe, Aline; Fu, Mao; Walker, Mark; Borecki, Ingrid B.; Dedoussis, George V.; Fritsche, Andreas; Ohlsson, Claes; Boehnke, Michael; Bandinelli, Stefania; van Duijn, Cornelia M.; Ebrahim, Shah; Lawlor, Debbie A.; Gudnason, Vilmundur; Harris, Tamara B.; Sorensen, Thorkild I. A.; Mohlke, Karen L.; Hofman, Albert; Uitterlinden, Andre G.; Tuomilehto, Jaakko; Lehtimaki, Terho; Raitakari, Olli; Isomaa, Bo; Njolstad, Pal R.; Florez, Jose C.; Liu, Simin; Ness, Andy; Spector, Timothy D.; Tai, E. Shyong; Froguel, Philippe; Boeing, Heiner; Laakso, Markku; Marmot, Michael; Bergmann, Sven; Power, Chris; Khaw, Kay-Tee; Chasman, Daniel; Ridker, Paul; Hansen, Torben; Monda, Keri L.; Illig, Thomas; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Hu, Frank B.; Groop, Leif C.; Orho-Melander, Marju; Ekelund, Ulf; Franks, Paul W.; Loos, Ruth J. F.

    2011-01-01

    Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute

  8. Factors affecting gene transformation in mangosteen

    Directory of Open Access Journals (Sweden)

    Sompong Te-chato

    2003-05-01

    Full Text Available Factors affecting gene transformation in mangosteen (Garcinia mangostana L. were investigated. Types of explants, strains and densities of Agrobacterium tumefaciens, and co-culture methods were examined to optimize gene transformation. The results showed that among strains of Agrobacterium tumefaciens tested, LBA 4404 containing pBI 121 gave the calli with the highest resistance to kanamycin. Kanamycin at the concentration of 50-100 mg/l was the best range for selection of transformants. Higher density of agrobacteria tended to promote higher frequency of transformation. The best co-culture method was dipping the explant in a solution of agrobacteria for 10 minutes, followed by culturing onto co-culture medium without antibiotic for 48 hours. Among the explants used to co- culture with bacteria, half leaf treatment gave the best result for transformation; however, callus proliferation and plantlet regeneration were inferior to whole leaf treatment. Activity of β-Glucuronidase (GUS could not be detected, thus resistance to kanamycin was used for detecting transformability. Shoot primordia could be induced from kanamycin-resistant calli grown in regeneration medium. After maintenance by subculturing to the same medium 2 to 3 times in 2-3 months, the developed shoots turned brown and finally died. Hence, the transformed plant of mangosteen was not obtained from this experiment.

  9. Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans

    DEFF Research Database (Denmark)

    Grau, K; Hansen, Torben; Holst, C;

    2009-01-01

    BACKGROUND: The A risk allele of rs9939609 of the fat mass- and obesity-associated gene (FTO) increases body fat mass. OBJECTIVE: To examine whether FTO rs9939609 affects obese individuals' response to a high-fat, low-carbohydrate (CHO) (HF) or low-fat, high-CHO (LF), hypo-energetic diet...... and whether the effect of the FTO variant depends on dietary fat and CHO content. DESIGN: In a 10-week, European, multi-centre dietary intervention study 771 obese women and men were randomized to either LF (20-25% of energy (%E) from fat, 60-65%E from CHO) or HF (40-45%E from fat, 40-45%E from CHO), hypo......-energetic diet (measured resting metabolic rate multiplied by 1.3-600 kcal day(-1)). Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation as % of REE (FatOx), insulin release (HOMA-beta) and a surrogate measure of insulin resistance...

  10. Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents

    Science.gov (United States)

    Downer, Mary K.; Kilpeläinen, Tuomas O.; Taal, H. Rob; Barton, Sheila J.; Ntalla, Ioanna; Standl, Marie; Boraska, Vesna; Huikari, Ville; Kiefte-de Jong, Jessica C.; Körner, Antje; Lakka, Timo A.; Liu, Gaifen; Magnusson, Jessica; Okuda, Masayuki; Raitakari, Olli; Richmond, Rebecca; Scott, Robert A.; Bailey, Mark E.S.; Scheuermann, Kathrin; Holloway, John W.; Inskip, Hazel; Isasi, Carmen R.; Mossavar-Rahmani, Yasmin; Jaddoe, Vincent W.V.; Laitinen, Jaana; Lindi, Virpi; Melén, Erik; Pitsiladis, Yannis; Pitkänen, Niina; Snieder, Harold; Heinrich, Joachim; Timpson, Nicholas J.; Wang, Tao; Yuji, Hinoda; Zeggini, Eleftheria; Dedoussis, George V.; Kaplan, Robert C.; Wylie-Rosett, Judith; Loos, Ruth J.F.; Hu, Frank B.

    2015-01-01

    The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents. PMID:25720386

  11. Differences in body mass index according to fat mass- and obesity-associated (FTO) genotype in Mexican patients with bipolar disorder.

    Science.gov (United States)

    Díaz-Anzaldúa, Adriana; Ocampo-Mendoza, Yolanda; Hernández-Lagunas, José Octavio; Díaz-Madrid, Federico Alejandro; Romo-Nava, Francisco; Juárez-García, Francisco; Ortega-Ortiz, Hiram; Díaz-Anzaldúa, Alejandro; Gutiérrez-Mora, Doris; Becerra-Palars, Claudia; Berlanga-Cisneros, Carlos

    2015-09-01

    The prevalence of obesity has dramatically increased in many countries and it is particularly high in patients with bipolar disorder (BD). A region in the first intron of the fat mass- and obesity-associated (FTO) gene, encompassing markers rs9939973, rs8050136, and rs9939609, has been consistently associated with obesity and body mass index (BMI) in different populations. We sought to determine whether FTO is associated with BMI and/or obesity in patients with BD. The sample included 129 Mexican Mestizo patients with bipolar I or bipolar II disorder. After obtaining informed consent, participants were evaluated with the Structured Clinical Interview for DSM-IV Axis I Disorders and weight, height, and body measurements were recorded. DNA was extracted from a 5-mL blood sample and real-time polymerase chain reaction was performed. The results were analyzed with Haploview v4.2 and SPSS v21. Differences in mean BMI were explained by rs8050136 and rs9939609 genotypes, especially by comparing non-carriers and carriers of two copies of the risk allele (Tukey's p ≤ 0.019), with a mean difference in BMI as high as 7.81 kg/m(2) . Differences in BMI were also explained by the interaction of the genotype (rs8050136 and/or rs9939609), the use of second-generation antipsychotics, and the use of mood stabilizers (p ≤ 0.41). Obesity was also associated with these two markers when patients with and without obesity were compared. In patients with BD, differences in BMI may be affected by the presence of FTO risk alleles, especially in homozygous individuals for these variants. Besides evaluating the possible metabolic effects of certain antipsychotics or mood stabilizers, it is important to evaluate the role of other factors such as FTO risk alleles. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype.

    Directory of Open Access Journals (Sweden)

    Yeon-Jung Kim

    Full Text Available The single nucleotide polymorphism rs9939609 of the gene FTO, which encodes fat mass and obesity-associated protein, is strongly associated with obesity and type 2 diabetes (T2D in multiple populations; however, the underlying mechanism of this association is unclear. The present study aimed to investigate FTO genotype-dependent metabolic changes in obesity and T2D. To elucidate metabolic dysregulation associated with disease risk genotype, genomic and metabolomic datasets were recruited from 2,577 participants of the Korean Association REsource (KARE cohort, including 40 homozygous carriers of the FTO risk allele (AA, 570 heterozygous carriers (AT, and 1,967 participants carrying no risk allele (TT. A total of 134 serum metabolites were quantified using a targeted metabolomics approach. Through comparison of various statistical methods, seven metabolites were identified that are significantly altered in obesity and T2D based on the FTO risk allele (adjusted p < 0.05. These identified metabolites are relevant to phosphatidylcholine metabolic pathway, and previously reported to be metabolic markers of obesity and T2D. In conclusion, using metabolomics with the information from genome-wide association studies revealed significantly altered metabolites depending on the FTO genotype in complex disorders. This study may contribute to a better understanding of the biological mechanisms linking obesity and T2D.

  13. Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population.

    Science.gov (United States)

    Mačeková, Soňa; Bernasovský, Ivan; Gabriková, Dana; Bôžiková, Alexandra; Bernasovská, Jarmila; Boroňová, Iveta; Behulová, Regina; Svíčková, Petra; Petrejčíková, Eva; Soták, Miroslav; Sovičová, Adriana; Carnogurská, Jana

    2012-01-01

    The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.

  14. A variant in FTO shows association with melanoma risk not due to BMI

    NARCIS (Netherlands)

    Geno, M.E.L.C.; Iles, M.M.; Law, M.H.; Stacey, S.N.; Han, J.; Fang, S.; Pfeiffer, R.; Harland, M.; MacGregor, S.; Taylor, J.C.; Aben, K.K.H.; Akslen, L.A.; Avril, M.F.; Azizi, E.; Bakker, B.; Benediktsdottir, K.R.; Bergman, W.; Scarra, G.B.; Brown, K.M.; Calista, D.; Chaudru, V.; Fargnoli, M.C.; Cust, A.E.; Demenais, F.; Waal, A.C. de; Debniak, T.; Elder, D.E.; Friedman, E.; Galan, P.; Ghiorzo, P.; Gillanders, E.M.; Goldstein, A.M.; Gruis, N.A.; Hansson, J.; Helsing, P.; Hocevar, M.; Hoiom, V.; Hopper, J.L.; Ingvar, C.; Janssen, M.; Jenkins, M.A.; Kanetsky, P.A.; Kiemeney, L.A.L.M.; Lang, J.; Lathrop, G.M.; Leachman, S.; Lee, J.E.; Lubinski, J.; Mackie, R.M.; Mann, G.J.; Martin, N.G.; Mayordomo, J.I.; Molven, A.; Mulder, S.; Nagore, E.; Novakovic, S.; Okamoto, I.; Olafsson, J.H.; Olsson, H.; Pehamberger, H.; Peris, K.; Grasa, M.P.; Planelles, D.; Puig, S.; Puig-Butille, J.A.; Randerson-Moor, J.; Requena, C.; Rivoltini, L.; Rodolfo, M.; Santinami, M.; Sigurgeirsson, B.; Snowden, H.; Song, F.; Sulem, P.; Thorisdottir, K.; Tuominen, R.; Belle, P. Van; Stoep, N. van der; Rossum, M.M. van; Wei, Q.; Wendt, J.; Zelenika, D.; Zhang, M.; Landi, M.T.; Thorleifsson, G.; Bishop, D.T.; Amos, C.I.; Hayward, N.K.; Stefansson, K.; Bishop, J.A.; Barrett, J.H.

    2013-01-01

    We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs

  15. 'Fat mass and obesity associated' gene (FTO: No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Müller Timo D

    2008-09-01

    Full Text Available Abstract Background We have previously identified strong association of six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene to early onset extreme obesity within the first genome wide association study (GWA for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609 is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism. Methods We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR. For the association study (case-control approach, the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele. Results We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036. However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol. Conclusion We confirmed

  16. Preparation and investigation of nano-thick FTO/Ag/FTO multilayer transparent electrodes with high figure of merit.

    Science.gov (United States)

    Yu, Shihui; Li, Lingxia; Lyu, Xiaosong; Zhang, Weifeng

    2016-01-01

    In order to improve the conductivity of the single-layered nano-thick F doped SnO2 (FTO) thin films, an Ag mid-layer is embedded between the FTO layers. In our work, the effects of mid-layer Ag and top FTO layer on the structural, electrical and optical properties of FTO/Ag/FTO multilayered composite structures deposited on quartz glass substrates by magnetron sputtering at 100 °C have been investigated. As the thickness of Ag mid-layer increases, the resistivity decreases. As the top FTO layer thickness increases, the resistivity increases. The highest value of figure of merit φTC is 7.8 × 10(-2 ) Ω(-1) for the FTO (20 nm)/Ag (7 nm)/FTO (30 nm) multilayers, while the average optical transmittance is 95.5% in the visible range of wavelengths and the resistivity is 8.8 × 10(-5 ) Ω·cm. In addition, we also describe the influence of Ag and top FTO layer thickness on structural, electrical and optical properties of the nano-thick FTO (20 nm)/Ag/FTO multilayers and the mechanism of the changes of electrical and optical properties at different Ag and top FTO layer thicknesses.

  17. Relationship between single nucleotide polymorphism on FTO gene rs9939609 and obesity in children%FTO基因rs9939609位点多态性与儿童肥胖的相关性研究

    Institute of Scientific and Technical Information of China (English)

    吴燕明; 李卫国; 盛秋明; 戴劲盛; 张凌君; 吴敏; 龚惠君

    2014-01-01

    目的:探讨不同程度肥胖儿童的生化指标和脂肪含量与肥胖相关基因(FTO)rs9936609单核苷酸多态性位点(SNP)之间的相关性。方法纳入153例7~11岁儿童,其中肥胖102例、超重51例作为研究对象;160例正常体质量儿作为正常对照组。检测并比较各组间肝功能及其他生化指标的差异;利用PCR直接测序法检测FTO基因rs9939609的SNP,计算等位基因分布频率。结果 FTO基因rs9939609 TT、TA/AA基因型在肥胖、超重和正常三组间的分布差异有统计学意义(χ2=23.01,P<0.001);其中肥胖组和超重组TA/AA基因型表达频率均分别高于对照组,差异有统计学意义(P’<0.014)。T、A等位基因在正常对照组、超重组和肥胖组的频率分别为96.25%和3.75%,85.29%和14.71%,85.78%和14.22%,三组间的分布差异有统计学意义(χ2=21.72,P<0.001);肥胖组和超重组A等位基因频率均分别高于对照组,差异有统计学意义(P’<0.014)。TA、AA基因型携带者体质指数(BMI)高于TT型携带者,差异有统计学意义(P<0.05)。结论 FTO基因rs9939609多态性和儿童肥胖的发生与发展有相关性,A等位基因可导致携带者BMI升高。%Objective To investigate the relationship of single nucleotide polymorphism (SNP) on FTO gene rs9939609 with metabolism index and obesity in children. Methods One hundred and fifty-three children (age 7-11 year) were recruited in this study, 102 of them were obese and 51 of them were overweight. One hundred and sixty children with normal body weight were recruited as control. Height, weight and biochemical indicator of liver function were measured. PCR and direct sequence were applied to detect the polymorphism of rs9939609, and the frequency of the allele was calculated. Results TT or TA/AA genotype frequency on FTOgene rs9939609 was significantly different among overweight group, obesity group and normal con-trol group (

  18. A Novel Inhibitor of the Obesity-Related Protein FTO.

    Science.gov (United States)

    Qiao, Yan; Zhou, Bin; Zhang, Meizi; Liu, Weijia; Han, Zhifu; Song, Chuanjun; Yu, Wenquan; Yang, Qinghua; Wang, Ruiyong; Wang, Shaomin; Shi, Shuai; Zhao, Renbin; Chai, Jijie; Chang, Junbiao

    2016-03-15

    Fe(II) and α-ketoglutarate-dependent fat mass and obesity associated protein (FTO)-dependent demethylation of m⁶A is important for regulation of mRNA splicing and adipogenesis. Developing FTO-specific inhibitors can help probe the biology of FTO and unravel novel therapeutic targets for treatment of obesity or obesity-associated diseases. In the present paper, we have identified that 4-chloro-6-(6'-chloro-7'-hydroxy-2',4',4'-trimethyl-chroman-2'-yl)benzene-1,3-diol (CHTB) is an inhibitor of FTO. The crystal structure of CHTB complexed with human FTO reveals that the novel small molecule binds to FTO in a specific manner. The identification of the novel small molecule offers opportunities for further development of more selective and potent FTO inhibitors.

  19. Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype.

    Science.gov (United States)

    Brennan, Paul; McKay, James; Moore, Lee; Zaridze, David; Mukeria, Anush; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Chow, Wong-Ho; Rothman, Nathaniel; Chabrier, Amélie; Gaborieau, Valérie; Timpson, Nic; Hung, Rayjean J; Smith, George Davey

    2009-08-01

    Obesity is a risk factor for several cancers although appears to have an inverse association with cancers strongly related to tobacco. Studying obesity is difficult due to numerous biases and confounding. To avoid these biases we used a Mendelian randomization approach incorporating an analysis of variants in the FTO gene that are strongly associated with BMI levels among 7000 subjects from a study of lung, kidney and upper-aerodigestive cancer. The FTO A allele which is linked with increased BMI was associated with a decreased risk of lung cancer (allelic odds ratio (OR) = 0.92, 95% confidence interval (CI) 0.84-1.00). It was also associated with a weak increased risk of kidney cancer, which was more apparent before the age of 50 (OR = 1.44, CI 1.09-1.90). Our results highlight the potential for genetic variation to act as an unconfounded marker of environmentally modifiable factors, and offer the potential to obtain estimates of the causal effect of obesity. However, far larger sample sizes than studied here will be required to undertake this with precision.

  20. The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals

    Directory of Open Access Journals (Sweden)

    Ramos Adauto V

    2012-11-01

    Full Text Available Abstract Background Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported. Methods To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI and cardiovascular risk we genotyped SNPs rs9939609 (FTO and rs6536991, rs22705565 and rs12502572 (UCP-1 from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE. Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population. Results Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and pFTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO and rs6536991 (UCP-1 in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery. Conclusion Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.

  1. Cut-like Homeobox 1 (CUX1) Regulates Expression of the Fat Mass and Obesity-associated and Retinitis Pigmentosa GTPase Regulator-interacting Protein-1-like (RPGRIP1L) Genes and Coordinates Leptin Receptor Signaling*

    Science.gov (United States)

    Stratigopoulos, George; LeDuc, Charles A.; Cremona, Maria L.; Chung, Wendy K.; Leibel, Rudolph L.

    2011-01-01

    The first intron of FTO contains common single nucleotide polymorphisms associated with body weight and adiposity in humans. In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. This regulation occurs via a single AATAAATA regulatory site (conserved in the mouse) within the FTO intronic region associated with adiposity in humans. Single nucleotide polymorphism rs8050136 (located in this regulatory site) affects binding affinities of P200 and P110. Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). Association of the FTO locus with adiposity in humans may reflect functional consequences of A/C alleles at rs8050136. The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the

  2. FTO Genotype Interacts with Improvement in Aerobic Fitness on Body Weight Loss During Lifestyle Intervention.

    Science.gov (United States)

    Sailer, Corinna; Schmid, Vera; Fritsche, Louise; Gerter, Tsvetelina; Machicao, Fausto; Niess, Andreas; Häring, Hans-Ulrich; Stefan, Norbert; Fritsche, Andreas; Heni, Martin

    2016-01-01

    Not every participant responds with a comparable body weight loss to lifestyle intervention, despite the same compliance. Genetic factors may explain parts of this difference. Variation in fat mass and obesity-associated gene (FTO) is the strongest common genetic determinant of body weight. The aim of the present study was to evaluate the impact of FTO genotype differences in the link between improvement of fitness and reduction of body weight during a lifestyle intervention. We genotyped 292 healthy subjects for FTO rs8050136. Participants underwent a 9-month lifestyle intervention. Before and after intervention, aerobic fitness was tested by bicycle (VO2max) and treadmill spiroergometry (individual anaerobic threshold (IAT), subgroup of N = 192). Participants lost body weight (p fitness lost significantly less body weight. Our data reveal that genetic variation in FTO impacts on body weight reduction during lifestyle intervention only in subjects with marked improvement in aerobic fitness. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

  3. Phenome Wide Association Studies demonstrating pleiotropy of genetic variants within FTO with and without adjustment for body mass index

    Directory of Open Access Journals (Sweden)

    Robert Michael Cronin

    2014-08-01

    Full Text Available Phenome-wide association studies (PheWAS have demonstrated utility in validating genetic associations derived from traditional genetic studies as well as identifying novel genetic associations. Here we used an electronic health record (EHR-based PheWAS to explore pleiotropy of genetic variants in the fat mass and obesity associated gene (FTO, some of which have been previously associated with obesity and type 2 diabetes (T2D. We used a population of 10,487 individuals of European ancestry with genome-wide genotyping from the Electronic Medical Records and Genomics (eMERGE Network and another population of 13,711 individuals of European ancestry from the BioVU DNA biobank at Vanderbilt genotyped using Illumina HumanExome BeadChip. A meta-analysis of the two study populations replicated the well-described associations between FTO variants and obesity (odds ratio [OR]=1.25, 95% Confidence Interval=1.11-1.24, p=2.10 x 10 9 and FTO variants and T2D (OR=1.14, 95% CI=1.08-1.21, p=2.34 x 10 6. The meta-analysis also demonstrated that FTO variant rs8050136 was significantly associated with sleep apnea (OR=1.14, 95% CI=1.07-1.22, p=3.33 x 10 5; however, the association was attenuated after adjustment for body mass index (BMI. Novel phenotype associations with obesity-associated FTO variants included fibrocystic breast disease (rs9941349, OR=0.81, 95% CI=0.74-0.91, p=5.41x10 5 and trends toward associations with nonalcoholic liver disease and gram-positive bacterial infections. FTO variants not associated with obesity demonstrated other potential disease associations including noninflammatory disorders of the cervix and chronic periodontitis. These results suggest that genetic variants in FTO may have pleiotropic associations, some of which are not mediated by obesity.

  4. Mutations in many genes affect aggressive behavior in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Zwarts Liesbeth

    2009-06-01

    Full Text Available Abstract Background Aggressive behavior in animals is important for survival and reproduction. Identifying the underlying genes and environmental contexts that affect aggressive behavior is important for understanding the evolutionary forces that maintain variation for aggressive behavior in natural populations, and to develop therapeutic interventions to modulate extreme levels of aggressive behavior in humans. While the role of neurotransmitters and a few other molecules in mediating and modulating levels of aggression is well established, it is likely that many additional genetic pathways remain undiscovered. Drosophila melanogaster has recently been established as an excellent model organism for studying the genetic basis of aggressive behavior. Here, we present the results of a screen of 170 Drosophila P-element insertional mutations for quantitative differences in aggressive behavior from their co-isogenic control line. Results We identified 59 mutations in 57 genes that affect aggressive behavior, none of which had been previously implicated to affect aggression. Thirty-two of these mutants exhibited increased aggression, while 27 lines were less aggressive than the control. Many of the genes affect the development and function of the nervous system, and are thus plausibly relevant to the execution of complex behaviors. Others affect basic cellular and metabolic processes, or are mutations in computationally predicted genes for which aggressive behavior is the first biological annotation. Most of the mutations had pleiotropic effects on other complex traits. We characterized nine of these mutations in greater detail by assessing transcript levels throughout development, morphological changes in the mushroom bodies, and restoration of control levels of aggression in revertant alleles. All of the P-element insertions affected the tagged genes, and had pleiotropic effects on brain morphology. Conclusion This study reveals that many more

  5. FTO genotype is associated with phenotypic variability of body mass index.

    Science.gov (United States)

    Yang, Jian; Loos, Ruth J F; Powell, Joseph E; Medland, Sarah E; Speliotes, Elizabeth K; Chasman, Daniel I; Rose, Lynda M; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Mägi, Reedik; Waite, Lindsay; Smith, Albert Vernon; Yerges-Armstrong, Laura M; Monda, Keri L; Hadley, David; Mahajan, Anubha; Li, Guo; Kapur, Karen; Vitart, Veronique; Huffman, Jennifer E; Wang, Sophie R; Palmer, Cameron; Esko, Tõnu; Fischer, Krista; Zhao, Jing Hua; Demirkan, Ayşe; Isaacs, Aaron; Feitosa, Mary F; Luan, Jian'an; Heard-Costa, Nancy L; White, Charles; Jackson, Anne U; Preuss, Michael; Ziegler, Andreas; Eriksson, Joel; Kutalik, Zoltán; Frau, Francesca; Nolte, Ilja M; Van Vliet-Ostaptchouk, Jana V; Hottenga, Jouke-Jan; Jacobs, Kevin B; Verweij, Niek; Goel, Anuj; Medina-Gomez, Carolina; Estrada, Karol; Bragg-Gresham, Jennifer Lynn; Sanna, Serena; Sidore, Carlo; Tyrer, Jonathan; Teumer, Alexander; Prokopenko, Inga; Mangino, Massimo; Lindgren, Cecilia M; Assimes, Themistocles L; Shuldiner, Alan R; Hui, Jennie; Beilby, John P; McArdle, Wendy L; Hall, Per; Haritunians, Talin; Zgaga, Lina; Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana; Oostra, Ben A; Junttila, M Juhani; Grönberg, Henrik; Schreiber, Stefan; Peters, Annette; Hicks, Andrew A; Stephens, Jonathan; Foad, Nicola S; Laitinen, Jaana; Pouta, Anneli; Kaakinen, Marika; Willemsen, Gonneke; Vink, Jacqueline M; Wild, Sarah H; Navis, Gerjan; Asselbergs, Folkert W; Homuth, Georg; John, Ulrich; Iribarren, Carlos; Harris, Tamara; Launer, Lenore; Gudnason, Vilmundur; O'Connell, Jeffrey R; Boerwinkle, Eric; Cadby, Gemma; Palmer, Lyle J; James, Alan L; Musk, Arthur W; Ingelsson, Erik; Psaty, Bruce M; Beckmann, Jacques S; Waeber, Gerard; Vollenweider, Peter; Hayward, Caroline; Wright, Alan F; Rudan, Igor; Groop, Leif C; Metspalu, Andres; Khaw, Kay Tee; van Duijn, Cornelia M; Borecki, Ingrid B; Province, Michael A; Wareham, Nicholas J; Tardif, Jean-Claude; Huikuri, Heikki V; Cupples, L Adrienne; Atwood, Larry D; Fox, Caroline S; Boehnke, Michael; Collins, Francis S; Mohlke, Karen L; Erdmann, Jeanette; Schunkert, Heribert; Hengstenberg, Christian; Stark, Klaus; Lorentzon, Mattias; Ohlsson, Claes; Cusi, Daniele; Staessen, Jan A; Van der Klauw, Melanie M; Pramstaller, Peter P; Kathiresan, Sekar; Jolley, Jennifer D; Ripatti, Samuli; Jarvelin, Marjo-Riitta; de Geus, Eco J C; Boomsma, Dorret I; Penninx, Brenda; Wilson, James F; Campbell, Harry; Chanock, Stephen J; van der Harst, Pim; Hamsten, Anders; Watkins, Hugh; Hofman, Albert; Witteman, Jacqueline C; Zillikens, M Carola; Uitterlinden, André G; Rivadeneira, Fernando; Zillikens, M Carola; Kiemeney, Lambertus A; Vermeulen, Sita H; Abecasis, Goncalo R; Schlessinger, David; Schipf, Sabine; Stumvoll, Michael; Tönjes, Anke; Spector, Tim D; North, Kari E; Lettre, Guillaume; McCarthy, Mark I; Berndt, Sonja I; Heath, Andrew C; Madden, Pamela A F; Nyholt, Dale R; Montgomery, Grant W; Martin, Nicholas G; McKnight, Barbara; Strachan, David P; Hill, William G; Snieder, Harold; Ridker, Paul M; Thorsteinsdottir, Unnur; Stefansson, Kari; Frayling, Timothy M; Hirschhorn, Joel N; Goddard, Michael E; Visscher, Peter M

    2012-10-11

    There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

  6. Characterization of seven genes affecting Caenorhabditis elegans hindgut development.

    Science.gov (United States)

    Chamberlin, H M; Brown, K B; Sternberg, P W; Thomas, J H

    1999-01-01

    We have identified and characterized 12 mutations in seven genes that affect the development of the Caenorhabditis elegans hindgut. We find that the mutations can disrupt the postembryonic development of the male-specific blast cells within the hindgut, the hindgut morphology in both males and hermaphrodites, and in some cases, the expression of a hindgut marker in hermaphrodite animals. Mutations in several of the genes also affect viability. On the basis of their mutant phenotypes, we propose that the genes fall into four distinct classes: (1) egl-5 is required for regional identity of the tail; (2) sem-4 is required for a variety of ectodermal and mesodermal cell types, including cells in the hindgut; (3) two genes, lin-49 and lin-59, affect development of many cells, including hindgut; and (4) three genes, mab-9, egl-38, and lin-48, are required for patterning fates within the hindgut, making certain hindgut cells different from others. We also describe a new allele of the Pax gene egl-38 that is temperature sensitive and affects the conserved beta-hairpin of the EGL-38 paired domain. Our results suggest that a combination of different factors contribute to normal C. elegans hindgut development. PMID:10511553

  7. Patterns of prokaryotic lateral gene transfers affecting parasitic microbial eukaryotes

    DEFF Research Database (Denmark)

    Alsmark, Cecilia; Foster, Peter G; Sicheritz-Pontén, Thomas

    2013-01-01

    , dramatically affecting the enzymes of core pathways, particularly amino acid and sugar metabolism, but also providing new genes of potential adaptive significance in the life of parasites. A broad range of prokaryotic donors is involved in such transfers, but there is clear and significant enrichment......BACKGROUND: The influence of lateral gene transfer on gene origins and biology in eukaryotes is poorly understood compared with those of prokaryotes. A number of independent investigations focusing on specific genes, individual genomes, or specific functional categories from various eukaryotes have...... for bacterial groups that share the same habitats, including the human microbiota, as the parasites investigated. CONCLUSIONS: Our data show that ecology and lifestyle strongly influence gene origins and opportunities for gene transfer and reveal that, although the outlines of the core eukaryotic metabolism...

  8. 肥胖相关基因rs9939609多态性与利培酮4周治疗所致体质量增加的关联分析%Association study of FTO gene polymorphism with weight gain associated with 4 week risperidone treatment

    Institute of Scientific and Technical Information of China (English)

    王芳; 宓为峰; 卢天兰; 阮燕燕; 张岱; 岳伟华

    2013-01-01

    目的:探讨肥胖相关基因与利培酮治疗所致体质量增加的关联.方法:收集符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断的236名汉族精神分裂症患者,所有患者均采用利培酮单一药物治疗,分别于治疗前和治疗4周后测量患者体质量与身高,计算体质量指数(BMI);本研究采用DNA测序检测方法对肥胖相关基因上的rs9939609多态性位点进行基因分型,采用stepwise线性多元回归的方法探索肥胖相关基因rs9939609多态性与利培酮治疗4周所致体质量增加的关联.结果:关联分析结果显示肥胖相关基因rs9939609多态性与基线BMI值无显著关联[AA/AT vs.TT=(23.0±3.6) vs.(22.7±3.5),P=0.245];4周末时,AA/AT基因型携带者与TT基因型携带者BMI值也无显著性差异[AA/AT vs.TT=(23.4±3.6)vs.(22.7±3.5),P=0.090];4周BMI变化值与rs9939609显著关联[AA/AT vs.TT=(0.6±1.1)vs.(0.2±1.3),P =0.040].结论:本研究结果提示在中国汉族样本人群中,肥胖相关基因rs9939609多态性可能与利培酮所致体质量增加有关联.%Objectives:To explore the association between the Fat Mass and Obesity Associated (FTO) gene polymorphism and weight gain associated with risperidone treatment Methods: Totally 236 schizophrenic patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were enrolled in our study. All the patients were treated with risperidone. The body weight and height of the patients were measured before and after 4week risperidone treatment to calculate body mass index. The FTO rs9939609 polymorphism was genotyped by using direct DNA sequencing method, and was analyzed for association with risperidone-induced weight gain. Results: There was no significant association between rs9939609 and baseline BMI[ AA/AT vs. TT = (23.0 ±3.6) vs. (22.7 ±3. 5),P>0.05] and rs9939609 was neither associated with 4-week BMI [AA/AT vs. TT = (23.4 ± 3. 6) vs. (22. 7 ± 3. 5

  9. The common FTO variant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924

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    Lannfelt Lars

    2009-12-01

    Full Text Available Abstract Background Common FTO (fat mass and obesity associated gene variants have recently been strongly associated with body mass index and obesity in several large studies. Here we set out to examine the association of the FTO variant rs9939609 with BMI in a 32 year follow up study of men born 1920-1924. Moreover, we analyzed the effect of physical activity on the different genotypes. Methods The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire. Results FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039 and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects. Conclusion Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.

