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Sample records for fto gene expression

  1. Cloning and characterization of chicken fat mass and obesity associated (Fto) gene: fasting affects Fto expression.

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    Tiwari, A; Krzysik-Walker, S M; Ramachandran, R

    2012-01-01

    Fat mass and obesity associated gene (Fto), also known as Fatso, is a member of the Fe-II and 2-oxoglutarate-dependent dioxygenase superfamily. Recent studies in humans and rodents suggest that Fto is involved in food intake regulation and lipid metabolism, whereas single nucleotide mutations in the Fto gene are associated with obesity and type 2 diabetes. The Fto gene is highly conserved from green algae to humans, but little is known about the avian Fto gene or protein. The objectives of the current study were to clone full-length chicken Fto cDNA and to determine the effect of age or feeding status on Fto expression. With the use of rapid amplification of cDNA ends, the full-length chicken Fto cDNA was cloned and found to share 63% to 66% homology with the mammalian Fto nucleotide sequence. Several regions of the chicken Fto protein, including the substrate (2-oxoglutarate) binding domains, were found to be identical to mammalian Fto protein. Western blotting with anti-human Fto antibody and reverse transcription PCR studies showed that Fto protein and gene were ubiquitously expressed in various tissues of the chicken. With the use of quantitative PCR, Fto mRNA levels were found to be higher in liver and skeletal muscle of 8-wk-old chickens than in 4-wk-old chickens. In addition, alterations in feeding status resulted in significant changes in Fto mRNA and Fto protein expression in the liver but not in skeletal muscle and adipose tissue of broiler chickens. Taken together, our data suggest that Fto probably plays a significant role in liver function and energy metabolism in the chicken. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Olszewski, Pawel K.; Fredriksson, Robert; Eriksson, Jenny D.; Mitra, Anaya; Radomska, Katarzyna J.; Gosnell, Blake A.; Solvang, Maria N.; Levine, Allen S.; Schioeth, Helgi B.

    2011-01-01

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → 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.

  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. Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies

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    Saeid Doaei

    2017-03-01

    Full Text Available The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.

  5. 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.

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

    Science.gov (United States)

    Guo, Jianjin; Ren, Wei; Ding, Ying; Li, Aimei; Jia, Lu; Su, Dongming; Liu, Xiang; Xu, Kuanfeng; Yang, Tao

    2012-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    developmental stages. Expression of the FTO transcript was detected in all tissues tested with significantly higher levels in brain tissues (cortex, cerebellum, and hippocampus; P development and between the specific parts of the brain studied (i.e., frontal cortex......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...

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

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    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.

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

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    McTaggart, James S; Lee, Sheena; Iberl, Michaela; Church, Chris; Cox, Roger D; Ashcroft, Frances M

    2011-01-01

    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.

  10. 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.

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

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    Xue Gao

    2010-11-01

    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.

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

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    Castellini, Giovanni; Franzago, Marica; 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.

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

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    Giovanni Castellini

    Full Text Available 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.

  14. 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.

  15. Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients.

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    Mitropoulos, Konstantinos; Merkouri Papadima, Eleni; Xiromerisiou, Georgia; Balasopoulou, Angeliki; Charalampidou, Kyriaki; Galani, Vasiliki; Zafeiri, Krystallia-Vassiliki; Dardiotis, Efthymios; Ralli, Styliani; Deretzi, Georgia; John, Anne; Kydonopoulou, Kyriaki; Papadopoulou, Elpida; di Pardo, Alba; Akcimen, Fulya; Loizedda, Annalisa; Dobričić, Valerija; Novaković, Ivana; Kostić, Vladimir S; Mizzi, Clint; Peters, Brock A; Basak, Nazli; Orrù, Sandro; Kiskinis, Evangelos; Cooper, David N; Gerou, Spyridon; Drmanac, Radoje; Bartsakoulia, Marina; Tsermpini, Evangelia-Eirini; Hadjigeorgiou, Georgios M; Ali, Bassam R; Katsila, Theodora; Patrinos, George P

    2017-12-08

    Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question. To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.

  16. Fasting induced cytoplasmic Fto expression in some neurons of rat hypothalamus.

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    Predrag Vujovic

    Full Text Available Fat mass and obesity associated protein (Fto is a nucleic acid demethylase, with a preference for thymine or uracil, according to the recent structural data. This fact suggests that methylated single-stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behavior. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we set out to investigate the effect of 48 h fasting on the Fto expression in lateral hypothalamic area, paraventricular, ventromedial and arcuate nucleus, the regulatory centres of energy homeostasis. We have demonstrated that 48 h fasting causes not only an increase in the overall hypothalamic levels of both Fto mRNA and protein, but also alters Fto intracellular distribution. This switch happens in some neurons of paraventricular and ventromedial nucleus, as well as lateral hypothalamic area, resulting in the majority of the enzyme being localized outside the cell nuclei. Interestingly, the change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, suggesting that fasting did not universally affect Fto in all of the hypothalmic sites involved in energy homeostasis regulation. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in fasting animals. This fact, combined with the knowledge of the Fto substrate preference, may provide further insight into monoamine metabolism in the state of disturbed energy homeostasis.

  17. 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

    Various twin studies revealed that the influence of genetic factors on psychological diseases or behavior is more expressed in socio‐economically advantaged environments. Other studies predominantly show an inverse relation between socio‐economic status (SES) and childhood obesity in western...... 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...... 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...

  18. 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.

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

    International Nuclear Information System (INIS)

    Apalasamy, Y.D.; Ming, M.F.; Rampal, S.; Bulgiba, A.; Mohamed, Z.

    2012-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes.

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    Jacobsson, Josefin A; Danielsson, Pernilla; Svensson, Victoria; Klovins, Janis; Gyllensten, Ulf; Marcus, Claude; Schiöth, Helgi B; Fredriksson, Robert

    2008-04-11

    Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.

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

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    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.

  3. Analysis of SNPs of MC4R , GNB3 and FTO gene polymorphism in ...

    African Journals Online (AJOL)

    Analysis of SNPs of MC4R , GNB3 and FTO gene polymorphism in obese Saudi subjects. Said Salama Moselhy, Yasmeen A Alhetari, Archana Iyer, Etimad A Huwait, Maryam A AL-Ghamdi, Shareefa AL-Ghamdi, Khadijah Saeed Balamash, Ashraf A Basuni, Mohamed N Alama, Taha A Kumosani, Soonham Sami Yaghmoor ...

  4. Analysis of SNPs of MC4R , GNB3 and FTO gene polymorphism in ...

    African Journals Online (AJOL)

    aliquots for biochemical and hormonal analysis. They were kept frozen at –80°C for further ..... FTO regulates GH and/ or other hormones secreted by .... Ramsay M. 2012. Appetite regulation genes are associated with body mass index in black South. African adolescents: a genetic association study. BMJ. Open. 2: e000873.

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

    Science.gov (United States)

    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

    Background Depression 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. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The 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. Results In 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 FTO Conclusions This 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Vanni Caruso

    Full Text Available 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.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.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.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 data. No effect of maternal obesity was observed

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

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, Věra; Bartenschlager, H.; Stratil, Antonín; Horák, P.; Stupka, R.; Čítek, J.; Šprysl, M.; Hrdlicová, Anna; Geidermann, H.

    2012-01-01

    Roč. 44, č. 13 (2012), s. 1-9 ISSN 0999-193X R&D Projects: GA ČR(CZ) GA523/06/1302; GA ČR GA523/09/0844 Institutional research plan: CEZ:AV0Z50450515 Keywords : FTO gene * pig crosses Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 2.859, year: 2012

  9. 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

    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...... to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system....

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Zhaojing Zheng

    Full Text Available To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity.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.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.The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort.

  13. 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)

    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 ...

  14. 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...

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

    Science.gov (United States)

    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 early life growth development, the FTO gene and exclusive breastfeeding on child BMI trajectories.

    Science.gov (United States)

    Wu, Yan Yan; Lye, Stephen; Briollais, Laurent

    2017-10-01

    Recent studies have implicated the FTO gene in child and adult obesity. A longer duration of exclusive breastfeeding (EXBF) has been shown to reduce body mass index (BMI) and the risk of being overweight in the general population and among FTO gene carriers. However, it remains unclear whether the preventive effect of EXBF could be explained by its impact on early life growth development, e.g. ages at adiposity peak (AP) and adiposity rebound (AR) and BMI velocities in the first years of life, which are major determinants of overweight and obesity later in life. We studied 5590 children from the British Avon Longitudinal Study of Parents and Children (ALSPAC) cohort and modelled their longitudinal BMI profiles with mixed effects models from birth to 16 years of age, as well as their ages at AP, AR and BMI velocities in relation to the FTO gene variant and EXBF. A longer duration of EXBF (i.e. at least 5 months) has substantial impact on BMI growth trajectories among children carrying the FTO adverse variant by modulating the age at AP, age at AR and BMI velocities. EXBF acts antagonistically to the FTO rs9939609 risk allele and by the age of 15, the predicted reduction in BMI after 5 months of EXBF is 0.56 kg/m2 [95% confidence interval (CI) 0.11-1.01; P = 0.003] and 1.14 kg/m2 (95% CI 0.67-1.62; P < 0.0001) in boys and girls, respectively. EXBF influences early life growth development and thus plays a critical role in preventing the risks of overweight and obesity even when those are exacerbated by genetic factors. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

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

    Directory of Open Access Journals (Sweden)

    Xianli Cai

    Full Text Available 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.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.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.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.

  18. FTO gene variant and association with overweight in Brazilian male students

    Directory of Open Access Journals (Sweden)

    José Fernando Vila Nova de Moraes

    2016-07-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n3p259   Obesity is considered a disease with multiple etiologies. Recent advances in technology have pointed candidate genes that are related to weight gain in several populations. However, in countries with ethnic miscegenation, such as Brazil, studies of this nature with students are still scarce. The aim of the present study was to compare anthropometric variables of Brazilian male students according to the genotypes of the rs9939609 of the FTO gene. In order to do so, 205 participants underwent body mass, height, waist circumference and skinfold thickness measurements. Body mass index (BMI, waist-to-height ratio and body fat percentage were calculated. Volunteers were characterized as overweight according to the BMI-for-age z-score. Participants were genotyped according to the single nucleotide polymorphism rs9939609 of the FTO gene (AA, AT and TT. ANOVA one-way with Bonferroni’s post hoc was performed to compare genotypes and anthropometric variables. Odds Ratio was calculated to reveal increased chances of presenting higher body mass index z-score, waist-to-height ratio and body fat percentage. Participants homozygous for the A allele presented significantly higher values of BMI-for-age z-score (0.38±1.01 vs. -0.29±1.15, waist circumference (77.15±6.51 vs. 72.85±7.36 cm and waist-to-height ratio (0.44±0.04 vs. 0.42±0.04 when compared to individuals with the TT genotype. The A allele of the rs9939609 of the FTO gene seems to influence in the adiposity of male students.

  19. 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.

  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

    We investigated the role of the fat mass and obesity associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) in modulating habitual intake of total energy and macronutrients, glycemic index, glycemic load, dietary energy density, and energy from 20 food groups in adults...

  1. Homozygosity for the rs9939609T allele of the FTO gene may have ...

    Indian Academy of Sciences (India)

    2011-08-19

    e.g. corticosteroids) but also environ- mental and social aspects (Gregory and Reilly 2004; Branca et al. 2007). Metabolic effect of the FTO appears in children aged ≥7 years (Frayling et al. 2007), therefore genotyping.

  2. 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

    Various twin studies revealed that the influence of genetic factors on psychological diseases or behavior is more expressed in socio‐economically advantaged environments. Other studies predominantly show an inverse relation between socio‐economic status (SES) and childhood obesity in western...... that SES and FTO interact in their effect on childhood obesity (Δχ2=7.3, df=2, p=0.03) insofar as children carrying the protective TT genotype are more susceptible to a favorable social environment....

  3. Association of SNP rs9939609 in FTO gene with metabolic syndrome in type 2 diabetic subjects, rectruited from a tertiary care unit of Karachi, Pakistan

    OpenAIRE

    Fawwad, Asher; Siddiqui, Iftikhar Ahmed; Zeeshan, Nimra Fatima; Shahid, Syed Muhammad; Basit, Abdul

    2015-01-01

    Objective: To determine the association of SNP in FTO gene, rs9939609, with Metabolic Syndrome (MS) in type 2 diabetic subjects at a tertiary care unit of Karachi, Pakistan. Methods: We genotyped FTO rs9939609 SNP in 296 patients with type 2 diabetes from the Out Patient Department (OPD) of Baqai Institute of Diabetology and Endocrinology (BIDE). MS was defined on the basis of International Diabetes Federation (IDF) and National Cholesterol Education program (NCEP) criterion. Association betw...