  10. Influences of the common FTO rs9939609 variant on inflammatory markers throughout a broad range of body mass index

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Skogstrand, Kristin; Hougaard, David M

    2011-01-01

    A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating...

  11. Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample

    DEFF Research Database (Denmark)

    Al-Attar, Salam A; Pollex, Rebecca L; Ban, Matthew R

    2008-01-01

    BACKGROUND: The rs9939609 T>A single-nucleotide polymorphism (SNP) in the FTO gene has previously been found to be associated with obesity in European Caucasian samples. The objective of this study is to examine whether this association extends to metabolic syndrome (MetS) and applies in non...

  12. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  13. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Qi, Lu; Brage, Soren

    2011-01-01

    Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute......>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were.......20–1.26), but PA attenuated this effect (pinteraction = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1...

  14. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

    National Research Council Canada - National Science Library

    Ortega-Azorín, Carolina; Sorlí, Jose V; Asensio, Eva M; Coltell, Oscar; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Covas, Maria-Isabel; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Fiol, Miquel; Sáez-Tormo, Guillermo; Pintó, Xavier; Muñoz, Miguel Angel; Ros, Emilio; Ordovás, Jose M; Estruch, Ramon; Corella, Dolores

    2012-01-01

    Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial...

  15. Identification of an MSI-H Tumor-Specific Cytotoxic T Cell Epitope Generated by the (−1 Frame of U79260(FTO

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    Michael Linnebacher

    2010-01-01

    Full Text Available Microsatellite instability (MSI-H induced by defects of the DNA mismatch repair system results in insertion or deletion of single nucleotides at short repetitive DNA sequences. About 15% of sporadic and approximately 90% of hereditary nonpolyposis colorectal cancers display MSI-H. When affecting coding regions, MSI-H results in frameshift mutations and expression of corresponding frameshift peptides (FSPs. Functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by MSI-H. Contrary, immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers. Here, we provide conclusive data that the (−1 frame of U79260(FTO encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV. T cells specific for FSP11 efficiently recognized HLA-A0201(pos tumor cells harboring the mutated reading frame. Considering the exceptionally high mutation rate of U79260(FTO in MSI-H colorectal carcinoma (81.8%, this recommends that FSP11 be a component of future vaccines.

  16. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge.

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    Balraj Singh

    Full Text Available We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90% inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern

  17. Hydrophobin gene expression affects hyphal wall composition in Schizophyllum commune

    NARCIS (Netherlands)

    van Wetter, MA; Wosten, HAB; Sietsma, JH; Wessels, JGH

    2000-01-01

    Disruption of the SC3 hydrophobin gene of Schizophyllum commune (Delta SC3 strain) affected the composition of the cell wall. Compared to a wild-type strain the amount of mucilage (i.e., water-soluble (1-3)beta -glucan with single glucose residues attached by (I-G)P-linkages) increased considerably,

  18. FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study.

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    Cindy Thron

    Full Text Available Single nucleotide polymorphisms (SNPs within the Fat mass and obesity associated (FTO gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS, one of the most frequent cardiovascular diseases in the Western world.In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004. Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A had a higher risk to develop AVS (p = 0.017, odds ratio (OR 1.727; 95% confidence interval (CI 1.087-2.747, recessive model, whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384-0.828, overdominant model. After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369-0.861.This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus.

  19. Association of FTO polymorphisms with obesity and metabolic parameters in Han Chinese adolescents.

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    Junqing Wu

    Full Text Available BACKGROUND: Previous studies have suggested that fat mass-and obesity-associated (FTO gene is associated with body mass index (BMI and the risk of obesity. This study aims to assess the association of five FTO polymorphisms (rs9939609, rs8050136, rs1558902, rs3751812 and rs6499640 with obesity and relative parameters in Han Chinese adolescents. METHODS: We examined a total of 401 adolescents, 223 normal weights (58.7% boys, 41.3% girls, 178 overweight (60.1% boys, 39.9% girls, aging from 14 to 18-years-old, recruited randomly from public schools in the central region of Wuxi, a southern city of China. DNA samples were genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG, fasting insulin (FIns, triglyceride (TG and cholesterol (TC were investigated. RESULTS: 1 Serum FPG, FIns, TG and TC were statistically significant higher than that in normal control group. 2 We found that BMI was higher in the rs9939609 TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;, CC genotypes(rs8050136: P = 0.024 and GG genotypes (rs3751812: P = 0.024, which were not significant on adjusting for multiple testing. 3 In case-control studies, five polymorphisms were not significantly associated with overweight (p>0.05, haplotype analyses showed non-haplotype is significantly associated with a higher risk of being overweight (p>0.05. 4 There existed no significant statistical difference about FPG, FIns, TG and TC in genotype model for any SNP. CONCLUSIONS: Our study has conducted a genetic association study of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG, fasting insulin (FIns, triglyceride (TG and cholesterol (TC. Our study found BMI of subjects with A allele of FTO rs9939609 is higher than that with T allele. Further studies on other polymorphisms from FTO and increasing

  20. Identifying sexual differentiation genes that affect Drosophila life span

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    Tower John

    2009-12-01

    Full Text Available Abstract Background Sexual differentiation often has significant effects on life span and aging phenotypes. For example, males and females of several species have different life spans, and genetic and environmental manipulations that affect life span often have different magnitude of effect in males versus females. Moreover, the presence of a differentiated germ-line has been shown to affect life span in several species, including Drosophila and C. elegans. Methods Experiments were conducted to determine how alterations in sexual differentiation gene activity might affect the life span of Drosophila melanogaster. Drosophila females heterozygous for the tudor[1] mutation produce normal offspring, while their homozygous sisters produce offspring that lack a germ line. To identify additional sexual differentiation genes that might affect life span, the conditional transgenic system Geneswitch was employed, whereby feeding adult flies or developing larvae the drug RU486 causes the over-expression of selected UAS-transgenes. Results In this study germ-line ablation caused by the maternal tudor[1] mutation was examined in a long-lived genetic background, and was found to increase life span in males but not in females, consistent with previous reports. Fitting the data to a Gompertz-Makeham model indicated that the maternal tudor[1] mutation increases the life span of male progeny by decreasing age-independent mortality. The Geneswitch system was used to screen through several UAS-type and EP-type P element mutations in genes that regulate sexual differentiation, to determine if additional sex-specific effects on life span would be obtained. Conditional over-expression of transformer female isoform (traF during development produced male adults with inhibited sexual differentiation, however this caused no significant change in life span. Over-expression of doublesex female isoform (dsxF during development was lethal to males, and produced a limited

  1. An Obesity-Related FTO Variant and the Risk of Preeclampsia in a Finnish Study Population

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    Miira Klemetti

    2011-01-01

    Full Text Available Previous studies have demonstrated a common variant of the obesity and fat mass-related FTO gene, rs9939609, to be associated with obesity, type 2 diabetes, and elevated blood pressure. We investigated whether the FTO SNP rs9939609 is associated with the risk of preeclampsia (PE in a Finnish study population. 485 women with prior PE and 449 women who had given birth after a normotensive pregnancy were genotyped (TaqMan for the SNP rs9939609. The prevalences of genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE cases, and 16%, 47%, and 37%, respectively, among the controls (P=0.199. We found no evidence of an association between the FTO SNP rs9939609 and PE. However, our cases were dominated by severe, early-onset PE. Thus, we are unable to exclude an association with the milder, later-onset form of the disease in which the role of maternal metabolic predisposition could be more significant.

  2. Association of FTO polymorphisms with obesity and obesity-related outcomes in Portuguese children.

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    David Albuquerque

    Full Text Available BACKGROUND: Several studies have reported an association between single nucleotide polymorphisms in the first intron of the FTO gene and body mass index (BMI or obesity. However, this association has not yet been studied among the Portuguese population. This study aims to assess the association of three FTO polymorphisms (rs1861868, rs1421085 and rs9939609 with obesity-related outcomes in a sample of Portuguese children. METHODS: We examined a total of 730 children, 256 normal-weight (55.9% girls, 320 overweight (45.3% girls and 154 obese (53.2% girls, aging from 6 to 12-years-old, recruited randomly from public schools in the central region of Portugal. DNA samples were genotyped for the three polymorphisms by allelic discrimination TaqMan assay. Association of the FTO polymorphisms with several anthropometric traits was investigated. Additionally, we tested association with the risk of obesity using overweight and obese vs. normal-weight children. RESULTS: We found significant associations of rs9939609 and rs1421085 polymorphisms with weight, BMI, BMI Z-score, waist circumference and hip circumference, even after age and gender adjustment (p0.05. Haplotype analyses identified two combinations (ACA and GCA associated with a higher risk of obesity (OR 1.53; 95% CI, 1.06-2.22; p = 0.023; OR 1.73; 95% CI, 1.06-2.87; p = 0.030, respectively. CONCLUSIONS: This study provides the first evidence for the association of FTO polymorphisms with anthropometric traits and risk of obesity in Portuguese children.

  3. Progress of the genetics of obesity: FTO%肥胖症易感基因——FTO的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨曦; 沈沭彤; 郭军

    2011-01-01

    FTO (fat mass and obesity associated) is expressed widely in many tissues and extremly highly in hypothalamus.It encodes a nucleic acid demethylase and influences expression of other genes by its nucleic acid demethylation activity.It was revealed that FTO gene variance is associated with body mass index(BMI) and the risk of obesity.FTO can lead to obesity and many complications such as type 2 diabetes through its effect on energy intake or expenditure and many other pathways.Inactivation of FTO can also protect mice from obesity.In this review, recent progress of the relationship between FTO variance and obesity, possible mechanisms of FTO and its effect on energy balance in humans will be summarized.%FTO(fat mass and obesity associated)是肥胖症易感基因,表达于人体各组织,且在下丘脑中高表达.它能编码核酸去甲基化酶,通过去甲基化作用影响其他相关基因表达.FTO的基因多态性与体重指数(BMI)及肥胖症密切相关.FTO能够影响能量摄入及能量消耗,并通过多种途径诱导人群中肥胖症及2型糖尿病等相关疾病的发生,而FTO失活的小鼠能够避免肥胖发生.主要综述了FTO基因多态性与肥胖等疾病易感性的相关性、FTO可能的作用机制和FTO对人群中能量平衡的影响.

  4. Blacking FTO by strongly cathodic polarization with enhanced photocurrent

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yun; Lu, Xiaoqing; Huang, Wei, E-mail: hjhw9513@163.com; Li, Zelin, E-mail: lizelin@hunnu.edu.cn

    2015-08-30

    Graphical abstract: - Highlights: • Transparent FTO became blackish under strongly cathodic polarization. • Part of SnO{sub 2} coating on the FTO can be reduced into Sn nanoparticles. • The black FTO increased solar absorption and enhanced photocurrent responses. • Take care in photoelectrochemistry test while FTO is strongly cathodically polarized. - Abstract: Transparent fluorine-doped tin oxide (TFTO) coating on quartz glass is widely used as substrate in photoelectrochemistry for solar energy transformation, sensing and so on. We observed that the TFTO could become blackish by strongly cathodic polarization. Characterization of the black FTO (BFTO) by scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy revealed that part of SnO{sub 2} on the TFTO was reduced into metal Sn nanoparticles during the cathodic polarization. The BFTO greatly increased solar absorption and enhanced photocurrent responses in comparison with TFTO. It might be necessary to take caution in photoelectrochemical measurements while the FTO is strongly cathodically polarized.

  5. Association of FTO rs9939609 SNP with Obesity and Obesity- Associated Phenotypes in a North Indian Population

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    Jai Prakash

    2016-03-01

    Full Text Available Objectives: Obesity is a common disorder that has a significant impact on morbidity and mortality. Twin and adoption studies support the genetic influence on variation of obesity, and the estimates of the heritability of body mass index (BMI is significantly high (30 to 70%. Variants in the fat mass and obesity-associated (FTO gene have been associated with obesity and obesity-related phenotypes in different populations. The aim of this study was to examine the association of FTO rs9939609 with obesity and related phenotypes in North Indian subjects.   Methods: Gene variants were investigated for association with obesity in 309 obese and 333 non-obese patients. Genotyping of the FTO rs9939609 single nucleotide polymorphism (SNP was analyzed using Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments. We also measured participants fasting glucose and insulin levels, lipid profile, percentage body fat, fat mass and fat free mass. Results: Waist to hip ratio, systolic blood pressure, diastolic blood pressure, percentage body fat, fat mass, insulin concentration, and homeostasis model assessment index (HOMA-Index showed a significant difference between the study groups. Significant associations were found for FTO rs9939609 SNP with obesity and obesity-related phenotypes. The significant associations were observed between the rs9939609 SNP and blood pressure, fat mass, insulin, and HOMA-index under a different model.   Conclusion: This study presents significant association between FTO rs9939609 and obesity defined by BMI and also established the strong association with several measures of obesity in North Indian population.

  6. Enhanced Water Splitting by Fe2O3-TiO2-FTO Photoanode with Modified Energy Band Structure

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    Eul Noh

    2013-01-01

    Full Text Available The effect of TiO2 layer applied to the conventional Fe2O3/FTO photoanode to improve the photoelectrochemical performance was assessed from the viewpoint of the microstructure and energy band structure. Regardless of the location of the TiO2 layer in the photoanodes, that is, Fe2O3/TiO2/FTO or TiO2/Fe2O3/FTO, high performance was obtained when α-Fe2O3 and H-TiNT/anatase-TiO2 phases existed in the constituent Fe2O3 and TiO2 layers after optimized heat treatments. The presence of the Fe2O3 nanoparticles with high uniformity in the each layer of the Fe2O3/TiO2/FTO photoanode achieved by a simple dipping process seemed to positively affect the performance improvement by modifying the energy band structure to a more favorable one for efficient electrons transfer. Our current study suggests that the application of the TiO2 interlayer, together with α-Fe2O3 nanoparticles present in the each constituent layers, could significantly contribute to the performance improvement of the conventional Fe2O3 photoanode.

  7. Common risk genes for affective and schizophrenic psychoses.

    Science.gov (United States)

    Maier, Wolfgang

    2008-06-01

    The familial-genetic relationship between affective and schizophrenic disorders is receiving a re-emergence of interest. The reasons are a series of cross-diagnostic molecular-genetic discoveries: specific alleles in the genes for dysbindin (DTNBP1), neuregulin (NRG1) and DAOA (G72/G30) reveal associations for each of both groups of disorders in the same direction in some but not all reported studies. These findings cannot just be false positives because of confirming metaanalyses. Furthermore there is some pathophysiological support: the mentioned genes are involved in biochemical pathways, which are contributing to both disorders partly in a similar and partly in a different manner. The new levels of evidence enrich the classical continuity/discontinuity debate on the relationship between both groups of disorders.

  8. Deletion of PLCB1 gene in schizophrenia-affected patients.

    Science.gov (United States)

    Lo Vasco, Vincenza Rita; Cardinale, Giuseppina; Polonia, Patrizia

    2012-04-01

    A prevalence of 1% in the general population and approximately 50% concordance rate in monozygotic twins was reported for schizophrenia, suggesting that genetic predisposition affecting neurodevelopmental processes might combine with environmental risk factors. A multitude of pathways seems to be involved in the aetiology and/or pathogenesis of schizophrenia, including dopaminergic, serotoninergic, muscarinic and glutamatergic signalling. The phosphoinositide signal transduction system and related phosphoinositide-specific phospholipase C (PI-PLC) enzymes seem to represent a point of convergence in these networking pathways during the development of selected brain regions. The existence of a susceptibility locus on the short arm of chromosome 20 moved us to analyse PLCB1, the gene codifying for PI-PLC β1 enzyme, which maps on 20p12. By using interphase fluorescent in situ hybridization methodology, we found deletions of PLCB1 in orbito-frontal cortex samples of schizophrenia-affected patients.

  9. Multiple controls affect arsenite oxidase gene expression in Herminiimonas arsenicoxydans

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    Coppée Jean-Yves

    2010-02-01

    Full Text Available Abstract Background Both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. These transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. Herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of As(III to As(V as a detoxification mechanism. Results In the present study, a differential transcriptome analysis was used to identify genes, including arsenite oxidase encoding genes, involved in the response of H. arsenicoxydans to As(III. To get insight into the molecular mechanisms of this enzyme activity, a Tn5 transposon mutagenesis was performed. Transposon insertions resulting in a lack of arsenite oxidase activity disrupted aoxR and aoxS genes, showing that the aox operon transcription is regulated by the AoxRS two-component system. Remarkably, transposon insertions were also identified in rpoN coding for the alternative N sigma factor (σ54 of RNA polymerase and in dnaJ coding for the Hsp70 co-chaperone. Western blotting with anti-AoxB antibodies and quantitative RT-PCR experiments allowed us to demonstrate that the rpoN and dnaJ gene products are involved in the control of arsenite oxidase gene expression. Finally, the transcriptional start site of the aoxAB operon was determined using rapid amplification of cDNA ends (RACE and a putative -12/-24 σ54-dependent promoter motif was identified upstream of aoxAB coding sequences. Conclusion These results reveal the existence of novel molecular regulatory processes governing arsenite oxidase expression in H. arsenicoxydans. These data are summarized in a model that functionally integrates arsenite oxidation in the adaptive response to As(III in this microorganism.

  10. Effects of FTO genotype on weight loss and metabolic risk factors in response to calorie restriction among Japanese women.

    Science.gov (United States)

    Matsuo, Tomoaki; Nakata, Yoshio; Murotake, Yukako; Hotta, Kikuko; Tanaka, Kiyoji

    2012-05-01

    Effects of gene variants in the fat-mass and obesity-associated (FTO) gene (primarily rs9939609) on weight loss induced by lifestyle intervention are controversial. The aim of this study was to investigate whether FTO gene variations are associated with weight-reduction and changes in metabolic risk factors in response to a 14-week calorie restriction. In total, 204 Japanese women (aged 24-66 years; BMI ≥ 25 kg/m(2)) enrolled as subjects and attended dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Fat mass, both at baseline (P = 0.100) and after the intervention (P = 0.020), was higher in subjects with the AA genotype (n = 15; 7.3%) than in those with TT (n = 114; 55.9%) and TA (n = 75; 36.8%) genotypes. The change in fat-mass tended to be smaller in subjects with the AA genotype than in those with other genotypes (P = 0.065). However, the subjects with the risk allele could still decrease their body weight and improve metabolic risk factors significantly. Our data suggest that the impact of FTO rs9939609 in Japanese women may not be great enough to change body weight or metabolic risk factors in response to calorie restriction. Environmental and behavioral factors may overcome the effects of genes on weight reduction.

  11. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population.

    Science.gov (United States)

    Duicu, Carmen; Mărginean, Cristina Oana; Voidăzan, Septimiu; Tripon, Florin; Bănescu, Claudia

    2016-05-01

    Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations.The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children.A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR-RFLP) method.Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose.This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors' knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels.

  12. Brief isoflurane anaesthesia affects differential gene expression, gene ontology and gene networks in rat brain.

    Science.gov (United States)

    Lowes, Damon A; Galley, Helen F; Moura, Alessandro P S; Webster, Nigel R

    2017-01-15

    Much is still unknown about the mechanisms of effects of even brief anaesthesia on the brain and previous studies have simply compared differential expression profiles with and without anaesthesia. We hypothesised that network analysis, in addition to the traditional differential gene expression and ontology analysis, would enable identification of the effects of anaesthesia on interactions between genes. Rats (n=10 per group) were randomised to anaesthesia with isoflurane in oxygen or oxygen only for 15min, and 6h later brains were removed. Differential gene expression and gene ontology analysis of microarray data was performed. Standard clustering techniques and principal component analysis with Bayesian rules were used along with social network analysis methods, to quantitatively model and describe the gene networks. Anaesthesia had marked effects on genes in the brain with differential regulation of 416 probe sets by at least 2 fold. Gene ontology analysis showed 23 genes were functionally related to the anaesthesia and of these, 12 were involved with neurotransmitter release, transport and secretion. Gene network analysis revealed much greater connectivity in genes from brains from anaesthetised rats compared to controls. Other importance measures were also altered after anaesthesia; median [range] closeness centrality (shortest path) was lower in anaesthetized animals (0.07 [0-0.30]) than controls (0.39 [0.30-0.53], pgenes after anaesthesia and suggests future targets for investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 'Obesity Gene' Doesn't Affect Ability to Lose Weight: Report

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161090.html 'Obesity Gene' Doesn't Affect Ability to Lose Weight: ... 21, 2016 (HealthDay News) -- Having the so-called "obesity gene" doesn't affect people's ability to shed ...

  14. Microarray analysis of genes affected by salt stress in tomato | Zhou ...

    African Journals Online (AJOL)

    Microarray analysis of genes affected by salt stress in tomato. ... African Journal of Environmental Science and Technology ... key enzyme genes in the metabolic pathways of carbohydrates, amino acids, and fatty acids, were also affected by ...

  15. Association of FTO and PPARG polymorphisms with obesity in Portuguese women

    Directory of Open Access Journals (Sweden)

    Ferreira Carlos F

    2013-07-01

    Full Text Available Fábio Ferreira Carlos,1,2 José Silva-Nunes,3,4 Orfeu Flores,1 Miguel Brito,3 Gonçalo Doria,1 Luísa Veiga,3 Pedro Viana Baptista1 1Centro de Investigação em Genética Molecular Humana, Universidade Nova de Lisboa, Caparica, Portugal; 2Investigação e Serviços em Ciências Biológicas, Stab Vida, Caparica, Portugal; 3Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal; 4Endocrinology Department, Curry Cabral Hospital, Lisbon, Portugal Purpose: We evaluated the association between risk of obesity in the Portuguese population and two obesity-related single-nucleotide gene polymorphisms: fat-mass and obesity-associated (FTO rs9939609 and peroxisome proliferator-activated receptor gamma (PPARG rs1801282. Patients and methods: A total of 194 Portuguese premenopausal female Caucasians aged between 18 and 50 years (95 with body mass index [BMI] ≥30 g/m2, 99 controls with BMI 18.5–24.9 kg/m2 participated in this study. The association of the single-nucleotide polymorphisms with obesity was determined by odds ratio calculation with 95% confidence intervals. Results: Significant differences in allelic expression of FTO rs9939609 (P0.05. Conclusion: For the first time, a study involving an adult Portuguese population shows that individuals harboring both risk alleles in the FTO gene locus are at higher risk for obesity, which is in agreement to what has been reported for other European populations. Keywords: rs9939609, rs1801282, BMI, SNP, odds ratio

  16. FTO genetic variants, dietary intake and body mass index

    DEFF Research Database (Denmark)

    Qi, Qibin; Oskari Kilpeläinen, Tuomas; Downer, Mary K

    2014-01-01

    FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small...

  17. Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African- and European-American youth

    NARCIS (Netherlands)

    Liu, Gaifen; Zhu, Haidong; Dong, Yanbin; Podolsky, Robert H.; Treiber, Frank A.; Snieder, Harold

    Recent genome-wide association (GWA) studies identified several common variants for obesity: rs9939609 in FTO, rs7566605 near INSIG2 and both rs17782313 and rs17700633 near the MC4R gene. This study aimed to assess the influence of these polymorphisms on development of adiposity in European- (EA)

  18. Physical activity attenuates the effect of the FTO genotype on obesity-related traits in European adults: Findings from the Food4Me study

    Science.gov (United States)

    Background. The FTO gene harbours the strongest known susceptibility locus for obesity. Studies of the interaction between genetic and environmental factors such as physical activity (PA) could contribute to the understanding of how lifestyle can modulate genetic susceptibility to obesity. In this s...

  19. The FRIABLE1 gene product affects cell adhesion in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lutz Neumetzler

    Full Text Available Cell adhesion in plants is mediated predominantly by pectins, a group of complex cell wall associated polysaccharides. An Arabidopsis mutant, friable1 (frb1, was identified through a screen of T-DNA insertion lines that exhibited defective cell adhesion. Interestingly, the frb1 plants displayed both cell and organ dissociations and also ectopic defects in organ separation. The FRB1 gene encodes a Golgi-localized, plant specific protein with only weak sequence similarities to known proteins (DUF246. Unlike other cell adhesion deficient mutants, frb1 mutants do not have reduced levels of adhesion related cell wall polymers, such as pectins. Instead, FRB1 affects the abundance of galactose- and arabinose-containing oligosaccharides in the Golgi. Furthermore, frb1 mutants displayed alteration in pectin methylesterification, cell wall associated extensins and xyloglucan microstructure. We propose that abnormal FRB1 action has pleiotropic consequences on wall architecture, affecting both the extensin and pectin matrices, with consequent changes to the biomechanical properties of the wall and middle lamella, thereby influencing cell-cell adhesion.

  20. FTO基因rs9939609单核苷酸多态性与新疆哈萨克族超重及肥胖儿童的关联研究%Association of the rs9939609 polymorphism of FTO gene with overweight or obesity in Hazakh Children

    Institute of Scientific and Technical Information of China (English)

    李敏; 刘洋; 徐佩茹; 叶明刚; 刘玉

    2010-01-01

    目的 研究体脂量和肥胖症相关基因(fat mass and obesity associated gene,FTO)单核苷酸多态性与新疆哈萨克族学龄儿童超重及肥胖症的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对141例超重及肥胖(病例组)的哈萨克族学龄儿童和138名健康对照儿童FTO基因rs9939609位点进行分析,同时进行血糖、血脂、胰岛素测定.结果 FTO基因rs9939609在病例组和健康对照组中基因型频率分别为:AA型0.071和0.029,AT型0.511和0.428,TT型0.418和0.543,两组AA、AT和TT 3种基因型频率分布差异无统计学意义(x2=5.74,P=0.057),但AA+AT(突变纯合子+突变杂合子)在病例组[0.582(82/141)]明显高于对照组[0.457(63/138)],差异具有统计学意义(x2=4.368,P=0.037);且在两组人群中A等位基因频率差异具有统计学意义(x2=4.772,P=0.029).病例组中AA+AT基因型携带者的血糖水平[(4.88±0.51)mol/L]较TT基因型携带者[(4.68±0.56)mol/L]高,差异具有统计学意义.Logistic回归分析显示,A等位基因是超重及肥胖的独立危险因素(OR=0.527;95%CI:0.319~0.869).结论 体脂量和肥胖症相关基因第1内含子rs9939609多态性和新疆哈萨克族学龄儿童超重及肥胖的发生具有相关性.%Objective To study the association of rs9939609 polymorphism of the fat mass and obesity associated gene FTO) with overweight or obesity in Hazakh children. Methods PCR-restriction fragment length polymorphism was used to determine the rs9939609 polymorphism in 141 patients with overweight or obesity and 138 healthy controls. Height and weight were measured for body mass index (BMI). Serum lipid levels including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol, blood pressure, plasma glucose levels, and plasma insulin were also determined. Results The genotype distributions of both groups were in the Hardy-Weinberg equilibrium. The frequencies of AA, AT and TT were 0. 071, 0

  1. Blacking FTO by strongly cathodic polarization with enhanced photocurrent

    Science.gov (United States)

    Xie, Yun; Lu, Xiaoqing; Huang, Wei; Li, Zelin

    2015-08-01

    Transparent fluorine-doped tin oxide (TFTO) coating on quartz glass is widely used as substrate in photoelectrochemistry for solar energy transformation, sensing and so on. We observed that the TFTO could become blackish by strongly cathodic polarization. Characterization of the black FTO (BFTO) by scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy revealed that part of SnO2 on the TFTO was reduced into metal Sn nanoparticles during the cathodic polarization. The BFTO greatly increased solar absorption and enhanced photocurrent responses in comparison with TFTO. It might be necessary to take caution in photoelectrochemical measurements while the FTO is strongly cathodically polarized.

  2. Resistance Switching Induced by Electric Field and Light Illumination in Device of FTO/CeO2/Electrolyte/FTO

    CERN Document Server

    Wang, Xiaoqi

    2012-01-01

    A heterojunction-like device consisting of FTO/CeO2/electrolyte/FTO is established with distinct transport performance, where FTO denotes F-doped transparent conducting glass, and the electrolyte is LiI and I2 in acetonitrile. The resistive switching behavior is observed, being induced through applying sufficient negative pulse as well as light illumination. The endurance measurements confirm that the write/erase periodic operation is reproducible and stable in the present device. Furthermore, the retention measurements demonstrate that the information can be stored temporarily for about 100 seconds. A possible mechanism regarding the formation of diiodide radical is proposed to give a reasonable explanation for the observed switching behavior.

  3. Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population.

    Science.gov (United States)

    Poveda, Alaitz; Ibáñez, María Eugenia; Rebato, Esther

    2014-01-01

    The objective of this study is to investigate the association between previously GWAS identified genetic variants predisposing to obesity in Europeans and obesity-related phenotypes in Roma population. A total of 24 representative single nucleotide polymorphisms (SNPs) were genotyped in 372 individuals belonging to 50 extended families of Roma population. SNPs were tested for association with seven quantitative obesity-related phenotypes in the PLINK program. Risk variants in NEGR1, FAIM2, FTO, and SH2B1 genes were associated with increased adiposity accumulation in Roma population with effect sizes between 0.21 and 0.34 Z-scores for each copy of the BMI increasing allele. Additionally, variants in BDNF and MC4R were significantly associated with adiposity distribution but not with overall fatness. No significant association was detected between obesity-related phenotypes and variants in the first intron of the FTO gene (e.g., rs9939609). The results of this study suggest that SNPs in or near six genes (BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1) are significantly associated with body fat accumulation and distribution in Roma people. However, the association observed among variants in the first intron of FTO and obesity in European derived populations is not evident in the analyzed Roma sample. © 2014 Wiley Periodicals, Inc.

  4. Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

    Science.gov (United States)

    Jacobsson, Josefin A; Almén, Markus Sällman; Benedict, Christian; Hedberg, Lilia A; Michaëlsson, Karl; Brooks, Samantha; Kullberg, Joel; Axelsson, Tomas; Johansson, Lars; Ahlström, Håkan; Fredriksson, Robert; Lind, Lars; Schiöth, Helgi B

    2011-01-01

    The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution. To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans. Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women. Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

  5. FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth

    Directory of Open Access Journals (Sweden)

    Dong Yanbin

    2010-04-01

    Full Text Available Abstract Background Genome-wide association studies found common variants in the fat mass and obesity-associated (FTO gene associated with adiposity in Caucasians and Asians but the association was not confirmed in African populations. Association of FTO variants with insulin resistance and energy intake showed inconsistent results in previous studies. This study aimed to assess the influence of FTO variant rs9939609 on adiposity, insulin resistance, energy intake and physical activity in European - (EA and African-American (AA youth. Methods We conducted a cross-sectional study in EA and AA youths. One thousand, nine hundred and seventy-eight youths (48.2% EAs, 47.1% male, mean age 16.5 years had measures of anthropometry. Percent body fat (%BF was measured by dual-energy X-ray absorptiometry, visceral adipose tissue (VAT and subcutaneous abdominal adipose tissue (SAAT by magnetic resonance imaging. Energy intake and physical activity were based on self report from up to 7 24-hour recalls. Physical activity was also measured by accelerometry. Results FTO rs9939609 was significantly associated with body mass index (BMI (P = 0.01, weight (P = 0.03 and waist circumference (P = 0.04, with per-allele effects of 0.4 kg/m2, 1.3 kg and 0.8 cm, respectively. No significant association was found between rs9939609 and %BF, VAT, SAAT or insulin resistance (P > 0.05, or between rs9939609 and energy intake or vigorous physical activity (P > 0.05. No significant interactions of rs9939609 with ethnicity, gender, energy intake or physical activity were observed (P > 0.05. Conclusions The FTO variant rs9939609 is modestly associated with BMI and waist circumference, but not with energy intake or physical activity. Moreover, these effects were similar for EAs and AAs. Improved understanding of the effect of the FTO variant will offer new insights into the etiology of excess adiposity.