  4. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

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

    Science.gov (United States)

    Brunkwall, Louise; Ericson, Ulrika; Hellstrand, Sophie; Gullberg, Bo; Orho-Melander, Marju; Sonestedt, Emily

    2013-01-01

    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 ppastry 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. PMID:23589710

  6. Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France.

    Science.gov (United States)

    Attaoua, R; Ait El Mkadem, S; Lautier, C; Kaouache, S; Renard, E; Brun, J-F; Fedou, C; Gris, J-C; Bringer, J; Grigorescu, F

    2009-12-01

    The objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene. This case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n=128), and women (n=119) of various degrees of obesity (body mass index [BMI] mean+/-S.D.: 39.3+/-7.4kg/m(2)) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide-polymerase chain reaction (SSO-PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing. The FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (Presistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI. These data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.

  7. Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

    Science.gov (United States)

    Villalobos-Comparán, Marisela; Antuna-Puente, Bárbara; Villarreal-Molina, María Teresa; Canizales-Quinteros, Samuel; Velázquez-Cruz, Rafael; León-Mimila, Paola; Villamil-Ramírez, Hugo; González-Barrios, Juan Antonio; Merino-García, José Luis; Thompson-Bonilla, María Rocío; Jarquin, Diego; Sánchez-Hernández, Osvaldo Erik; Rodríguez-Arellano, Martha Eunice; Posadas-Romero, Carlos; Vargas-Alarcón, Gilberto; Campos-Pérez, Francisco; Quiterio, Manuel; Salmerón-Castro, Jorge; Carnevale, Alessandra; Romero-Hidalgo, Sandra

    2017-05-02

    The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.

  8. Fat phenotype, associated factors and rs9939609 polymorphism of the FTO gene DOI:10.5007/1980-0037.2010v12n2p164

    Directory of Open Access Journals (Sweden)

    William Alves Lima

    2010-07-01

    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.

  9. FTO gene is related to obesity in Chilean Amerindian children and impairs HOMA-IR in prepubertal girls.

    Science.gov (United States)

    Riffo, Benilde; Asenjo, Sylvia; Sáez, Katia; Aguayo, Claudio; Muñoz, Isabel; Bustos, Paulina; Celis-Morales, Ca; Lagos, Jenny; Sapunar, Jorge; Ulloa, Natalia

    2012-08-01

    The objective of this study was to investigate the allelic frequency of the fat mass and obesity-associated (FTO) gene (rs9939609) and its influences on obesity and metabolic risk biomarkers in a cohort of normal weight and obese Chilean children determining its ethnicity. A total of 136 normal weight children and 238 obese children (between 6 and 11 yr old) from an urban setting were recruited for this case-control study. The children were classified as normal weight [body mass index (BMI) ≥ 5th and 95th percentile), according to the international age- and gender-specific percentiles defined by the Center for Disease Control and Prevention. The analysis of serum markers was carried out using commercial kits. The FTO polymorphism was determined through a high-resolution melting enabled real time polymerase chain reaction. Ethnicity was determined by analyzing mitochondrial DNA by the restriction fragment length polymorphism method. As much as 85% of the cohort was Amerindian. The minor A allele of rs9939609 was associated with obesity (odds ratio (OR): 1.422 [95% confidence interval (CI) 1.068-1.868] p = 0.015), calculated using an additive model. In sex-stratified analysis we found that the risk variant (A) of rs9939609 was associated with a higher homeostasis model of assessment for insulin (HOMA-IR) in prepubertal obese girls. In male carriers of the A allele, HOMA-IR showed no further deterioration than that already associated with obesity. In summary, we confirm the association of the FTO gene single-nucleotide polymorphism rs9939609 with obesity in Chilean Amerindian children. Furthermore we show an association between the risk allele (A) and insulin resistance-related markers in prepubertal obese girls. © 2011 John Wiley & Sons A/S.

  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

    OpenAIRE

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

    2014-01-01

    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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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......BACKGROUND: Association studies have identified a number of loci that contribute to an increased body mass index (BMI), the strongest of which is in the first intron of the FTO gene on human chromosome 16q12.2. However, this region is both non-coding and under strong linkage disequilibrium, making...... in an expanded male cohort and an independent female study group. Finally, we compare our variant data with a previous study describing IRX3 and FTO interactions in this region. RESULTS: We obtain deep coverage across the entire region, allowing accurate and unequivocal determination of almost every single...

  13. Hypomorphism of Fto and Rpgrip1l causes obesity in mice.

    Science.gov (United States)

    Stratigopoulos, George; Burnett, Lisa Cole; Rausch, Richard; Gill, Richard; Penn, David Barth; Skowronski, Alicja A; LeDuc, Charles A; Lanzano, Anthony J; Zhang, Pumin; Storm, Daniel R; Egli, Dieter; Leibel, Rudolph L

    2016-05-02

    Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons. There were allele-dosage effects on FTO, RPGRIP1L, and AKT-interacting protein (AKTIP) expression, but expression of other vicinal genes, including IRX3, IRX5, and RBL2, which have been implicated in mediating functional effects, was not altered. In vivo manipulation of CUX1, Fto, and/or Rpgrip1l expression in mice affected adiposity in a manner that was consistent with CUX1 influence on adiposity via remote effects on Fto and Rpgrip1l expression. In support of a mechanism, mice hypomorphic for Rpgrip1l exhibited hyperphagic obesity, as the result of diminished leptin sensitivity in Leprb-expressing neurons. Together, the results of this study indicate that the effects of FTO-associated SNPs on energy homeostasis are due in part to the effects of these genetic variations on hypothalamic FTO, RPGRIP1L, and possibly other genes.

  14. Differential distribution and association of FTO rs9939609 gene polymorphism with obesity: A cross-sectional study among two tribal populations of India with East-Asian ancestry.

    Science.gov (United States)

    Ningombam, Somorjit Singh; Chhungi, Varhlun; Newmei, Masan Kambo; Rajkumari, Sunanda; Devi, Naorem Kiranmala; Mondal, Prakash Ranjan; Saraswathy, Kallur Nava

    2018-03-20

    The fat mass and obesity associated (FTO) rs9939609 gene polymorphism is most widely studied in terms of obesity in various populations. Recently, the prevalence of obesity has been reported to be very high among the North-Eastern State of India. The major aim of the present study is to understand the extent of FTO rs9939609 gene polymorphism and its association with obesity among the two North-East Indian tribal populations with similar East Asian ancestry. Somatometric data and fasting blood sample were collected from 521 tribal individuals (258 Liangmai and 263 Mizo) of Manipur after obtaining written informed consent. Genotyping of FTO rs9939609 single nucleotide polymorphism (SNP) was done using restriction fragment length polymorphism method for PCR-amplified fragments. Both the presently studied populations were not following Hardy-Weinberg law. The prevalence of obesity and minor allele frequency of FTO rs9939609 polymorphism was found to be significantly higher among the Mizo tribe compared to that of Liangmai. The selected polymorphism was found to be significantly associated with obesity (BMI) only among the Liangmai tribe (Odds ratio-3.0; 95% CI-1.4, 6.4; p-0.003), after adjusting for age and occupation. Age-cohort wise distribution and absolute fitness analysis indicated the lower fitness of minor allele in the higher age group among the Liangmai tribe. To the best of the author's knowledge this is the first study, associating FTO rs9939609 gene polymorphism and obesity in the North-eastern Indian tribal populations with East-Asian ancestry. This study revealed the FTO rs9939609 polymorphism is observed to be associated with obesity only among the Liangmai tribe not among the Mizo tribe. The differential distribution and association observed in the two selected tribes, inhabited in a similar geographical region, could be attributed to differences in their migratory histories in terms of both route and time of settlement. Copyright © 2018 Elsevier B

  15. 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.

  16. Association of Glutathione-S-Transferase (GSTM1 and GSTT1) and FTO Gene Polymorphisms with Type 2 Diabetes Mellitus Cases in Northern India.

    Science.gov (United States)

    Raza, St; Abbas, S; Ahmad, A; Ahmed, F; Zaidi, Zh; Mahdi, F

    2014-06-01

    Type 2 diabetes mellitus (T2DM) is growing in an epidemic manner across the world and India has the world's largest number of diabetic subjects. The present study was carried out to investigate the association of glutathione-S-transferase (GSTM1, GSTT1) and fat mass and obesity associated (FTO) gene polymorphisms with T2DM patients and controls, and its role in increasing the susceptibility to T2DM. A total of 198 subjects (101 T2DM patients and 97 controls) participated in this study. GSTM1, GSTT1 and FTO gene polymorphisms in the patients and controls were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). We observed significant association of GSTM1 positive (p = 0.046) and GSTM1 null (p = 0.046) genotypes with T2DM, while no significant association was found with the FTO gene polymorphism in our study. It seems that the GSTM1 gene polymorphism can be a predictive marker for early identification of a population at risk of T2DM. The potential role of GST and FTO gene polymorphisms as a marker of susceptibility to T2DM needs further studies in a larger number of patients.

  17. Association of Glutathione-S-Transferase (GSTM1 and GSTT1 and FTO Gene Polymorphisms with Type 2 Diabetes Mellitus Cases in Northern India

    Directory of Open Access Journals (Sweden)

    S.T. Raza

    2014-06-01

    Full Text Available Type 2 diabetes mellitus (T2DM is growing in an epidemic manner across the world and India has the world’s largest number of diabetic subjects. The present study was carried out to investigate the association of glutathione-S-transferase (GSTM1, GSTT1 and fat mass and obesity associated (FTO gene polymorphisms with T2DM patients and controls, and its role in increasing the susceptibility to T2DM. A total of 198 subjects (101 T2DM patients and 97 controls participated in this study. GSTM1, GSTT1 and FTO gene polymorphisms in the patients and controls were evaluated by polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLP. We observed significant association of GSTM1 positive (p = 0.046 and GSTM1 null (p = 0.046 genotypes with T2DM, while no significant association was found with the FTO gene polymorphism in our study. It seems that the GSTM1 gene polymorphism can be a predictive marker for early identification of a population at risk of T2DM. The potential role of GST and FTO gene polymorphisms as a marker of susceptibility to T2DM needs further studies in a larger number of patients.

  18. The FTO rs9939609 and LEPR rs1137101 mothers–newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns

    Science.gov (United States)

    Mărginean, Claudiu; Mărginean, Cristina Oana; Iancu, Mihaela; Meliţ, Lorena Elena; Tripon, Florin; Bănescu, Claudia

    2016-01-01

    Abstract The aim of this study was to assess the impact of mothers’ and newborns’ fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity. We performed a cross-sectional study on 355 mother–newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101). Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG + GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P > 0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA + AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA + AT genotype whose mothers had AA + AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG + GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs. Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on

  19. gene structure, gene expression

    Indian Academy of Sciences (India)

    and seedling leaves were sampled at 6 h after the treatment. For cold stress, the seedlings were transferred to 4◦C growth chamber for 30 min. Control seedlings were exposed to none of these treatments. To examine the expression patterns of these predicted genes in Poplar and to further confirm their stress responsive-.

  20. The rs9939609 polymorphism in the FTO gene is associated with fat and fiber intakes in patients with type 2 diabetes.

    Science.gov (United States)

    Steemburgo, Thais; Azevedo, Mirela J; Gross, Jorge L; Milagro, Fermin I; Campión, Javier; Martínez, Jose Alfredo

    2013-01-01

    The common polymorphism in the FTO gene (rs9939609) has been associated with obesity, type 2 diabetes, and appetite regulation. The aim of this study was to evaluate possible associations of FTO rs9939609 with dietary factors in patients with type 2 diabetes. This was a cross-sectional study of 236 patients with type 2 diabetes (age 60.0 ± 10.3 years; diabetes duration 12.7 ± 8.2 years; 53.4% females) who were genotyped for FTO rs9939609. Patients underwent clinical and laboratory evaluations and 3-day weighed diet records. Data on dietary intake were categorized as high or low, based on median values. The AA genotype in the FTO gene was positively associated with high fat (>34% energy; OR = 2.17; 95% CI 1.02-4.63) and low fiber intakes (<16 g/day; OR = 2.42; 95% CI 1.05-5.57), adjusted for gender, BMI, total energy intake, systolic blood pressure, and HbA1c. When gender was taken into account, AA females had higher fat (37.4 ± 5.3 vs. 32.6 ± 7.5 and 32.2 ± 6.2% energy; p = 0.005) and lower fiber intakes (12.4 ± 4.4 vs. 15.1 ± 6.3 and 16.7 ± 5.6 g/day; p = 0.023) than patients with TT and AT genotypes. Multiple logistic regression models confirmed female associations for high fat (OR = 9.73; 95% CI 2.12-44.66) and low fiber intakes (OR = 4.28; 95% CI 1.14-16.06; p < 0.05 for all models). Patients with type 2 diabetes, who were carriers of the AA genotype of the FTO rs9939609, had increased fat and decreased fiber consumption, independently of BMI. Copyright © 2013 S. Karger AG, Basel.