  6. The study of FTO surface texturing fabrication using Argon plasma etching technique for DSSC applications

    Science.gov (United States)

    Jayanti, Lindha; Kusumandari; Sujitno, Tjipto; Suryana, Risa

    2016-02-01

    This paper is aimed to investigate the fabrication of the fluorine-doped tin oxide (FTO) texturing by using Argon (Ar) plasma etching. The pressure and temperature of Ar gas during plasma etching were 1.6 mbar and 240-285oC, respectively. The plasma etching time was varied from 3 and 10 min. We also prepared without etching samples as reference. UV-Vis spectrophotometer showed that the transmittances of etching samples are higher than the without etching samples. The root mean square roughness (Rq) of etching samples are lower than the without etching samples. It is considered that the Ar ions bombardment can modify the FTO surfaces. However, the etching time does not significantly affect the FTO surfaces for 3 min and 10 min. The Rq of the without etching sample, the etching sample for 3 min, and the etching sample for 10 min are 11.697 nm, 9.859 nm, and 9.777 nm, respectively. These results are good agreement with the four point probe measurement that indicated that the sheet resistance (RS) for each the without sample, the etching sample for 3 min, and the etching sample for 10 min are 16.817 Ωsq, 16.067 Ω/sq, and 15.990 Ω/sq. In addition, the optical transmittance of the etching sample for 3 min and the etching sample for 10 min at wavelengths of 350 - 850 nm are almost similar. This is evidence that the etching time below 10 min cannot significantly change the morphology, optical and electrical properties.

  7. Age- and sex-dependent association between FTO rs9939609 and obesity-related traits in Chinese children and adolescents.

    Directory of Open Access Journals (Sweden)

    Meixian Zhang

    Full Text Available BACKGROUND: The associations between common variants in the fat mass- and obesity-associated (FTO gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of FTO rs9939609 with body mass index (BMI and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident. METHODS: Totally 757 obese and 2,746 non-obese Chinese children aged 6-18 years were genotyped for FTO rs9939609. Of these, a young sub-cohort (n = 777 aged 6-11 years was reexamined 6 years later. Obesity was defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force. RESULTS: The associations of FTO rs9939609 with BMI and obesity did not appear until children reached 12-14 years. The variant was associated with an increased BMI in boys (β = 1.50, P = 0.004 and girls (β = 0.97, P = 0.018, respectively. Thereafter, the magnitude of association increased in girls at ages 15-18 years (β = 2.02, P0.05. Age was found to interact with the variant on BMI (P<0.001 and obesity (P = 0.042 only in girls. In the sub-cohort, the associations of FTO rs9939609 with BMI (β = 1.07, P = 0.008 and obesity (OR = 2.09, 95% CI: 1.12, 3.91 were only observed 6 years later (ages 12-18 years in girls, even after adjusting for baseline BMI. CONCLUSIONS: The association between FTO rs9939609 and obesity-related traits may change from childhood to adolescence in Chinese individuals, and the association may start as early as age 12 years, especially in girls.

  8. Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Wojciechowski, P; Lipowska, A; Rys, P; Ewens, K G; Franks, S; Tan, S; Lerchbaum, E; Vcelak, J; Attaoua, R; Straczkowski, M; Azziz, R; Barber, T M; Hinney, A; Obermayer-Pietsch, B; Lukasova, P; Bendlova, B; Grigorescu, F; Kowalska, I; Goodarzi, M O; Strauss, J F; McCarthy, M I; Malecki, M T

    2012-10-01

    FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.

  9. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency.

  10. The Common FTO Genetic Polymorphism rs9939609 is Associated with Increased BMI in Type 1 Diabetes  but not with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Harvest F. Gu

    2010-04-01

    Full Text Available The fat mass and obesity associated (FTO gene has an important genetic effect on body mass index (BMI and risk of obesity, and obesity contributes to the progression of renal diseases, including diabetic nephropathy. We thus conducted a genetic association study to evaluate whether the FTO gene confers the risk susceptibility to the development of diabetic nephropathy. Genotyping experiments of the common FTO polymorphism, rs9939609, in 1170 type 1 diabetes patients with (n = 597 or without diabetic nephropathy (n = 573 were performed with TaqMan allelic discrimination. All subjects are of European descent and selected from the Genetics of Kidney Diseases in Diabetes (GoKinD study. The frequency of T allele of this polymorphism was 0.414 in the studied population. There was no allelic association of this polymorphism with diabetic nephropathy. But, the risk susceptibility of A allele conferring to the increased BMI among type 1 diabetes patients was observed. The subjects carrying with AA genotype had higher BMI compared to the carriers with TA and/or TT genotype(s (P # 0.019. The present study provides evidence that the common FTO genetic polymorphism, rs9939609, is associated with increased BMI in type 1 diabetes but not with diabetic nephropathy.

  11. Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case-control study in Japan.

    Science.gov (United States)

    Lin, Yingsong; Ueda, Junko; Yagyu, Kiyoko; Ishii, Hiroshi; Ueno, Makoto; Egawa, Naoto; Nakao, Haruhisa; Mori, Mitsuru; Matsuo, Keitaro; Kikuchi, Shogo

    2013-07-08

    It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. We conducted a hospital-based case-control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk. The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07-2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70-3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07-1.85). There were no significant interactions between TA/AA genotypes and body mass index. Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples.

  12. Influences of the common FTO rs9939609 variant on inflammatory markers throughout a broad range of body mass index.

    Directory of Open Access Journals (Sweden)

    Esther Zimmermann

    Full Text Available BACKGROUND: A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI among Danish men. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1 a random 1% sample and 2 all obese men (BMI = 31.0 kg/m(2, all of whom were above the 99(th percentile of this population. At an average age of 49 years (range: 39 through 65 years, 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively. CONCLUSION: No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.

  13. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius;

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  14. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  15. Effect of anneal temperature on fluorine doped tin oxide (FTO) nanostructured fabricated using hydrothermal method

    Science.gov (United States)

    Ahmad, M. K.; Marzuki, N. A.; Soon, C. F.; Nafarizal, N.; Sanudin, R.; Suriani, A. B.; Mohamed, A.; Shimomura, M.; Murakami, K.; Mamat, M. H.; Malek, M. F.

    2017-01-01

    FTO thin films were prepared by the hydrothermal method at anneal temperature of 100°C-400°C using pentahydrate stannic chloride (SnCl4.5H2O) and ammonium fluoride (NH4F) as precursors, and a mixture of DI water, acetone and hydrochloride as a solvent. The X-ray diffraction studies confirmed the tetragonal structure with polycrystalline nature. The preferred directions of crystal growth appeared in the diffractogram of FTO thin films prepared with different anneal temperature were correspond to the reflection from the (101), (200) and (211) planes, respectively. The electrical study reveals that the films have degenerate and exhibit n-type electrical conductivity. For films prepared at 400°C, the relatively higher transmittance of about 85-90% at 800nm has been observed. The transmission attained in this study is greater than the values reported for tin oxide films prepared at anneal temperature 400°C, from an aqueous solution of SnCl4.5H2O precursor. Resistivity is smaller than the value reported. The obtained results revealed that the structures and properties of the films were greatly affected by anneal temperature

  16. Genes affecting heading date in cocksfoot (Dactylis glomerata)

    Science.gov (United States)

    Several genes cause well known effects on heading date in cool-season forages: Vrn1, Constans, and FloweringTime. Vrn1 is a MADs box transcription factor that is induced upon vernalization and necessary for flowering. Constans genes are induced upon long days in cool-season grasses and induce exp...

  17. Physical activity, but not dietary intake, attenuates the effect of the FTO rs9939609 polymorphism on obesity and metabolic syndrome in Lithuanian adult population.

    Science.gov (United States)

    Petkeviciene, J; Smalinskiene, A; Klumbiene, J; Petkevicius, V; Kriaucioniene, V; Lesauskaite, V

    2016-06-01

    This study aimed to examine the associations between the fat mass and obesity associated (FTO) gene rs9939609 variant with obesity and metabolic syndrome and interactions between FTO alleles, dietary intake and physical activity in Lithuanian adult population. Cross-sectional study. A health survey was carried out in randomly selected municipalities of Lithuania. The random sample was obtained from the lists of 25-64 year-old inhabitants. The data from 1020 individuals were analyzed. The single-nucleotide polymorphism, rs9939609, in the FTO gene was assessed using a real-time polymerase chain reaction. 24-hour recall was used for evaluation of dietary habits. Information on physical activity at work, traveling to and from work and at leisure time was gathered by a standard questionnaire. The carriers of the AA genotype had the highest mean values of body mass index (BMI) and waist circumference (WC). They had 1.72 time higher odds of obesity (P = 0.009) and 1.67 time higher odds of increased WC (P = 0.013) than those with the TT genotype. Carriers of the T allele had lower prevalence of metabolic syndrome compared to carriers of the AA genotype (33.8% and 42.5% respectively; P = 0.018). No interaction between the rs9939609 variant and energy or dietary intakes on weight status was found. Significant effect of the interactions 'genotype×age' and 'genotype×physical activity' on BMI was demonstrated. The FTO rs9939609 polymorphism was associated with anthropometric parameters and metabolic syndrome in the younger age group (25-44 years) and in individuals having low level of physical activity. Age and physical activity modulated the effect of the FTO polymorphism on weight status and metabolic syndrome in Lithuanian adult population. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  18. Directed mutagenesis affects recombination in Azospirillum brasilense nif genes

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    C.P. Nunes

    2000-12-01

    Full Text Available In order to improve the gene transfer/mutagenesis system for Azospirillum brasilense, gene-cartridge mutagenesis was used to replace the nifD gene with the Tn5 kanamycin resistance gene. The construct was transferred to A. brasilense by electrotransformation. Of the 12 colonies isolated using the suicide plasmid pSUP202 as vector, only four did not show vector integration into the chromosome. Nevertheless, all 12 colonies were deficient in acetylene reduction, indicating an Nif- phenotype. Four Nif- mutants were analyzed by Southern blot, using six different probes spanning the nif and Km r genes and the plasmid vector. Apparently, several recombination events occurred in the mutant genomes, probably caused mainly by gene disruption owing to the mutagenesis technique used: resistance gene-cartridge mutagenesis combined with electrotransformation.Com o objetivo de melhorar os sistemas de transferência gênica e mutagênese para Azospirillum brasilense, a técnica de mutagênese através do uso de um gene marcador ("gene-cartridge mutagenesis" foi utilizada para substituir a região genômica de A. brasilense correspondente ao gene nifD por um segmento de DNA do transposon Tn5 contendo o gene que confere resistência ao antibiótico canamicina. A construção foi transferida para a linhagem de A. brasilense por eletrotransformação. Doze colônias transformantes foram isoladas com o plasmídeo suicida pSUP202 servindo como vetor. Dessas, somente quatro não possuíam o vetor integrado no cromossomo da bactéria. Independentemente da integração ou não do vetor, as 12 colônias foram deficientes na redução do gás acetileno, evidenciando o fenótipo Nif -. Quatro mutantes Nif - foram analisados através da técnica de Southern blot, utilizando-se seis diferentes fragmentos contendo genes nif, de resistência à canamicina e do vetor como sondas. Os resultados sugerem a ocorrência de eventos recombinacionais variados no genoma dos mutantes. A

  19. How the Neanderthal in Your Genes Affects Your Health

    Science.gov (United States)

    ... however, how that modified protein is connected to schizophrenia or height, the researchers said. The study also found that, overall, Neanderthal genes are least active in the brain and testes. ...

  20. Y-chromosomal genes affecting male fertility: A review

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    Jasdeep Kaur Dhanoa

    2016-07-01

    Full Text Available The mammalian sex-chromosomes (X and Y have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility.

  1. Diaphanous gene mutation affects spiral cleavage and chirality in snails

    Science.gov (United States)

    Kuroda, Reiko; Fujikura, Kohei; Abe, Masanori; Hosoiri, Yuji; Asakawa, Shuichi; Shimizu, Miho; Umeda, Shin; Ichikawa, Futaba; Takahashi, Hiromi

    2016-01-01

    L-R (left and right) symmetry breaking during embryogenesis and the establishment of asymmetric body plan are key issues in developmental biology, but the onset including the handedness-determining gene locus still remains unknown. Using pure dextral (DD) and sinistral (dd) strains of the pond snail Lymnaea stagnalis as well as its F2 through to F10 backcrossed lines, the single handedness-determining-gene locus was mapped by genetic linkage analysis, BAC cloning and chromosome walking. We have identified the actin-related diaphanous gene Lsdia1 as the strongest candidate. Although the cDNA and derived amino acid sequences of the tandemly duplicated Lsdia1 and Lsdia2 genes are very similar, we could discriminate the two genes/proteins in our molecular biology experiments. The Lsdia1 gene of the sinistral strain carries a frameshift mutation that abrogates full-length LsDia1 protein expression. In the dextral strain, it is already translated prior to oviposition. Expression of Lsdia1 (only in the dextral strain) and Lsdia2 (in both chirality) decreases after the 1-cell stage, with no asymmetric localization throughout. The evolutionary relationships among body handedness, SD/SI (spiral deformation/spindle inclination) at the third cleavage, and expression of diaphanous proteins are discussed in comparison with three other pond snails (L. peregra, Physa acuta and Indoplanorbis exustus). PMID:27708420

  2. Genes from Lycopersicon chmielewskii affecting tomato quality during fruit ripening.

    Science.gov (United States)

    Azanza, F; Kim, D; Tanksley, S D; Juvik, J A

    1995-08-01

    Three chromosomal segments from the wild tomato, L. chmielewskii, introgressed into the L. esculentum genome have been previously mapped to the middle and terminal regions of chromosome 7 (7M, 7T respectively), and to the terminal region of chromosome 10 (10T). The present study was designed to investigate the physiological mechanisms controlled by the 7M and 7T segments on tomato soluble solids (SS) and pH, and their genetic regulation during fruit development. The effects of 7M and 7T were studied in 64 BC2F5 backcross inbred lines (BILs) developed from a cross between LA 1501 (an L. esculentum line containing the 7M and 7T fragments from L. chmielewskii), and VF145B-7879 (a processing cultivar). BILs were classified into four homozygous genotypes with respect to the introgressed segments based on RFLP analysis, and evaluated for fruit chemical characteristics at different harvest stages. Gene(s) in the 7M fragment reduce fruit water uptake during ripening increasing pH, sugars, and SS concentration. Gene(s) in the 7T fragment were found to be associated with higher mature green fruit starch concentration and red ripe fruit weight. Comparisons between tomatoes ripened on or off the vine suggest that the physiological mechanisms influenced by the L. chmielewskii alleles are dependent on the translocation of photosynthates and water during fruit ripening.

  3. Genetic variation in genes affecting milk composition and quality

    DEFF Research Database (Denmark)

    Bertelsen, Henriette Pasgaard

    In the past decade major advances in next generation sequencing technologies have provided new opportuneties for the detection of genetic variation. Combining the knowlegde of genetic variation with phenotypic distributions provides considerable possibilites for detection of candidate genes....... In addition, exploring genetic variation related to the major milk proteins of bovine milk indntified genetic variations with possitive effects on milk coagulation...

  4. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    Directory of Open Access Journals (Sweden)

    Galina Lurie

    Full Text Available Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2. This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively. In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR  = 1.17; 95% confidence interval (CI: 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI, suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68. FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  5. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

    Directory of Open Access Journals (Sweden)

    Tuomas O Kilpeläinen

    2011-11-01

    Full Text Available The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166 and nine studies of children and adolescents (n = 19,268.All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2>0.8] and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A- allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26, but PA attenuated this effect (p(interaction  = 0.001. More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25 than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36. No such interaction was found in children and adolescents.The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

  6. Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders.

    Science.gov (United States)

    Leszczyńska-Rodziewicz, Anna; Szczepankiewicz, Aleksandra; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2013-01-01

    Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  7. Association, Haplotype, and Gene-Gene Interactions of the HPA Axis Genes with Suicidal Behaviour in Affective Disorders

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    Anna Leszczyńska-Rodziewicz

    2013-01-01

    Full Text Available Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA. Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1. The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  8. C-B3-02: Association of FTO, INSIG2, MC4R, and PCSK1 Obesity SNPs With Binge Eating in Morbidly Obese Patients

    Science.gov (United States)

    Gerhard, Glenn S; Still, Christopher D; Wood, G Craig; Chu, Xin; Erdman, Robert; Susek, Meghan; Gerst, Heather; Derr, Kim; AlAgha, Mouna; Hartman, Christina; Carey, David; Benotti, Peter

    2010-01-01

    Background/Aims: Obesity has a strong genetic component. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in or near over a dozen genes that are related to body mass index (BMI). Despite the association of these SNPs with BMI, the mechanism by which they influence the determination of body weight is not yet known. Recently, the fat- mass and obesity-associated (FTO) obesity SNP was related to energy intake and preference for foods of high caloric density in children. FTO genotype was not associated with resting energy expenditure. We have extended this type of analysis to eating behaviors in the morbidly obese. Methods: DNA was obtained from approximately 900 morbidly obese (BMI>40 kg/m2) patients and used to genotype obesity SNPs in or near the FTO, INSIG2, MC4R, and PCSK1 genes. Binge eating status (normal, episodic overeating, or any binge eating) was determined using the validated Questionnaire on Eating and Weight Patterns (QEWP). Binge eating status was correlated with each individual genotype, the combined obesity allele burden, and the combined homozygous obesity gene burden. Results: Binge eating data was obtained from 640 patients who had completed the QEWP. Of these 640, 116 (18%) were classified as manifesting binge eating behavior. No association was present between heterozygous or homozygous FTO (P=0.59), MC4R (P=0.30), or PSK1 (P=0.77) obesity SNPs. However, 29% of those who were homozygous for the INSIG2 obesity SNP were classified as binge eaters, versus 17% of heterozygous or homozygous normal patients (P=0.006). Association was also found with binge eating status and the presence of 2 or more homozygous obesity genotypes (28% versus 17%, P=0.041), likely due to the INSIG2 gene. Cumulative obesity allele burden (0–8 alleles for the 4 genes) was not associated with binge eating status (P=0.42). Conclusions: The INSIG2 obesity SNP appears to influence binge eating behavior in morbidly obese adults. The

  9. FTO is necessary for the induction of leptin resistance by high-fat feeding

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    Y.C. Loraine Tung

    2015-04-01

    Conclusions: Our study demonstrates that, independent of body weight, Fto influences the metabolic outcomes of a HFD through alteration of hypothalamic NFкB signalling. This supports the notion that pharmacological modulation of FTO activity might have the potential for therapeutic benefit in improving leptin sensitivity, in a manner that is influenced by the nutritional environment.

  10. Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

    Science.gov (United States)

    Michaillat, Lydie; Mayer, Andreas

    2013-01-01

    The equilibrium of membrane fusion and fission influences the volume and copy number of organelles. Fusion of yeast vacuoles has been well characterized but their fission and the mechanisms determining vacuole size and abundance remain poorly understood. We therefore attempted to systematically characterize factors necessary for vacuole fission. Here, we present results of an in vivo screening for deficiencies in vacuolar fragmentation activity of an ordered collection deletion mutants, representing 4881 non-essential genes of the yeast Saccharomyces cerevisiae. The screen identified 133 mutants with strong defects in vacuole fragmentation. These comprise numerous known fragmentation factors, such as the Fab1p complex, Tor1p, Sit4p and the V-ATPase, thus validating the approach. The screen identified many novel factors promoting vacuole fragmentation. Among those are 22 open reading frames of unknown function and three conspicuous clusters of proteins with known function. The clusters concern the ESCRT machinery, adaptins, and lipases, which influence the production of diacylglycerol and phosphatidic acid. A common feature of these factors of known function is their capacity to change membrane curvature, suggesting that they might promote vacuole fragmentation via this property. PMID:23383298

  11. Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

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    Josefin A Jacobsson

    Full Text Available BACKGROUND: The rs9939609 single-nucleotide polymorphism (SNP in the fat mass and obesity (FTO gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution. OBJECTIVE: To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans. DESIGN: Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS cohort. RESULTS: Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women. CONCLUSIONS: Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

  12. Laser-assisted preparation and photoelectric properties of grating-structured Pt/FTO thin films

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Nai-fei, E-mail: rnf_ujs@126.com [School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China); Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); Huang, Li-jing, E-mail: lij_huang@126.com [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Li, Bao-jia [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Zhou, Ming [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); The State Key Laboratory of Tribology, Tsinghua University, Beijing 100084 (China)

    2014-09-30

    Highlights: • Pt layers were deposited by DC magnetron sputtering on commercial FTO glasses. • Pt/FTO films were irradiated by laser for inducing gratings and annealing. • An ideal grating-structured Pt/FTO film was obtained using a fluence of 1.05 J/cm{sup 2}. • The grating-structured Pt/FTO film exhibited excellent photoelectric properties. • Laser-assisted treatment is effective for improving performance of FTO-based films. - Abstract: In order to improve the transparency and conductivity of commercial fluorine-doped tin oxide (FTO) glass, platinum (Pt) layers were deposited on the FTO film by direct current (DC) magnetron sputtering, followed by being irradiating with a 532 nm nanosecond pulsed laser for the dual purpose of inducing grating structures and annealing. Introducing a Pt layer decreased the average transmittance (400–800 nm) and the sheet resistance of the initial FTO film from 80.2% and 8.4 Ω/sq to 68.6% and 7.9 Ω/sq, respectively. The ideal grating-structured Pt/FTO film was obtained by laser irradiation with a fluence of 1.05 J/cm{sup 2}, and X-ray diffraction (XRD) analysis confirmed that this film underwent optimal annealing. As a result, it exhibited an average transmittance (400–800 nm) of 84.1% and a sheet resistance of 6.8 Ω/sq. These results indicated that laser-assisted treatment combined with introduction of metal layer can effectively improve photoelectric properties of FTO single-layer films.

  13. Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

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    Yun-Hua Yue

    2016-07-01

    Full Text Available Background/Aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔLDL and ΔLDL/LDL (p < 0.05; the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL/(LDL/HDL (p < 0.01 and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05. In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔTG (p < 0.05; the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL/(LDL/HDL (p < 0.01. In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of ΔHDL (p < 0.05; the SNP rs662799 significantly affected the ratio of ΔLDL/LDL (p < 0.05 and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05. Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

  14. Factors affecting the concordance between orthologous gene trees and species tree in bacteria

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    González Víctor

    2008-10-01

    Full Text Available Abstract Background As originally defined, orthologous genes implied a reflection of the history of the species. In recent years, many studies have examined the concordance between orthologous gene trees and species trees in bacteria. These studies have produced contradictory results that may have been influenced by orthologous gene misidentification and artefactual phylogenetic reconstructions. Here, using a method that allows the detection and exclusion of false positives during identification of orthologous genes, we address the question of whether putative orthologous genes within bacteria really reflect the history of the species. Results We identified a set of 370 orthologous genes from the bacterial order Rhizobiales. Although manifesting strong vertical signal, almost every orthologous gene had a distinct phylogeny, and the most common topology among the orthologous gene trees did not correspond with the best estimate of the species tree. However, each orthologous gene tree shared an average of 70% of its bipartitions with the best estimate of the species tree. Stochastic error related to gene size affected the concordance between the best estimated of the species tree and the orthologous gene trees, although this effect was weak and distributed unevenly among the functional categories. The nodes showing the greatest discordance were those defined by the shortest internal branches in the best estimated of the species tree. Moreover, a clear bias was evident with respect to the function of the orthologous genes, and the degree of divergence among the orthologous genes appeared to be related to their functional classification. Conclusion Orthologous genes do not reflect the history of the species when taken as individual markers, but they do when taken as a whole. Stochastic error affected the concordance of orthologous genes with the species tree, albeit weakly. We conclude that two important biological causes of discordance among

  15. Thioridazine affects transcription of genes involved in cell wall biosynthesis in methicillin-resistant Staphylococcus aureus

    DEFF Research Database (Denmark)

    Bonde, Mette; Højland, Dorte Heidi; Kolmos, Hans Jørn

    2011-01-01

    and affect the ability of the bacteria to sustain oxacillin treatment. Furthermore, we found that thioridazine itself reduces the expression level of selected virulence genes and that selected toxin genes are not induced by thioridazine. In the present study, we find indications that the mechanism underlying...

  16. Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample

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    Hanley Anthony JG

    2008-03-01

    Full Text Available Abstract Background The rs9939609 T>A single-nucleotide polymorphism (SNP in the FTO gene has previously been found to be associated with obesity in European Caucasian samples. The objective of this study is to examine whether this association extends to metabolic syndrome (MetS and applies in non-Caucasian samples. Methods The FTO rs9939609 SNP was genotyped in 2121 subjects from four different non-Caucasian geographical ancestries. Subjects were classified for the presence or absence of MetS according to the International Diabetes Federation (IDF and National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III definitions. Results Carriers of ≥ 1 copy of the rs9939609 A allele were significantly more likely to have IDF-defined MetS (35.8% than non-carriers (31.2%, corresponding to a carrier odds ratio (OR of 1.23 (95% confidence interval [CI] 1.01 to 1.50, with a similar trend for the NCEP ATP III-defined MetS. Subgroup analysis showed that the association was particularly strong in men. The association was related to a higher proportion of rs9939609 A allele carriers meeting the waist circumference criterion; a higher proportion also met the HDL cholesterol criterion compared with wild-type homozygotes. Conclusion Thus, the FTO rs9939609 SNP was associated with an increased risk for MetS in this multi-ethnic sample, confirming that the association extends to non-Caucasian population samples.

  17. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Grunnet, Louise G; Nilsson, Emma; Ling, Charlotte

    2009-01-01

    and adipose tissue, and their influence on in vivo glucose and fat metabolism. Research Design and Methods. The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years...... expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle...

  18. DISC1 gene and affective psychopathology : A combined structural and functional MRI study

    NARCIS (Netherlands)

    Opmeer, Esther M.; van Tol, Marie-Jose; Kortekaas, Rudie; van der Wee, Nic J. A.; Woudstra, Saskia; van Buchem, Mark A.; Penninx, Brenda W.; Veltman, Dick J.; Aleman, Andre

    The gene Disrupted-In-Schizophrenia-1 (DISCI) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISCI

  19. Au{sup 3+} ion implantation on FTO coated glasses: Effect on structural, electrical, optical and phonon properties

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bindu; Dey, Ranajit; Bajpai, P.K., E-mail: bajpai.pk1@gmail.com

    2017-06-01

    Highlights: • Effects of 11.00 MeV Au{sup 3+} ions implanted in FTO coated (thickness ≈300 nm) silicate glasses at varying fluence. • Metal clustering near the surface and subsurface region below glass-FTO interface changes electrical and optical properties significantly. • Ion implantation does not affect the crystalline structure of the coated films; however, the tetragonal distortion increases with increasing ion fluence. • Significant surface reconstruction takes place with ion beam fluence; The average roughness also decreases with increasing fluence. • The sheet resistivity increases with increasing fluence. • Raman analysis also corroborates the re-crystallization process inducing due to ion implantation. • Optical properties of the implanted surfaces changes significantly. - Abstract: Effects of 11.00 MeV Au{sup 3+} ions implanted in FTO coated (thickness ≈300 nm) silicate glasses on structural, electrical optical and phonon behavior have been explored. It has been observed that metal clustering near the surface and sub-surface region below glass-FTO interface changes electrical and optical properties significantly. Ion implantation does not affect the crystalline structure of the coated films; however, the unit cell volume decreases with increase in fluence and the tetragonal distortion (c/a ratio) also decreases systematically in the implanted samples. The sheet resistivity of the films increases from 11 × 10{sup −5} ohm-cm (in pristine) to 7.5 × 10{sup −4} ohm-cm for highest ion beam fluence ≈10{sup 15} ions/cm{sup 2}. The optical absorption decreases with increasing fluence whereas, the optical transmittance as well as reflectance increases with increasing fluence. The Raman spectra are observed at ∼530 cm{sup −1} and ∼1103 cm{sup −1} in pristine sample. The broad band at 530 cm{sup −1} shifts towards higher wave number in the irradiated samples. This may be correlated with increased disorder and strain relaxation in

  20. Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) SNP are positively associated with obesity and blood pressure in Mexican school-aged children.

    Science.gov (United States)

    García-Solís, Pablo; Reyes-Bastidas, Marissa; Flores, Karla; García, Olga P; Rosado, Jorge L; Méndez-Villa, Lorena; Garcia-G, Carlota; García-Gutiérrez, David; Kuri-García, Aarón; Hernández-Montiel, Hebert L; Soriano-Leon, Ofelia; Villagrán-Herrera, Maria Elena; Solis-Sainz, Juan C

    2016-11-10

    Childhood overweight and obesity are worldwide public health problems and risk factors for chronic diseases. The presence of SNP in several genes has been associated with the presence of obesity. A total of 580 children (8-13 years old) from Queretaro, Mexico, participated in this cross-sectional study, which evaluated the associations of rs9939609 (fat mass obesity-associated (FTO)), rs17782313 (melanocortin 4 receptor (MC4R)) and rs6548238 (transmembrane protein 18 (TMEM18)) SNP with obesity and metabolic risk factors. Overweight and obesity prevalence was 19·8 and 19·1 %, respectively. FTO, MC4R and TMEM18 risk allele frequency was 17, 9·8 and 89·5 %, respectively. A significant association between FTO homozygous and MC4R heterozygous risk alleles and obesity was found (OR 3·9; 95 % CI 1·46, 10·22, and OR 2·1; 95 % CI 1·22, 3·71; respectively). The FTO heterozygous subjects showed higher systolic and diastolic blood pressures, compared with the homozygous for the ancestral allele subjects. These results remain significant after considering adiposity as a covariate. The FTO and MC4R genotypes were not significantly associated with total cholesterol, HDL-cholesterol and insulin concentration. No association was found between TMEM18 risk allele and obesity and/or metabolic alterations. Our results show that, in addition to a higher BMI, there is also an association of the risk genotype with blood pressure in the presence of the FTO risk genotype. The possible presence of a risk genotype in obese children must be considered to offer a more comprehensive therapeutic approach in order to delay and/or prevent the development of chronic diseases.

  1. High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Evert van den Broek

    Full Text Available Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA and structural variants (SVs. Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC and to determine the clinical relevance of recurrent breakpoint genes.Primary CRC samples of patients with metastatic disease from CAIRO and CAIRO2 clinical trials were previously characterized by array-comparative genomic hybridization. These data were now used to determine the prevalence of CNA-associated chromosomal breaks within genes across 352 CRC samples. In addition, mutation status of the commonly affected APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS genes was determined for 204 CRC samples by targeted massive parallel sequencing. Clinical relevance was assessed upon stratification of patients based on gene mutations and gene breakpoints that were observed in >3% of CRC cases.In total, 748 genes were identified that were recurrently affected by chromosomal breaks (FDR 3% of cases, indicating that prevalence of gene breakpoints is comparable to the prevalence of well-known gene point mutations. Patient stratification based on gene breakpoints and point mutations revealed one CRC subtype with very poor prognosis.We conclude that CNA-associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC.

  2. Parental vitamin deficiency affects the embryonic gene expression of immune-, lipid transport- and apolipoprotein genes

    Science.gov (United States)

    Skjærven, Kaja H.; Jakt, Lars Martin; Dahl, John Arne; Espe, Marit; Aanes, Håvard; Hamre, Kristin; Fernandes, Jorge M. O.

    2016-10-01

    World Health Organization is concerned for parental vitamin deficiency and its effect on offspring health. This study examines the effect of a marginally dietary-induced parental one carbon (1-C) micronutrient deficiency on embryonic gene expression using zebrafish. Metabolic profiling revealed a reduced 1-C cycle efficiency in F0 generation. Parental deficiency reduced the fecundity and a total of 364 genes were differentially expressed in the F1 embryos. The upregulated genes (53%) in the deficient group were enriched in biological processes such as immune response and blood coagulation. Several genes encoding enzymes essential for the 1-C cycle and for lipid transport (especially apolipoproteins) were aberrantly expressed. We show that a parental diet deficient in micronutrients disturbs the expression in descendant embryos of genes associated with overall health, and result in inherited aberrations in the 1-C cycle and lipid metabolism. This emphasises the importance of parental micronutrient status for the health of the offspring.

  3. Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets Early after Isolation Affects Results of Gene Expression Studies.