  1. 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.

  2. Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

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    Aleksey G. Nikitin

    2017-07-01

    Full Text Available Background The association of type 2 diabetes mellitus (T2DM with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs of the genes using real-time PCR (TaqMan assays. HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

  3. The FTO rs9939609 and LEPR rs1137101 mothers-newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns: A cross-sectional study on mothers-newborns gene polymorphisms-The FTO-LEPR Study (STROBE-compliant article).

    Science.gov (United States)

    Mărginean, Claudiu; Mărginean, Cristina Oana; Iancu, Mihaela; Meliţ, Lorena Elena; Tripon, Florin; Bănescu, Claudia

    2016-12-01

    The aim of this study was to assess the impact of mothers' and newborns' fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity.We performed a cross-sectional study on 355 mother-newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101).Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG + GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P > 0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA + AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA + AT genotype whose mothers had AA + AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG + GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs.Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on newborns' BMI by

  4. Higher prevalence of FTO gene risk genotypes AA rs9939609, CC rs1421085, and GG rs17817449 and saliva containing Staphylococcus aureus in obese women in Croatia.

    Science.gov (United States)

    Huđek, Ana; Škara, Lucija; Smolkovič, Barbara; Kazazić, Snježana; Ravlić, Sanda; Nanić, Lucia; Osvatić, Martina Matovinović; Jelčić, Jozo; Rubelj, Ivica; Bačun-Družina, Višnja

    2018-02-01

    Obesity is composed of multifunctional interactions of eating habits, behaviors, microbiota, genetics, and other unknown factors. We hypothesize that correlations occur between the fat mass and obesity-associated single nucleotide polymorphisms (FTO SNPs), the composition of microorganisms in the saliva, and life habits in obese women from Zagreb County. Our results of the analysis of 3 FTO SNPs showed a statistically significant positive correlation among the frequencies of the high-risk genotypes AA rs9939609 (P = .0367), CC rs1421085 (P = .0367), and GG rs17817449 (P = .0065) of the FTO gene in obese cases. Interestingly, 39.13% of obese women were triple homozygous for all 3 risk alleles. Furthermore, the composition of the oral microbiota in the obese group showed a higher occurrence of a major human pathogen, bacterium Staphylococcus aureus, but a significantly low presence of bacteria Streptococcus oralis, Streptococcus mitis, and Serratia ureilytica compared with the control group. The investigation also revealed that obese women prefer to consume candy and snacks and more meat and meat-derived products, sleep less than 6 hours per day, and had higher hypertension in comparison with the control group. These results support the hypothesis that female obesity is strongly related to all 3 variants of the FTO gene and perhaps a specific composition of microbiota in saliva due to dietary habits. Considering the bimodal distribution of the SNPs and bacterial content of saliva in obese women taken together are factors to consider for risk of obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Association of SNP rs9939609 in FTO gene with metabolic syndrome in type 2 diabetic subjects, rectruited from a tertiary care unit of Karachi, Pakistan.

    Science.gov (United States)

    Fawwad, Asher; Siddiqui, Iftikhar Ahmed; Zeeshan, Nimra Fatima; Shahid, Syed Muhammad; Basit, Abdul

    2015-01-01

    To determine the association of SNP in FTO gene, rs9939609, with Metabolic Syndrome (MS) in type 2 diabetic subjects at a tertiary care unit of Karachi, Pakistan. We genotyped FTO rs9939609 SNP in 296 patients with type 2 diabetes from the Out Patient Department (OPD) of Baqai Institute of Diabetology and Endocrinology (BIDE). MS was defined on the basis of International Diabetes Federation (IDF) and National Cholesterol Education program (NCEP) criterion. Association between the rs9939609 SNP and MS was tested through chi-square and Z-tests by using odds ratio (OR) with 95% confidence intervals. The frequency of MS as defined by IDF criterion was significantly higher in female subjects as compared to male subjects (p= 0.006). Carriers of ≥ 1 copy of the rs9939609 A allele were significantly more likely to had MS (69.6%) than non-carriers (30.4%), corresponding to a carrier odds ratio (OR) of 0.52 (95% confidence interval [CI] (0.29-0.93), with a similar trend for the ATP III-defined MS."A" allele carriers under dominant model, carry all the criterion of MS more significantly as compared to non-carriers. The FTO rs9939609 SNP was associated with an increased risk for Metabolic Syndrome in type 2 diabetic populations at a tertiary care unit of Karachi, Pakistan.

  6. 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...... 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....

  7. 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 (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). Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R

  8. 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

  9. 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 (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

  10. 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...

  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.

    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.

  12. 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.

  13. Recombinant gene expression protocols

    National Research Council Canada - National Science Library

    Tuan, Rocky S

    1997-01-01

    .... A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of...

  14. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  15. Effect of dietary consumption as a modifier on the association between FTO gene variants and excess body weight in children from an admixed population in Brazil: the Social Changes, Asthma and Allergy in Latin America (SCAALA) cohort study.

    Science.gov (United States)

    Vilella, Marília; Nunes de Oliveira Costa, Gustavo; Lima Barreto, Maurício; Alexandrina Figueredo, Camila; Maria Alcantara-Neves, Neuza; Cunha Rodrigues, Laura; Maria Alvim de Matos, Sheila; Leovigildo Fiaccone, Rosemeire; Oliveira, Pablo; Rocha, Aline; de Cássia Ribeiro-Silva, Rita

    2017-06-01

    Previous studies have shown associations of variants of the FTO gene with body weight, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the north-eastern Brazilian population. This study evaluated the association between SNP in the FTO gene and excess weight in Salvador, Bahia, Brazil. In addition, the effect of diet as a modifier on this association was also investigated. This cross-sectional study included 1191 participants aged 4-11 years, who were genotyped for 400 variants of the FTO gene. Direct anthropometric measures were made and dietary data were obtained by 24-h food recall. Multivariate logistic regression analyses were used to assess the associations of interest. Overall, 11·2 % of the individuals included in the study were overweight/obese. Interactions were identified between the percentage energy intake from proteins and obesity risk linked to the rs62048379 SNP (P interaction=0·01) and also between fat intake (PUFA:SFA ratio) and obesity risk linked to the rs62048379 SNP (P interaction=0·01). The T allele for the variant rs62048379 was positively associated with overweight/obesity in individuals whose percentage energy intake from protein was above the median (OR 2·00; 95 % CI 1·05, 3·82). The rs62048379 SNP was also associated with overweight/obesity in individuals whose PUFA:SFA ratio was below the median (OR 1·63; 95 % CI 1·05, 2·55). The association between FTO gene variants and excess body weight can be modulated by dietary characteristics, particularly by fatty acid distribution and dietary protein intake in children.

  16. 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.

  17. Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population.

    Science.gov (United States)

    Liu, Zi-Wei; Zhang, Ji-Tai; Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Yu-Huan; Yan, Hong-Tao; Wu, Hong-Mei; Yang, Xin-Jun

    2016-01-01

    To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population. Seventy-five neonates and their mothers were recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section. High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas.

  18. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Gene Expression in Bone

    Science.gov (United States)

    D'Ambrogio, A.

    Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

  1. 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...... circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity......, sample size, sex, and baseline body mass index and age category. CONCLUSIONS: We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally...

  2. 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.

    2013-01-01

    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. PMID:23867619

  3. A novel MC4R deletion coexisting with FTO and MC1R gene variants, causes severe early onset obesity.

    Science.gov (United States)

    Neocleous, Vassos; Shammas, Christos; Phelan, Marie M; Fanis, Pavlos; Pantelidou, Maria; Skordis, Nicos; Mantzoros, Christos; Phylactou, Leonidas A; Toumba, Meropi

    2016-07-01

    Heterozygous mutations on the melanocortin-4-receptor gene (MC4R) are the most frequent cause of monogenic obesity. We describe a novel MC4R deletion in a girl with severe early onset obesity, tall stature, pale skin and red hair. Clinical and hormonal parameters were evaluated in a girl born full-term by non-consanguineous parents. Her body mass index (BMI) at presentation (3 years) was 30 kg/m 2 (z-score: +4.5SDS). By the age of 5.2 years, she exhibited extreme linear growth acceleration and developed hyperinsulinemia. Direct sequencing of the MC4R, MC1Rand for the knownFTOsingle nucleotide polymorphism (SNP) rs9939609was performed for the patient and her family. A novel heterozygous MC4R p.Met215del (c.643_645delATG) deletion was identified in the patient, her father and her brother, both of whom exhibited a milder phenotype. 3D structural dynamic simulation studies investigated the conformational changes induced by the p.Met215del. The patient and her mother were also found to be carriers of the obesity risk associated FTOrs9939609SNP. Finally, the identification of the known p.Arg160Trp MC1Rvariant in the patient accounts for the red hair and pale skin phenotypic features. The p.Met215del causes global conformational and functional changes as it is localized at the alpha-helical transmembrane regions and the membrane spanning regions of the beta-barrel. This novel mutation produces a severe overgrowth phenotype that is apparent as from infancy and is progressive in childhood. The additional negative effect of environmental and unhealthy lifestyle habits as well as a possible co-interaction of FTOrs9939609 SNP may worsen the phenotype.

  4. Expression and significance of fat mass and obesity associated gene and forkhead transcription factor O1 in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zhang, Jielei; Li, Shan; Li, Jingyi; Han, Chao; Wang, Zhifang; Li, Chong; Wang, Xiaoman; Liu, Zhenzhen; Wen, Jianguo; Zheng, Lili

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a complex disorder and has been closely linked to obesity. The fat mass and obesity-associated (FTO) gene is a newly discovered gene related to obesity, which enhances oxidative stress and lipogenesis in NAFLD. The forkhead transcription factor O1 (FoxO1) is another important gene involved in NAFLD, which causes lipid disorders when insulin resistance appears in the liver. However, the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated. This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD. This study includes two parts referred to as animal and cell experiments. Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglyceride (TG), total cholesterol (TC), alkaline phosphatase (ALP), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Immunohistochemical analysis was used to detect the expression and histological localization of FTO, FoxO1, and adenosine monophosphate (AMP)-activated protein kinase (AMPK). The L02 cells were exposed to high fat for 24, 48, or 72 hours. Oil red O staining was used to detect intracellular lipid droplets. Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA. At the end of 10 weeks, ALP, ALT, AST, and LDL were significantly increased (P < 0.01), while TC and TG were also significantly higher (P < 0.05). In addition, HDL was significantly decreased (P < 0.05). The FTO and FoxO1 proteins were weakly expressed in the control group, but both FTO and FoxO1 were expressed significantly higher (P < 0.01) in the experimental group, and the expression of the two factors was significantly correlated. AMPK in the high-fat group showed a low level of correlation with FTO, but not with FoxO1. Oil Red

  5. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  6. Evolution of gene expression after gene amplification.

    Science.gov (United States)

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-04-24

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Regulation of eucaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Brent, R.; Ptashne, M.S

    1989-05-23

    This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

  8. Differential Gene Expression and Aging

    Directory of Open Access Journals (Sweden)

    Laurent Seroude

    2002-01-01

    Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. FTO genotype and weight loss

    DEFF Research Database (Denmark)

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

    2016-01-01

    : 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...

  11. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each......' C, and clustered Dukes' D separately. Real-time PCR of 10 known genes and 5 ESTs demonstrated excellent reproducibility of the array-based findings. The most frequently altered genes belonged to functional categories of metabolism (22%), transcription and translation (11%), and cellular processes (9...

  12. Human Lacrimal Gland Gene Expression.

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Aakalu

    Full Text Available The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development.We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium.The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described.Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.