    Directory of Open Access Journals (Sweden)

    Lucie Kosinová

    Full Text Available The use of RT-qPCR provides a powerful tool for gene expression studies; however, the proper interpretation of the obtained data is crucially dependent on accurate normalization based on stable reference genes. Recently, strong evidence has been shown indicating that the expression of many commonly used reference genes may vary significantly due to diverse experimental conditions. The isolation of pancreatic islets is a complicated procedure which creates severe mechanical and metabolic stress leading possibly to cellular damage and alteration of gene expression. Despite of this, freshly isolated islets frequently serve as a control in various gene expression and intervention studies. The aim of our study was to determine expression of 16 candidate reference genes and one gene of interest (F3 in isolated rat pancreatic islets during short-term cultivation in order to find a suitable endogenous control for gene expression studies. We compared the expression stability of the most commonly used reference genes and evaluated the reliability of relative and absolute quantification using RT-qPCR during 0-120 hrs after isolation. In freshly isolated islets, the expression of all tested genes was markedly depressed and it increased several times throughout the first 48 hrs of cultivation. We observed significant variability among samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During the first 48 hrs, relative quantification failed to reflect the real changes in respective mRNA concentrations while in the interval 48-120 hrs, the relative expression generally paralleled the results determined by absolute quantification. Thus, our data call into question the suitability of relative quantification for gene expression analysis in pancreatic islets during the first 48 hrs of cultivation, as the results may be significantly affected by unstable expression of reference genes. However, this method could provide reliable information

  4. Systematic identification of novel, essential host genes affecting bromovirus RNA replication.

    Directory of Open Access Journals (Sweden)

    Brandi L Gancarz

    Full Text Available Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol levels were significantly increased in strains depleted for a heat shock protein (HSF1 or proteasome components (PRE1 and RPT6, suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.

  5. Systematic identification of novel, essential host genes affecting bromovirus RNA replication.

    Science.gov (United States)

    Gancarz, Brandi L; Hao, Linhui; He, Qiuling; Newton, Michael A; Ahlquist, Paul

    2011-01-01

    Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol) levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol) localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.

  6. Analysis of thirteen trinucleotide repeat loci as candidate genes for Schizophrenia and bipolar affective disorder

    Energy Technology Data Exchange (ETDEWEB)

    Jain, S.; Leggo, J.; Ferguson-Smith, M.A.; Rubinsztein, D.C. [Addenbrooke`s NHS Trust, Cambridge (United Kingdom)] [and others

    1996-04-09

    A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases. 26 refs., 1 fig., 2 tabs.

  7. Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet.

    Science.gov (United States)

    Zhao, Hua; Li, Ke; Tang, Jia-Yong; Zhou, Ji-Chang; Wang, Kang-Ning; Xia, Xin-Jie; Lei, Xin Gen

    2015-07-01

    Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy-based control diet or that diet containing 3-7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. The high-fat diet elevated (P obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic reticulum protein degradation, and phosphorylation of lipids. This porcine model may be used to study interactive mechanisms between excess fat intake and selenoprotein function. © 2015 American Society for

  8. Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression.

    NARCIS (Netherlands)

    H. Russcher (Henk); P. Smit (Pauline); E.L.T. van den Akker (Erica); E.F.C. van Rossum (Liesbeth); A.O. Brinkmann (Albert); F.H. de Jong (Frank); S.W.J. Lamberts (Steven); J.W. Koper (Jan)

    2005-01-01

    textabstractCONTEXT: Interindividual variation in glucocorticoid (GC)-sensitivity can be partly explained by polymorphisms in the GC receptor (GR) gene. The ER22/23EK and N363S polymorphisms have been described to be associated with lower and higher GC sensitivity, respectively. OBJECTIVE AND DESIGN

  9. Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 ...

    African Journals Online (AJOL)

    The completion of the human genome a decade ago has paved a ... (FTO), which is the strongest obesity genetic risk factor ... class II transmembrane glycoprotein that interacts with ...... be strengthened by inclusion of environmental factors.

  10. FTO films deposited in transition and oxide modes by magnetron sputtering using tin metal target.

    Science.gov (United States)

    Liao, Bo-Huei; Chan, Shih-Hao; Lee, Cheng-Chung; Kuo, Chien-Cheng; Chen, Sheng-Hui; Chiang, Donyau

    2014-02-01

    Fluorine-doped tin oxide (FTO) films were prepared by pulsed DC magnetron sputtering with a metal Sn target. Two different modes were applied to deposit the FTO films, and their respective optical and electrical properties were evaluated. In the transition mode, the minimum resistivity of the FTO film was 1.63×10(-3)  Ω cm with average transmittance of 80.0% in the visible region. Furthermore, FTO films deposited in the oxide mode and mixed simultaneously with H2 could achieve even lower resistivity to 8.42×10(-4)  Ω cm and higher average transmittance up to 81.1% in the visible region.

  11. Association Between FTO Variant and Change in Body Weight and Its Interaction With Dietary Factors

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Angquist, Lars; Hansen, Rikke D;

    2012-01-01

    of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak......Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.......8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition...

  12. Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob Eg

    2006-01-01

    Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22......q13 may harbor two shared susceptibility loci for BPD and SZ. The aim of the Ph.D. project was to identify and characterize susceptibility genes for BPD and SZ located in these two loci on 22q13, primarily by association analyses of selected positional candidate genes in a number of population...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

  13. Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects.

    Science.gov (United States)

    Lucht, Michael J; Barnow, Sven; Sonnenfeld, Christine; Rosenberger, Albert; Grabe, Hans Joergen; Schroeder, Winnie; Völzke, Henry; Freyberger, Harald J; Herrmann, Falko H; Kroemer, Heyo; Rosskopf, Dieter

    2009-08-01

    Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.

  14. Age and diet affect gene expression profiles in canine liver tissue.

    Directory of Open Access Journals (Sweden)

    Dong Yong Kil

    Full Text Available BACKGROUND: The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs. METHODOLOGY/PRINCIPAL FINDINGS: Liver tissue samples were collected from six senior (12-year old and six young adult (1-year old female beagles fed an animal protein-based diet (APB or a plant protein-based diet (PPB for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes as compared to senior dogs (3 genes. CONCLUSION: Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction.

  15. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni

    Science.gov (United States)

    Anderson, Letícia; Gomes, Monete Rajão; daSilva, Lucas Ferreira; Pereira, Adriana da Silva Andrade; Mourão, Marina M.; Romier, Christophe; Pierce, Raymond

    2017-01-01

    Background Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. Methodology/Principal findings TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality. Conclusions/Significance Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression

  16. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Brahmachari Samir K

    2001-10-01

    Full Text Available Abstract Background Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. Results A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg. Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. Conclusion We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells.

  17. Caenorhabditis elegans Genes Affecting Interindividual Variation in Life-span Biomarker Gene Expression.

    Science.gov (United States)

    Mendenhall, Alexander; Crane, Matthew M; Tedesco, Patricia M; Johnson, Thomas E; Brent, Roger

    2017-10-01

    Genetically identical organisms grown in homogenous environments differ in quantitative phenotypes. Differences in one such trait, expression of a single biomarker gene, can identify isogenic cells or organisms that later manifest different fates. For example, in isogenic populations of young adult Caenorhabditis elegans, differences in Green Fluorescent Protein (GFP) expressed from the hsp-16.2 promoter predict differences in life span. Thus, it is of interest to determine how interindividual differences in biomarker gene expression arise. Prior reports showed that the thermosensory neurons and insulin signaling systems controlled the magnitude of the heat shock response, including absolute expression of hsp-16.2. Here, we tested whether these regulatory signals might also influence variation in hsp-16.2 reporter expression. Genetic experiments showed that the action of AFD thermosensory neurons increases interindividual variation in biomarker expression. Further genetic experimentation showed the insulin signaling system acts to decrease interindividual variation in life-span biomarker expression; in other words, insulin signaling canalizes expression of the hsp-16.2-driven life-span biomarker. Our results show that specific signaling systems regulate not only expression level, but also the amount of interindividual expression variation for a life-span biomarker gene. They raise the possibility that manipulation of these systems might offer means to reduce heterogeneity in the aging process. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Small mosquitoes, large implications: crowding and starvation affects gene expression and nutrient accumulation in Aedes aegypti.

    Science.gov (United States)

    Price, David P; Schilkey, Faye D; Ulanov, Alexander; Hansen, Immo A

    2015-04-28

    Environmental factors such as temperature, nutrient availability, and larval density determine the outcome of postembryonic development in mosquitoes. Suboptimal temperatures, crowding, and starvation during the larval phase reduce adult mosquito size, nutrient stores and affect vectorial capacity. In this study we compared adult female Aedes aegypti, Rockefeller strain, raised under standard laboratory conditions (Large) with those raised under crowded and nutritionally deprived conditions (Small). To compare the gene expression and nutritional state of the major energy storage and metabolic organ, the fat body, we performed transcriptomics using Illumina based RNA-seq and metabolomics using GC/MS on females before and 24 hours following blood feeding. Analysis of fat body gene expression between the experimental groups revealed a large number of significantly differentially expressed genes. Transcripts related to immunity, reproduction, autophagy, several metabolic pathways; including amino acid degradation and metabolism; and membrane transport were differentially expressed. Metabolite profiling identified 60 metabolites within the fat body to be significantly affected between small and large mosquitoes, with the majority of detected free amino acids at a higher level in small mosquitoes compared to large. Gene expression and metabolites in the adult fat body reflect the individual post-embryonic developmental history of a mosquito larva. These changes affect nutritional storage and utilization, immunity, and reproduction. Therefore, it is apparent that changes in larval environment due to weather conditions, nutrition availability, vector control efforts, and other factors can affect adult vectorial capacity in the field.

  19. ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation

    Science.gov (United States)

    The objective of this study was to determine whether 5-lipoxygenase (ALOX5) gene variants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g of fish oil daily, containing 2.0 g ...

  20. Identifying candidate genes affecting developmental time in Drosophila melanogaster: pervasive pleiotropy and gene-by-environment interaction

    Directory of Open Access Journals (Sweden)

    Hasson Esteban

    2008-08-01

    Full Text Available Abstract Background Understanding the genetic architecture of ecologically relevant adaptive traits requires the contribution of developmental and evolutionary biology. The time to reach the age of reproduction is a complex life history trait commonly known as developmental time. In particular, in holometabolous insects that occupy ephemeral habitats, like fruit flies, the impact of developmental time on fitness is further exaggerated. The present work is one of the first systematic studies of the genetic basis of developmental time, in which we also evaluate the impact of environmental variation on the expression of the trait. Results We analyzed 179 co-isogenic single P[GT1]-element insertion lines of Drosophila melanogaster to identify novel genes affecting developmental time in flies reared at 25°C. Sixty percent of the lines showed a heterochronic phenotype, suggesting that a large number of genes affect this trait. Mutant lines for the genes Merlin and Karl showed the most extreme phenotypes exhibiting a developmental time reduction and increase, respectively, of over 2 days and 4 days relative to the control (a co-isogenic P-element insertion free line. In addition, a subset of 42 lines selected at random from the initial set of 179 lines was screened at 17°C. Interestingly, the gene-by-environment interaction accounted for 52% of total phenotypic variance. Plastic reaction norms were found for a large number of developmental time candidate genes. Conclusion We identified components of several integrated time-dependent pathways affecting egg-to-adult developmental time in Drosophila. At the same time, we also show that many heterochronic phenotypes may arise from changes in genes involved in several developmental mechanisms that do not explicitly control the timing of specific events. We also demonstrate that many developmental time genes have pleiotropic effects on several adult traits and that the action of most of them is sensitive

  1. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

    Science.gov (United States)

    Murdoch, Brenda; Owen, Nichole; Stevense, Michelle; Smith, Helen; Nagaoka, So; Hassold, Terry; McKay, Michael; Xu, Huiling; Fu, Jun; Revenkova, Ekaterina; Jessberger, Rolf; Hunt, Patricia

    2013-01-01

    Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC) and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  2. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

    Directory of Open Access Journals (Sweden)

    Brenda Murdoch

    Full Text Available Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  3. Superhydrophobic and anti-reflective ZnO nanorod-coated FTO transparent conductive thin films prepared by a three-step method

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bao-jia, E-mail: li_bjia@126.com [School of Materials Science and Engineering, Jiangsu University, Zhenjiang, 212013 (China); Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang, 212013 (China); Huang, Li-jing; Ren, Nai-fei [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang, 212013 (China); School of Mechanical Engineering, Jiangsu University, Zhenjiang, 212013 (China); Kong, Xia; Cai, Yun-long; Zhang, Jie-lu [Jiangsu Tailong Reduction Box Co. Ltd., Taixing, 225400 (China)

    2016-07-25

    A ZnO nanorod-coated FTO film was prepared by sputtering an AZO layer on FTO glass, thermal annealing of the AZO/FTO film, and hydrothermal growth of ZnO nanorods at 70 °C on the annealed AZO/FTO film using zinc foils as zinc source. Two other ZnO nanorod-coated FTO films were also prepared by hydrothermal growths of ZnO nanorods on the FTO glass and the unannealed AZO/FTO film respectively for comparison purpose. The results were observed in detail using X-ray diffraction, scanning electron microscopy, water contact/sliding angle measurement, spectrophotometry and four-point probe measurement. The ZnO nanorods on the annealed AZO/FTO film were found to exhibit denser distribution and better orientation than those on the FTO glass and the unannealed AZO/FTO film. As a result, the ZnO nanorod-coated annealed AZO/FTO film demonstrated superhydrophobicity, high transparency and low reflectance in the visible range. Also this film had the lowest sheet resistance of 4.0 Ω/sq, implying its good electrical conductivity. This investigation provides a valuable reference for developing multifunctional transparent conductive films. - Highlights: • ZnO nanorod-coated annealed AZO/FTO film was obtained by a three-step method. • FTO and unannealed AZO/FTO films were also used as substrates for comparison. • ZnO nanorods on the annealed AZO/FTO film were denser and more vertically-oriented. • The ZnO nanorod-coated annealed AZO/FTO film (Z/TA-FTO) had superhydrophobicity. • The Z/TA-FTO exhibited high transparency, low reflectance and good conductivity.

  4. Genotypic carriers of the obesity-associated FTO polymorphism exhibit different cardiometabolic profiles after an intervention

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    GREICE G. MORAES

    Full Text Available ABSTRACT Background: Children and adolescents with at-risk genotypes (AA/AT of the rs9939609 polymorphism in FTO, a fat mass and obesity-associated gene, may exhibit different cardiometabolic profile responses than subjects with the TT genotype after an interdisciplinary intervention. Methods: The sample consisted of 36 school children from southern Brazil. We used DNA quantitation and real-time polymerase chain reaction (PCR for polymorphism genotyping. We measured anthropometric parameters (body mass index (BMI, waist circumference, hip circumference, waist-hip ratio, body fat percentage and skinfold sum, biochemical parameters (glucose, lipid profile, ultra-sensitive C-reactive protein, uric acid, alanine aminotransferase, aspartate aminotransferase, insulin and adiponectin and blood pressure. The 4-month intervention consisted of physical education classes, nutritional counseling, and postural and oral health counseling. Results: We observed no significant differences among the groups (AA, AT and TT after the intervention. However, we observed improvements in three parameters (waist circumference, hip circumference and C-reactive protein in the AT/AA genotype group and in two parameters (hip circumference and uric acid in the TT genotype group. Conclusions: After an intervention program, carriers of at-risk genotypes for obesity (AA/AT do not exhibit differences in biochemical parameters, blood pressure and anthropometric parameters compared with carriers of the TT genotype.

  5. FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

    Science.gov (United States)

    Qi, Qibin; Kilpeläinen, Tuomas O.; Downer, Mary K.; Tanaka, Toshiko; Smith, Caren E.; Sluijs, Ivonne; Sonestedt, Emily; Chu, Audrey Y.; Renström, Frida; Lin, Xiaochen; Ängquist, Lars H.; Huang, Jinyan; Liu, Zhonghua; Li, Yanping; Asif Ali, Muhammad; Xu, Min; Ahluwalia, Tarunveer Singh; Boer, Jolanda M.A.; Chen, Peng; Daimon, Makoto; Eriksson, Johan; Perola, Markus; Friedlander, Yechiel; Gao, Yu-Tang; Heppe, Denise H.M.; Holloway, John W.; Houston, Denise K.; Kanoni, Stavroula; Kim, Yu-Mi; Laaksonen, Maarit A.; Jääskeläinen, Tiina; Lee, Nanette R.; Lehtimäki, Terho; Lemaitre, Rozenn N.; Lu, Wei; Luben, Robert N.; Manichaikul, Ani; Männistö, Satu; Marques-Vidal, Pedro; Monda, Keri L.; Ngwa, Julius S.; Perusse, Louis; van Rooij, Frank J.A.; Xiang, Yong-Bing; Wen, Wanqing; Wojczynski, Mary K; Zhu, Jingwen; Borecki, Ingrid B.; Bouchard, Claude; Cai, Qiuyin; Cooper, Cyrus; Dedoussis, George V.; Deloukas, Panos; Ferrucci, Luigi; Forouhi, Nita G.; Hansen, Torben; Christiansen, Lene; Hofman, Albert; Johansson, Ingegerd; Jørgensen, Torben; Karasawa, Shigeru; Khaw, Kay-Tee; Kim, Mi-Kyung; Kristiansson, Kati; Li, Huaixing; Lin, Xu; Liu, Yongmei; Lohman, Kurt K.; Long, Jirong; Mikkilä, Vera; Mozaffarian, Dariush; North, Kari; Pedersen, Oluf; Raitakari, Olli; Rissanen, Harri; Tuomilehto, Jaakko; van der Schouw, Yvonne T.; Uitterlinden, André G.; Zillikens, M. Carola; Franco, Oscar H.; Shyong Tai, E.; Ou Shu, Xiao; Siscovick, David S.; Toft, Ulla; Verschuren, W.M. Monique; Vollenweider, Peter; Wareham, Nicholas J.; Witteman, Jacqueline C.M.; Zheng, Wei; Ridker, Paul M.; Kang, Jae H.; Liang, Liming; Jensen, Majken K.; Curhan, Gary C.; Pasquale, Louis R.; Hunter, David J.; Mohlke, Karen L.; Uusitupa, Matti; Cupples, L. Adrienne; Rankinen, Tuomo; Orho-Melander, Marju; Wang, Tao; Chasman, Daniel I.; Franks, Paul W.; Sørensen, Thorkild I.A.; Hu, Frank B.; Loos, Ruth J. F.; Nettleton, Jennifer A.; Qi, Lu

    2014-01-01

    FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity. PMID:25104851

  6. Vitrification affects nuclear maturation and gene expression of immature human oocytes

    Directory of Open Access Journals (Sweden)

    Abbas Shahedi

    2017-02-01

    Full Text Available Background: Vitrification of oocytes is a fast-freezing technique, which may affect the quality of the human oocyte, and consequently affects the embryo development, pregnancy and birth. The aim of the current study was to investigate the consequence of in-vitro vitrification on maturation status of immature human oocytes, additionally, expression levels of stress, and apoptosis related genes. Materials and Methods: The total of 213 human immature oocytes which routinely discarded from assisted reproduction clinics were collected and divided into two groups including: (I fresh germinal vesicle (GV oocytes (n=106 (matured in-vitro  (fIVM , and  (II GV oocytes (n=107 that initially vitrified, then matured in  in-vitro (vIVM. After 36 hours of incubation, the oocytes were evaluated for nuclear maturation and expression level of DNA methyltransferase (DNMT1, stress related genes (Sod1 and Hsp70, and apoptotic related genes (Bax and Bcl-2 by quantitative Real-Time PCR. Results: Oocyte maturation rates were reduced in vIVM compared to fIVM oocytes (P=0.001. The expression of stress (Sod1 and Hsp70, and apoptotic-related genes (Bax and Bcl-2 in vIVM were significantly higher compared to the fIVM group. Additionally, pro-apoptotic gene up-regulated 4.3 times more than anti-apoptotic gene in vIVM oocyte. However, DNMT1 gene expression was reduced in vIVM oocyte (P = 0.047. Conclusions: The low survival rate of vitrified In-vitro matured GV oocytes could definitely be explained by the alterations of their gene expression profile. 

  7. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low.

    Science.gov (United States)

    Ortega-Azorín, Carolina; Sorlí, Jose V; Asensio, Eva M; Coltell, Oscar; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Covas, Maria-Isabel; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Fiol, Miquel; Sáez-Tormo, Guillermo; Pintó, Xavier; Muñoz, Miguel Angel; Ros, Emilio; Ordovás, Jose M; Estruch, Ramon; Corella, Dolores

    2012-11-06

    Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these

  8. The expression of tga1a gene from tobacco affects the expression of exogenous gene in transgenic plant

    Institute of Scientific and Technical Information of China (English)

    路子显; 常团结; 李旭刚; 徐军望; 李慧芬; 陈宛新; 冯德江; 肖桂芳; 朱祯

    2003-01-01

    The DNA-binding protein TGA1a of tobacco can specially interact with the enhancer sequence as-1 (-83 to -63) of CaMV35S promoter and show the function of transcriptional activation. In order to study the expression of exogenous gene affected by TGA1a, a trans-actingregulation system was formed by tandem connecting tga1a under the control of the phloem-specific promoter rolC with reporter gene under the control of CaMV35S. Then, the system abovewas utilized to construct a plant expression vector. Moreover, two plant expression vectors wereconstructed with the report gene controlled by CaMV35S and rolC promoter respectively as positive controls. Tobacco leaf disc transformed by Agrobacterium-mediated method and transgenic plants were regenerated. It was proved that the reporter gene existed in the genome of transgenic plants by Southern hybridization. The results of GUS activity indicated that the expression of tga1a controlled by rolC remarkably increased the expression of the reporter gene controlled by CaMV35S. GUS activity of transgenic plants containing trans-acting regulation system was higher than that of transgenic plants containing the reporter gene under the control of CaMV35S and rolC respectively, with the highest GUS activity of about tenfolds of two positive controls. Histochemical method demonstrated that GUS staining amassed mainly in phloem tissue of transgenic plantscontaining the trans-acting regulation system. A new model for arising the expression level and tissue-specific expression of exogenous gene in transgenic plant was established in this study.

  9. Gene-Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril.

    Science.gov (United States)

    Oliveira-Paula, Gustavo H; Luizon, Marcelo R; Lacchini, Riccardo; Fontana, Vanessa; Silva, Pamela S; Biagi, Celso; Tanus-Santos, Jose E

    2017-03-01

    Protein kinase C (PKC) signalling is critically involved in the control of blood pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with the responses to ACEi. We examined whether PRKCA (protein kinase C, alpha) polymorphisms (rs887797 C>T, rs1010544 T>C and rs16960228 G>A), or haplotypes, and gene-gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with enalapril as monotherapy. Patients were classified as poor responders (PR) or good responders (GR) to enalapril if their changes in mean arterial pressure were lower or higher than the median value, respectively. Multi-factor dimensionality reduction was used to characterize interactions among PRKCA, NOS3 (nitric oxide synthase 3) and BDKRB2 (bradykinin receptor B2) polymorphisms. The TC+CC genotypes for the rs1010544 polymorphism were more frequent in GR than in PR (p = 0.037). Conversely, the GA+AA genotypes for the rs16960228 polymorphism, and the CTA haplotype, were more frequent in PR than in GR (p = 0.040 and p = 0.008, respectively). Moreover, the GG genotype for the PRKCA rs16960228 polymorphism was associated with PR or GR depending on the genotypes for the rs2070744 (NOS3) and rs1799722 (BDKRB2) polymorphisms (p = 0.012). Our results suggest that PRKCA polymorphisms and gene-gene interactions within the ACEi pathway affect the antihypertensive responses to enalapril. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  10. Epigenetic and Genetic Alterations Affect the WWOX Gene in Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Ekizoglu, Seda; Bulut, Pelin; Karaman, Emin; Kilic, Erkan; Buyru, Nur

    2015-01-01

    Different types of genetic and epigenetic changes are associated with HNSCC. The molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. WWOX gene expression is altered in many cancers and in a recent work reduced WWOX expression has been associated with miR-134 expression in HNSCC. In this study we investigated the WWOX messenger RNA expression levels in association with the promoter methylation of the WWOX gene and miR-134 expression levels in 80 HNSCC tumor and non-cancerous tissue samples. Our results show that WWOX expression is down-regulated especially in advanced-stage tumor samples or in tumors with SCC. This down-regulation was associated with methylation of the WWOX promoter region but not with miR-134 expression. There was an inverse correlation between the expression level and promoter methylation. We also analyzed whole exons and exon/intron boundries of the WWOX gene by direct sequencing. In our study group we observed 10 different alterations in the coding sequences and 18 different alterations in the non-coding sequences of the WWOX gene in HNSCC tumor samples. These results indicate that the WWOX gene can be functionally inactivated by promoter methylation, epigenetically or by mutations affecting the sequences coding for the enzymatic domain of the gene, functionally. We conclude that inactivation of WWOX gene contributes to the progression of HNSCC. PMID:25612104

  11. Influences of Pr and Ta doping concentration on the characteristic features of FTO thin film deposited by spray pyrolysis

    Science.gov (United States)

    Güven, Turgut; Adem, Koçyiğit; Erdal, Sönmez

    2015-10-01

    The Pr and Ta separately doped FTO (10 at.% F incorporated SnO2) films are fabricated via spray pyrolysis. The microstructural, topographic, optical, and electrical features of fluorine-doped TO (FTO) films are investigated as functions of Pr and Ta dopant concentrations. The x-ray diffraction (XRD) measurements reveal that all deposited films show polycrystalline tin oxide crystal property. FTO film has (200) preferential orientation, but this orientation changes to (211) direction with Pr and Ta doping ratio increasing. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) analyses show that all films have uniform and homogenous nanoparticle distributions. Furthermore, morphologies of the films depend on the ratio between Pr and Ta dopants. From ultraviolet-visible (UV-Vis) spectrophotometer measurements, it is shown that the transmittance value of FTO film decreases with Pr and Ta doping elements increasing. The band gap value of FTO film increases only at 1 at.% Ta doping level, it drops off with Pr and Ta doping ratio increasing at other doped FTO films. The electrical measurements indicate that the sheet resistance value of FTO film initially decreases with Pr and Ta doping ratio decreasing and then it increases with Pr and Ta doping ratio increasing. The highest value of figure of merit is obtained for 1 at.% Ta- and Pr-doped FTO film. These results suggest that Pr- and Ta-doped FTO films may be appealing candidates for TCO applications.

  12. Influences of Pr and Ta doping concentration on the characteristic features of FTO thin film deposited by spray pyrolysis

    Institute of Scientific and Technical Information of China (English)

    G ¨uven Turgut; Adem Koc¸ yi˘git; Erdal S ¨onmez

    2015-01-01

    The Pr and Ta separately doped FTO (10 at.%F incorporated SnO2) films are fabricated via spray pyrolysis. The mi-crostructural, topographic, optical, and electrical features of fl uorine-doped TO (FTO) films are investigated as functions of Pr and Ta dopant concentrations. The x-ray diffraction (XRD) measurements reveal that all deposited films show polycrys-talline tin oxide crystal property. FTO film has (200) preferential orientation, but this orientation changes to (211) direction with Pr and Ta doping ratio increasing. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) anal-yses show that all films have uniform and homogenous nanoparticle distributions. Furthermore, morphologies of the films depend on the ratio between Pr and Ta dopants. From ultraviolet-visible (UV-Vis) spectrophotometer measurements, it is shown that the transmittance value of FTO film decreases with Pr and Ta doping elements increasing. The band gap value of FTO film increases only at 1 at.%Ta doping level, it drops off with Pr and Ta doping ratio increasing at other doped FTO films. The electrical measurements indicate that the sheet resistance value of FTO film initially decreases with Pr and Ta doping ratio decreasing and then it increases with Pr and Ta doping ratio increasing. The highest value of figure of merit is obtained for 1 at.%Ta-and Pr-doped FTO film. These results suggest that Pr-and Ta-doped FTO films may be appealing candidates for TCO applications.

  13. Risk of type 2 diabetes and obesity is differentially associated with variation in FTO in whites and African-Americans in the ARIC study.

    Directory of Open Access Journals (Sweden)

    Jan Bressler

    Full Text Available Single nucleotide polymorphisms (SNPs in the fat mass and obesity associated (FTO gene are associated with body mass index (BMI in populations of European descent. The FTO rs9939609 variant, first detected in a genome-wide association study of diabetes, conferred an increased disease risk that was abolished after adjustment for BMI, suggesting that the association may be due to variation in adiposity. The relationship between diabetes, four previously identified FTO polymorphisms that span a 19.6-kb genomic region, and obesity was therefore evaluated in the biracial population-based Atherosclerosis Risk in Communities Study with the goal of further refining the association by comparing results between the two ethnic groups. The prevalence of diabetes and obesity (BMI > or = 30 kg/m(2 was established at baseline, and diabetes was determined by either self-report, a fasting glucose level > or = 126 mg/dL, or non-fasting glucose > or = 200 mg/dL. There were 1,004 diabetes cases and 10,038 non-cases in whites, and 670 cases and 2,780 non-cases in African-Americans. Differences in mean BMI were assessed by a general linear model, and multivariable logistic regression was used to predict the risk of diabetes and obesity. For white participants, the FTO rs9939609 A allele was associated with an increased risk of diabetes (odds ratio (OR = 1.19, p<0.001 and obesity (OR = 1.22, p<0.001 under an additive genetic model that was similar for all of the SNPs analyzed. In African-Americans, only the rs1421085 C allele was a determinant of obesity risk (OR = 1.17, p = 0.05, but was found to be protective against diabetes (OR = 0.79, p = 0.03. Adjustment for BMI did not eliminate any of the observed associations with diabetes. Significant statistical interaction between race and the FTO variants suggests that the effect on diabetes susceptibility may be context dependent.

  14. Goat's αS1-casein polymorphism affects gene expression profile of lactating mammary gland.

    Science.gov (United States)

    Ollier, S; Chauvet, S; Martin, P; Chilliard, Y; Leroux, C

    2008-04-01

    Goat's αS1-casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell-cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function.

  15. Bovine growth hormone gene polymorphism affects stress response in Japanese Black cattle.

    Science.gov (United States)

    Tachi, Noriko; Tanaka, Sigefumi; Ardiyanti, Astrid; Katoh, Kazuo; Sato, Shusuke

    2014-06-01

    We investigate the associations between growth hormone (GH) gene polymorphism and behavioral and physiological responses to stressors and learning ability in Japanese Black cattle. Flight distance test was conducted in the first experiment. Steers with haplotype C of GH gene polymorphism avoided human approaches at a significantly greater distance than ones without haplotype C (C: 1.9 ± 0.9, non-C: 1.0 ± 0.2 m, P affect stress responses through GH concentration in steers.

  16. CCAAT/Enhancer-Binding Protein α Is a Crucial Regulator of Human Fat Mass and Obesity Associated Gene Transcription and Expression

    Directory of Open Access Journals (Sweden)

    Wei Ren

    2014-01-01

    Full Text Available Several susceptibility loci have been reported associated with obesity and T2DM in GWAS. Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes in diverse patient populations. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. While much is known about the epigenetic mutations contributing to obesity and T2DM, less is certain with the expression regulation of FTO gene. In this study, a highly conserved canonical C/EBPα binding site was located around position −45~−54 bp relative to the human FTO gene transcriptional start site. Site-directed mutagenesis of the putative C/EBPα binding sites decreased FTO promoter activity. Overexpression and RNAi studies also indicated that C/EBPα was required for the expression of FTO. Chromatin immunoprecipitation (ChIP experiment was carried out and the result shows direct binding of C/EBPα to the putative binding regions in the FTO promoter. Collectively, our data suggest that C/EBPα may act as a positive regulator binding to FTO promoter and consequently, activates the gene transcription.

  17. Genes influencing milk production traits predominantly affect one of four biological pathways

    Directory of Open Access Journals (Sweden)

    Goddard Michael

    2008-01-01

    Full Text Available Abstract In this study we introduce a method that accounts for false positive and false negative results in attempting to estimate the true proportion of quantitative trait loci that affect two different traits. This method was applied to data from a genome scan that was used to detect QTL for three independent milk production traits, Australian Selection Index (ASI, protein percentage (P% and fat percentage corrected for protein percentage (F% – P%. These four different scenarios are attributed to four biological pathways: QTL that (1 increase or decrease total mammary gland production (affecting ASI only; (2 increase or decrease lactose synthesis resulting in the volume of milk being changed but without a change in protein or fat yield (affecting P% only; (3 increase or decrease protein synthesis while milk volume remains relatively constant (affecting ASI and P% in the same direction; (4 increase or decrease fat synthesis while the volume of milk remains relatively constant (affecting F% – P% only. The results indicate that of the positions that detected a gene, most affected one trait and not the others, though a small proportion (2.8% affected ASI and P% in the same direction.