  13. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    Science.gov (United States)

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-12-15

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

  14. 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 the plasma samples was investigated at the subject level using supervised multivariate classification in the form of extended canonical variate analysis, classification tree modeling and Lasso (L1) regularized linear logistic regression model (GLMNET). Univariate hypothesis testing of peak intensities...... was used to explore the genotypic effect on the plasma at the population level. The multivariate classification approaches indicated poor discriminative power of the metabolic profiles whereas univariate hypothesis testing provided seven spectral regions with p ..., no reliable markers could be identified, which was confirmed by test set validation. We conclude that it is very unlikely that an FTO-correlated signal can be identified in these 1H CPMG NMR plasma metabolic profiles and speculate that high-throughput un-targeted genotype-metabolic correlations will in many...

  15. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  16. Remote control of gene expression.

    Science.gov (United States)

    Long, Xiaochun; Miano, Joseph M

    2007-06-01

    The elucidation of a growing number of species' genomes heralds an unprecedented opportunity to ascertain functional attributes of non-coding sequences. In particular, cis regulatory modules (CRMs) controlling gene expression constitute a rich treasure trove of data to be defined and experimentally validated. Such information will provide insight into cell lineage determination and differentiation and the genetic basis of heritable diseases as well as the development of novel tools for restricting the inactivation of genes to specific cell types or conditions. Historically, the study of CRMs and their individual transcription factor binding sites has been limited to proximal regions around gene loci. Two important by-products of the genomics revolution, artificial chromosome vectors and comparative genomics, have fueled efforts to define an increasing number of CRMs acting remotely to control gene expression. Such regulation from a distance has challenged our perspectives of gene expression control and perhaps the very definition of a gene. This review summarizes current approaches to characterize remote control of gene expression in transgenic mice and inherent limitations for accurately interpreting the essential nature of CRM activity.

  17. 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

  18. 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); K. Scheuermann (Kathrin); J. Holloway (John); H.M. Inskip (Hazel); C.R. Isasi (Carmen R.); Y. Mossavar-Rahmani (Yasmin); V.W.V. Jaddoe (Vincent); 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

  19. The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.

    Science.gov (United States)

    Khella, Mina S; Salem, Ahmed M; Abdel-Rahman, Omar; Saad, Amr S

    2018-02-01

    Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk. FTO rs9939609 (T >A) genotypes were screened using a TaqMan ® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design. In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025). The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.

  20. 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

  1. Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds

    DEFF Research Database (Denmark)

    Cirera, S.; Jensen, M. S.; Elbrønd, V. S.

    2014-01-01

    Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies. The complex genetic architecture behind obesity has...... triggered a need for the development of better animal models than rodents. The pig has emerged as a very promising biomedical model to study human obesity traits. In this study, we have characterized the expression patterns of six obesity-related genes, leptin (LEP), leptin receptor (LEPR), melanocortin 4...... minipigs) that deviate phenotypically and genetically from each other with respect to obesity traits. We observe significant differential expression for LEP, LEPR and ADIPOQ in muscle and in all three adipose tissues. Interestingly, in pancreas, LEP expression is only detected in the fat minipigs. FTO...

  2. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  3. Human papillomavirus gene expression

    International Nuclear Information System (INIS)

    Chow, L.T.; Hirochika, H.; Nasseri, M.; Stoler, M.H.; Wolinsky, S.M.; Chin, M.T.; Hirochika, R.; Arvan, D.S.; Broker, T.R.

    1987-01-01

    To determine the role of tissue differentiation on expression of each of the papillomavirus mRNA species identified by electron microscopy, the authors prepared exon-specific RNA probes that could distinguish the alternatively spliced mRNA species. Radioactively labeled single-stranded RNA probes were generated from a dual promoter vector system and individually hybridized to adjacent serial sections of formalin-fixed, paraffin-embedded biopsies of condylomata. Autoradiography showed that each of the message species had a characteristic tissue distribution and relative abundance. The authors have characterized a portion of the regulatory network of the HPVs by showing that the E2 ORF encodes a trans-acting enhancer-stimulating protein, as it does in BPV-1 (Spalholz et al. 1985). The HPV-11 enhancer was mapped to a 150-bp tract near the 3' end of the URR. Portions of this region are duplicated in some aggressive strains of HPV-6 (Boshart and zur Hausen 1986; Rando et al. 1986). To test the possible biological relevance of these duplications, they cloned tandem arrays of the enhancer and demonstrated, using a chloramphenicol acetyltransferase (CAT) assay, that they led to dramatically increased transcription proportional to copy number. Using the CAT assays, the authors found that the E2 proteins of several papillomavirus types can cross-stimulate the enhancers of most other types. This suggests that prior infection of a tissue with one papillomavirus type may provide a helper effect for superinfection and might account fo the HPV-6/HPV-16 coinfections in condylomata that they have observed

  4. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa. Not...

  5. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    an analytical approach to examine the suitability of correction methods by considering the inter-treatment bias as well as the inter-replicate variance, which allows use of the best correction method with minimum residual bias. Analyses of RNA sequencing and microarray data showed that the efficiencies......This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  6. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  7. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  8. Gene expression profile of pulpitis

    Science.gov (United States)

    Galicia, Johnah C.; Henson, Brett R.; Parker, Joel S.; Khan, Asma A.

    2016-01-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the Significance Analysis of Microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (≥30mm on VAS) compared to those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology. PMID:27052691

  9. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

  10. Gene Expression in Trypanosomatid Parasites

    Directory of Open Access Journals (Sweden)

    Santiago Martínez-Calvillo

    2010-01-01

    Full Text Available The parasites Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids. In silico analyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

  11. FTO

    Indian Academy of Sciences (India)

    The qualities of isolated genomic DNAs were checked using the agarose gel electrophoresis and the quantities determined using spectrophotometry. All SNP genotypings were performed using the Taqman. SNP genotyping assay (ABI: Applied Biosystems, Foster. City, USA). The primers and probes of SNPs were from ABI.

  12. FTO

    Indian Academy of Sciences (India)

    1College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan ... obesity by influencing a central regulation of food intake .... an overnight fast. Blood pressure was measured to the nearest. 2 mmHg using an appropriately sized cuff and a standard mercury sphygmomanometer in a sitting position ...

  13. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    Science.gov (United States)

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  14. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  15. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1......, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion...

  16. FTO Genotype and Aging: Pleiotropic Longitudinal Effects on Adiposity, Brain function, Impulsivity and Diet

    Science.gov (United States)

    Chuang, Yi-Fang; Tanaka, Toshiko; Beason-Held, Lori L.; An, Yang; Terracciano, Antonio; Sutin, Angelina R.; Kraut, Michael; Singleton, Andrew B.; Resnick, Susan M.; Thambisetty, Madhav

    2014-01-01

    While 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 (BLSA), 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. PMID:24863145

  17. Adaptive Evolution of Gene Expression in Drosophila

    Directory of Open Access Journals (Sweden)

    Armita Nourmohammad

    2017-08-01

    Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

  18. 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

  19. 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

  20. 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

  1. Nonlinear dimensionality reduction of gene expression data

    OpenAIRE

    Nilsson, Jens

    2006-01-01

    Using microarray measurements techniques, it is possible to measure the activity of genes simultaneously across the whole genome. Since genes influence each others activity levels through complex regulatory networks, such gene expression measurements are state samples of a dynamical system. Gene expression data has proven useful for diagnosis and definition of disease subgroups, for inference of the functional role of a given gene or for the deciphering of complex disease mechanisms. However,...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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 whe...... 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).......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...

  3. Prediction of the gene expression in normal lung tissue by the gene expression in blood.

    Science.gov (United States)

    Halloran, Justin W; Zhu, Dakai; Qian, David C; Byun, Jinyoung; Gorlova, Olga Y; Amos, Christopher I; Gorlov, Ivan P

    2015-11-17

    Comparative analysis of gene expression in human tissues is important for understanding the molecular mechanisms underlying tissue-specific control of gene expression. It can also open an avenue for using gene expression in blood (which is the most easily accessible human tissue) to predict gene expression in other (less accessible) tissues, which would facilitate the development of novel gene expression based models for assessing disease risk and progression. Until recently, direct comparative analysis across different tissues was not possible due to the scarcity of paired tissue samples from the same individuals. In this study we used paired whole blood/lung gene expression data from the Genotype-Tissue Expression (GTEx) project. We built a generalized linear regression model for each gene using gene expression in lung as the outcome and gene expression in blood, age and gender as predictors. For ~18 % of the genes, gene expression in blood was a significant predictor of gene expression in lung. We found that the number of single nucleotide polymorphisms (SNPs) influencing expression of a given gene in either blood or lung, also known as the number of quantitative trait loci (eQTLs), was positively associated with efficacy of blood-based prediction of that gene's expression in lung. This association was strongest for shared eQTLs: those influencing gene expression in both blood and lung. In conclusion, for a considerable number of human genes, their expression levels in lung can be predicted using observable gene expression in blood. An abundance of shared eQTLs may explain the strong blood/lung correlations in the gene expression.

  4. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

    2006-01-01

    The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...... be met by using promoter libraries. This approach generally consists of inserting a library of promoters in front of the gene to be studied, whereby the individual promoters might deviate either in their spacer sequences or bear slight deviations from the consensus sequence of a vegetative promoter. Here......, we describe the two different methods for obtaining promoter libraries and compare their applicability....

  5. Profiling Gene Expression in Germinating Brassica Roots.

    Science.gov (United States)

    Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

    2014-01-01

    Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism.

  6. Polycistronic gene expression in Aspergillus niger.

    Science.gov (United States)

    Schuetze, Tabea; Meyer, Vera

    2017-09-25

    Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

  7. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    Result: Between the diabetic rat group and the wild-type group, 1339 functional genes showed differences in expression levels (p < 0.05). ... Genes whose expression normalized were mainly those affected by the disease state and associated with glucose and lipid metabolism, cell growth, apoptosis, biosynthesis, olfactory ...

  8. Expression of conserved signalling pathway genes during

    Indian Academy of Sciences (India)

    Hence, we analysed the expression of Notch, Wnt and Sonic Hedgehog (Shh) pathway genes during differentiation of R1 cells into early vascular lineages. Notch-, Wnt-and Shh-mediated signalling is important during embryonic development. Regulation of gene expression through these signalling molecules is a frequently ...

  9. Serial analysis of gene expression (SAGE)

    NARCIS (Netherlands)

    van Ruissen, Fred; Baas, Frank

    2007-01-01

    In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

  10. Arabidopsis gene expression patterns during spaceflight

    Science.gov (United States)

    Paul, A.-L.; Ferl, R. J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments resulted in the differential expression of hundreds of genes. A 5 day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the β -Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on two fronts. First, expression patterns visualized with the Adh/GUS transgene were used to address specifically the possibility that spaceflight induces a hypoxic stress response, and to assess whether any spaceflight response was similar to control terrestrial hypoxia-induced gene expression patterns. (Paul et al., Plant Physiol. 2001, 126:613). Second, genome-wide patterns of native gene expression were evaluated utilizing the Affymetrix ATH1 GeneChip? array of 8,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes identified with the arrays was further characterized with quantitative Real-Time RT PCR (ABI - TaqmanTM). Comparison of the patterns of expression for arrays of hybridized with RNA isolated from plants exposed to spaceflight compared to the control arrays revealed hundreds of genes that were differentially expressed in response to spaceflight, yet most genes that are hallmarks of hypoxic stress were unaffected. These results will be discussed in light of current models for plant responses to the spaceflight environment, and with regard to potential future flight opportunities.

  11. Expression of Sox genes in tooth development.

    Science.gov (United States)

    Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

    2015-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

  12. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...... on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently...

  13. Gene set analysis for longitudinal gene expression data

    Directory of Open Access Journals (Sweden)

    Piepho Hans-Peter

    2011-07-01

    Full Text Available Abstract Background Gene set analysis (GSA has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information with

  14. Positron emission tomography imaging of gene expression

    International Nuclear Information System (INIS)

    Tang Ganghua

    2001-01-01

    The merging of molecular biology and nuclear medicine is developed into molecular nuclear medicine. Positron emission tomography (PET) of gene expression in molecular nuclear medicine has become an attractive area. Positron emission tomography imaging gene expression includes the antisense PET imaging and the reporter gene PET imaging. It is likely that the antisense PET imaging will lag behind the reporter gene PET imaging because of the numerous issues that have not yet to be resolved with this approach. The reporter gene PET imaging has wide application into animal experimental research and human applications of this approach will likely be reported soon

  15. Effects of a High-Protein/Low-Carbohydrate Diet versus a Standard Hypocaloric Diet on Weight and Cardiovascular Risk Factors: Role of a Genetic Variation in the rs9939609 FTO Gene Variant.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; Primo, David; Urdiales, Silvia; Romero, Enrique

    2015-01-01

    The common polymorphism rs9939609 of the fat mass- and obesity-associated gene (FTO) has been linked to obesity. Our aim was to investigate its role in weight loss after the administration of a high-protein/low-carbohydrate diet compared to a standard hypocaloric diet (1,000 kcal/day). During 9 months, 195 patients were randomly allocated to a high-protein hypocaloric diet (HP diet) and a standard hypocaloric diet (S diet). With the HP diet, BMI (-1.9 ± 1.2 vs. -2.10 ± 1.8; p < 0.05), weight (-6.5 ± 2.1 vs. -10.1 ± 4.1 kg; p < 0.05), fat mass (-3.9 ± 3.2 vs. -6.0 ± 3.4 kg; p < 0.05) and waist circumference (-5.7 ± 5.0 vs. -9.9 ± 5.5 cm; p < 0.05) decreased in both genotype groups (TT vs. AT + AA). With the S diet, BMI (-0.9 ± 1.1 vs. -1.8 ± 1.2; p < 0.05), weight (-3.2 ± 3.0 vs. -9.1 ± 3.6 kg; p < 0.05), fat mass (-3.0 ± 3.1 vs. -5.2 ± 3.1 kg; p < 0.05) and waist circumference (-3.1 ± 4.0 vs. -8.1 ± 4.9 cm; p < 0.05) decreased in both genotype groups. With the HP diet and in both genotype groups, glucose, insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides and low-density lipoprotein (LDL) decreased. With the S diet, total cholesterol and LDL decreased. Weight loss was better in A allele carriers than noncarriers, and metabolic improvement was better with the HP diet. © 2015 S. Karger AG, Basel.

  16. '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

  17. Photosynthetic gene expression in higher plants.

    Science.gov (United States)

    Berry, James O; Yerramsetty, Pradeep; Zielinski, Amy M; Mure, Christopher M

    2013-11-01

    Within the chloroplasts of higher plants and algae, photosynthesis converts light into biological energy, fueling the assimilation of atmospheric carbon dioxide into biologically useful molecules. Two major steps, photosynthetic electron transport and the Calvin-Benson cycle, require many gene products encoded from chloroplast as well as nuclear genomes. The expression of genes in both cellular compartments is highly dynamic and influenced by a diverse range of factors. Light is the primary environmental determinant of photosynthetic gene expression. Working through photoreceptors such as phytochrome, light regulates photosynthetic genes at transcriptional and posttranscriptional levels. Other processes that affect photosynthetic gene expression include photosynthetic activity, development, and biotic and abiotic stress. Anterograde (from nucleus to chloroplast) and retrograde (from chloroplast to nucleus) signaling insures the highly coordinated expression of the many photosynthetic genes between these different compartments. Anterograde signaling incorporates nuclear-encoded transcriptional and posttranscriptional regulators, such as sigma factors and RNA-binding proteins, respectively. Retrograde signaling utilizes photosynthetic processes such as photosynthetic electron transport and redox signaling to influence the expression of photosynthetic genes in the nucleus. The basic C3 photosynthetic pathway serves as the default form used by most of the plant species on earth. High temperature and water stress associated with arid environments have led to the development of specialized C4 and CAM photosynthesis, which evolved as modifications of the basic default expression program. The goal of this article is to explain and summarize the many gene expression and regulatory processes that work together to support photosynthetic function in plants.

  18. Development of gene expression assays measuring immune ...

    African Journals Online (AJOL)

    Using qPCR, the relative expression stability of the reference genes ACTB, GAPDH, YWHAZ and TBP in these samples was determined as well as the mean fold change in the expression of IFNG, CXCL8, CXCL9, CXCL10 and CXCL11 in M. bovis-antigen stimulated blood. The expression of YWHAZ and TBP showed ...

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

    Directory of Open Access Journals (Sweden)

    Laura Johnson

    Full Text Available 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.

  20. 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.

  1. Caleydo: connecting pathways and gene expression.

    Science.gov (United States)

    Streit, Marc; Lex, Alexander; Kalkusch, Michael; Zatloukal, Kurt; Schmalstieg, Dieter

    2009-10-15

    Understanding the relationships between pathways and the altered expression of their components in disease conditions can be addressed in a visual data analysis process. Caleydo uses novel visualization techniques to support life science experts in their analysis of gene expression data in the context of pathways and functions of individual genes. Pathways and gene expression visualizations are placed in a 3D scene where selected entities (i.e. genes) are visually connected. This allows Caleydo to seamlessly integrate interactive gene expression visualization with cross-database pathway exploration. The Caleydo visualization framework is freely available on www.caleydo.org for non-commercial use. It runs on Windows and Linux and requires a 3D capable graphics card.

  2. Adaptive Evolution of Gene Expression in Drosophila.

    Science.gov (United States)

    Nourmohammad, Armita; Rambeau, Joachim; Held, Torsten; Kovacova, Viera; Berg, Johannes; Lässig, Michael

    2017-08-08

    Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Differential gene expression during Trypanosoma cruzi metacyclogenesis

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Krieger

    1999-09-01

    Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

  4. EXPRESSION OF BACTERIOOPSIN GENES IN ESCHERICHIA COLI

    OpenAIRE

    TSUJIUCHI, Yutaka; IWASA, Tatsuo; TOKUNAGA, Fumio

    1994-01-01

    An inducible expression vector pUBO was constructed with native codons in order to express the gene of Bacteriorhodopsin (BOP) in Escherichia coli (E. coli). Vector pUBO contains lac-promoter followed by the partial structural gene of lacZ and the structural gene of BOP. The expression of this fusion protein was detected by ELISA with anti-BOP antiserum. The fusion protein obtained from E. coli trnsformed with pUBO formed approximately 0.1% of the total protein of the E. coli membrane fraction.

  5. Differential expression of cell adhesion genes

    DEFF Research Database (Denmark)

    Stein, Wilfred D; Litman, Thomas; Fojo, Tito

    2005-01-01

    that compare cells grown in suspension to similar cells grown attached to one another as aggregates have suggested that it is adhesion to the extracellular matrix of the basal membrane that confers resistance to apoptosis and, hence, resistance to cytotoxins. The genes whose expression correlates with poor...... survival might, therefore, act through such a matrix-to-cell suppression of apoptosis. Indeed, correlative mining of gene expression and patient survival databases suggests that poor survival in patients with metastatic cancer correlates highly with tumor expression of a common theme: the genes involved...

  6. Drosophila melanogaster gene expression changes after spaceflight.

    Data.gov (United States)

    National Aeronautics and Space Administration — Gene expression levels were determined in 3rd instar and adult Drosophila melanogaster reared during spaceflight to elucidate the genetic and molecular mechanisms...

  7. PRAME gene expression profile in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Tânia Maria Vulcani-Freitas

    2011-02-01

    Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

  8. Homeobox genes expressed during echinoderm arm regeneration.

    Science.gov (United States)

    Ben Khadra, Yousra; Said, Khaled; Thorndyke, Michael; Martinez, Pedro

    2014-04-01

    Regeneration in echinoderms has proved to be more amenable to study in the laboratory than the more classical vertebrate models, since the smaller genome size and the absence of multiple orthologs for different genes in echinoderms simplify the analysis of gene function during regeneration. In order to understand the role of homeobox-containing genes during arm regeneration in echinoderms, we isolated the complement of genes belonging to the Hox class that are expressed during this process in two major echinoderm groups: asteroids (Echinaster sepositus and Asterias rubens) and ophiuroids (Amphiura filiformis), both of which show an extraordinary capacity for regeneration. By exploiting the sequence conservation of the homeobox, putative orthologs of several Hox genes belonging to the anterior, medial, and posterior groups were isolated. We also report the isolation of a few Hox-like genes expressed in the same systems.

  9. Evaluation of suitable reference genes for gene expression studies ...

    Indian Academy of Sciences (India)

    2011-12-14

    Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...

  10. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  11. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Odelta dos Santos

    Full Text Available Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR, one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  12. Inferring gene networks from discrete expression data

    KAUST Repository

    Zhang, L.

    2013-07-18

    The modeling of gene networks from transcriptional expression data is an important tool in biomedical research to reveal signaling pathways and to identify treatment targets. Current gene network modeling is primarily based on the use of Gaussian graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which generate counts of mRNAtranscripts in cell samples.We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution.We restrict the gene network structures to decomposable graphs and derive the graphs by selecting the covariance matrix of the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we incorporate prior network models based on gene ontology information, which avails existing biological information on the genes of interest. We conduct simulation studies to examine the performance of our discrete graphical model and apply the method to two real datasets for gene network inference. © The Author 2013. Published by Oxford University Press. All rights reserved.

  13. Perspectives: Gene Expression in Fisheries Management

    Science.gov (United States)

    Nielsen, Jennifer L.; Pavey, Scott A.

    2010-01-01

    Functional genes and gene expression have been connected to physiological traits linked to effective production and broodstock selection in aquaculture, selective implications of commercial fish harvest, and adaptive changes reflected in non-commercial fish populations subject to human disturbance and climate change. Gene mapping using single nucleotide polymorphisms (SNPs) to identify functional genes, gene expression (analogue microarrays and real-time PCR), and digital sequencing technologies looking at RNA transcripts present new concepts and opportunities in support of effective and sustainable fisheries. Genomic tools have been rapidly growing in aquaculture research addressing aspects of fish health, toxicology, and early development. Genomic technologies linking effects in functional genes involved in growth, maturation and life history development have been tied to selection resulting from harvest practices. Incorporating new and ever-increasing knowledge of fish genomes is opening a different perspective on local adaptation that will prove invaluable in wild fish conservation and management. Conservation of fish stocks is rapidly incorporating research on critical adaptive responses directed at the effects of human disturbance and climate change through gene expression studies. Genomic studies of fish populations can be generally grouped into three broad categories: 1) evolutionary genomics and biodiversity; 2) adaptive physiological responses to a changing environment; and 3) adaptive behavioral genomics and life history diversity. We review current genomic research in fisheries focusing on those that use microarrays to explore differences in gene expression among phenotypes and within or across populations, information that is critically important to the conservation of fish and their relationship to humans.

  14. Expression of Deinococcus geothermalis trehalose synthase gene ...

    African Journals Online (AJOL)

    A novel trehalose synthase gene from Deinococcus geothermalis (DSMZ 11300) containing 1692 bp reading-frame encoding 564 amino acids was amplified using polymerase chain reaction (PCR). The gene was ligated into pET30Ek/LIC vector and expressed after isopropyl β-D-thiogalactopyranoside induction in ...

  15. Physical activity modifies the FTO effect on BMI change in Japanese adolescents.

    Science.gov (United States)

    Shinozaki, Keiko; Okuda, Masayuki; Okayama, Naoko; Kunitsugu, Ichiro

    2018-04-14

    Evidence of the effects of fat mass and obesity-associated (FTO) gene variation and long-term effects of physical activity (PA) on adiposity in adolescents is largely scarce. This study aimed to investigate whether physical activity modulates the effects of the FTO gene on body mass index (BMI) changes in Japanese adolescents between the ages of 13 and 18 years. Data of 343 subjects (156 boys; 187 girls) who were enrolled in 2006 and 2007 from schools on Shunan City, Japan, were collected. Genotyping (rs1558902) was conducted, and anthropometric measurements and blood test results were recorded for subjects in the eighth grade. A second survey involving self-reporting of anthropometric measurements was conducted when the subjects were in the twelfth grade. PA was estimated using the International Physical Activity Questionnaire in this survey. BMI and the standard deviation score for BMI (BMI-SDS) were calculated. BMI changes and BMI-SDS changes were compared among FTO genotypes using a multivariate model. The effect of the interaction between PA and the FTO genotype on BMI changes was significant among boys but not girls. Among boys, PA had a significant negative influence on BMI-SDS changes in those with the AA genotype and a significant positive influence on BMI and BMI-SDS changes in those with the TT genotype. These data suggest that the influence of PA on BMI changes and BMI-SDS changes varied on the basis of genotype. PA modified the effect of the FTO gene on BMI changes in Japanese boys. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial.

    Science.gov (United States)

    Huang, Tao; Qi, Qibin; Li, Yanping; Hu, Frank B; Bray, George A; Sacks, Frank M; Williamson, Donald A; Qi, Lu

    2014-05-01

    A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated (FTO) gene was recently shown to affect appetite, and the gene is sensitive to the regulation of amino acids. We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial. We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies trial and assessed 4 appetite-related traits including cravings, fullness, hunger, and prospective consumption. We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age, sex, ethnicity, baseline body mass index, weight change, and baseline value for respective outcomes (P-interaction = 0.027 and 0.048, respectively). The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein-diet intake (P = 0.027 and 0.047, respectively) but not in subjects in the low-protein-diet group (P = 0.384 and 0.078, respectively). The weight regain from 6 to 24 mo attenuated gene-protein interactions. Protein intakes did not modify FTO genotype effects on other appetite measures. Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet. This trial was registered at clinicaltrials.gov as NCT00072995.