  18. Functional Gene Discovery and Characterization of Genes and Alleles Affecting Wood Biomass Yield and Quality in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Busov, Victor [Michigan Technological Univ., Houghton, MI (United States)

    2017-02-12

    Adoption of biofuels as economically and environmentally viable alternative to fossil fuels would require development of specialized bioenergy varieties. A major goal in the breeding of such varieties is the improvement of lignocellulosic biomass yield and quality. These are complex traits and understanding the underpinning molecular mechanism can assist and accelerate their improvement. This is particularly important for tree bioenergy crops like poplars (species and hybrids from the genus Populus), for which breeding progress is extremely slow due to long generation cycles. A variety of approaches have been already undertaken to better understand the molecular bases of biomass yield and quality in poplar. An obvious void in these undertakings has been the application of mutagenesis. Mutagenesis has been instrumental in the discovery and characterization of many plant traits including such that affect biomass yield and quality. In this proposal we use activation tagging to discover genes that can significantly affect biomass associated traits directly in poplar, a premier bioenergy crop. We screened a population of 5,000 independent poplar activation tagging lines under greenhouse conditions for a battery of biomass yield traits. These same plants were then analyzed for changes in wood chemistry using pyMBMS. As a result of these screens we have identified nearly 800 mutants, which are significantly (P<0.05) different when compared to wild type. Of these majority (~700) are affected in one of ten different biomass yield traits and 100 in biomass quality traits (e.g., lignin, S/G ration and C6/C5 sugars). We successfully recovered the position of the tag in approximately 130 lines, showed activation in nearly half of them and performed recapitulation experiments with 20 genes prioritized by the significance of the phenotype. Recapitulation experiments are still ongoing for many of the genes but the results are encouraging. For example, we have shown successful

  19. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

    Energy Technology Data Exchange (ETDEWEB)

    Owerbach, D.; Gabbay, K.H. (Baylor College of Medicine, Houston, TX (United States))

    1994-05-01

    Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.

  20. Cis-regulatory Mutations in the Caenorhabditis elegans Homeobox Gene Locus cog-1 Affect Neuronal Development

    Science.gov (United States)

    O'Meara, M. Maggie; Bigelow, Henry; Flibotte, Stephane; Etchberger, John F.; Moerman, Donald G.; Hobert, Oliver

    2009-01-01

    We apply here comparative genome hybridization as a novel tool to identify the molecular lesion in two Caenorhabditis elegans mutant strains that affect a neuronal cell fate decision. The phenotype of the mutant strains resembles those of the loss-of-function alleles of the cog-1 homeobox gene, an inducer of the fate of the gustatory neuron ASER. We find that both lesions map to the cis-regulatory control region of cog-1 and affect a phylogenetically conserved binding site for the C2H2 zinc-finger transcription factor CHE-1, a previously known regulator of cog-1 expression in ASER. Identification of this CHE-1-binding site as a critical regulator of cog-1 expression in the ASER in vivo represents one of the rare demonstrations of the in vivo relevance of an experimentally determined or predicted transcription-factor-binding site. Aside from the mutationally defined CHE-1-binding site, cog-1 contains a second, functional CHE-1-binding site, which in isolation is sufficient to drive reporter gene expression in the ASER but in an in vivo context is apparently insufficient for promoting appropriate ASER expression. The cis-regulatory control regions of other ASE-expressed genes also contain ASE motifs that can promote ASE neuron expression when isolated from their genomic context, but appear to depend on multiple ASE motifs in their normal genomic context. The multiplicity of cis-regulatory elements may ensure the robustness of gene expression. PMID:19189954

  1. Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression.

    Directory of Open Access Journals (Sweden)

    Ariadna Amador

    Full Text Available The nuclear receptors REV-ERBα and REV-ERBβ are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes. The circadian rhythm is an endogenous mechanism, which generates entrainable biological changes that follow a 24-hour period. It regulates a number of physiological processes, including sleep/wakeful cycles and feeding behaviors. We recently demonstrated that REV-ERB-specific small molecules affect sleep and anxiety. The orexinergic system also plays a significant role in mammalian physiology and behavior, including the regulation of sleep and food intake. Importantly, orexin genes are expressed in a circadian manner. Given these overlaps in function and circadian expression, we wanted to determine whether the REV-ERBs might regulate orexin. We found that acute in vivo modulation of REV-ERB activity, with the REV-ERB-specific synthetic ligand SR9009, affects the circadian expression of orexinergic genes in mice. Long term dosing with SR9009 also suppresses orexinergic gene expression in mice. Finally, REV-ERBβ-deficient mice present with increased orexinergic transcripts. These data suggest that the REV-ERBs may be involved in the repression of orexinergic gene expression.

  2. Three-dimensional photonic crystal fluorinated tin oxide (FTO) electrodes: synthesis and optical and electrical properties.

    Science.gov (United States)

    Yang, Zhenzhen; Gao, Shanmin; Li, Wei; Vlasko-Vlasov, Vitalii; Welp, Ulrich; Kwok, Wai-Kwong; Xu, Tao

    2011-04-01

    Photovoltaic (PV) schemes often encounter a pair of fundamentally opposing requirements on the thickness of semiconductor layer: a thicker PV semiconductor layer provides enhanced optical density, but inevitably increases the charge transport path length. An effective approach to solve this dilemma is to enhance the interface area between the terminal electrode, i.e., transparent conducting oxide (TCO) and the semiconductor layer. As such, we report a facile, template-assisted, and solution chemistry-based synthesis of 3-dimensional inverse opal fluorinated tin oxide (IO-FTO) electrodes. Synergistically, the photonic crystal structure possessed in the IO-FTO exhibits strong light trapping capability. Furthermore, the electrical properties of the IO-FTO electrodes are studied by Hall effect and sheet resistance measurement. Using atomic layer deposition method, an ultrathin TiO(2) layer is coated on all surfaces of the IO-FTO electrodes. Cyclic voltammetry study indicates that the resulting TiO(2)-coated IO-FTO shows excellent potentials as electrodes for electrolyte-based photoelectrochemical solar cells.

  3. SiFTO: An Empirical Method for Fitting SNe Ia Light Curves

    CERN Document Server

    Conley, A; Hsiao, E Y; Guy, J; Astier, Pierre; Balam, D; Balland, C; Basa, S; Carlberg, R G; Fouchez, D; Hardin, D; Howell, D A; Hook, I M; Pain, R; Perrett, K; Pritchet, C J; Regnault, N

    2008-01-01

    We present SiFTO, a new empirical method for modeling type Ia supernovae (SNe Ia) light curves by manipulating a spectral template. We make use of high-redshift SN observations when training the model, allowing us to extend it bluer than rest frame U. This increases the utility of our high-redshift SN observations by allowing us to use more of the available data. We find that when the shape of the light curve is described using a stretch prescription, applying the same stretch at all wavelengths is not an adequate description. SiFTO therefore uses a generalization of stretch which applies different stretch factors as a function of both the wavelength of the observed filter and the stretch in the rest-frame B band. We compare SiFTO to other published light-curve models by applying them to the same set of SN photometry, and demonstrate that SiFTO and SALT2 perform better than the alternatives when judged by the scatter around the best fit luminosity distance relationship. We further demonstrate that when SiFTO ...

  4. Phosphoinositide-specific Phospholipase C β1 gene deletion in bipolar disorder affected patient.

    Science.gov (United States)

    Lo Vasco, Vincenza Rita; Longo, Lucia; Polonia, Patrizia

    2013-03-01

    The involvement of phosphoinositides (PI) signal transduction pathway and related molecules, such as the Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes, in the pathophysiology of mood disorders is corroborated by a number of recent evidences. Our previous works identified the deletion of PLCB1 gene, which codifies for the PI-PLC β1 enzyme, in 4 out 15 patients affected with schizophrenia, and no deletion both in major depression affected patients and in normal controls. By using interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 in paraffin embedded samples of orbito-frontal cortex of 15 patients affected with bipolar disorder. Deletion of PLCB1 was identified in one female patient.

  5. A comparative study of different M(M = Al, Ag, Cu)/FTO bilayer composite films irradiated with nanosecond pulsed laser

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-jing, E-mail: lij_huang@126.com [School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); Ren, Nai-fei, E-mail: rnf_ujs@126.com [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China); Li, Bao-jia [School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); Zhou, Ming [Jiangsu Provincial Key Laboratory of Center for Photon Manufacturing Science and Technology, Jiangsu University, Zhenjiang 212013 (China); The State Key Laboratory of Tribology, Tsinghua University, Beijing 100084 (China)

    2014-12-25

    Highlights: • Different metal (i.e. Al, Ag and Cu) layers were sputtered on commercial FTO glass. • All the metal/FTO films were annealed by nanosecond pulsed laser irradiation. • Grating structures were also formed on the laser-irradiated Ag/FTO and Cu/FTO films. • The laser-irradiated Ag/FTO composite film had the better figure of merit. • Inducing gratings and annealing in one step is effective to improve film quality. - Abstract: Aluminium (Al), silver (Ag) and copper (Cu) layers were deposited on commercial fluorine-doped tin oxide (FTO) glass by direct current (DC) magnetron sputtering, so as to form Al/FTO, Ag/FTO and Cu/FTO bilayer films. Then all the as-deposited metal/FTO films were irradiated using a 532 nm nanosecond pulsed laser with a fluences of 1.05 J/cm{sup 2}. X-ray diffraction (XRD) analysis confirmed that all the laser-irradiated films were annealed by the laser and showed increased average crystallite size in FTO layers. Laser-induced grating structures were also obtained on the surfaces of the laser-irradiated Ag/FTO and Cu/FTO films, resulting in higher surface roughnesses and average transmittances of the films. But due to the broken continuity of the Ag and Cu layers, the sheet resistances of these two films slightly decreased as compared to that of the laser-irradiated Al/FTO film. It was also found that the laser-irradiated Ag/FTO film, whose average transmittance in 400–800 nm waveband and sheet resistance was 81.5% and 6.6 Ω/sq respectively, had the better figure of merit, indicating that the photoelectric property of FTO-based bilayer films could be further optimized through achieving fabrication of laser-induced grating structures and laser annealing in one step.

  6. Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore) Cattle Are Modulators of Growth

    Science.gov (United States)

    Milanesi, Marco; Torrecilha, Rafaela B. P.; Carmo, Adriana S.; Neves, Haroldo H. R.; Carvalheiro, Roberto; Ajmone-Marsan, Paolo; Sonstegard, Tad S.; Sölkner, Johann; Contreras-Castillo, Carmen J.; Garcia, José F.

    2016-01-01

    Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS), were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore) cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV) for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1) as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1), IGF2 (insulin like growth factor 2), GH1 (growth hormone 1), IGF1R (insulin like growth factor 1 receptor) and GHR (growth hormone receptor), suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway. PMID:27410030

  7. Mutation in fucose synthesis gene of Klebsiella pneumoniae affects capsule composition and virulence in mice.

    Science.gov (United States)

    Pan, Po-Chang; Chen, Hui-Wen; Wu, Po-Kuan; Wu, Yu-Yang; Lin, Chun-Hung; Wu, June H

    2011-02-01

    The emerging pathogenicity of Klebsiella pneumoniae (KP) is evident by the increasing number of clinical cases of liver abscess (LA) due to KP infection. A unique property of KP is its thick mucoid capsule. The bacterial capsule has been found to contain fucose in KP strains causing LA but not in those causing urinary tract infections. The products of the gmd and wcaG genes are responsible for converting mannose to fucose in KP. A KP strain, KpL1, which is known to have a high death rate in infected mice, was mutated by inserting an apramycin-resistance gene into the gmd. The mutant expressed genes upstream and downstream of gmd, but not gmd itself, as determined by reverse transcriptase polymerase chain reaction. The DNA mapping confirmed the disruption of the gmd gene. This mutant decreased its ability to kill infected mice and showed decreased virulence in infected HepG2 cells. Compared with wild-type KpL1, the gmd mutant lost fucose in capsular polysaccharides, increased biofilm formation and interacted more readily with macrophages. The mutant displayed morphological changes with long filament forms and less uniform sizes. The mutation also converted the serotype from K1 of wild-type to K2 and weak K3. The results indicate that disruption of the fucose synthesis gene affected the pathophysiology of this bacterium and may be related to the virulence of this KpL1 strain.

  8. Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore Cattle Are Modulators of Growth.

    Directory of Open Access Journals (Sweden)

    Anirene G T Pereira

    Full Text Available Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS, were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1 as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1, IGF2 (insulin like growth factor 2, GH1 (growth hormone 1, IGF1R (insulin like growth factor 1 receptor and GHR (growth hormone receptor, suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway.

  9. Cholesterol affects gene expression of the Jun family in colon carcinoma cells using different signaling pathways.

    Science.gov (United States)

    Scheinman, Eyal J; Rostoker, Ran; Leroith, Derek

    2013-07-15

    Hyperlipidemia and hypercholesterolemia have been found to be important factors in cancer development and metastasis. However, the metabolic mechanism and downstream cellular processes following cholesterol stimulation are still unknown. Here we tested the effect of cholesterol on MC-38 colon cancer cells. Using Illumina gene array technology we found a number of genes that were differentially expressed following short term (20-40 min) and longer term (between 2 and 5h) cholesterol stimulation. Three genes were consistently increased at these time points; c-Jun, Jun-B and the chemokine CXCL-1. We have previously shown that cholesterol stimulation leads to PI3K/Akt phosphorylation, and now demonstrated that cholesterol inhibits ERK1/2 phosphorylation; both effects reversed when cholesterol is depleted from lipid rafts using methyl-β-cyclodextrin (MBCD). In addition, vanadate, an inhibitor of phosphatases, reversed the cholesterol inhibition of ERK1/2 phosphorylation. Specific inhibition of p-Akt by wortmannin did not affect cholesterol's stimulation of the expression of c-Jun and Jun-B, however the vanadate effect of increasing p-ERK1/2, inhibited c-Jun expression, specifically, and the MBCD effect of increasing p-ERK and inhibiting p-Akt reduced c-Jun expression. In contrast MBCD and vanadate both enhanced Jun-B gene expression in the presence of cholesterol and elevation of ERK phosphorylation. Thus there is apparently, a differential signaling pathway whereby cholesterol enhances gene expression of the Jun family members.

  10. Functional dissection of sugar signals affecting gene expression in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Sabine Kunz

    Full Text Available BACKGROUND: Sugars modulate expression of hundreds of genes in plants. Previous studies on sugar signaling, using intact plants or plant tissues, were hampered by tissue heterogeneity, uneven sugar transport and/or inter-conversions of the applied sugars. This, in turn, could obscure the identity of a specific sugar that acts as a signal affecting expression of given gene in a given tissue or cell-type. METHODOLOGY/PRINCIPAL FINDINGS: To bypass those biases, we have developed a novel biological system, based on stem-cell-like Arabidopsis suspension culture. The cells were grown in a hormone-free medium and were sustained on xylose as the only carbon source. Using functional genomics we have identified 290 sugar responsive genes, responding rapidly (within 1 h and specifically to low concentration (1 mM of glucose, fructose and/or sucrose. For selected genes, the true nature of the signaling sugar molecules and sites of sugar perception were further clarified using non-metabolizable sugar analogues. Using both transgenic and wild-type A. thaliana seedlings, it was shown that the expression of selected sugar-responsive genes was not restricted to a specific tissue or cell type and responded to photoperiod-related changes in sugar availability. This suggested that sugar-responsiveness of genes identified in the cell culture system was not biased toward heterotrophic background and resembled that in whole plants. CONCLUSIONS: Altogether, our research strategy, using a combination of cell culture and whole plants, has provided an unequivocal evidence for the identity of sugar-responsive genes and the identity of the sugar signaling molecules, independently from their inter-conversions or use for energy metabolism.

  11. Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.

    Directory of Open Access Journals (Sweden)

    Andrea G Edlow

    Full Text Available OBJECTIVE: One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. METHODS: This prospective pilot study included eight obese (BMI≥30 and eight lean (BMI<25 women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05. Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. RESULTS: In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold. Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. CONCLUSION: Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women.

  12. Methods for interpreting lists of affected genes obtained in a DNA microarray experiment

    Directory of Open Access Journals (Sweden)

    Hedegaard Jakob

    2009-07-01

    Full Text Available Abstract Background The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experiment.

  13. A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency.

    Science.gov (United States)

    Manco, L; Ribeiro, M L; Máximo, V; Almeida, H; Costa, A; Freitas, O; Barbot, J; Abade, A; Tamagnini, G

    2000-09-01

    Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region. We now report a novel point mutation A-->G on nucleotide 72, upstream from the initiation codon of the PKLR gene, in four Portuguese PK-deficient patients. This new regulatory mutation occurs within the most proximal of the four GATA motifs (GATA-A element) in the R-type promoter region. In two patients who were homozygous for this mutation, a semiquantitative reverse transcription polymerase chain reaction (PCR) procedure was used to evaluate the amount of R-PK mRNA transcript in the reticulocytes. The mRNA level was about five times lower than in normal controls, demonstrating that the PKLR gene transcription is severely affected, most probably because the -72A-->G point mutation disables the binding of the erythroid transcription factor GATA-1 to the GATA-A element. Supporting these data, the two patients homozygous for the -72A-->G mutation had severe haemolytic anaemia and were transfusion dependent until splenectomy. Two other patients who were compound heterozygous for this mutation and the previously described missense mutation 1456C-->T had a mild condition.

  14. Association between FTO variant and change in body weight and its interaction with dietary factors; the DiOGenes study

    NARCIS (Netherlands)

    Vimaleswaran, K.S.; Angquist, L.; Hansen, R.D.; A, van der D.L.; Bouatia-Naji, N.; Holst, C.; Tjonneland, A.; Overvad, K.; Jakobsen, M.U.; Boeing, H.; Meidtner, K.; Palli, D.; Masala, G.; Saris, W.H.M.; Feskens, E.J.M.; Wareham, N.J.; Sorensen, T.I.A.; Loos, R.J.F.

    2012-01-01

    Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8

  15. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

    DEFF Research Database (Denmark)

    Andreasen, Camilla H; Stender-Petersen, Kirstine L; Mogensen, Mette S

    2008-01-01

    was examined. RESEARCH DESIGN AND METHODS: The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS: In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated......(-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive...... activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation....

  16. Film formation of CdSe quantum dot embedded phosphate glass on an FTO glass substrate

    Science.gov (United States)

    Han, Karam; Kim, Yoon Hwa; Im, Won Bin; Chung, Woon Jin

    2015-07-01

    A thick film with CdSe quantum dot (QD) embedded glass was formed on a fluorine-doped tin oxide (FTO) glass substrate. Phosphate glasses with different CdO and ZnSe concentrations were synthesized, and the heat treatment conditions were varied to determine the appropriate QD and film formation conditions. Phosphate glass with 1 mol. % CdO and 1.5 mol. % ZnSe showed controlled crystallization of CdSe QDs when they were heat treated at 550℃ for 1 hr. Absorption spectra and Raman spectroscopy identified the QD formation. Precursor glass was ground into powder and pasted onto FTO only and TiO2/FTO glass substrates via the screen printing method. Glass film embedded with QDs was successfully formed after sintering, thus demonstrating its potential for film applications. [Figure not available: see fulltext.

  17. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.

    Science.gov (United States)

    Sullivan, D; Pinsonneault, J K; Papp, A C; Zhu, H; Lemeshow, S; Mash, D C; Sadee, W

    2013-01-22

    Epistatic gene-gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3'-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene-gene-drug interaction affecting risk of fatal cocaine intoxication.

  18. Possible association between the dopamine D3 receptor gene and bipolar affective disorder

    Energy Technology Data Exchange (ETDEWEB)

    Todd, R.D.; Chakraverty, S.; Parsian, A. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-09-01

    A variety of studies have reported possible genetic associations between bipolar affective disorder and different loci using relative risk approaches. An alternative approach is to determine untransmitted genotypes from families selected through a single affected individual. We have used both approaches to test for possible associations between alleles of the dopamine D3 receptor gene and bipolar affective disorder. For relative risk studies, the probands of multiple incidence bipolar affective disorder (n=66) and alcoholism (n=132) families and psychiatric normal controls (n=91) have been compared. Non-transmitted allele approaches have used bipolar affective disorder (n=28) and alcoholic (n=25) probands in which both parents were available for genotyping. Using the Bal I restriction enzyme site polymorphism of Lannfelt, we have found no differences in the allele or genotype frequencies for bipolar or alcoholic probands versus psychiatrically normal controls. In contrast, we have found evidence for an increased frequency of allele 1 and allele 1 containing genotypes in transmitted alleles from bipolar families.

  19. Identification of genes affecting alginate biosynthesis in Pseudomonas fluorescens by screening a transposon insertion library.

    Science.gov (United States)

    Ertesvåg, Helga; Sletta, Håvard; Senneset, Mona; Sun, Yi-Qian; Klinkenberg, Geir; Konradsen, Therese Aursand; Ellingsen, Trond E; Valla, Svein

    2017-01-03

    Polysaccharides often are necessary components of bacterial biofilms and capsules. Production of these biopolymers constitutes a drain on key components in the central carbon metabolism, but so far little is known concerning if and how the cells divide their resources between cell growth and production of exopolysaccharides. Alginate is an industrially important linear polysaccharide synthesized from fructose 6-phosphate by several bacterial species. The aim of this study was to identify genes that are necessary for obtaining a normal level of alginate production in alginate-producing Pseudomonas fluorescens. Polysaccharide biosynthesis is costly, since it utilizes nucleotide sugars and sequesters carbon. Consequently, transcription of the genes necessary for polysaccharide biosynthesis is usually tightly regulated. In this study we used an engineered P. fluorescens SBW25 derivative where all genes encoding the proteins needed for biosynthesis of alginate from fructose 6-phosphate and export of the polymer are expressed from inducible Pm promoters. In this way we would avoid identification of genes merely involved in regulating the expression of the alginate biosynthetic genes. The engineered strain was subjected to random transposon mutagenesis and a library of about 11500 mutants was screened for strains with altered alginate production. Identified inactivated genes were mainly found to encode proteins involved in metabolic pathways related to uptake and utilization of carbon, nitrogen and phosphor sources, biosynthesis of purine and tryptophan and peptidoglycan recycling. The majority of the identified mutants resulted in diminished alginate biosynthesis while cell yield in most cases were less affected. In some cases, however, a higher final cell yield were measured. The data indicate that when the supplies of fructose 6-phosphate or GTP are diminished, less alginate is produced. This should be taken into account when bacterial strains are designed for

  20. The flhDC gene affects motility and biofilm formation in Yersinia pseudotuberculosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The flagella master regulatory gene flhDC of Yersinia pseudotuberculosis serotype Ⅲ (YPⅢ) was mutated by deleting the middle region and replaced by a tetracycline resistant gene, and the subsequent mutant strain named YPⅢ△flhDC was obtained. Swimming assay showed that the swimming motility of the mutant strain was completely abolished. The promoter region of the flagella second-class regulatory gene fliA was fused with the lux box, and was conjugated with the mutant and the parent strains respectively for the first cross. LUCY assay result demonstrated that flhDC regulated the expression of fliA in YPⅢ as reported in E. Coli. Biofilm formation of the mutant strain on abiotic and biotic surfaces was observed and quantified. The results showed that mutation of flhDC decreased biofilm formation on both abiotic and biotic surfaces, and abated the infection on Caenorhabdtis elegans. Our results suggest that mutation of the flagella master regulatory gene flhDC not only abolished the swimming motility, but also affected biofilm formation of YPⅢ on different surfaces. The new function of flhDC identified in this study provides a novel viewpoint for the control of bacterial biofilm formation.

  1. The ANK3 gene and facial affect processing: An ERP study.

    Science.gov (United States)

    Zhao, Wan; Zhang, Qiumei; Yu, Ping; Zhang, Zhifang; Chen, Xiongying; Gu, Huang; Zhai, Jinguo; Chen, Min; Du, Boqi; Deng, Xiaoxiang; Ji, Feng; Wang, Chuanyue; Xiang, Yu-Tao; Li, Dawei; Wu, Hongjie; Dong, Qi; Luo, Yuejia; Li, Jun; Chen, Chuansheng

    2016-09-01

    ANK3 is one of the most promising candidate genes for bipolar disorder (BD). A polymorphism (rs10994336) within the ANK3 gene has been associated with BD in at least three genome-wide association studies of BD [McGuffin et al., 2003; Kieseppä, 2004; Edvardsen et al., 2008]. Because facial affect processing is disrupted in patients with BD, the current study aimed to explore whether the BD risk alleles are associated with the N170, an early event-related potential (ERP) component related to facial affect processing. We collected data from two independent samples of healthy individuals (Ns = 83 and 82, respectively) to test the association between rs10994336 and an early event-related potential (ERP) component (N170) that is sensitive to facial affect processing. Repeated-measures analysis of covariance in both samples consistently revealed significant main effects of rs10994336 genotype (Sample I: F (1, 72) = 7.24, P = 0.009; Sample II: F (1, 69) = 11.81, P = 0.001), but no significant interaction of genotype × electrodes (Ps > 0.05) or genotype × emotional conditions (Ps > 0.05). These results suggested that rs10994336 was linked to early ERP component reflecting facial structural encoding during facial affect processing. These results shed new light on the brain mechanism of this risk SNP and associated disorders such as BD. © 2016 Wiley Periodicals, Inc.

  2. DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

    Science.gov (United States)

    Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

    2015-02-01

    The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects.

  3. Landscape features affect gene flow of Scottish Highland red deer (Cervus elaphus).

    Science.gov (United States)

    Pérez-Espona, S; Pérez-Barbería, F J; McLeod, J E; Jiggins, C D; Gordon, I J; Pemberton, J M

    2008-02-01

    Landscape features have been shown to strongly influence dispersal and, consequently, the genetic population structure of organisms. Studies quantifying the effect of landscape features on gene flow of large mammals with high dispersal capabilities are rare and have mainly been focused at large geographical scales. In this study, we assessed the influence of several natural and human-made landscape features on red deer gene flow in the Scottish Highlands by analysing 695 individuals for 21 microsatellite markers. Despite the relatively small scale of the study area (115 x 87 km), significant population structure was found using F-statistics (F(ST) = 0.019) and the program structure, with major differentiation found between populations sampled on either side of the main geographical barrier (the Great Glen). To assess the effect of landscape features on red deer population structure, the ArcMap GIS was used to create cost-distance matrices for moving between populations, using a range of cost values for each of the landscape features under consideration. Landscape features were shown to significantly affect red deer gene flow as they explained a greater proportion of the genetic variation than the geographical distance between populations. Sea lochs were found to be the most important red deer gene flow barriers in our study area, followed by mountain slopes, roads and forests. Inland lochs and rivers were identified as landscape features that might facilitate gene flow of red deer. Additionally, we explored the effect of choosing arbitrary cell cost values to construct least cost-distance matrices and described a method for improving the selection of cell cost values for a particular landscape feature.

  4. Co-stimulatory CD28 and transcription factor NFKB1 gene variants affect idiopathic recurrent miscarriages.

    Science.gov (United States)

    Misra, Maneesh Kumar; Singh, Bharti; Mishra, Aditi; Agrawal, Suraksha

    2016-12-01

    Co-stimulatory CD28 and transcription factor NFKB1 genes are considered as a crucial player in the determination of inflammatory responses; genetic variability in these may modulate the risk for idiopathic recurrent miscarriages (IRM). We investigated the association of functional variants of CD28 (rs3116496 T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) with IRM cases. We recruited 200 IRM women with a history of at least three consecutive pregnancy losses before 20th week of pregnancy and 300 fertile control women. Determination of CD28 (rs3116496 T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) gene variants were based on the polymerase chain reaction pursued by restriction fragment length polymorphism analysis and validated with Sanger sequencing. Single marker analysis and multifactor dimensionality reduction (MDR) model used to predict the IRM risk. We observed nearly three- to twofold increased risk in single marker analysis for minor homozygous genotypes of rs3116496 T/C, rs28362491 ins/del and rs696 A/G tag-SNPs in IRM cases, suggesting the risk association. In MDR analysis, we observed 10.5-fold augmented risk among IRM women in three-SNP model (rs3116496 T/C, rs28362491 ins/del and rs696 A/G). The eQTL mapping analyses was performed to strengthen the results of our study. The eQTL mapping analysis revealed that the variations in CD28 and NFKB1 gene content might affect the abundance of transcripts of CD28 and Family with sequence similarity 177 member A1 (FAM177A1) genes, respectively. These results suggest that CD28 and NFKB1 gene variants may be associated with increased risks to IRM.

  5. Two-step preparation of laser-textured Ni/FTO bilayer composite films with high photoelectric properties

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bao-jia, E-mail: li_bjia@126.com [School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Jiangsu Provincial Key Laboratory for Science and Technology of Photon Manufacturing, Jiangsu University, Zhenjiang 212013 (China); Huang, Li-jing [School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013 (China); Jiangsu Provincial Key Laboratory for Science and Technology of Photon Manufacturing, Jiangsu University, Zhenjiang 212013 (China); Ren, Nai-fei [Jiangsu Provincial Key Laboratory for Science and Technology of Photon Manufacturing, Jiangsu University, Zhenjiang 212013 (China); School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China); Kong, Xia; Cai, Yun-long; Zhang, Jie-lu [Jiangsu Tailong Reduction Box Co. Ltd, Taixing 225400 (China)

    2015-08-15

    Highlights: • A two-step strategy was proposed to prepare laser-textured Ni/FTO composite films. • Ni/FTO film with a 10-nm-thick Ni layer (Ni{sub 10}/FTO film) had the best performance. • The Ni{sub 10}/FTO film underwent magnetic-field-assisted and -free laser irradiations. • All the magnetic laser-irradiated (MLI-NF) films were textured and annealed. • The MLI-NF film using a fluence of 1.0 J/cm{sup 2} showed the highest figure of merit. - Abstract: A two-step strategy, i.e. sputtering Ni layers on FTO glass combined with magnetic-field-assisted laser irradiation, was proposed to prepare laser-textured Ni/FTO bilayer composite films. By analyzing surface morphology, crystal structure and photoelectric properties of Ni/FTO films with different Ni layer thicknesses, the Ni/FTO film with a 10-nm-thick Ni layer (Ni{sub 10}/FTO film), which had the best overall photoelectric property, was chosen to undergo magnetic-field-assisted laser irradiation with different laser fluences. Magnetic-field-free laser irradiation of the Ni{sub 10}/FTO film was also carried out for comparison purpose. It was found that magnetic-field-assisted laser irradiation using a fluence of 1.0 J/cm{sup 2} was more effective for simultaneously achieving texturing and annealing, resulting in formation of ideal grating textures and significantly increased grain size. The corresponding film (MLI-NF1.0 film) showed the highest figure of merit of 22.8 × 10{sup −3} Ω{sup −1} compared to 13.1 × 10{sup −3} Ω{sup −1} of the FTO glass and 1.4 × 10{sup −3} Ω{sup −1} of the Ni{sub 10}/FTO film, suggesting that the two-step strategy is excellent for preparing textured Ni/FTO films with high photoelectric properties.

  6. Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.

    Science.gov (United States)

    Abdi, Samia; Bahloul, Amel; Behlouli, Asma; Hardelin, Jean-Pierre; Makrelouf, Mohamed; Boudjelida, Kamel; Louha, Malek; Cheknene, Ahmed; Belouni, Rachid; Rous, Yahia; Merad, Zahida; Selmane, Djamel; Hasbelaoui, Mokhtar; Bonnet, Crystel; Zenati, Akila; Petit, Christine

    2016-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations), CDH23 (4 of 7 mutations), PCDH15 (1 mutation), USH1C (1 mutation), USH1G (1 mutation), and USH2A (1 of 2 mutations), had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn) and the in-frame single codon deletion in USH1G (p.Ala397del) on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC) domains of cadherin-23 and the sterile alpha motif (SAM) domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes.

  7. Changes in gravity affect gene expression, protein modulation and metabolite pools of arabidopsis

    Science.gov (United States)

    Hampp, R.; Martzivanou, M.; Maier, R. M.; Magel, E.

    Callus cultures of Arabidopsis thaliana (cv. Columbia) in Petri dishes / suspension cultures were exposed to altered g-forces by centrifugation (1 to 10 g), klinorotation, and μ g (sounding rocket flights). Using semi-quantitative RT-PCR, transcripts of genes coding for metabolic key enzymes (ADP-glucose pyrophosphorylase, ADPG-PP; ß-amylase, fructose-1,6-bisphosphatase, FBPase; glyceraldehyde-P dehydrogenase, GAPDH; hydroxymethylglutaryl-CoA reductase, HMG; phenylalanine-ammonium-lyase, PAL; PEP carboxylase, PEPC) were used to monitor threshold conditions for g-number (all) and time of exposure (ß-amylase) which led to altered amounts of the gene product. Exposure to approx. 5 g and higher for 1h resulted in altered transcript levels: transcripts of ß-amylase, PAL, and PEPC were increased, those of ADPG-PP decreased, while those of FBPase, GAPDH, and HMG were not affected. This probably indicates a shift from starch synthesis to starch degradation and increased rates of anaplerosis (PEPC: supply of ketoacids for amino acid synthesis). In order to get more information about g-related effects on gene expression, we used a 1h-exposure to 7 g for a microarray analysis. Transcripts of more than 200 genes were significantly increased in amount (ratio 7g / 1g control; 21.6 and larger). They fall into several categories. Transcripts coding for enzymes of major pathways form the largest group (25%), followed by gene products involved in cellular organisation and cell wall formation / rearrangement (17%), signalling, phosphorylation/dephosphorylation (12%), proteolysis and transport (10% each), hormone synthesis plus related events (8%), defense (4%), stress-response (2%), and gravisensing (2%). Many of the alterations are part of a general stress response, but some changes related to the synthesis / rearrangement of cell wall components could be more hyper-g-specific. Using macroarrays with selected genes according to our hypergravity study (metabolism / signalling

  8. Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

    1996-08-09

    Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

  9. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2017-01-01

    Full Text Available Induced pluripotent stem cells (iPSCs are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs.

  10. Subchromoplast sequestration of carotenoids affects regulatory mechanisms in tomato lines expressing different carotenoid gene combinations.

    Science.gov (United States)

    Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M A; Bramley, Peter M; Fraser, Paul D

    2013-11-01

    Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed.

  11. A 57-bp deletion in the ovine KAP6-1 gene affects wool fibre diameter.

    Science.gov (United States)

    Zhou, H; Gong, H; Li, S; Luo, Y; Hickford, J G H

    2015-08-01

    High glycine-tyrosine keratin-associated proteins (HGT-KAPs) are predominantly present in the orthocortex of wool fibres. They vary in abundance in different wools and have been implicated in regulating wool fibre properties, but little is known about the functional roles of these proteins in the fibre matrix. In this study, we used polymerase chain reaction--single-strand conformational polymorphism (PCR-SSCP) analysis to screen for variation in a gene encoding the ovine HGT-KAP6-1 protein. We identified three gene variants (A, B and C). Variants A and B were similar to each other, with only three nucleotide differences occurring downstream of the coding sequence. However, variant C had a 57-bp deletion that would notionally result in a loss of 19 amino acids in the protein. The presence of C was found to be associated with an increase in mean fibre diameter (MFD), fibre diameter standard deviation (FDSD), coefficient of variation of fibre diameter (CVFD) and prickle factor (percentage of fibres over 30 microns; PF). Sheep of genotype BC produced wool of greater MFD, FDSD and PF than sheep of genotypes AA, AB and BB. The CVFD was greater in the BC sheep than the AB sheep. The results suggest that variation in ovine KRTAP6-1 affects wool fibre diameter-associated traits and that the 57-bp deletion in this gene would lead to coarser wool with greater FDSD, CVFD and PF.

  12. Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects.

    Science.gov (United States)

    Kriesel, John D; Bhatia, Amiteshwar; Thomas, Alun

    2014-01-01

    Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. We present here a genotype-phenotype analysis of CSSG-1 in a new, unrelated human population. Seven hundred fifty-eight human subjects were enrolled in a case/control Cold Sore Study. CSSG-1 genotyping, herpes simplex virus 1 (HSV1) serotyping, demographic and phenotypic data was available from 622 analyzed subjects. Six major alleles (H1-H6) were tested for associations with each of the self-reported phenotypes. The statistical analysis was adjusted for age, sex and ethnicity. Genotype-phenotype associations were analyzed from 388 HSV1-seropositive subjects. There were significant CSSG-1 haplotype effects on annual cold sore outbreaks (P=0.006), lifetime cold sores (P=0.012) and perceived cold sore severity (P=0.012). There were relatively consistent trends toward protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2, and H4 haplotypes tended to have more frequent and more severe episodes. Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study.

  13. Vanillin differentially affects azoxymethane-injected rat colon carcinogenesis and gene expression.

    Science.gov (United States)

    Ho, Ket Li; Chong, Pei Pei; Yazan, Latifah Saiful; Ismail, Maznah

    2012-12-01

    Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.

  14. Polymorphisms in the Perilipin Gene May Affect Carcass Traits of Chinese Meat-type Chickens

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2015-06-01

    Full Text Available Improved meat quality and greater muscle yield are highly sought after in high-quality chicken breeding programs. Past studies indicated that polymorphisms of the Perilipin gene (PLIN1 are highly associated with adiposity in mammals and are potential molecular markers for improving meat quality and carcass traits in chickens. In the present study, we screened single nucleotide polymorphisms (SNPs in all exons of the PLIN1 gene with a direct sequencing method in six populations with different genetic backgrounds (total 240 individuals. We evaluated the association between the polymorphisms and carcass and meat quality traits. We identified three SNPs, located on the 5′ flanking region and exon 1 of PLIN1 on chromosome 10 (rs315831750, rs313726543, and rs80724063, respectively. Eight main haplotypes were constructed based on these SNPs. We calculated the allelic and genotypic frequencies, and genetic diversity parameters of the three SNPs. The polymorphism information content (PIC ranged from 0.2768 to 0.3750, which reflected an intermediate genetic diversity for all chickens. The CC, CT, and TT genotypes influenced the percentage of breast muscle (PBM, percentage of leg muscle (PLM and percentage of abdominal fat at rs315831750 (p<0.05. Diplotypes (haplotype pairs affected the percentage of eviscerated weight (PEW and PBM (p<0.05. Compared with chickens carrying other diplotypes, H3H7 had the greatest PEW and H2H2 had the greatest PBM, and those with diplotype H7H7 had the smallest PEW and PBM. We conclude that PLIN1 gene polymorphisms may affect broiler carcass and breast muscle yields, and diplotypes H3H7 and H2H2 could be positive molecular markers to enhance PEW and PBM in chickens.

  15. The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by FAK Inhibitor Y15 and Combination of Y15 and Temozolomide

    OpenAIRE

    2014-01-01

    Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarr...

  16. The Association of FTO SNP rs9939609 with Weight Gain at University

    NARCIS (Netherlands)

    Meisel, S.F.; Beeken, R.J.; Jaarsveld, C.H.M. van; Wardle, J.

    2015-01-01

    AIM: We tested the hypothesis that the obesity-associated FTO SNP rs9939609 would be associated with clinically significant weight gain (>/= 5% of initial body weight) in the first year of university; a time identified as high risk for weight gain. METHODS: We collected anthropometric data from

  17. Improved performance of organic light-emitting diode with vanadium pentoxide layer on the FTO surface

    Science.gov (United States)

    Saikia, D.; Sarma, R.

    2017-06-01

    Vanadium pentoxide layer deposited on the fluorine-doped tin oxide (FTO) anode by vacuum deposition has been investigated in organic light-emitting diode (OLED). With 12 nm optimal thickness of V2O5, the luminance efficiency is increased by 1.66 times compared to the single FTO-based OLED. The improvement of current efficiency implies that there is a better charge injection and better controlling of hole current. To investigate the performance of OLED by the buffer layer, V2O5 films of different thicknesses were deposited on the FTO anode and their J- V and L- V characteristics were studied. Further analysis was carried out by measuring sheet resistance, optical transmittance and surface morphology with the FE-SEM images. This result indicates that the V2O5 (12 nm) buffer layer is a good choice for increasing the efficiency of FTO-based OLED devices within the tunnelling region. Here the maximum value of current efficiency is found to be 2.83 cd / A.

  18. Reference of Temperature and Time during tempering process for non-stoichiometric FTO films

    Science.gov (United States)

    Yang, J. K.; Liang, B.; Zhao, M. J.; Gao, Y.; Zhang, F. C.; Zhao, H. L.

    2015-10-01

    In order to enhance the mechanical strength of Low-E glass, Fluorine-doped tin oxide (FTO) films have to be tempered at high temperatures together with glass substrates. The effects of tempering temperature (600 °C ~ 720 °C) and time (150 s ~ 300 s) on the structural and electrical properties of FTO films were investigated. The results show all the films consist of non-stoichiometric, polycrystalline SnO2 without detectable amounts of fluoride. 700 °C and 260 s may be the critical tempering temperature and time, respectively. FTO films tempered at 700 °C for 260 s possesses the resistivity of 7.54 × 10-4 Ω•cm, the average transmittance in 400 ~ 800 nm of ~80%, and the calculated emissivity of 0.38. Hall mobility of FTO films tempered in this proper condition is mainly limited by the ionized impurity scattering. The value of [O]/[Sn] at the film surface is much higher than the stoichiometric value of 2.0 of pure crystalline SnO2.

  19. Improved performance of organic light-emitting diode with vanadium pentoxide layer on the FTO surface

    Indian Academy of Sciences (India)

    D SAIKIA; R SARMA

    2017-06-01

    Vanadium pentoxide layer deposited on the fluorine-doped tin oxide (FTO) anode by vacuum deposition has been investigated in organic light-emitting diode (OLED).With 12nm optimal thickness of $V_{2}O_{5}$, the luminance efficiency is increased by 1.66 times compared to the single FTO-based OLED. The improvement of current efficiency implies that there is a better charge injection and better controlling of hole current. To investigate the performance of OLED by the buffer layer, $V_{2}O_{5}$ films of different thicknesses were deposited on the FTO anode and their $J–V$ and $L–V$ characteristics were studied. Further analysis was carried out by measuring sheet resistance, optical transmittance and surface morphology with the FE-SEM images. This result indicates that the $V_{2}O_{5}$ (12 nm) buffer layer is a good choice for increasing the efficiency of FTO-based OLED devices within the tunnelling region. Here the maximum value of current efficiency is found to be 2.83 cd/A.

  20. FTO Biology and Obesity: Why do a billion of us weigh 3 kg more?

    Directory of Open Access Journals (Sweden)

    Man-Ka Marcella Cheung

    2011-02-01

    Full Text Available Few would dispute that the current obesity epidemic has been driven by lifestyle and environmental changes. However, it is clear that individuals respond differently to these ‘obesigenic’ changes and this variation in response has a strong genetic element. Genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs in Fat mass and obesity associated transcript (FTO are robustly associated with body mass index and obesity. Although the effect of these risk alleles are modest, with heterozygous and homozygous carriers weighing approximately 1.5kg and 3kg more respectively, there are an estimated one billion homozygous carriers in the world, spanning multiple different ethnicities and populations. Yet despite its broad impact, the biological function of FTO, particularly its role in controlling energy balance, remains unknown. Although the study of severe mendelian obesity has been invaluable in illuminating critical pathways controlling food intake, the major burden of disease is carried by those of us with ‘common obesity’, which to date has resisted yielding meaningful biological insights. FTO has at last given us a handle on a huge, worldwide, common problem. In this review, we focus on the available genetic and in vivo evidence to date that implicates FTO in the control of energy balance.

  1. Lysine intake affects gene expression of anabolic hormones in Atlantic salmon, Salmo salar.

    Science.gov (United States)

    Hevrøy, E M; El-Mowafi, A; Taylor, R G; Olsvik, P A; Norberg, B; Espe, M

    2007-05-15

    Nutritional factors influence regulation of the growth hormone (GH) and the insulin-like growth factor (IGF) system in fish, but so far there are no published studies describing how single indispensable amino acids influence these systems. Therefore, the present study aimed to test whether lysine (Lys) intake at low (LL=2.85 g/16 gN), medium (ML=4.91 g/16 gN) and high levels (HL=9.19 g/16 gN) affected the expression of genes related to the GH-IGF system (i.e. GH receptor, GH-R, IGF-I, IGF-II, IGF binding protein 1, IGFBP-1, IGF-I receptor IGF-IR) in Atlantic salmon during seawater growth phase. Salmon fed the HL diet significantly up-regulated hepatic IGF-I mRNA level by a factor of 2.2 as compared to those with medium Lys intake. In addition a significant up-regulation of 2.7-fold in muscle IGF-II mRNA was present. Low Lys intake decreased the nitrogen deposition and muscle protein accretion in fish and significantly down-regulated hepatic IGFBP-1 as well as muscle GH-R and IGF-II, as compared to those fed the ML diet. mRNA of IGF-IR on the other hand was not affected by Lys intake. High Lys intake resulted in a 7-fold up-regulation of muscle IGF-II mRNA level as compared to low Lys intake, and thus might be an important local anabolic regulator in fast muscle tissue. The single indispensable amino acid Lys indeed affected signalling through the genes of IGF-I, IGFBP-1 in hepatic tissue and GH-R, IGF-II in fast muscle in Atlantic salmon. Concomitantly the higher Lys intake increased nitrogen deposition to a certain level.

  2. FTO Genotype and Type 2 Diabetes Mellitus: Spatial Analysis and Meta-Analysis of 62 Case-Control Studies from Different Regions

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2017-02-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a global health problem that results from the interaction of environmental factors with genetic variants. Although a number of studies have suggested that genetic polymorphisms in the fat mass and obesity-associated (FTO gene are associated with T2DM risk, the results have been inconsistent. To investigate whether FTO polymorphisms associate with T2DM risk and whether this association is region-related, we performed this spatial analysis and meta-analysis. More than 60,000 T2DM patients and 90,000 controls from 62 case-control studies were included in this study. Odds ratios (ORs, 95% confidence intervals (CIs and Moran’s I statistic were used to estimate the association between FTO rs9939609, rs8050136, rs1421085, and rs17817499, and T2DM risk in different regions. rs9939609 (OR = 1.15, 95% CI 1.11–1.19 and rs8050136 (OR = 1.14, 95% CI 1.10–1.18 conferred a predisposition to T2DM. After adjustment for body mass index (BMI, the association remained statistically significant for rs9939609 (OR = 1.11, 95% CI 1.05–1.17 and rs8050136 (OR = 1.08, 95% CI 1.03–1.12. In the subgroup analysis of rs9939609 and rs8050136, similar results were observed in East Asia, while no association was found in North America. In South Asia, an association for rs9939609 was revealed but not for rs8050136. In addition, no relationship was found with rs1421085 or rs17817499 regardless of adjustment for BMI. Moran’s I statistic showed that significant positive spatial autocorrelations existed in rs9939609 and rs8050136. Studies on rs9939609 and rs8050136 focused on East Asia and South Asia, whereas studies on rs1421085 and rs17817499 were distributed in North America and North Africa. Our data suggest that the associations between FTO rs9939609, rs8050136 and T2DM are region-related, and the two single-nucleotide polymorphisms contribute to an increased risk of T2DM. Future studies should investigate this issue in more regions.

  3. FTO Genotype and Type 2 Diabetes Mellitus: Spatial Analysis and Meta-Analysis of 62 Case-Control Studies from Different Regions

    Science.gov (United States)

    Yang, Ying; Liu, Boyang; Xia, Wei; Yan, Jing; Liu, Huan-Yu; Hu, Ling; Liu, Song-Mei

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is a global health problem that results from the interaction of environmental factors with genetic variants. Although a number of studies have suggested that genetic polymorphisms in the fat mass and obesity-associated (FTO) gene are associated with T2DM risk, the results have been inconsistent. To investigate whether FTO polymorphisms associate with T2DM risk and whether this association is region-related, we performed this spatial analysis and meta-analysis. More than 60,000 T2DM patients and 90,000 controls from 62 case-control studies were included in this study. Odds ratios (ORs), 95% confidence intervals (CIs) and Moran’s I statistic were used to estimate the association between FTO rs9939609, rs8050136, rs1421085, and rs17817499, and T2DM risk in different regions. rs9939609 (OR = 1.15, 95% CI 1.11–1.19) and rs8050136 (OR = 1.14, 95% CI 1.10–1.18) conferred a predisposition to T2DM. After adjustment for body mass index (BMI), the association remained statistically significant for rs9939609 (OR = 1.11, 95% CI 1.05–1.17) and rs8050136 (OR = 1.08, 95% CI 1.03–1.12). In the subgroup analysis of rs9939609 and rs8050136, similar results were observed in East Asia, while no association was found in North America. In South Asia, an association for rs9939609 was revealed but not for rs8050136. In addition, no relationship was found with rs1421085 or rs17817499 regardless of adjustment for BMI. Moran’s I statistic showed that significant positive spatial autocorrelations existed in rs9939609 and rs8050136. Studies on rs9939609 and rs8050136 focused on East Asia and South Asia, whereas studies on rs1421085 and rs17817499 were distributed in North America and North Africa. Our data suggest that the associations between FTO rs9939609, rs8050136 and T2DM are region-related, and the two single-nucleotide polymorphisms contribute to an increased risk of T2DM. Future studies should investigate this issue in more regions. PMID

  4. Leptin Receptor Gene Polymorphism may Affect Subclinical Atherosclerosis in Patients with Acromegaly

    Science.gov (United States)

    Turgut, Sebahat; Topsakal, Senay; Ata, Melek Tunç; Herek, Duygu; Akın, Fulya; Özkan, Şeyma; Turgut, Günfer

    2016-01-01

    Background: Acromegaly is associated with increased morbidity and mortality related to cardiovascular diseases. Leptin (LEP) and Leptin Receptor (LEPR) gene polymorphisms can increase cardiovascular risks. The aim of this study was to investigate association between the frequencies of LEP and LEPR gene polymorphisms and subclinical atherosclerosis in acromegalic patients. Methods: Forty-four acromegalic patients and 30 controls were admitted to study. The polymorphisms were identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose, fasting insulin, IGF-I, GH, IGFBP3, leptin, triglyceride, carotid Intima Media Thickness (cIMT) and HDL and LDL cholesterol concentrations were evaluated. Results: There was statistically significant difference between the LEPR genotypes of acromegalic patients (GG 11.4%, GA 52.3%, and AA 36.4%) and controls (GG 33.3%, GA 50%, and AA 16.7%) although their LEP genotype distribution was similar. In addition, the prevalence of the LEPR gene G and A alleles was significantly different between patients and controls. No significant difference was found among the G(-2548) A leptin genotypes of groups in terms of the clinical parameters. cIMT significantly increased homozygote LEPR GG genotype group compared to AA subjects in patients. But the other parameters were not different between LEPR genotypes groups of patients and controls. Conclusion: It can be said that the LEPR gene polymorphism may affect cIMT in patients. The reason is that LEPR GG genotype carriers may have more risk than other genotypes in the development of subclinical atherosclerosis in acromegaly. PMID:27563428

  5. Interfering with TGFβ-induced Smad3 nuclear accumulation differentially affects TGFβ-dependent gene expression

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    Dittmer Jürgen

    2003-03-01

    Full Text Available Abstract Background Transforming growth factor-β (TGFβ plays an important role in late-stage carcinogenesis by stimulating invasive behavior of cancer cells, promoting neo-angiogenesis and by helping cancer cells to escape surveillance by the immune system. It also supports colonization of the bone by metastatic breast cancer cells by increasing expression of osteolytic parathyroid hormone-related protein (PTHrP. Interfering with TGFβ signalling may thus weaken the malignant properties of cancer cells. We investigated to what extent two inhibitors, SB-202190 and SB-203580, interfere with TGFβ-signalling in invasive MDA-MB-231 breast cancer cells. These compounds, formerly used as p38-MAPK-specific inhibitors, were recently also demonstrated to inhibit TGFβ type I receptor kinase. Results Our results show that these inhibitors delay the onset of TGFβ-induced nuclear accumulation of Smad3 and reduces its amplitude. This effect was accompanied by a strong reduction in TGFβ-responsivess of the slow-responder genes pthrp, pai-1 and upa, while the reactivity of the fast-responder gene smad7 to TGFβ remained almost unchanged. Neither was the TGFβ response of the fast-responder ese-1/esx gene, whose expression we found to be strongly downregulated by TGFβ, affected by the inhibitors. Conclusion The data show that SB-202190 and SB-203580 suppress TGFβ-dependent activation of genes that are important for the acquisition of invasive behavior, while having no effect on the expression of the natural TGFβ inhibitor Smad7. This suggests that these compounds are potent inhibitors of malignant behavior of cancer cells.

  6. Escherichia coli tol and rcs genes participate in the complex network affecting curli synthesis.

    Science.gov (United States)

    Vianney, Anne; Jubelin, Grégory; Renault, Sophie; Dorel, Corine; Lejeune, Philippe; Lazzaroni, Jean Claude

    2005-07-01

    Curli are necessary for the adherence of Escherichia coli to surfaces, and to each other, during biofilm formation, and the csgBA and csgDEFG operons are both required for their synthesis. A recent survey of gene expression in Pseudomonas aeruginosa biofilms has identified tolA as a gene activated in biofilms. The tol genes play a fundamental role in maintaining the outer-membrane integrity of Gram-negative bacteria. RcsC, the sensor of the RcsBCD phosphorelay, is involved, together with RcsA, in colanic acid capsule synthesis, and also modulates the expression of tolQRA and csgDEFG. In addition, the RcsBCD phosphorelay is activated in tol mutants or when Tol proteins are overexpressed. These results led the authors to investigate the role of the tol genes in biofilm formation in laboratory and clinical isolates of E. coli. It was shown that the adherence of cells was lowered in the tol mutants. This could be the result of a drastic decrease in the expression of the csgBA operon, even though the expression of csgDEFG was slightly increased under such conditions. It was also shown that the Rcs system negatively controls the expression of the two csg operons in an RcsA-dependent manner. In the tol mutants, activation of csgDEFG occurred via OmpR and was dominant upon repression by RcsB and RcsA, while these two regulatory proteins repressed csgBA through a dominant effect on the activator protein CsgD, thus affecting curli synthesis. The results demonstrate that the Rcs system, previously known to control the synthesis of the capsule and the flagella, is an additional component involved in the regulation of curli. Furthermore, it is shown that the defect in cell motility observed in the tol mutants depends on RcsB and RcsA.

  7. Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

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    Ming-Wei Chang

    2013-12-01

    Full Text Available The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM, with coarse particles (2.5–10 μm having higher endotoxin levels than did fine particles (0.5–2.5 μm. After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL-6 release and activated epidermal growth factor receptor (EGFR, transforming growth factor (TGF-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1 gene expression, but not of matrix metallopeptidase (MMP-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers.

  8. Identification of rare high-risk copy number variants affecting the dopamine transporter gene in mental disorders

    DEFF Research Database (Denmark)

    Hoeffding, Louise K; Duong, Linh T T; Ingason, Andrés;

    2015-01-01

    BACKGROUND: The dopamine transporter, also known as solute carrier 6A3 (SLC6A3), plays an important role in synaptic transmission by regulating the reuptake of dopamine in the synapses. In line with this, variations in the gene encoding this transporter have been linked to both schizophrenia...... rare high-risk variants of psychiatric disorders. METHODS: We performed a systematic screening for CNVs affecting SLC6A3 in 761 healthy controls, 672 schizophrenia patients, and 194 patients with bipolar disorder in addition to 253 family members from six large pedigrees affected by mental disorders...... sizes and two affected several genes in addition to SLC6A3. CONCLUSION: Our findings suggest that rare high-risk CNVs affecting the gene encoding the dopamine transporter contribute to the pathogenesis of schizophrenia and affective disorders....

  9. Silver nanoparticles administered to chicken affect VEGFA and FGF2 gene expression in breast muscle and heart

    DEFF Research Database (Denmark)

    Hotowy, Anna Malgorzata; Sawosz, Ewa; Pineda, Lane Manalili

    2012-01-01

    Nanoparticles of colloidal silver (AgNano) can influence gene expression. Concerning trials of AgNano application in poultry as antimicrobial and metabolic agents, it is useful to reveal whether they affect the expression of genes crucial for bird development. AgNano were administered to broiler...

  10. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable.

    Science.gov (United States)

    Lawlor, Debbie A; Timpson, Nicholas J; Harbord, Roger M; Leary, Sam; Ness, Andy; McCarthy, Mark I; Frayling, Timothy M; Hattersley, Andrew T; Smith, George Davey

    2008-03-11

    The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis. We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was -0.08 (95% CI: -0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17). Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9-11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.

  11. Genetic variation of the IL-28B promoter affecting gene expression.

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    Masaya Sugiyama

    Full Text Available The current standard of care for the treatment of chronic hepatitis C is pegylated interferon-α (PEG-IFNα and ribavirin (RBV. The treatment achieves a sustained viral clearance in only approximately 50% of patients. Recent whole genome association studies revealed that single nucleotide polymorphisms (SNPs around IL-28B have been associated with response to the standard therapy and could predict treatment responses at approximately 80%. However, it is not clear which SNP is most informative because the genomic region containing significant SNPs shows strong linkage disequilibrium. We focused on SNPs in close proximity to the IL-28B gene to evaluate the function of each and identify the SNP affecting the IL-28B expression level most. The structures of IL-28A/B from 5' to 3'-UTR were determined by complete cDNA cloning. Both IL-28A and 28B genes consisted of 6 exons, differing from the CCDS data of NCBI. Two intron SNPs and a nonsynonymous SNP did not affect IL-28B gene function and expression levels but a SNP located in the proximal promoter region influenced gene expression. A (TA dinucleotide repeat, rs72258881, located in the promoter region was discovered by our functional studies of the proximal SNPs upstream of IL-28B; the transcriptional activity of the promoter increased gradually in a (TA(n length-dependent manner following IFN-α and lipopolysaccharide stimulation. Healthy Japanese donors exhibited a broad range of (TA dinucleotide repeat numbers from 10 to 18 and the most prevalent genotype was 12/12 (75%, differing from the database (13/13. However, genetic variation of IL-28A corresponding to that of IL-28B was not detected in these Japanese donors. These findings suggest that the dinucleotide repeat could be associated with the transcriptional activity of IL-28B as well as being a marker to improve the prediction of the response to interferon-based hepatitis C virus treatment.

  12. Polymorphism of the prion protein gene (PRNP) in Polish cattle affected by classical bovine spongiform encephalopathy.

    Science.gov (United States)

    Gurgul, Artur; Czarnik, Urszula; Urszula, Czarnik; Larska, Magdalena; Polak, Mirosław P; Strychalski, Janusz; Słota, Ewa

    2012-05-01

    Recent attempts to discover genetic factors affecting cattle resistance/susceptibility to bovine spongiform encephalopathy (BSE) have led to the identification of two insertion/deletion (indel) polymorphisms, located within the promoter and intron 1 of the prion protein gene PRNP, showing a significant association with the occurrence of classical form of the disease. Because the effect of the polymorphisms was studied only in few populations, in this study we investigated whether previously described association of PRNP indel polymorphisms with BSE susceptibility in cattle is also present in Polish cattle population. We found a significant relation between the investigated PRNP indel polymorphisms (23 and 12 bp indels), and susceptibility of Polish Holstein-Friesian cattle to classical BSE (P < 0.05). The deletion variants of both polymorphisms were related to increased susceptibility, whereas insertion variants were protective against BSE.

  13. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

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    Yamini Kashimshetty

    Full Text Available Tropical lowland rain forest (TLRF biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG, which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively than spatial logging pattern (0.2% and 4.7% respectively, with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene

  14. Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome

    Science.gov (United States)

    Abdi, Samia; Bahloul, Amel; Behlouli, Asma; Hardelin, Jean-Pierre; Makrelouf, Mohamed; Boudjelida, Kamel; Louha, Malek; Cheknene, Ahmed; Belouni, Rachid; Rous, Yahia; Merad, Zahida; Selmane, Djamel; Hasbelaoui, Mokhtar; Bonnet, Crystel; Zenati, Akila; Petit, Christine

    2016-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations), CDH23 (4 of 7 mutations), PCDH15 (1 mutation), USH1C (1 mutation), USH1G (1 mutation), and USH2A (1 of 2 mutations), had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn) and the in-frame single codon deletion in USH1G (p.Ala397del) on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC) domains of cadherin-23 and the sterile alpha motif (SAM) domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes. PMID:27583663

  15. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

    Science.gov (United States)

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  16. Aging affects mechanical properties and lubricin/PRG4 gene expression in normal ligaments.

    Science.gov (United States)

    Thornton, Gail M; Lemmex, Devin B; Ono, Yohei; Beach, Cara J; Reno, Carol R; Hart, David A; Lo, Ian K Y

    2015-09-18

    Age-related changes in ligament properties may have clinical implications for injuries in the mature athlete. Previous preclinical models documented mechanical and biochemical changes in ligaments with aging. The purpose of this study was to investigate the effect of aging on ligament properties (mechanical, molecular, biochemical) by comparing medial collateral ligaments (MCLs) from 1-year-old and 3-year-old rabbits. The MCLs underwent mechanical (n=7, 1-year-old; n=7, 3-year-old), molecular (n=8, 1-year-old; n=6, 3-year-old), collagen and glycosaminoglycan (GAG) content (n=8, 1-year-old; n=6, 3-year-old) and water content (n=8, 1-year-old; n=5, 3-year-old) assessments. Mechanical assessments evaluated total creep strain, failure strain, ultimate tensile strength and modulus. Molecular assessments using RT-qPCR evaluated gene expression for collagens, proteoglycans, hormone receptors, and matrix metalloproteinases and their inhibitors. While total creep strain and ultimate tensile strength were not affected by aging, failure strain was increased and modulus was decreased comparing MCLs from 3-year-old rabbits to those from 1-year-old rabbits. The mRNA expression levels for lubricin/proteoglycan 4 (PRG4) and tissue inhibitor of metalloproteinase-3 increased with aging; whereas, the mRNA expression levels for estrogen receptor and matrix metalloproteinase-1 decreased with aging. Collagen and GAG content assays and water content assessments did not demonstrate any age-related changes. The increased failure strain and decreased modulus with aging may have implications for increased susceptibility to ligament damage/injury with aging. Lubricin/PRG4 gene expression was affected by aging and its speculated role in ligament function may be related to interfascicular lubrication, which in turn may lead to altered mechanical function with aging and increases in potential for injury.

  17. FIRING PROPERTY OF INFERIOR COLLICULUS NEURONS AFFECTED BY FMR1 GENE MUTATION

    Institute of Scientific and Technical Information of China (English)

    Brittany Mott; SUN Wei

    2014-01-01

    Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn-drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor-mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound (hyperacusis). The molecular basis of fragile X syndrome is thoroughly understood;however, the neural mechanisms underly-ing hyperacusis have not yet been determined. As the inferior colliculus (IC) is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob-served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.

  18. Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.

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    Mathew D Littlejohn

    Full Text Available Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content. We aimed to further investigate this locus in two independent cattle populations, consisting of a Holstein-Friesian x Jersey crossbreed pedigree of 711 F2 cows, and a collection of 32,530 mixed ancestry Bos taurus cows. Bayesian genome-wide association mapping using markers imputed from the Illumina BovineHD chip revealed a large quantitative trait locus (QTL for milk fat percentage on chromosome 27, present in both populations. We also investigated a range of other milk composition phenotypes, and report additional associations at this locus for fat yield, protein percentage and yield, lactose percentage and yield, milk volume, and the proportions of numerous milk fatty acids. We then used mammary RNA sequence data from 212 lactating cows to assess the transcript abundance of genes located in the milk fat percentage QTL interval. This analysis revealed a strong eQTL for AGPAT6, demonstrating that high milk fat percentage genotype is also additively associated with increased expression of the AGPAT6 gene. Finally, we used whole genome sequence data from six F1 sires to target a panel of novel AGPAT6 locus variants for genotyping in the F2 crossbreed population. Association analysis of 58 of these variants revealed highly significant association for polymorphisms mapping to the 5'UTR exons and intron 1 of AGPAT6. Taken together, these data suggest that variants affecting the expression of AGPAT6 are causally involved in differential milk fat synthesis, with pleiotropic consequences for a diverse range of other milk components.