  17. Bayesian assignment of gene ontology terms to gene expression experiments.

    Science.gov (United States)

    Sykacek, P

    2012-09-15

    Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

  18. Bayesian assignment of gene ontology terms to gene expression experiments

    Science.gov (United States)

    Sykacek, P.

    2012-01-01

    Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

  19. Mismatch repair gene expression in gastroesophageal cancers.

    Science.gov (United States)

    Dracea, Amelia; Angelescu, Cristina; Danciulescu, Mihaela; Ciurea, Marius; Ioana, Mihai; Burada, Florin

    2015-09-01

    Mismatch repair (MMR) genes play a critical role in maintaining genomic stability, and the impairment of MMR machinery is associated with different human cancers, mainly colorectal cancer. The purpose of our study was to analyze gene expression patterns of three MMR genes (MSH2, MHS6, and EXO1) in gastroesophageal cancers, a pathology in which the contribution of DNA repair genes remains essentially unclear. A total of 45 Romanian patients diagnosed with sporadic gastroesophageal cancers were included in this study. For each patient, MMR mRNA levels were measured in biopsied tumoral (T) and peritumoral (PT) tissues obtained by upper endoscopy. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) with specific TaqMan probes was used to measure gene expression levels for MSH2, MSH6, and EXO1 genes. A significant association was observed for the investigated MMR genes, all of which were detected to be upregulated in gastroesophageal tumor samples when compared with paired normal samples. In the stratified analysis, the association was limited to gastric adenocarcinoma samples. We found no statistically significant associations between MMR gene expression and tumor site or histological grade. In our study, MSH2, MSH6, and EXO1 genes were overexpressed in gastroesophageal cancers. Further investigations based on more samples are necessary to validate our findings.

  20. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    in pig with genetic propensity for higher growth rate were identified by sequence analysis of 12 differentially expressed clones selected by differential screening following the generation of the subtracted cDNA population. Real-time PCR analysis con- firmed difference in expression profiles of the identified genes in ...

  1. Regulation of gene expression in human tendinopathy

    Directory of Open Access Journals (Sweden)

    Archambault Joanne M

    2011-05-01

    Full Text Available Abstract Background Chronic tendon injuries, also known as tendinopathies, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure, yet little is known about the molecular mechanisms leading to tendinopathy. Methods We have used histological evaluation and molecular profiling to determine gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy. Results Diseased tendons exhibit altered extracellular matrix, fiber disorientation, increased cellular content and vasculature, and the absence of inflammatory cells. Global gene expression profiling identified 983 transcripts with significantly different expression patterns in the diseased tendons. Global pathway analysis further suggested altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response. Conclusions Identification of the pathways and genes that are differentially regulated in tendinopathy samples will contribute to our understanding of the disease and the development of novel therapeutics.

  2. Noise minimization in eukaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-15

    All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

  3. Global gene expression in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Schembri, Mark; Kjærgaard, K.; Klemm, Per

    2003-01-01

    It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance...... to antimicrobial treatments and host immune defence responses. Escherichia coli has been used as a model organism to study the mechanisms of growth within adhered communities. In this study, we use DNA microarray technology to examine the global gene expression profile of E. coli during sessile growth compared...... the transition to biofilm growth, and these included genes expressed under oxygen-limiting conditions, genes encoding (putative) transport proteins, putative oxidoreductases and genes associated with enhanced heavy metal resistance. Of particular interest was the observation that many of the genes altered...

  4. 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 body weight (p 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.

  5. Human AZU-1 gene, variants thereof and expressed gene products

    Science.gov (United States)

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  6. Expression Study of Banana Pathogenic Resistance Genes

    Directory of Open Access Journals (Sweden)

    Fenny M. Dwivany

    2016-10-01

    Full Text Available Banana is one of the world's most important trade commodities. However, infection of banana pathogenic fungi (Fusarium oxysporum race 4 is one of the major causes of decreasing production in Indonesia. Genetic engineering has become an alternative way to control this problem by isolating genes that involved in plant defense mechanism against pathogens. Two of the important genes are API5 and ChiI1, each gene encodes apoptosis inhibitory protein and chitinase enzymes. The purpose of this study was to study the expression of API5 and ChiI1 genes as candidate pathogenic resistance genes. The amplified fragments were then cloned, sequenced, and confirmed with in silico studies. Based on sequence analysis, it is showed that partial API5 gene has putative transactivation domain and ChiI1 has 9 chitinase family GH19 protein motifs. Data obtained from this study will contribute in banana genetic improvement.

  7. Gene expression analysis of flax seed development

    Directory of Open Access Journals (Sweden)

    Sharpe Andrew

    2011-04-01

    Full Text Available Abstract Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages seed coats (globular and torpedo stages and endosperm (pooled globular to torpedo stages and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST (GenBank accessions LIBEST_026995 to LIBEST_027011 were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152 had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid

  8. Gene expression analysis of flax seed development.

    Science.gov (United States)

    Venglat, Prakash; Xiang, Daoquan; Qiu, Shuqing; Stone, Sandra L; Tibiche, Chabane; Cram, Dustin; Alting-Mees, Michelle; Nowak, Jacek; Cloutier, Sylvie; Deyholos, Michael; Bekkaoui, Faouzi; Sharpe, Andrew; Wang, Edwin; Rowland, Gordon; Selvaraj, Gopalan; Datla, Raju

    2011-04-29

    Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise even low-expressed genes such as

  9. 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.

  10. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne

    2007-01-01

    ) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...... with the control muscles. Most interestingly, no changes in the expression of proteins involved in inflammatory responses or muscle regeneration was detected, indicating limited muscle damage and regeneration. Histological analysis revealed structural changes with loss of cell integrity and striation pattern......BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...

  11. Visualizing Gene Expression In Situ

    Energy Technology Data Exchange (ETDEWEB)

    Burlage, R.S.

    1998-11-02

    Visualizing bacterial cells and describing their responses to the environment are difficult tasks. Their small size is the chief reason for the difficulty, which means that we must often use many millions of cells in a sample in order to determine what the average response of the bacteria is. However, an average response can sometimes mask important events in bacterial physiology, which means that our understanding of these organisms will suffer. We have used a variety of instruments to visualize bacterial cells, all of which tell us something different about the sample. We use a fluorescence activated cell sorter to sort cells based on the fluorescence provided by bioreporter genes, and these can be used to select for particular genetic mutations. Cells can be visualized by epifluorescent microscopy, and sensitive photodetectors can be added that allow us to find a single bacterial cell that is fluorescent or bioluminescent. We have also used standard photomultipliers to examine cell aggregates as field bioreporter microorganisms. Examples of each of these instruments show how our understanding of bacterial physiology has changed with the technology.

  12. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

    Science.gov (United States)

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

  13. Sequencing and Gene Expression Analysis of Leishmania tropica LACK Gene.

    Science.gov (United States)

    Hammoudeh, Nour; Kweider, Mahmoud; Abbady, Abdul-Qader; Soukkarieh, Chadi

    2014-01-01

    Leishmania Homologue of receptors for Activated C Kinase (LACK) antigen is a 36-kDa protein, which provokes a very early immune response against Leishmania infection. There are several reports on the expression of LACK through different life-cycle stages of genus Leishmania, but only a few of them have focused on L.tropica. The present study provides details of the cloning, DNA sequencing and gene expression of LACK in this parasite species. First, several local isolates of Leishmania parasites were typed in our laboratory using PCR technique to verify of Leishmania parasite species. After that, LACK gene was amplified and cloned into a vector for sequencing. Finally, the expression of this molecule in logarithmic and stationary growth phase promastigotes, as well as in amastigotes, was evaluated by Reverse Transcription-PCR (RT-PCR) technique. The typing result confirmed that all our local isolates belong to L.tropica. LACK gene sequence was determined and high similarity was observed with the sequences of other Leishmania species. Furthermore, the expression of LACK gene in both promastigotes and amastigotes forms was confirmed. Overall, the data set the stage for future studies of the properties and immune role of LACK gene products.

  14. [Imprinting genes and it's expression in Arabidopsis].

    Science.gov (United States)

    Zhang, Hong-Yu; Xu, Pei-Zhou; Yang, Hua; Wu, Xian-Jun

    2010-07-01

    Genomic imprinting refers to the phenomenon that the expression of a gene copy depends on its parent of origin. The Arabidopsis imprinted FIS (Fertilisation-independent seed) genes, mea, fis2, and fie, play essential roles in the repression of central cell and the regulation of early endosperm development. fis mutants display two phenotypes: autonomous diploid endosperm development when fertilization is absent and un-cellularised endosperm formation when fertilization occurs. The FIS Polycomb protein complex including the above three FIS proteins catalyzes histone H3 K27 tri-methylation on target loci. DME (DEMETER), a DNA glycosylase, and AtMET1 (Methyltransferase1), a DNA methyltransferase, are involved in the regulation of imprinted expression of both mea and fis2. This review summarizes the studies on the Arabidopsis imprinted FIS genes and other related genes. Recent works have shown that the insertion of transposons may affect nearby gene expression, which may be the main driving force behind the evolution of genomic imprinting. This summary covers the achievements on Arabidopsis imprinted genes will provide important information for studies on genomic imprinting in the important crops such as rice and maize.

  15. Gene expression profiling for pharmaceutical toxicology screening.

    Science.gov (United States)

    Bugelski, Peter J

    2002-01-01

    Advances in medicinal chemistry and high-throughput pharmacological screening are creating a multitude of potential lead compounds. There is also heightened concern about drug-induced toxicity, which is all too often uncovered late in development or at the post marketing stage. Together, these factors have created a need for novel approaches to screen for toxicity. There have been technological advances that enable study of changes in the gene expression profile caused by toxic insults and important steps made toward unraveling target organ toxicity at the molecular level. Thus, gene expression profile-based screens hold the promise to revolutionize the way in which compounds are selected for development. For screens focused on specific mechanisms of toxicity, reporter gene systems have proven utility, albeit modest because of our limited knowledge of which genes are true surrogate markers for toxicity. For broader forecasts of toxicity, DNA microarrays hold great promise for delivering practical gene expression profile screens (GEPS). For this promise to be realized, however, a number of technological hurdles must be cleared: (i) cost; (ii) reproducibility; (iii) throughput; and (iv) data analysis. Of equal if not greater importance, issues relating to the test systems used, the requisite number of genes to be studied and the size and scope of the database upon which forecasts will be based must be addressed. At present, the proof-of-concept for GEPS for toxicity is in hand, and we are poised to realize the goal of creating practical GEPS for application in compound prioritization.

  16. Differential testicular gene expression in seasonal fertility

    Science.gov (United States)

    Maywood, Elizabeth S.; Chahad-Ehlers, Samira; Garabette, Martine L.; Pritchard, Claire; Underhill, Phillip; Greenfield, Andrew; Ebling, Francis J. P.; Kyriacou, Charalambos P.; Hastings, Michael H.; Reddy, Akhilesh B.

    2012-01-01

    Spermatogenesis is an essential precursor for successful sexual reproduction. Recently, there has been an expansion in our knowledge of the genes associated with particular stages of normal, physiological testicular development and pubertal activation. What has been lacking, however, is an understanding of those genes that are involved in specifically regulating sperm production, rather than in maturation and elaboration of the testis as an organ. By utilising the reversible (seasonal) fertility of the Syrian hamster as a model system, we sought to discover genes which are specifically involved in turning off sperm production and not in tissue specification and/or maturation. Using gene expression microarrays and in situ hybridisation in hamsters and genetically infertile mice, we have identified a variety of known and novel factors involved in reversible, transcriptional, translational and post-translational control of testicular function, as well those involved in cell division and macromolecular metabolism. The novel genes uncovered could be potential targets for therapies against fertility disorders. PMID:19346449

  17. Gene expression during normal and FSHD myogenesis

    Directory of Open Access Journals (Sweden)

    Sowden Janet

    2011-09-01

    Full Text Available Abstract Background Facioscapulohumeral muscular dystrophy (FSHD is a dominant disease linked to contraction of an array of tandem 3.3-kb repeats (D4Z4 at 4q35. Within each repeat unit is a gene, DUX4, that can encode a protein containing two homeodomains. A DUX4 transcript derived from the last repeat unit in a contracted array is associated with pathogenesis but it is unclear how. Methods Using exon-based microarrays, the expression profiles of myogenic precursor cells were determined. Both undifferentiated myoblasts and myoblasts differentiated to myotubes derived from FSHD patients and controls were studied after immunocytochemical verification of the quality of the cultures. To further our understanding of FSHD and normal myogenesis, the expression profiles obtained were compared to those of 19 non-muscle cell types analyzed by identical methods. Results Many of the ~17,000 examined genes were differentially expressed (> 2-fold, p DUX4 RNA isoform was detected by RT-PCR in FSHD myoblast and myotube preparations only at extremely low levels. Unique insights into myogenesis-specific gene expression were also obtained. For example, all four Argonaute genes involved in RNA-silencing were significantly upregulated during normal (but not FSHD myogenesis relative to non-muscle cell types. Conclusions DUX4's pathogenic effect in FSHD may occur transiently at or before the stage of myoblast formation to establish a cascade of gene dysregulation. This contrasts with the current emphasis on toxic effects of experimentally upregulated DUX4 expression at the myoblast or myotube stages. Our model could explain why DUX4's inappropriate expression was barely detectable in myoblasts and myotubes but nonetheless linked to FSHD.