  19. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study

    Directory of Open Access Journals (Sweden)

    Rotter I

    2016-11-01

    Full Text Available Iwona Rotter,1 Karolina Skonieczna-Żydecka,2 Danuta Kosik-Bogacka,3 Grażyna Adler,2 Aleksandra Rył,4 Maria Laszczyńska4 1Department of Medical Rehabilitation, 2Department of Gerontobiology, 3Department of Biology and Medical Parasitology, 4Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland Purpose: Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARɣ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations. Subjects and methods: This study involved 272 men of Caucasian descent aged 50–75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPARɣ genes were identified using polymerase chain reaction-restriction fragments length polymorphism. Results: This study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively. Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005. Conclusion: FTO rs9939609, MC4R rs17782313, and PPARɣ rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men

  20. Low intensity infrared laser affects expression of oxidative DNA repair genes in mitochondria and nucleus

    Science.gov (United States)

    Fonseca, A. S.; Magalhães, L. A. G.; Mencalha, A. L.; Geller, M.; Paoli, F.

    2014-11-01

    Practical properties and physical characteristics of low intensity lasers have made possible their application to treat soft tissue diseases. Excitation of intracellular chromophores by red and infrared radiation at low energy fluences with increase of mitochondrial metabolism is the basis of the biostimulation effect but free radicals can be produced. DNA lesions induced by free radicals are repaired by the base excision repair pathway. In this work, we evaluate the expression of POLγ and APEX2 genes related to repair of mitochondrial and nuclear DNA, respectively. Skin and muscle tissue of Wistar rats were exposed to low intensity infrared laser at different fluences. One hour and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of POLγ and APEX2 mRNA expression by real time quantitative polymerase chain reaction. Skin and muscle tissue of Wistar rats exposed to laser radiation show different expression of POLγ and APEX2 mRNA depending of the fluence and time after exposure. Our study suggests that a low intensity infrared laser affects expression of genes involved in repair of oxidative lesions in mitochondrial and nuclear DNA.

  1. Overexpression of a glutamine synthetase gene affects growth and development in sorghum.

    Science.gov (United States)

    Urriola, Jazmina; Rathore, Keerti S

    2015-06-01

    Nitrogen is a primary macronutrient in plants, and nitrogen fertilizers play a critical role in crop production and yield. In this study, we investigated the effects of overexpressing a glutamine synthetase (GS) gene on nitrogen metabolism, and plant growth and development in sorghum (Sorghum bicolor L., Moench). GS catalyzes the ATP dependent reaction between ammonia and glutamate to produce glutamine. A 1,071 bp long coding sequence of a sorghum cytosolic GS gene (Gln1) under the control of the maize ubiquitin (Ubq) promoter was introduced into sorghum immature embryos by Agrobacterium-mediated transformation. Progeny of the transformants exhibited higher accumulation of the Gln1 transcripts and up to 2.2-fold higher GS activity compared to the non-transgenic controls. When grown under optimal nitrogen conditions, these Gln1 transgenic lines showed greater tillering and up to 2.1-fold increase in shoot vegetative biomass. Interestingly, even under greenhouse conditions, we observed a seasonal component to both these parameters and the grain yield. Our results, showing that the growth and development of sorghum Gln1 transformants are also affected by N availability and other environmental factors, suggest complexity of the relationship between GS activity and plant growth and development. A better understanding of other control points and the ability to manipulate these will be needed to utilize the transgenic technology to improve nitrogen use efficiency of crop plants.

  2. Niemann-Pick C1 affects the gene delivery efficacy of degradable polymeric nanoparticles.

    Science.gov (United States)

    Eltoukhy, Ahmed A; Sahay, Gaurav; Cunningham, James M; Anderson, Daniel G

    2014-08-26

    Despite intensive research effort, the rational design of improved nanoparticulate drug carriers remains challenging, in part due to a limited understanding of the determinants of nanoparticle entry and transport in target cells. Recent studies have shown that Niemann-Pick C1 (NPC1), the lysosome membrane protein that mediates trafficking of cholesterol in cells, is involved in the endosomal escape and subsequent infection caused by filoviruses, and that its absence promotes the retention and efficacy of lipid nanoparticles encapsulating siRNA. Here, we report that NPC1 deficiency results in dramatic reduction in internalization and transfection efficiency mediated by degradable cationic gene delivery polymers, poly(β-amino ester)s (PBAEs). PBAEs utilized cholesterol and dynamin-dependent endocytosis pathways, and these were found to be heavily compromised in NPC1-deficient cells. In contrast, the absence of NPC1 had minor effects on DNA uptake mediated by polyethylenimine or Lipofectamine 2000. Strikingly, stable overexpression of human NPC1 in chinese hamster ovary cells was associated with enhanced gene uptake (3-fold) and transfection (10-fold) by PBAEs. These findings reveal a role of NPC1 in the regulation of endocytic mechanisms affecting nanoparticle trafficking. We hypothesize that in-depth understanding sites of entry and endosomal escape may lead to highly efficient nanotechnologies for drug delivery.

  3. Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-04-01

    Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

  4. Gene envY of Escherichia coli K-12 affects thermoregulation of major porin expression.

    Science.gov (United States)

    Lundrigan, M D; Earhart, C F

    1984-01-01

    The temperature-dependent expression of OmpF and OmpC, the major channel-forming proteins of the Escherichia coli K-12 outer membrane, was studied. In wild-type cells, decreasing growth temperatures resulted in increased amounts of OmpF protein and correspondingly decreased quantities of OmpC protein. Bacteria deleted for the 13-min chromosomal region did not exhibit this temperature-dependent fluctuation in porin proteins. Plasmid pML22, which consists of pBR322 containing a 0.5-megadalton E. coli chromosomal DNA insert, complemented the thermoregulatory defect. The regulatory gene was named envY. In minicells, pML22 directed the synthesis of an envelope polypeptide (EnvY) having an apparent molecular weight of 25,000. The EnvY protein was synthesized in minicells in greater amounts at 27 degrees C than at 37 degrees C, and a reducing agent was necessary in the solubilization buffer for its subsequent detection on polyacrylamide gels. The results describe the initial characterization of a regulatory system which, along with proteins of the ompB operon, the cyclic AMP system, and the tolC gene product, is involved in a complex network affecting major porin expression. Images PMID:6317653

  5. Deletion of the homeobox gene PRX-2 affects fetal but not adult fibroblast wound healing responses.

    Science.gov (United States)

    White, Philip; Thomas, David W; Fong, Steven; Stelnicki, Eric; Meijlink, Fritz; Largman, Corey; Stephens, Phil

    2003-01-01

    The phenotype of fibroblasts repopulating experimental wounds in vivo has been shown to influence both wound healing responses and clinical outcome. Recent studies have demonstrated that the human homeobox gene PRX-2 is strongly upregulated in fibroblasts within fetal, but not adult, mesenchymal tissues during healing. Differential homeobox gene expression by fibroblasts may therefore be important in mediating the scarless healing exhibited in early fetal wounds. RNase protection analysis demonstrated that murine Prx-2 expression was involved in fetal but not adult wound healing responses in vitro. Using fibroblasts established from homozygous mutant (Prx-2-/-) and wild-type (Prx-2+/+) murine skin tissues it was demonstrated that Prx-2 affected a number of fetal fibroblastic responses believed to be important in mediating scarless healing in vivo; namely cellular proliferation, extracellular matrix reorganization, and matrix metalloproteinase 2 and hyaluronic acid production. These data demonstrate how Prx-2 may contribute to the regulation of fetal, but not adult, fibroblasts and ultimately the wound healing phenotype. This study provides further evidence for the importance of homeobox transcription factors in the regulation of scarless wound healing. A further understanding of these processes will, it is hoped, enable the targeting of specific therapies in wound healing, both to effect scarless healing and to stimulate healing in chronic, nonhealing wounds such as venous leg ulcers.

  6. Arabidopsis flower specific defense gene expression patterns affect resistance to pathogens

    KAUST Repository

    Ederli, Luisa

    2015-02-20

    We investigated whether the Arabidopsis flower evolved protective measures to increase reproductive success. Firstly, analyses of available transcriptome data show that the most highly expressed transcripts in the closed sepal (stage 12) are enriched in genes with roles in responses to chemical stimuli and cellular metabolic processes. At stage 15, there is enrichment in transcripts with a role in responses to biotic stimuli. Comparative analyses between the sepal and petal in the open flower mark an over-representation of transcripts with a role in responses to stress and catalytic activity. Secondly, the content of the biotic defense-associated phytohormone salicylic acid (SA) in sepals and petals is significantly higher than in leaves. To understand whether the high levels of stress responsive transcripts and the higher SA content affect defense, wild-type plants (Col-0) and transgenic plants defective in SA accumulation (nahG) were challenged with the biotrophic fungus Golovinomyces cichoracearum, the causal agent of powdery mildew, and the necrotrophic fungus Botrytis cinerea. NahG leaves were more sensitive than those of Col-0, suggesting that in leaves SA has a role in the defense against biotrophs. In contrast, sepals and petals of both genotypes were resistant to G. cichoracearum, indicating that in the flower, resistance to the biotrophic pathogen is not critically dependent on SA, but likely dependent on the up-regulation of stress-responsive genes. Since sepals and petals of both genotypes are equally susceptible to B. cinerea, we conclude that neither stress-response genes nor increased SA accumulation offers protection against the necrotrophic pathogen. These results are interpreted in the light of the distinctive role of the flower and we propose that in the early stages, the sepal may act as a chemical defense barrier of the developing reproductive structures against biotrophic pathogens.

  7. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Directory of Open Access Journals (Sweden)

    Tejasvi S Niranjan

    Full Text Available X-linked Intellectual Disability (XLID is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  8. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Science.gov (United States)

    Niranjan, Tejasvi S; Skinner, Cindy; May, Melanie; Turner, Tychele; Rose, Rebecca; Stevenson, Roger; Schwartz, Charles E; Wang, Tao

    2015-01-01

    X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome) in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families) using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  9. Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

    Science.gov (United States)

    Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2012-01-01

    Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

  10. Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing

    Energy Technology Data Exchange (ETDEWEB)

    Wong, A.; Boutis, P.; Hekimi, S. [McGill Univ., Quebec (Canada)

    1995-03-01

    We have identified three allelic, maternal-effect mutations that affect developmental and behavioral timing in Caenorhabditis elegans. They result in a mean lengthening of embryonic and postembryonic development, the cell cycle period and life span, as well as the periods of the defecation, swimming and pumping cycles. These mutants also display a number of additional phenotypes related to timing. For example, the variability in the length of embryonic development is several times larger in the mutants than in the wild type, resulting in the occasional production of mutant embryos developing more rapidly than the most rapidly developing wild-type embryos. In addition, the duration of embryonic development of the mutants, but not of the wild type, depends on the temperature at which their parents were raised. Finally, individual variations in the severity of distinct mutant phenotypes are correlated in a counterintuitive way. For example, the animals with the shortest embryonic development have the longest defecation cycle and those with the longest embryonic development have the shortest defecation cycle. Most of the features affected by these mutations are believed to be controlled by biological clocks, and we therefore call the gene defined by these mutations clk-1, for {open_quotes}abnormal function of biological clocks.{close_quotes} 52 refs., 5 figs., 4 tabs.

  11. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis.

    Science.gov (United States)

    Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

    2015-03-01

    The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite development and directly increased HNK-1(+) neural crest cell (NCC) migration and TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development.

  12. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum

    Energy Technology Data Exchange (ETDEWEB)

    Tsukue, Naomi [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Japan Automobile Research Institute, Health Effects Research Group, Energy and Environment Research Division, Tsukuba, Ibaraki (Japan); Watanabe, Manabu; Kumamoto, Takayuki; Takeda, Ken [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Takano, Hirohisa [Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); National Institute for Environmental Studies, Pathophysiology Research Team, Tsukuba, Ibaraki (Japan)

    2009-11-15

    Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function. (orig.)

  13. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum.

    Science.gov (United States)

    Tsukue, Naomi; Watanabe, Manabu; Kumamoto, Takayuki; Takano, Hirohisa; Takeda, Ken

    2009-11-01

    Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function.

  14. Facile solution deposition of Cu{sub 2}ZnSnS{sub 4} (CZTS) nano-worm films on FTO substrates and its photoelectrochemical property

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yaohan; Li, Guangli; Fan, Qingfei; Zhang, Meili; Lan, Qi [School of Materials Science and Engineering, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Chengdu 610031 (China); Fan, Ximei, E-mail: fanximei@126.com [School of Materials Science and Engineering, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Chengdu 610031 (China); Zhou, Zuowan [School of Materials Science and Engineering, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Chengdu 610031 (China); Zhang, Chaoliang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 (China)

    2016-02-28

    Graphical abstract: - Highlights: • Cu{sub 2}ZnSnS{sub 4} nanoworm thin films were synthesized directly on FTO substrates. • Polyethylene glycol-400 was used as solvent and structure-directing agent. • CZTS nanoworm film showed a photoelectrical conversion efficiency of 1.18%. - Abstract: In this work, Cu{sub 2}ZnSnS{sub 4} (CZTS) nanoworm films have been directly deposited on fluorine-doped tin oxide (FTO) conductive glass substrates by a solvothermal method using polyethylene glycol 400 (PEG-400) as the solvent and structure-directing agent. The as-obtained CZTS thin films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectrum (XPS), UV–vis spectra and photoelectrochemical measurement. The synthetic conditions, such as reaction temperature, reaction time, solvents, were investigated to know the formation of CZTS thin films. The results showed that PEG-400 plays a key role in the formation of the nanoworms by affecting the crystal growth process. The p-type CZTS nanoworm film with the band gap of 1.62 eV was synthesized at 180 °C for 22 h and the photovoltaic performance was studied by forming a photoelectrochemical cell.

  15. Genes of the most conserved WOX clade in plants affect root and flower development in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Moreau Hervé

    2008-10-01

    Full Text Available Abstract Background The Wuschel related homeobox (WOX family proteins are key regulators implicated in the determination of cell fate in plants by preventing cell differentiation. A recent WOX phylogeny, based on WOX homeodomains, showed that all of the Physcomitrella patens and Selaginella moellendorffii WOX proteins clustered into a single orthologous group. We hypothesized that members of this group might preferentially share a significant part of their function in phylogenetically distant organisms. Hence, we first validated the limits of the WOX13 orthologous group (WOX13 OG using the occurrence of other clade specific signatures and conserved intron insertion sites. Secondly, a functional analysis using expression data and mutants was undertaken. Results The WOX13 OG contained the most conserved plant WOX proteins including the only WOX detected in the highly proliferating basal unicellular and photosynthetic organism Ostreococcus tauri. A large expansion of the WOX family was observed after the separation of mosses from other land plants and before monocots and dicots have arisen. In Arabidopsis thaliana, AtWOX13 was dynamically expressed during primary and lateral root initiation and development, in gynoecium and during embryo development. AtWOX13 appeared to affect the floral transition. An intriguing clade, represented by the functional AtWOX14 gene inside the WOX13 OG, was only found in the Brassicaceae. Compared to AtWOX13, the gene expression profile of AtWOX14 was restricted to the early stages of lateral root formation and specific to developing anthers. A mutational insertion upstream of the AtWOX14 homeodomain sequence led to abnormal root development, a delay in the floral transition and premature anther differentiation. Conclusion Our data provide evidence in favor of the WOX13 OG as the clade containing the most conserved WOX genes and established a functional link to organ initiation and development in Arabidopsis, most

  16. Molecular characterization and expression analysis of fat mass and obesity-associated gene in rabbit.

    Science.gov (United States)

    Xing, Jinyi; Jing, Wenqian; Jiang, Yunliang

    2013-12-01

    Fat mass and obesity-associated (FTO) gene codes for a nuclear protein of the AlkB related nonhaem iron and 2-oxoglutaratedependent oxygenase superfamily, and is involved in animal fat deposition and human obesity. In this work, the molecular characterization and expression features of rabbit (Oryctolagus cuniculus) FTO cDNA were analysed. The rabbit FTO cDNA with a size of 2158 bp was cloned, including 1515 bp of the open reading frame that encoded a basic protein of 504 amino acids. Homologous comparison indicated that the rabbit FTO shared 36.36-91.88% identity with those from other species and phylogenetic analysis showed that the rabbit FTO is closely related to human, but more distantly related to zebrafish. The New Zealand rabbit FTO mRNA was detected in all tissues examined, with the highest levels found in the spleen and the lowest found in the kidney. However, no significant differences were seen in cerebellum, corpora quadrigemina, medulla oblongata and cerebral cortex of commercial adult rabbits. Moreover, mRNA levels of FTO in liver tissues were significantly increased in lactating New Zealand rabbits compared with 70-day-old, 90-day-old and gestating rabbits (P rabbits than in 70-day-old rabbits (P rabbits were not significantly different (P > 0.05).

  17. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.

    Science.gov (United States)

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J; Cook, Edwin; Das, Soma; Ratain, Mark J

    2014-10-15

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.

  18. Validation of Candidate Causal Genes for Abdominal Obesity Which Affect Shared Metabolic Pathways and Networks

    OpenAIRE

    Yang, Xia; Deignan, Joshua L; Qi, Hongxiu; Zhu, Jun; Qian, Su; Zhong, Judy; Torosyan, Gevork; Majid, Sana; Falkard, Brie; Kleinhanz, Robert R; Karlsson, Jenny; Castellani, Lawrence W.; Mumick, Sheena; Wang, Kai; Xie, Tao

    2009-01-01

    A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with...

  19. Folate-related gene variants in Irish families affected by neural tube defects

    Directory of Open Access Journals (Sweden)

    Ridgely eFisk Green

    2013-11-01

    Full Text Available Periconceptional folic acid use can often prevent neural tube defects (NTDs. Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017. We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential

  20. Facile fabrication of hierarchical SnO(2) microspheres film on transparent FTO glass.

    Science.gov (United States)

    Wang, Yu-Fen; Lei, Bing-Xin; Hou, Yuan-Fang; Zhao, Wen-Xia; Liang, Chao-Lun; Su, Cheng-Yong; Kuang, Dai-Bin

    2010-02-15

    Hierarchical SnO(2) microspheres consisting of nanosheets on the fluorine-doped tin oxide (FTO) glass substrates are successfully prepared via a facile hydrothermal synthesis process. The as-prepared novel microsphere films were characterized in detail by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), UV-vis diffuse reflectance spectroscopy. Moreover, SnO(2) nanoparticles with 30-80 nm in size covered on the surface of nanosheets/microspheres were also obtained by optimizing the hydrothermal reaction temperature, time, or volume ratio of acetylacetone/H(2)O. The detailed investigations disclose the experimental parameters, such as acetylacetone, NH(4)F, and seed layer play important roles in the morphology of hierarchical SnO(2) microspheres on the FTO glass. The formation process of SnO(2) microspheres is also proposed based on the observations of time dependent samples.

  1. Optically transparent FTO-free cathode for dye-sensitized solar cells.

    Science.gov (United States)

    Kavan, Ladislav; Liska, Paul; Zakeeruddin, Shaik M; Grätzel, Michael

    2014-12-24

    The woven fabric containing electrochemically platinized tungsten wire is an affordable flexible cathode for liquid-junction dye-sensitized solar cells with the I3(-)/I(-) redox mediator and electrolyte solution consisting of ionic liquids and propionitrile. The fabric-based electrode outperforms the thermally platinized FTO in serial ohmic resistance and charge-transfer resistance for triiodide reduction, and it offers comparable or better optical transparency in the visible and particularly in the near-IR spectral region. The electrode exhibits good stability during electrochemical loading and storage at open circuit. The dye-sensitized solar cells with a C101-sensitized titania photoanode and either Pt-W/PEN or Pt-FTO cathodes show a comparable performance.

  2. Effect of the cathodic polarization on structural and morphological proprieties of FTO and ITO thin films

    Energy Technology Data Exchange (ETDEWEB)

    Cid, C.C. Plá [LabSiN, Departamento de Física, Universidade Federal de Santa Catarina, Caixa Postal 476, 88040-900 Florianópolis, SC (Brazil); Spada, E.R., E-mail: edspada@gmail.com [LabSiN, Departamento de Física, Universidade Federal de Santa Catarina, Caixa Postal 476, 88040-900 Florianópolis, SC (Brazil); Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-970 São Carlos, SP (Brazil); Sartorelli, M.L. [LabSiN, Departamento de Física, Universidade Federal de Santa Catarina, Caixa Postal 476, 88040-900 Florianópolis, SC (Brazil)

    2013-05-15

    This paper deals on the influence of the potentiodynamic stress on structural and morphological proprieties of fluorine-doped tin oxide (FTO, SnO{sub 2}:F) and indium tin oxide (ITO, In{sub 2}O{sub 3}:Sn) commercial substrates. The potential range is between 0.0 and −2.0 (V/SCE) using an electrolyte with neutral pH. The electrochemical behavior was investigated from cyclic voltammetry technique and chronopotentiometric curves. These electrochemical results were associated to the X-ray diffraction (XRD) spectra and morphology images acquired by scanning electron microscopy (SEM). The main results show that structural and morphological properties of FTO substrates after cathodic polarization remain near constant when compared with ITO films. The ITO substrates show morphological changes after treatment and the XRD patterns indicate the formation of a crystalline structure with In metallic characteristic, at neutral pH.

  3. The effects of genetic variation in FTO rs9939609 on obesity and dietary preferences in Chinese Han children and adolescents.

    Directory of Open Access Journals (Sweden)

    Min Yang

    Full Text Available The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs were 1.47 (95% CI: 1.25-1.71, P = 1.73×10-6, and 3.32 (95% CI: 2.01-5.47, P = 2.68×10-6, respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005. Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21. The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8-5.81 compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic

  4. The effects of genetic variation in FTO rs9939609 on obesity and dietary preferences in Chinese Han children and adolescents.

    Science.gov (United States)

    Yang, Min; Xu, Yuyang; Liang, Li; Fu, Junfen; Xiong, Feng; Liu, Geli; Gong, Chunxiu; Luo, Feihong; Chen, Shaoke; Xu, Chunxiao; Zhang, Dandan; Li, Zhengli; Zhang, Shuai; Zhang, Yan; Wang, Hao; Zhu, Yimin

    2014-01-01

    The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25-1.71, P = 1.73×10-6), and 3.32 (95% CI: 2.01-5.47, P = 2.68×10-6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8-5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of

  5. The microarray gene profiling analysis of glioblastoma cancer cells reveals genes affected by FAK inhibitor Y15 and combination of Y15 and temozolomide.

    Science.gov (United States)

    Huang, Grace; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Qiang, Hu; Golubovskaya, Vita

    2014-01-01

    Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in DBTRG and U87 cells, respectively (ptemozolomide and by combination of Y15 and temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and temozolomide more significantly than by each agent alone were: COX7B; interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and in response to combination of Y15 with temozolomide that is important for glioblastoma therapy.

  6. The Association of FTO SNP rs9939609 with Weight Gain at University

    Directory of Open Access Journals (Sweden)

    Susanne F. Meisel

    2015-07-01

    Full Text Available Aim: We tested the hypothesis that the obesity-associated FTO SNP rs9939609 would be associated with clinically significant weight gain (≥5% of initial body weight in the first year of university; a time identified as high risk for weight gain. Methods: We collected anthropometric data from university students (n = 1,411, mean age: 22.4 ± 2.5 years, 49.1% male at the beginning and end of the academic year. DNA was analysed for FTO rs9939609. Associations of FTO genotype with BMI at baseline were analysed using ANCOVA, and with risk of 5% weight gain over follow-up with logistic regression; both analyses adjusting for age and sex. The alpha level was reduced to 0.0125 to account for multiple testing. Results: Using an additive model, FTO status was not associated with higher BMI at baseline (22.2 vs. 21.9 kg/m2, p = 0.059. Dropout was high but unrelated to genotype. Among the 310 (21.9% completing follow-up, those with AT genotypes had twice the odds of ≥5% weight gain compared with TTs (OR = 2.05, 95% CI = 1.05-4.01, p = 0.036, but this was no longer significant after Bonferroni correction. There was a trend for AA carriers for ≥5% weight gain compared with TT carriers (p = 0.089, but sample size was small. Conclusion: This study provides nominal evidence for the genetic susceptibility hypothesis, but findings need to be replicated.

  7. Resistive switching effect of Ag/MoS2/FTO device

    Science.gov (United States)

    Sun, Bai; Zhao, Wenxi; Liu, Yonghong; Chen, Peng

    2015-09-01

    The electric-pulse-driven resistance change of metal/oxides/metal structure, which is called resistive switching effect, is a fascinating phenomenon for the development of next generation non-volatile memory. In this work, an outstanding bipolar resistive switching behavior of Ag/MoS2/fluorine-doped tin oxide (FTO) device is demonstrated. The device can maintain superior reversible stability over 100 cycles with an OFF/ON-state resistance ratio of about 103 at room temperature.

  8. Serotonin transporter gene-linked polymorphism affects detection of facial expressions.

    Directory of Open Access Journals (Sweden)

    Ai Koizumi

    Full Text Available Previous studies have demonstrated that the serotonin transporter gene-linked polymorphic region (5-HTTLPR affects the recognition of facial expressions and attention to them. However, the relationship between 5-HTTLPR and the perceptual detection of others' facial expressions, the process which takes place prior to emotional labeling (i.e., recognition, is not clear. To examine whether the perceptual detection of emotional facial expressions is influenced by the allelic variation (short/long of 5-HTTLPR, happy and sad facial expressions were presented at weak and mid intensities (25% and 50%. Ninety-eight participants, genotyped for 5-HTTLPR, judged whether emotion in images of faces was present. Participants with short alleles showed higher sensitivity (d' to happy than to sad expressions, while participants with long allele(s showed no such positivity advantage. This effect of 5-HTTLPR was found at different facial expression intensities among males and females. The results suggest that at the perceptual stage, a short allele enhances the processing of positive facial expressions rather than that of negative facial expressions.

  9. Polymorphisms within beta-catenin encoding gene affect multiple myeloma development and treatment.

    Science.gov (United States)

    Butrym, Aleksandra; Rybka, Justyna; Łacina, Piotr; Gębura, Katarzyna; Frontkiewicz, Diana; Bogunia-Kubik, Katarzyna; Mazur, Grzegorz

    2015-12-01

    Recent studies have suggested that cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, and that dysregulation of Wnt/β-catenin pathway may be one of possible reasons of lenalidomide resistance. This prompted us to analyze the effect of polymorphisms within the genes coding for cereblon (CRBN (rs121918368 C>T)) and β-catenin (CTNNB1 (rs4135385 A>G; rs4533622 A>C)). MM patients (n=142) and healthy individuals (n=123) were genotyped using the Light SNiP assays. The presence of the CTNNB1 (rs4533622) A allele was more frequently detected in patients presented with stage II-III disease according to International Staging System (63/82 vs. 26/44, p=0.043) and Durie-Salmon criteria (75/99 vs. 14/26, p=0.049). The CTNNB1 (rs4135385) AA homozygosity was more frequent among patients with better response to CTD, i.e., cyclophosphamide-thalidomide-dexamethasone (18/23 vs. 32/60, p=0.047). Patients carrying the CTNNB1 (rs4533622) AA genotype were better responders to the first line therapy with thalidomide containing regimens (pCRBN polymorphism. These results suggest that the CTNNB1 polymorphisms may affect the clinical course and response to chemotherapy in patients with multiple myeloma.

  10. Transcription factor organic cation transporter 1 (OCT-1 affects the expression of porcine Klotho (KL gene

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-07-01

    Full Text Available Klotho (KL, originally discovered as an aging suppressor, is a membrane protein that shares sequence similarity with the β-glucosidase enzymes. Recent reports showed Klotho might play a role in adipocyte maturation and systemic glucose metabolism. However, little is known about the transcription factors involved in regulating the expression of porcine KL gene. Deletion fragment analysis identified KL-D2 (−418 bp to −3 bp as the porcine KL core promoter. MARC0022311SNP (A or G in KL intron 1 was detected in Landrace × DIV pigs using the Porcine SNP60 BeadChip. The pGL-D2-A and pGL-D2-G were constructed with KL-D2 and the intron fragment of different alleles and relative luciferase activity of pGL3-D2-G was significantly higher than that of pGL3-D2-A in the PK cells and ST cells. This was possibly the result of a change in KL binding ability with transcription factor organic cation transporter 1 (OCT-1, which was confirmed using electrophoretic mobility shift assays (EMSA and chromatin immune-precipitation (ChIP. Moreover, OCT-1 regulated endogenous KL expression by RNA interference experiments. Our study indicates SNP MARC0022311 affects porcine KL expression by regulating its promoter activity via OCT-1.

  11. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

    DEFF Research Database (Denmark)

    Li, H; Oskari Kilpeläinen, Tuomas; Liu, C;

    2012-01-01

    FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus...... with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians....

  12. Molecular characterization and expression analysis of fat mass and obesity-associated gene in rabbit

    Indian Academy of Sciences (India)

    Jinyi Xing; Wenqian Jing; Yunliang Jiang

    2013-12-01

    Fat mass and obesity-associated (FTO) gene codes for a nuclear protein of the AlkB related nonhaem iron and 2-oxoglutarate-dependent oxygenase superfamily, and is involved in animal fat deposition and human obesity. In this work, the molecular characterization and expression features of rabbit (Oryctolagus cuniculus) FTO cDNA were analysed. The rabbit FTO cDNA with a size of 2158 bp was cloned, including 1515 bp of the open reading frame that encoded a basic protein of 504 amino acids. Homologous comparison indicated that the rabbit FTO shared 36.36–91.88% identity with those from other species and phylogenetic analysis showed that the rabbit FTO is closely related to human, but more distantly related to zebrafish. The New Zealand rabbit FTO mRNA was detected in all tissues examined, with the highest levels found in the spleen and the lowest found in the kidney. However, no significant differences were seen in cerebellum, corpora quadrigemina, medulla oblongata and cerebral cortex of commercial adult rabbits. Moreover, mRNA levels of FTO in liver tissues were significantly increased in lactating New Zealand rabbits compared with 70-day-old, 90-day-old and gestating rabbits $(P \\lt 0.05)$. In contrast, FTO mRNA levels were significantly lower in longissimus dorsi muscle of 90-day-old New Zealand rabbits than in 70-day-old rabbits $(P \\lt 0.05)$. However, the expression levels of FTO in mammary gland and ovary of gestating and lactating rabbits were not significantly different $(P \\gt 0.05)$.

  13. A mutation in the aroE gene affects pigment production, virulence, and chemotaxis in Xanthomonas oryzae pv. oryzae.

    Science.gov (United States)

    Kim, Hong-Il; Noh, Tae-Hwan; Lee, Chang-Soo; Park, Young-Jin

    2015-01-01

    Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB) in rice. To study its function, a random insertion mutation library of Xoo was constructed using the Tn5 transposon. A mutant strain with decreased virulence against the susceptible rice cultivar IR24 was isolated from the library (aroE mutant), which also had extremely low pigment production. Thermal asymmetric interlaced-polymerase chain reaction (TAIL-PCR) and sequence analysis of the mutant revealed that the transposon was inserted into the aroE gene (encoding shikimate dehydrogenase). To investigate gene expression changes in the pigment- and virulence-deficient mutant, DNA microarray analysis was performed, which showed downregulation of 20 genes involved in the chemotaxis of Xoo. Our findings reveal that mutation of the aroE gene affects virulence and pigment production, as well as expression of genes involved in Xoo chemotaxis.

  14. Short 5'-flanking regions of the Amy gene of Drosophila kikkawai affect amylase gene expression and respond to food environments.

    Science.gov (United States)

    Inomata, Nobuyuki; Nakashima, Shuichi

    2008-04-15

    Evolution of the duplicated genes and regulation in gene expression is of great interest, especially in terms of adaptation. Molecular population genetic and evolutionary studies on the duplicated amylase genes of Drosophila species have suggested that their 5'-flanking (cis-regulatory) regions play an important role in evolution of these genes. For better understanding of evolution of the duplicated amylase genes and gene expression, we studied functional significance of the Amy1 gene of Drosophila kikkawai using in vitro deletion mutagenesis followed by P-element-mediated germline transformation. We found that a 1.6-kb of the 5'-flanking region can produce strikingly higher level of larval amylase activity on starch food compared with that on glucose food. We found two cis-regulatory elements, which increase larval amylase activity on starch food. We also found a larval cis-regulatory element, which responds to the food difference. This food-response element is necessary for the function of the element increasing larval activity on starch food. A 5-bp deletion in a putative GRE caused high amylase activity, indicating a cis-regulatory element decreasing amylase activity. These cis-regulatory elements identified in the 5'-flanking region could be the targets of natural selection.