  18. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

  19. Gene expression analysis of zebrafish heart regeneration.

    Directory of Open Access Journals (Sweden)

    Ching-Ling Lien

    2006-08-01

    Full Text Available Mammalian hearts cannot regenerate. In contrast, zebrafish hearts regenerate even when up to 20% of the ventricle is amputated. The mechanism of zebrafish heart regeneration is not understood. To systematically characterize this process at the molecular level, we generated transcriptional profiles of zebrafish cardiac regeneration by microarray analyses. Distinct gene clusters were identified based on temporal expression patterns. Genes coding for wound response/inflammatory factors, secreted molecules, and matrix metalloproteinases are expressed in regenerating heart in sequential patterns. Comparisons of gene expression profiles between heart and fin regeneration revealed a set of regeneration core molecules as well as tissue-specific factors. The expression patterns of several secreted molecules around the wound suggest that they play important roles in heart regeneration. We found that both platelet-derived growth factor-a and -b (pdgf-a and pdgf-b are upregulated in regenerating zebrafish hearts. PDGF-B homodimers induce DNA synthesis in adult zebrafish cardiomyocytes. In addition, we demonstrate that a chemical inhibitor of PDGF receptor decreases DNA synthesis of cardiomyocytes both in vitro and in vivo during regeneration. Our data indicate that zebrafish heart regeneration is associated with sequentially upregulated wound healing genes and growth factors and suggest that PDGF signaling is required.

  20. Gene expression in early stage cervical cancer

    NARCIS (Netherlands)

    Biewenga, Petra; Buist, Marrije R.; Moerland, Perry D.; van Thernaat, Emiel Ver Loren; van Kampen, Antoine H. C.; ten Kate, Fiebo J. W.; Baas, Frank

    2008-01-01

    Objective. Pelvic lymph node metastases are the main prognostic factor for survival in early stage cervical cancer, yet accurate detection methods before surgery are lacking. In this study, we examined whether gene expression profiling can predict the presence of lymph node metastasis in early stage

  1. Identification of genes showing differential expression profile

    Indian Academy of Sciences (India)

    Suppression subtractive hybridization was used to identify genes showing differential expression profile associated withgrowth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus-culus longissimus muscle tissues of selected pigs with extreme expected ...

  2. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    Abstract. Suppression subtractive hybridization was used to identify genes showing differential expression profile associated with growth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus- culus longissimus muscle tissues of selected pigs with extreme ...

  3. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    diet. The rats were continuously fed for 16 months, and blood glucose monitored by a glucose meter. One wild-type rat and 4 high- fat/high-glucose rats died during ..... therapy not only changed gene expression patterns in type 2 diabetes but also improved immune activity and reduced the likelihood of cancer development.

  4. Genomics analysis of genes expressed reveals differential ...

    African Journals Online (AJOL)

    Genomics analysis of genes expressed reveals differential responses to low chronic nitrogen stress in maize. ... Most induced clones were largely involved in various metabolism processes including physiological process, organelle regulation of biological process, nutrient reservoir activity, transcription regulator activity and ...

  5. Global gene expression in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Schembri, Mark; Kjærgaard, K.; Klemm, Per

    2003-01-01

    to antimicrobial treatments and host immune defence responses. Escherichia coli has been used as a model organism to study the mechanisms of growth within adhered communities. In this study, we use DNA microarray technology to examine the global gene expression profile of E. coli during sessile growth compared...

  6. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    Suppression subtractive hybridization was used to identify genes showing differential expression profile associated withgrowth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus-culus longissimus muscle tissues of selected pigs with extreme expected ...

  7. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

    DEFF Research Database (Denmark)

    Hustinx, Steven R; Cao, Dengfeng; Maitra, Anirban

    2004-01-01

    genome and better biocomputational techniques have substantially improved the assignment of differentially expressed SAGE "tags" to human genes. These improvements have provided us with an opportunity to re-evaluate global gene expression in pancreatic cancer using existing SAGE libraries. SAGE libraries...... generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags....... Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify...

  8. Regulation of methane genes and genome expression

    Energy Technology Data Exchange (ETDEWEB)

    John N. Reeve

    2009-09-09

    At the start of this project, it was known that methanogens were Archaeabacteria (now Archaea) and were therefore predicted to have gene expression and regulatory systems different from Bacteria, but few of the molecular biology details were established. The goals were then to establish the structures and organizations of genes in methanogens, and to develop the genetic technologies needed to investigate and dissect methanogen gene expression and regulation in vivo. By cloning and sequencing, we established the gene and operon structures of all of the “methane” genes that encode the enzymes that catalyze methane biosynthesis from carbon dioxide and hydrogen. This work identified unique sequences in the methane gene that we designated mcrA, that encodes the largest subunit of methyl-coenzyme M reductase, that could be used to identify methanogen DNA and establish methanogen phylogenetic relationships. McrA sequences are now the accepted standard and used extensively as hybridization probes to identify and quantify methanogens in environmental research. With the methane genes in hand, we used northern blot and then later whole-genome microarray hybridization analyses to establish how growth phase and substrate availability regulated methane gene expression in Methanobacterium thermautotrophicus ΔH (now Methanothermobacter thermautotrophicus). Isoenzymes or pairs of functionally equivalent enzymes catalyze several steps in the hydrogen-dependent reduction of carbon dioxide to methane. We established that hydrogen availability determine which of these pairs of methane genes is expressed and therefore which of the alternative enzymes is employed to catalyze methane biosynthesis under different environmental conditions. As were unable to establish a reliable genetic system for M. thermautotrophicus, we developed in vitro transcription as an alternative system to investigate methanogen gene expression and regulation. This led to the discovery that an archaeal protein

  9. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  10. Gene Expression Commons: an open platform for absolute gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Jun Seita

    Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

  11. Comparative gene expression of intestinal metabolizing enzymes.

    Science.gov (United States)

    Shin, Ho-Chul; Kim, Hye-Ryoung; Cho, Hee-Jung; Yi, Hee; Cho, Soo-Min; Lee, Dong-Goo; Abd El-Aty, A M; Kim, Jin-Suk; Sun, Duxin; Amidon, Gordon L

    2009-11-01

    The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3, CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3 and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly expressed in the mouse. The rat revealed predominant expression of glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1, acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human, glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3, GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore, current data indicated substantial interspecies differences in the pattern of intestinal gene expression both for P450 enzymes and phase II drug-metabolizing enzymes. This genomic database is expected to improve our understanding of interspecies variations in estimating intestinal prehepatic clearance of oral drugs.

  12. FTO POLYMORPHISM AND PHYSICAL FITNESS IN OBESE SCHOOLCHILDREN AFTER AN INTERVENTION PROGRAM

    Directory of Open Access Journals (Sweden)

    Greice Graziela Moraes

    Full Text Available ABSTRACT Introduction: Recent studies have shown that the association of FTO rs9939609 gene polymorphism with obesity depends on the level of the individual’s physical activity. However, there are some studies that evaluated physical fitness, health, and motor performance in relation to the rs9939609 FTO gene polymorphism. Objective: To evaluate how the rs9939609 FTO gene polymorphism affects the results of physical fitness tests related to health and athletic performance in schoolchildren after 4 months of intervention of physical exercise. Method: The rs9939609 FTO gene polymorphism was genotyped in a total of 36 schoolchildren from southern Brazil, aged 8 to 16 years. Body mass index (BMI, health-related physical fitness (cardiorespiratory fitness, abdominal strength/endurance, and flexibility and motor performance (upper and lower limb strength, agility, and speed were evaluated. The intervention included exercise strategies based on Physical Education, healthy eating, and oral and postural care. Results: In the experimental group, after the intervention, significant differences were noted in individuals with the TT genotype. These individuals showed improvements in abdominal strength (p=0.025, lower limb strength (p=0.037 and agility (p=0.021. For individuals with the AA/AT genotype, improvements in flexibility (p=0.026, abdominal strength (p=0.002, upper limb strength (p=0.008 and lower limb strength (p=0.001 were observed. However, these differences were not statistically significant when comparing the TT and AT/AA genotypes. Conclusions: The experimental group showed improvements in abdominal strength, lower limb strength, and speed. Yet, individuals with different genotypes (AA/AT and TT for polymorphism rs9939609 exhibited similar values for indicators of physical fitness, health, and motor performance. Level of Evidence II; Lesser quality RCT.

  13. Gene expression profiling of laterally spreading tumors.

    Science.gov (United States)

    Minemura, Shoko; Tanaka, Takeshi; Arai, Makoto; Okimoto, Kenichiro; Oyamada, Arata; Saito, Keiko; Maruoka, Daisuke; Matsumura, Tomoaki; Nakagawa, Tomoo; Katsuno, Tatsuro; Kishimoto, Takashi; Yokosuka, Osamu

    2015-06-06

    Laterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs. The expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining. The expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption. LSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.

  14. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    ) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant......A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...... immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes...

  15. Ru/FTO: Heterogeneous catalyst for glycerol hydrogenolysis

    Science.gov (United States)

    Samad, Wan Zurina; Isahak, Wan Nor Roslam Wan; Liew, Kin Hong; Nordin, Norazzizi; Yarmo, Mohd Ambar; Yusop, Muhammad Rahimi

    2014-09-01

    An introduction of Fluorine-doped tin oxide (FTO) as new catalyst support with Ru metal had enhanced the conversion and selectivity for glycerol hydrogenolysis. A small cluster of Ru were highly dispersed and intercalated over FTO via simple chemical mixture and reduction method. In comparison with various metal (Pd, Os, Cu), Ru/FTO catalyst showed the highest conversion (100%) and highly selectivity of 1,2-propanediol (94%) in the hydrogenolysis of glycerol. The reaction was optimally conducted at 150 °C, 20 bar of H2 pressure and at 8 hours. Ru/FTO catalyst was ascribed as active catalyst due to the amphoteric sites of FTO and small size of Ru metal. This provides high surface concentration of reduction process that involves the chemical bond dissociation in the glycerol hydrogenolysis.

  16. Coevolution of gene expression among interacting proteins

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Wall, Dennis P.; Eisen,Michael B.

    2004-03-01

    Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically interacting proteins coevolve. We estimate average expression levels of genes from four closely related fungi of the genus Saccharomyces using the codon adaptation index and show that expression levels of interacting proteins exhibit coordinated changes in these different species. We find that this coevolution of expression is a more powerful predictor of physical interaction than is coevolution of amino acid sequence. These results demonstrate previously uncharacterized coevolution of gene expression, adding a different dimension to the study of the coevolution of interacting proteins and underscoring the importance of maintaining coexpression of interacting proteins over evolutionary time. Our results also suggest that expression coevolution can be used for computational prediction of protein protein interactions.