  15. Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.

    Science.gov (United States)

    Zambonelli, Paolo; Zappaterra, Martina; Soglia, Francesca; Petracci, Massimiliano; Sirri, Federico; Cavani, Claudio; Davoli, Roberta

    2016-12-01

    White Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broiler fillets present an impaired visual appearance that negatively affects consumers' acceptability. Previous studies have highlighted in affected fillets a severely damaged muscle, showing profound inflammation, fibrosis, and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation, and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further defining the transcription patterns associated with these myopathies. © 2016 Poultry Science Association Inc.

  16. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M. [Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2013-03-15

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g{sup -1}·min{sup -1}) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g{sup -1}·min{sup -1}) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  17. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

    Institute of Scientific and Technical Information of China (English)

    Lynnette R Ferguson; Claudia Huebner; Ivonne Petermann; Richard B Gearry; Murray L Barclay; Pieter Demmers; Alan McCulloch; Dug Yeo Han

    2008-01-01

    AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies.METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor:-238 G→A, -308 G→A and -857C→T, using a TaqmanRassay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, x2 = 17.36, P < 0.0001)increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, x2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variantdecreased the risk of ileocolonic CD (OR = 0.56, x2 =4.32, P = 0.037), and the need for a bowel resection(OR = 0.59, x2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis,(OR = 0.48, x2 = 4.86, P = 0.028).CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The-857 C/T SNP may decrease IBD risk in certain groups.Pharmaco- or nutrigenomic approaches may be desir-able for individuals with such affected genotypes.

  18. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring.

    Science.gov (United States)

    Pinheiro, D F; Pacheco, P D G; Alvarenga, P V; Buratini, J; Castilho, A C S; Lima, P F; Sartori, D R S; Vicentini-Paulino, M L M

    2013-03-01

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g-1·min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g-1·min-1) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  19. Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.

    Science.gov (United States)

    Raychaudhuri, Soumya; Korn, Joshua M; McCarroll, Steven A; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J

    2010-09-09

    Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied "pathway" analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package.

  20. Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

    Science.gov (United States)

    Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

    2010-01-01

    Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package

  1. Exploring the Developmental Overnutrition Hypothesis Using Parental–Offspring Associations and FTO as an Instrumental Variable

    Science.gov (United States)

    Lawlor, Debbie A; Timpson, Nicholas J; Harbord, Roger M; Leary, Sam; Ness, Andy; McCarthy, Mark I; Frayling, Timothy M; Hattersley, Andrew T; Smith, George Davey

    2008-01-01

    Background The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis. Methods and Findings We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)–determined fat mass measured at 9 to 11 y (4,091 parent–offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was −0.08 (95% CI: −0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17). Conclusions Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9–11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent

  2. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable.

    Directory of Open Access Journals (Sweden)

    Debbie A Lawlor

    2008-03-01

    Full Text Available The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI with offspring dual energy X-ray absorptiometry (DXA-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26 for maternal BMI versus 0.13 (95% CI: 0.11, 0.15 for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was -0.08 (95% CI: -0.56 to 0.41, with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17.Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9-11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.

  3. Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans

    Science.gov (United States)

    Saldaña-Alvarez, Yolanda; Salas-Martínez, María Guadalupe; García-Ortiz, Humberto; Luckie-Duque, Angélica; García-Cárdenas, Gustavo; Vicenteño-Ayala, Hermenegildo; Cordova, Emilio J.; Esparza-Aguilar, Marcelino; Contreras-Cubas, Cecilia; Carnevale, Alessandra; Chávez-Saldaña, Margarita; Orozco, Lorena

    2016-01-01

    To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m2 heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m2 and 0.9 kg/m2, respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m2, P = 1.17 x 10−10). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m2 (P = 1.15 x 10−5). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms

  4. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

    Directory of Open Access Journals (Sweden)

    Vita M. Golubovskaya

    2014-01-01

    Full Text Available Focal Adhesion Kinase (FAK is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53−/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05 in HCT116 p53+/+ cells but not in p53−/− cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.

  5. Social context-induced song variation affects female behavior and gene expression.

    Directory of Open Access Journals (Sweden)

    Sarah C Woolley

    2008-03-01

    Full Text Available Social cues modulate the performance of communicative behaviors in a range of species, including humans, and such changes can make the communication signal more salient. In songbirds, males use song to attract females, and song organization can differ depending on the audience to which a male sings. For example, male zebra finches (Taeniopygia guttata change their songs in subtle ways when singing to a female (directed song compared with when they sing in isolation (undirected song, and some of these changes depend on altered neural activity from a specialized forebrain-basal ganglia circuit, the anterior forebrain pathway (AFP. In particular, variable activity in the AFP during undirected song is thought to actively enable syllable variability, whereas the lower and less-variable AFP firing during directed singing is associated with more stereotyped song. Consequently, directed song has been suggested to reflect a "performance" state, and undirected song a form of vocal motor "exploration." However, this hypothesis predicts that directed-undirected song differences, despite their subtlety, should matter to female zebra finches, which is a question that has not been investigated. We tested female preferences for this natural variation in song in a behavioral approach assay, and we found that both mated and socially naive females could discriminate between directed and undirected song-and strongly preferred directed song. These preferences, which appeared to reflect attention especially to aspects of song variability controlled by the AFP, were enhanced by experience, as they were strongest for mated females responding to their mate's directed songs. We then measured neural activity using expression of the immediate early gene product ZENK, and found that social context and song familiarity differentially modulated the number of ZENK-expressing cells in telencephalic auditory areas. Specifically, the number of ZENK-expressing cells in the

  6. Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

    Science.gov (United States)

    Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo

    2017-01-07

    Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABAA receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABAA receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (Pallele=0.002; uncorrected) and rs1157122 (Pallele=0.006; uncorrected) showed top hits, followed by rs723432 (Pallele=0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology.

  7. D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians

    DEFF Research Database (Denmark)

    Andreou, Dimitrios; Saetre, Peter; Werge, Thomas;

    2012-01-01

    3918342 and rs1421292, were significantly associated with CSF HVA concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA concentrations. None of the polymorphisms were significantly associated with MHPG concentrations. Our results indicate that DAOA gene variation affects dopamine...

  8. Identification of a mutation in the CHAT gene of Old Danish Pointing Dogs affected with congenital myasthenic syndrome

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Flagstad, Annette; Cirera, Susanna;

    2007-01-01

    to decreased activity of the enzyme choline acetyltransferase. We sequenced exons 5-18 of the gene encoding choline acetyltransferase (CHAT) in 2 affected and 2 unaffected dogs and identified a G to A missense mutation in exon 6. The mutation causes a valine to methionine substitution and segregates...

  9. A Gene, ALCA, Affecting the Life Cycle Form Expressed in PHYSARUM POLYCEPHALUM.

    Science.gov (United States)

    Truitt, C L; Hoffman, C S; Holt, C E

    1982-05-01

    The usual sequence of forms in the Physarum polycephalum life cycle is plasmodium-spore-amoeba-plasmodium. So-called "amoebaless life cycle" or alc mutants of this Myxomycete undergo a simplified plasmodium-spore-plasmodium life cycle. We have analyzed three independently isolated alc mutants and found in each case that the failure of the spores to give rise to amoebae is due to a recessive Mendelian allele. The three mutations are tightly linked to one another and belong to a single complementation group, alcA. The mutations are pleiotropic, not only interfering with the establishment of the amoebal form at spore germination, but also affecting the phenotype of alc amoebae, which occasionally arise from alc spores. The alc amoebae (1) grow more slowly than wild type, particularly at elevated temperatures; (2) tend to transform directly into plasmodia, circumventing the sexual fusion of amoebae that usually accompanies plasmodium formation; and (3) form plasmodia by the sexual mechanism less efficiently than wild-type amoebae. The various effects of an alc mutation seem to derive from mutation of a single gene, since reversion for one effect is always accompanied by reversion for the other effects. Moreover, a mutation, aptA1, that blocks direct plasmodium formation by alcA amoebae, also increases their growth rate to near normal. The manner of plasmodium formation in alcA strains differs significantly from that in another class of mutants, the gad mutants. Unlike gad amoebae, alcA amoebae need not reach a critical density in order to differentiate directly into plasmodia and do not respond to the extracellular inducer of differentiation. In addition, alcA differentiation is not prevented by a mutation, npfA1, that blocks direct differentiation by most gad amoebae.

  10. Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

    Science.gov (United States)

    Fey, Vidal; Törmäkangas, Timo; Ronkainen, Paula H. A.; Taaffe, Dennis R.; Takala, Timo; Koskinen, Satu; Cheng, Sulin; Puolakka, Jukka; Kujala, Urho M.; Suominen, Harri; Sipilä, Sarianna; Kovanen, Vuokko

    2010-01-01

    At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria. Electronic supplementary material The online version of this

  11. Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

    Directory of Open Access Journals (Sweden)

    Ortega-Azorín Carolina

    2012-11-01

    Full Text Available Abstract Background Although the Fat Mass and Obesity (FTO and Melanocortin-4 Receptor (MC4R genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI. However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet. Methods Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. Results Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039, the MC4R-rs17782313 (P-interaction=0.009 and for their aggregate score (P-interaction=0.006. When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313 than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313. These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose

  12. 基于FTO/VO2/FTO结构的VO2薄膜电压诱导相变光调制特性∗%Optical mo dulation characteristics of VO2 thin film due to electric field induced phase transition in the FTO/VO2/FTO structure

    Institute of Scientific and Technical Information of China (English)

    郝如龙; 方宝英; 王晓华; 肖寒; 李毅; 刘飞; 孙瑶; 唐佳茵; 陈培祖; 蒋蔚; 伍征义; 徐婷婷

    2015-01-01

    VO2 thin films have been studied for their semiconductor–metal reversible transition from the monoclinic to the rutile structure, where the electrical and optical properties undergo a drastic change by increasing the temperature or by applying a voltage. VO2 film is becoming a promising material for optical switch, optical storage, optical modulator, smart window, and micro-bolometer. The preparation procedures of the FTO/VO2/FTO structure in detail are as follows:First, the F-doped SnO2 conductive glass (FTO) substrates are cleaned sequentially in acetone, ethanol, and deionized water for 10 min using an ultrasonic cleaning equipment at a frequency of 20 kHz. When the FTO substrates was cleaned, they are dried with nitrogen. Second, the dried FTO substrates are placed in the chamber of a DC magnetron sputtering system equipped with a high-purity metal target of V (99.9%). After argon (99.999%) of 80 sccm flux was discharged with the current of 2 A and the voltage of 400 V for 2 min, the vanadium films are deposited on the FTO substrates. Third, the prepared vanadium films are annealed for different annealing time in an atmosphere composed of different proportions of nitrogen-oxygen. Then another layer thickness of 350 nm of FTO conductive film is deposited on the VO2 thin film by using the plasma enhanced chemical vapor deposition method. Finally, different sizes of the FTO/VO2/FTO structure are prepared by using photolithography and chemical etching processes. The effect of different annealing time and different proportions of nitrogen-oxygen atmosphere on the VO2 thin films has been studied. X-ray diffraction (XRD), scanning electron microscope (SEM), atomic force microscope (AFM), X-ray photoelectron spectroscopy (XPS) and spectrophotometer are then used to test and analyze the crystal structure, surface morphology, surface roughness, the relative content of the surface elements, and transmittance of the VO2/FTO composite films. Results show that a relatively

  13. Pangenome evidence for extensive interdomain horizontal transfer affecting lineage core and shell genes in uncultured planktonic thaumarchaeota and euryarchaeota.

    Science.gov (United States)

    Deschamps, Philippe; Zivanovic, Yvan; Moreira, David; Rodriguez-Valera, Francisco; López-García, Purificación

    2014-06-12

    Horizontal gene transfer (HGT) is an important force in evolution, which may lead, among other things, to the adaptation to new environments by the import of new metabolic functions. Recent studies based on phylogenetic analyses of a few genome fragments containing archaeal 16S rRNA genes and fosmid-end sequences from deep-sea metagenomic libraries have suggested that marine planktonic archaea could be affected by high HGT frequency. Likewise, a composite genome of an uncultured marine euryarchaeote showed high levels of gene sequence similarity to bacterial genes. In this work, we ask whether HGT is frequent and widespread in genomes of these marine archaea, and whether HGT is an ancient and/or recurrent phenomenon. To answer these questions, we sequenced 997 fosmid archaeal clones from metagenomic libraries of deep-Mediterranean waters (1,000 and 3,000 m depth) and built comprehensive pangenomes for planktonic Thaumarchaeota (Group I archaea) and Euryarchaeota belonging to the uncultured Groups II and III Euryarchaeota (GII/III-Euryarchaeota). Comparison with available reference genomes of Thaumarchaeota and a composite marine surface euryarchaeote genome allowed us to define sets of core, lineage-specific core, and shell gene ortholog clusters for the two archaeal lineages. Molecular phylogenetic analyses of all gene clusters showed that 23.9% of marine Thaumarchaeota genes and 29.7% of GII/III-Euryarchaeota genes had been horizontally acquired from bacteria. HGT is not only extensive and directional but also ongoing, with high HGT levels in lineage-specific core (ancient transfers) and shell (recent transfers) genes. Many of the acquired genes are related to metabolism and membrane biogenesis, suggesting an adaptive value for life in cold, oligotrophic oceans. We hypothesize that the acquisition of an important amount of foreign genes by the ancestors of these archaeal groups significantly contributed to their divergence and ecological success.

  14. Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet123

    Science.gov (United States)

    Zhao, Hua; Li, Ke; Tang, Jia-Yong; Zhou, Ji-Chang; Wang, Kang-Ning; Xia, Xin-Jie; Lei, Xin Gen

    2015-01-01

    Background: Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. Objective: This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Methods: Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy–based control diet or that diet containing 3–7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. Results: The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29–42% and affected (P < 0.05–0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. Conclusions: The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue

  15. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

    Energy Technology Data Exchange (ETDEWEB)

    Golubovskaya, Vita M., E-mail: Vita.Golubovskaya@roswellpark.org; Ho, Baotran [Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Conroy, Jeffrey [Genomics Shared Resource, Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Liu, Song; Wang, Dan [Bioinformatics Core Facility, Biostatistics, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Cance, William G. [Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States)

    2014-01-21

    Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53{sup +/+} and p53{sup −/−} cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53{sup +/+} cells but not in p53{sup −/−} cells. Among up-regulated genes in HCT p53{sup +/+} cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53{sup +/+} colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.

  16. Facile solution deposition of Cu2ZnSnS4 (CZTS) nano-worm films on FTO substrates and its photoelectrochemical property

    Science.gov (United States)

    Huang, Yaohan; Li, Guangli; Fan, Qingfei; Zhang, Meili; Lan, Qi; Fan, Ximei; Zhou, Zuowan; Zhang, Chaoliang

    2016-02-01

    In this work, Cu2ZnSnS4 (CZTS) nanoworm films have been directly deposited on fluorine-doped tin oxide (FTO) conductive glass substrates by a solvothermal method using polyethylene glycol 400 (PEG-400) as the solvent and structure-directing agent. The as-obtained CZTS thin films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectrum (XPS), UV-vis spectra and photoelectrochemical measurement. The synthetic conditions, such as reaction temperature, reaction time, solvents, were investigated to know the formation of CZTS thin films. The results showed that PEG-400 plays a key role in the formation of the nanoworms by affecting the crystal growth process. The p-type CZTS nanoworm film with the band gap of 1.62 eV was synthesized at 180 °C for 22 h and the photovoltaic performance was studied by forming a photoelectrochemical cell.

  17. Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used.

    NARCIS (Netherlands)

    Mormann, M.; Rieth, H.; Hua, T.D.; Assohou-Luty, C.A.; Roupelieva, M.; Hu, S.L.; Kremsner, P.G.; Luty, J.F.; Kube, D.

    2004-01-01

    Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5'-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo-

  18. Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used.

    NARCIS (Netherlands)

    Mormann, M.; Rieth, H.; Hua, T.D.; Assohou-Luty, C.A.; Roupelieva, M.; Hu, S.L.; Kremsner, P.G.; Luty, J.F.; Kube, D.

    2004-01-01

    Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5'-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo- an

  19. Light affects ascorbate content and ascorbate-related gene expression in tomato leaves more than in fruits.

    Science.gov (United States)

    Massot, Capucine; Stevens, Rebecca; Génard, Michel; Longuenesse, Jean-Jacques; Gautier, Hélène

    2012-01-01

    Little is known about the light regulation of vitamin C synthesis in fruits. In contrast, previous studies in leaves revealed that VTC2 (coding for GDP-L: -galactose phosphorylase) was one of the key genes up-regulated by light in leaves. Our objective was to determine how the expression of ascorbate (AsA) synthesis genes in tomato (Solanum lycopersicum) was modified according to light irradiance in both leaves and fruits. Seven days of shading strongly decreased total ascorbate (reduced and oxidized form) content in leaves (50%) and to a lesser extent in fruits (10%). Among the last six steps of AsA biosynthesis, only two genes, VTC2 and GPP1 (one of the two unigenes coding for L: -galactose-1-P phosphatase in tomato), were down-regulated by long-term shading in red ripe fruits, compared to seven genes regulated in leaves. This underlines that light affects AsA-related gene expression more in leaves than in ripening fruits. Moreover, this study reveals strong daily changes in transcript levels of enzymes of the AsA biosynthetic pathway in leaves (11 of the 12 studied genes showed significant changes in their expression pattern). Among those genes, we found that diurnal variation in transcript levels of VTC2 and GME1 correlated to leaf AsA content measured 8 h later. This study provides a new hypothesis on the role of GME1 in addition to VTC2 in light-regulated AsA biosynthesis.

  20. Leukocyte count affects expression of reference genes in canine whole blood samples

    NARCIS (Netherlands)

    Piek, C.J.; Brinkhof, B.; Rothuizen, J.; Dekker, A.; Penning, L.C.

    2011-01-01

    Background The dog is frequently used as a model for hematologic human diseases. In this study the suitability of nine potential reference genes for quantitative RT-PCR studies in canine whole blood was investigated. Findings The expression of these genes was measured in whole blood samples of 263 i

  1. Gene expression in gut symbiotic organ of stinkbug affected by extracellular bacterial symbiont.

    Directory of Open Access Journals (Sweden)

    Ryo Futahashi

    Full Text Available The bean bug Riptortus pedestris possesses a specialized symbiotic organ in a posterior region of the midgut, where numerous crypts harbor extracellular betaproteobacterial symbionts of the genus Burkholderia. Second instar nymphs orally acquire the symbiont from the environment, and the symbiont infection benefits the host by facilitating growth and by occasionally conferring insecticide resistance. Here we performed comparative transcriptomic analyses of insect genes expressed in symbiotic and non-symbiotic regions of the midgut dissected from Burkholderia-infected and uninfected R. pedestris. Expression sequence tag analysis of cDNA libraries and quantitative reverse transcription PCR identified a number of insect genes expressed in symbiosis- or aposymbiosis-associated patterns. For example, genes up-regulated in symbiotic relative to aposymbiotic individuals, including many cysteine-rich secreted protein genes and many cathepsin protease genes, are likely to play a role in regulating the symbiosis. Conversely, genes up-regulated in aposymbiotic relative to symbiotic individuals, including a chicken-type lysozyme gene and a defensin-like protein gene, are possibly involved in regulation of non-symbiotic bacterial infections. Our study presents the first transcriptomic data on gut symbiotic organ of a stinkbug, which provides initial clues to understanding of molecular mechanisms underlying the insect-bacterium gut symbiosis and sheds light on several intriguing commonalities between endocellular and extracellular symbiotic associations.

  2. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease

    Science.gov (United States)

    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R

    2015-01-01

    Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891

  3. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

    Directory of Open Access Journals (Sweden)

    Baohu Ji

    2015-08-01

    Research in context: Due to lack of biological markers, diagnosis and treatment of psychiatric disorders are subjective. There is utmost urgency to identify biomarkers for clinics, research, and drug development. We found that XIST and KDM5C gene expression may be used as a biological marker for diagnosis of major affective disorders in a significantly large subset of female patients from the general population. Our studies show that over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX and the general population of female psychiatric patients.

  4. HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

    Science.gov (United States)

    Pérez-Bravo, Francisco; Martinez-Laso, Jorge; Martin-Villa, Jose M; Moscoso, Juan; Moreno, Almudena; Serrano-Vela, Juan I; Zamora, Jorge; Asenjo, Silvia; Gleisner, Andrea; Arnaiz-Villena, Antonio

    2006-01-01

    A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

  5. Parameters Affecting Image-guided, Hydrodynamic Gene Delivery to Swine Liver

    Directory of Open Access Journals (Sweden)

    Kenya Kamimura

    2013-01-01

    Full Text Available Development of a safe and effective method for gene delivery to hepatocytes is a critical step toward gene therapy for liver diseases. Here, we assessed the parameters for gene delivery to the livers of large animals (pigs, 40–65 kg using an image-guided hydrodynamics-based procedure that involves image-guided catheter insertion into the lobular hepatic vein and hydrodynamic injection of reporter plasmids using a computer-controlled injector. We demonstrated that injection parameters (relative position of the catheter in the hepatic vasculature, intravascular pressure upon injection, and injection volume are directly related to the safety and efficiency of the procedure. By optimizing these parameters, we explored for the first time, the advantage of the procedure for sequential injections to multiple lobes in human-sized pigs. The optimized procedure resulted in sustained expression of the human α-1 antitrypsin gene in livers for more than 2 months after gene delivery. In addition, repeated hydrodynamic gene delivery was safely conducted and no adverse events were seen in the entire period of the study. Our results support the clinical applicability of the image-guided hydrodynamic gene delivery method for the treatment of liver diseases.

  6. Accelerated evolution after gene duplication: a time-dependent process affecting just one copy.

    Science.gov (United States)

    Pegueroles, Cinta; Laurie, Steve; Albà, M Mar

    2013-08-01

    Gene duplication is widely regarded as a major mechanism modeling genome evolution and function. However, the mechanisms that drive the evolution of the two, initially redundant, gene copies are still ill defined. Many gene duplicates experience evolutionary rate acceleration, but the relative contribution of positive selection and random drift to the retention and subsequent evolution of gene duplicates, and for how long the molecular clock may be distorted by these processes, remains unclear. Focusing on rodent genes that duplicated before and after the mouse and rat split, we find significantly increased sequence divergence after duplication in only one of the copies, which in nearly all cases corresponds to the novel daughter copy, independent of the mechanism of duplication. We observe that the evolutionary rate of the accelerated copy, measured as the ratio of nonsynonymous to synonymous substitutions, is on average 5-fold higher in the period spanning 4-12 My after the duplication than it was before the duplication. This increase can be explained, at least in part, by the action of positive selection according to the results of the maximum likelihood-based branch-site test. Subsequently, the rate decelerates until purifying selection completely returns to preduplication levels. Reversion to the original rates has already been accomplished 40.5 My after the duplication event, corresponding to a genetic distance of about 0.28 synonymous substitutions per site. Differences in tissue gene expression patterns parallel those of substitution rates, reinforcing the role of neofunctionalization in explaining the evolution of young gene duplicates.

  7. Do candidate genes mediating conspecific sperm precedence affect sperm competitive ability within species? A test case in Drosophila.

    Science.gov (United States)

    Civetta, Alberto; Finn, Scott

    2014-07-16

    When females mate to multiple males, the last male to mate fathers the majority of progeny. When males of different species inseminate a female, the sperm of the male conspecific to the female is favored in fertilization in a process known as conspecific sperm precedence (CSP). A large number of studies in Drosophila have assayed the genetic basis of sperm competition, with a main focus on D. melanogaster and accessory gland protein genes. Only a few studies have attempted to disentangle the genetic basis of CSP between related species of Drosophila. Although there is no a priori reason to believe that genes influencing intraspecific sperm competitive ability might also mediate conspecific sperm precedence, no study has addressed the question. Here, we test a group of candidate CSP genes between D. simulans and D. mauritiana for their effect on sperm competition in D. melanogaster. The use of P-element insertion lines identified CG14891 gene disruption as the only one causing a significant decrease in second male paternity success relative to wild-type and ebony tester males. The gene disruption affected both sperm displacement and the sperm fertilizing ability. Out of five genes tested using RNA interference, only gene knockdown of CG6864(Mst89B) [corrected] significantly reduced the male's ability to father progeny when second to mate. Our results suggest that CG14891 and CG6468 might have been co-opted from an intraspecies gene function (i.e., sperm competition) into an interspecies avoidance phenotype (i.e., CSP). Alternatively, the dual role of these genes could be a consequence of their pleiotropic roles. Copyright © 2014 Civetta and Finn.

  8. Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study.

    Science.gov (United States)

    Celis-Morales, Carlos; Marsaux, Cyril F M; Livingstone, Katherine M; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; O'donovan, Clare B; Forster, Hannah; Woolhead, Clara; Fallaize, Rosalind; Macready, Anna L; Kolossa, Silvia; Hallmann, Jacqueline; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Parnell, Laurence D; Daniel, Hannelore; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Gibney, Mike; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim H M; Mathers, John C

    2016-04-01

    To examine whether the effect of FTO loci on obesity-related traits could be modified by physical activity (PA) levels in European adults. Of 1,607 Food4Me participants randomized, 1,280 were genotyped for FTO (rs9939609) and had available PA data. PA was measured objectively using accelerometers (TracmorD, Philips), whereas anthropometric measures [BMI and waist circumference (WC)] were self-reported via the Internet. FTO genotype was associated with a higher body weight [β: 1.09 kg per risk allele, (95% CI: 0.14-2.04), P = 0.024], BMI [β: 0.54 kg m(-2) , (0.23-0.83), P physically active lifestyle. © 2016 The Obesity Society.

  9. Enhanced photocatalytic performance of TiO2 nanotube based heterojunction photocatalyst via the coupling of graphene and FTO

    Science.gov (United States)

    Niu, Xiaoyou; Yu, Jianyuan; Wang, Likun; Fu, Chen; Wang, Jixia; Wang, Li; Zhao, Hongli; Yang, Jingkai

    2017-08-01

    The TiO2 nanotube (TONT) based heterojunction photocatalyst was developed via the coupling of reduced graphene oxide (rGO) and SnO2:F film (FTO). Based on the characterization of Raman analysis, XRD, SEM, TEM, XPS and ESR, the crystal phase, morphology, heterojunction interfacial interaction and the photoinduced electron chemical environment of the samples are studied. In the photodegradation of methylene blue (MB) solution under UV irradiation, the rGO-TONT/FTO heterojunction photocatalyst exhibits the improved photocatalytic reaction rate, 3 times greater than that of pure TONT. The enhanced photocatalytic mechanism was discussed by PL. The effectively separate charge in heterojunction structure of rGO-TONT/FTO is responsible for the enhanced photocatalytic activity. Wherein, the abundant oxygen vacancies at TiO2 surface and the chemically bonded interface in rGO-TONT heterojunction also contributes to the interfacial electron transfer. Besides, the introduction of rGO enhanced its optical absorption capacity.

  10. Alu insertion/deletion of ACE gene polymorphism might not affect ...

    African Journals Online (AJOL)

    Widodo

    2016-09-03

    Sep 3, 2016 ... Received 2 May 2016; accepted 1 August 2016. Available ... The Egyptian Journal of Medical Human Genetics (2017) 18, 187–191. HOSTED BY ..... insertion–deletion polymorphism of ACE gene and Alzheimer's · disease in ...

  11. Factors affecting the gene expression of in vitro cultured human preimplantation embryos

    NARCIS (Netherlands)

    Mantikou, E.; Jonker, M.J.; Wong, K.M.; van Montfoort, A.P.A.; de Jong, M.; Breit, T.M.; Repping, S.; Mastenbroek, S.

    2016-01-01

    STUDY QUESTION: What is the relative effect of common environmental and biological factors on transcriptome changes during human preimplantation development? SUMMARY ANSWER: Developmental stage and maternal age had a larger effect on the global gene expression profile of human preimplantation

  12. Resting-state brain and the FTO obesity risk allele: default mode, sensorimotor and salience network connectivity underlying different somatosensory integration and reward processing between genotypes.

    Directory of Open Access Journals (Sweden)

    Gaia eOlivo

    2016-02-01

    Full Text Available Single-nucleotide polymorphisms (SNPs of the fat mass and obesity associated (FTO gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN, sensorimotor (SMN, and salience network (SN in thirty male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS and Behavioral Activation System (BAS questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr accounting for features of both scores. A prominence of BIS over BAS (higher BBr resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

  13. Agrobacterium rhizogenes rolB gene affects photosynthesis and chlorophyll content in transgenic tomato (Solanum lycopersicum L.) plants.

    Science.gov (United States)

    Bettini, Priscilla P; Marvasi, Massimiliano; Fani, Fabiola; Lazzara, Luigi; Cosi, Elena; Melani, Lorenzo; Mauro, Maria Luisa

    2016-10-01

    Insertion of Agrobacterium rhizogenes rolB gene into plant genome affects plant development, hormone balance and defence. However, beside the current research, the overall transcriptional response and gene expression of rolB as a modulator in plant is unknown. Transformed rolB tomato plant (Solanum lycopersicum L.) cultivar Tondino has been used to investigate the differential expression profile. Tomato is a well-known model organism both at the genetic and molecular level, and one of the most important commercial food crops in the world. Through the construction and characterization of a cDNA subtracted library, we have investigated the differential gene expression between transgenic clones of rolB and control tomato and have evaluated genes specifically transcribed in transgenic rolB plants. Among the selected genes, five genes encoding for chlorophyll a/b binding protein, carbonic anhydrase, cytochrome b6/f complex Fe-S subunit, potassium efflux antiporter 3, and chloroplast small heat-shock protein, all involved in chloroplast function, were identified. Measurement of photosynthesis efficiency by the level of three different photosynthetic parameters (Fv/Fm, rETR, NPQ) showed rolB significant increase in non-photochemical quenching and a, b chlorophyll content. Our results point to highlight the role of rolB on plant fitness by improving photosynthesis.

  14. Knowledge-driven analysis identifies a gene-gene interaction affecting high-density lipoprotein cholesterol levels in multi-ethnic populations.

    Science.gov (United States)

    Ma, Li; Brautbar, Ariel; Boerwinkle, Eric; Sing, Charles F; Clark, Andrew G; Keinan, Alon

    2012-01-01

    Total cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels are among the most important risk factors for coronary artery disease. We tested for gene-gene interactions affecting the level of these four lipids based on prior knowledge of established genome-wide association study (GWAS) hits, protein-protein interactions, and pathway information. Using genotype data from 9,713 European Americans from the Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction between HMGCR and a locus near LIPC in their effect on HDL-C levels (Bonferroni corrected P(c) = 0.002). Using an adaptive locus-based validation procedure, we successfully validated this gene-gene interaction in the European American cohorts from the Framingham Heart Study (P(c) = 0.002) and the Multi-Ethnic Study of Atherosclerosis (MESA; P(c) = 0.006). The interaction between these two loci is also significant in the African American sample from ARIC (P(c) = 0.004) and in the Hispanic American sample from MESA (P(c) = 0.04). Both HMGCR and LIPC are involved in the metabolism of lipids, and genome-wide association studies have previously identified LIPC as associated with levels of HDL-C. However, the effect on HDL-C of the novel gene-gene interaction reported here is twice as pronounced as that predicted by the sum of the marginal effects of the two loci. In conclusion, based on a knowledge-driven analysis of epistasis, together with a new locus-based validation method, we successfully identified and validated an interaction affecting a complex trait in multi-ethnic populations.

  15. A loss-of-function mutation in Calmodulin2 gene affects pollen germination in Arabidopsis thaliana.

    Science.gov (United States)

    Landoni, Michela; De Francesco, Alessandra; Galbiati, Massimo; Tonelli, Chiara

    2010-10-01

    Calmodulin (CAM) is an ubiquitous calcium binding protein whose function is to translate the signals, perceived as calcium concentration variations, into the appropriate cellular responses. In Arabidopsis thaliana there are 4 CAM isoforms which are highly similar, encoded by 7 genes, and one possible explanation proposed for the evolutionary conservation of the CAM