  17. The FTO variant is associated with chronic complications of diabetes mellitus in Czech population.

    Science.gov (United States)

    Hubacek, Jaroslav A; Dlouha, Dana; Klementova, Marta; Lanska, Vera; Neskudla, Tomas; Pelikanova, Terezie

    2018-02-05

    Genome-wide association studies have resulted in the identification of the FTO gene as an important genetic determinant of diabetes mellitus. The aim of this study was to confirm the role of this gene in the development of DM in the Czech-Slavonic population and to analyse whether this gene is associated with common DM complications. Two groups of patients (814 with T1DM and 848 with T2DM) and a group of healthy controls (2339 individuals) - both of Czech origin - were genotyped for the FTO rs17817449 SNP. ANOVA and logistic regression were used for the statistical evaluations. The frequency of the GG genotype was significantly higher in T2DM (25.4% vs. 16.7%, Pdiabetic nephropathy was observed both for T1DM patients (GG vs. TT homozygotes, Pdiabetic neuropathy (GG vs. TT comparison; Pretinopathy was detected. All presented values are after adjustment for age, sex, BMI and duration of diabetes. We confirm the association between the FTO rs17817449 SNP and susceptibility to T2DM in the Czech-Slavonic population. The same variant is associated with a spectrum of chronic complications in both types of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Jacobsson, Josefin A; Risérus, Ulf; Axelsson, Tomas; Lannfelt, Lars; Schiöth, Helgi B; Fredriksson, Robert

    2009-12-09

    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. 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. 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. 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.

  19. Digital gene expression analysis of gene expression differences within Brassica diploids and allopolyploids.

    Science.gov (United States)

    Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping

    2015-01-27

    Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.

  20. Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay.

    Science.gov (United States)

    Daoud, Hussein; Zhang, Dong; McMurray, Fiona; Yu, Andrea; Luco, Stephanie M; Vanstone, Jason; Jarinova, Olga; Carson, Nancy; Wickens, James; Shishodia, Shifali; Choi, Hwanho; McDonough, Michael A; Schofield, Christopher J; Harper, Mary-Ellen; Dyment, David A; Armour, Christine M

    2016-03-01

    A homozygous loss-of-function mutation p.(Arg316Gln) in the fat mass and obesity-associated (FTO) gene, which encodes for an iron and 2-oxoglutarate-dependent oxygenase, was previously identified in a large family in which nine affected individuals present with a lethal syndrome characterised by growth retardation and multiple malformations. To date, no other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. We investigated a 21-month-old girl who presented distinctive facial features, failure to thrive, global developmental delay, left ventricular cardiac hypertrophy, reduced vision and bilateral hearing loss. We performed targeted next-generation sequencing of 4813 clinically relevant genes in the patient and her parents. We identified a novel FTO homozygous missense mutation (c.956C>T; p.(Ser319Phe)) in the affected individual. This mutation affects a highly conserved residue located in the same functional domain as the previously characterised mutation p.(Arg316Gln). Biochemical studies reveal that p.(Ser319Phe) FTO has reduced 2-oxoglutarate turnover and N-methyl-nucleoside demethylase activity. Our findings are consistent with previous reports that homozygous mutations in FTO can lead to rare growth retardation and developmental delay syndrome, and further support the proposal that FTO plays an important role in early development of human central nervous and cardiovascular systems. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Predicting gene expression from sequence: a reexamination.

    Directory of Open Access Journals (Sweden)

    Yuan Yuan

    2007-11-01

    Full Text Available Although much of the information regarding genes' expressions is encoded in the genome, deciphering such information has been very challenging. We reexamined Beer and Tavazoie's (BT approach to predict mRNA expression patterns of 2,587 genes in Saccharomyces cerevisiae from the information in their respective promoter sequences. Instead of fitting complex Bayesian network models, we trained naïve Bayes classifiers using only the sequence-motif matching scores provided by BT. Our simple models correctly predict expression patterns for 79% of the genes, based on the same criterion and the same cross-validation (CV procedure as BT, which compares favorably to the 73% accuracy of BT. The fact that our approach did not use position and orientation information of the predicted binding sites but achieved a higher prediction accuracy, motivated us to investigate a few biological predictions made by BT. We found that some of their predictions, especially those related to motif orientations and positions, are at best circumstantial. For example, the combinatorial rules suggested by BT for the PAC and RRPE motifs are not unique to the cluster of genes from which the predictive model was inferred, and there are simpler rules that are statistically more significant than BT's ones. We also show that CV procedure used by BT to estimate their method's prediction accuracy is inappropriate and may have overestimated the prediction accuracy by about 10%.

  2. Gene expression regulation in roots under drought.

    Science.gov (United States)

    Janiak, Agnieszka; Kwaśniewski, Mirosław; Szarejko, Iwona

    2016-02-01

    Stress signalling and regulatory networks controlling expression of target genes are the basis of plant response to drought. Roots are the first organs exposed to water deficiency in the soil and are the place of drought sensing. Signalling cascades transfer chemical signals toward the shoot and initiate molecular responses that lead to the biochemical and morphological changes that allow plants to be protected against water loss and to tolerate stress conditions. Here, we present an overview of signalling network and gene expression regulation pathways that are actively induced in roots under drought stress. In particular, the role of several transcription factor (TF) families, including DREB, AP2/ERF, NAC, bZIP, MYC, CAMTA, Alfin-like and Q-type ZFP, in the regulation of root response to drought are highlighted. The information provided includes available data on mutual interactions between these TFs together with their regulation by plant hormones and other signalling molecules. The most significant downstream target genes and molecular processes that are controlled by the regulatory factors are given. These data are also coupled with information about the influence of the described regulatory networks on root traits and root development which may translate to enhanced drought tolerance. This is the first literature survey demonstrating the gene expression regulatory machinery that is induced by drought stress, presented from the perspective of roots. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Gene expression profiles in skeletal muscle after gene electrotransfer

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    Eriksen Jens

    2007-06-01

    Full Text Available Abstract Background Gene transfer by electroporation (DNA electrotransfer to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 μs followed by a long low voltage pulse (LV, 100 V/cm, 400 ms; a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP and excised at 4 hours, 48 hours or 3 weeks after treatment. Results Differentially expressed genes were investigated by microarray analysis, and descriptive statistics were performed to evaluate the effects of 1 electroporation, 2 DNA injection, and 3 time after treatment. The biological significance of the results was assessed by gene annotation and supervised cluster analysis. Generally, electroporation caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related with the control muscles. Most interestingly, no changes in the expression of proteins involved in inflammatory responses or muscle regeneration was detected, indicating limited muscle damage and regeneration. Histological analysis revealed structural changes with loss of cell integrity and striation pattern in some fibres after DNA+HV+LV treatment, while HV+LV pulses alone showed preservation of cell integrity. No difference in the force generation capacity was observed in

  4. Monitoring the Efficacy of Oncolytic Viruses via Gene Expression

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    Ashley Ansel

    2017-11-01

    Full Text Available With the recent success of oncolytic viruses in clinical trials, efforts toward improved monitoring of the viruses and their mechanism have intensified. Four main gene expression strategies have been employed to date including: analyzing overall gene expression in tumor cells, looking at gene expression of a few specific genes in the tumor cells, focusing on gene expression of specific transgenes introduced into the virus, and following gene expression of certain viral genes. Each strategy presents certain advantages and disadvantages over the others. Various methods to organize the dysregulated genes into clusters have provided a window into the mechanism of action for these viruses. Methodologically, the combined approach of looking at both overall gene expression, the tumor cells and gene expression of viral genes, enables researchers to assess correlation between the introduction of the virus and the changes in the tumor. This would seem to be the most productive approach for future studies, providing much information on mechanism and timing.

  5. Enhanced gene expression from retroviral vectors

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    Micklem David R

    2008-02-01

    Full Text Available Abstract Background Retroviruses are widely used to transfer genes to mammalian cells efficiently and stably. However, genetic elements required for high-level gene expression are incompatible with standard systems. The retroviral RNA genome is produced by cellular transcription and post-transcriptional processing within packaging cells: Introns present in the retroviral genomic transcript are removed by splicing, while polyadenylation signals lead to the production of ineffective truncated genomes. Furthermore strong enhancer/promoters within the retroviral payload lead to detrimental competition with the retroviral enhancer/promoter. Results By exploiting a new method of producing the retroviral genome in vitro it is possible to produce infectious retroviral particles carrying a high-level expression cassette that completely prohibits production of infectious retroviral particles by conventional methods. We produced an expression cassette comprising a strong enhancer/promoter, an optimised intron, the GFP open reading frame and a strong polyadenylation signal. This cassette was cloned into both a conventional MMLV retroviral vector and a vector designed to allow in vitro transcription of the retroviral genome by T7 RNA polymerase. When the conventional retroviral vector was transfected into packaging cells, the expression cassette drove strong GFP expression, but no infectious retrovirus was produced. Introduction of the in vitro produced uncapped retroviral genomic transcript into the packaging cells did not lead to any detectable GFP expression. However, infectious retrovirus was easily recovered, and when used to infect target primary human cells led to very high GFP expression – up to 3.5 times greater than conventional retroviral LTR-driven expression. Conclusion Retroviral vectors carrying an optimized high-level expression cassette do not produce infectious virions when introduced into packaging cells by transfection of DNA

  6. Gene expression in Pseudomonas aeruginosa swarming motility

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    Déziel Eric

    2010-10-01

    Full Text Available Abstract Background The bacterium Pseudomonas aeruginosa is capable of three types of motilities: swimming, twitching and swarming. The latter is characterized by a fast and coordinated group movement over a semi-solid surface resulting from intercellular interactions and morphological differentiation. A striking feature of swarming motility is the complex fractal-like patterns displayed by migrating bacteria while they move away from their inoculation point. This type of group behaviour is still poorly understood and its characterization provides important information on bacterial structured communities such as biofilms. Using GeneChip® Affymetrix microarrays, we obtained the transcriptomic profiles of both bacterial populations located at the tip of migrating tendrils and swarm center of swarming colonies and compared these profiles to that of a bacterial control population grown on the same media but solidified to not allow swarming motility. Results Microarray raw data were corrected for background noise with the RMA algorithm and quantile normalized. Differentially expressed genes between the three conditions were selected using a threshold of 1.5 log2-fold, which gave a total of 378 selected genes (6.3% of the predicted open reading frames of strain PA14. Major shifts in gene expression patterns are observed in each growth conditions, highlighting the presence of distinct bacterial subpopulations within a swarming colony (tendril tips vs. swarm center. Unexpectedly, microarrays expression data reveal that a minority of genes are up-regulated in tendril tip populations. Among them, we found energy metabolism, ribosomal protein and transport of small molecules related genes. On the other hand, many well-known virulence factors genes were globally repressed in tendril tip cells. Swarm center cells are distinct and appear to be under oxidative and copper stress responses. Conclusions Results reported in this study show that, as opposed to

  7. Gene expression in Streptococcus mutans biofilms

    OpenAIRE

    Banu, L D

    2010-01-01

    Streptococcus mutans is considered the major aetiological agent of human dental caries. It is an obligate biofilm-forming bacterium, which resides on teeth and forms, together with other species, an oral biofilm that is often designated as supragingival plaque. This thesis consists of three distinct parts. The first part describes, using microarray analysis, how S. mutans modulates gene expression when grown under different conditions in biofilms. The goal of this analysis was to identify gen...

  8. Gene expression: RNA interference in adult mice

    Science.gov (United States)

    McCaffrey, Anton P.; Meuse, Leonard; Pham, Thu-Thao T.; Conklin, Douglas S.; Hannon, Gregory J.; Kay, Mark A.

    2002-07-01

    RNA interference is an evolutionarily conserved surveillance mechanism that responds to double-stranded RNA by sequence-specific silencing of homologous genes. Here we show that transgene expression can be suppressed in adult mice by synthetic small interfering RNAs and by small-hairpin RNAs transcribed in vivo from DNA templates. We also show the therapeutic potential of this technique by demonstrating effective targeting of a sequence from hepatitis C virus by RNA interference in vivo.

  9. Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

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    Richard Danger

    2018-01-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS, the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group, and 26 samples at or after BOS diagnosis (diagnosis group. An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group. We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1, T-cell leukemia/lymphoma protein 1A (TCL1A, and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01 and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

  10. Proteomic and gene expression patterns of keratoconus

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    Arkasubhra Ghosh

    2013-01-01

    Full Text Available Keratoconus is a progressive corneal thinning disease associated with significant tissue remodeling activities and activation of a variety of signaling networks. However, it is not understood how differential gene and protein expression direct function in keratoconus corneas to drive the underlying pathology, ectasia. Research in the field has focused on discovering differentially expressed genes and proteins and quantifying their levels and activities in keratoconus patient samples. In this study, both microarray analysis of total ribonucleic acid (RNA and whole proteome analyses are carried out using corneal epithelium and tears from keratoconus patients and compared to healthy controls. A number of structural proteins, signaling molecules, cytokines, proteases, and enzymes have been found to be deregulated in keratoconus corneas. Together, the data provide clues to the complex process of corneal degradation which suggest novel ways to clinically diagnose and manage the disease. This review will focus on discussing these recent advances in the knowledge of keratoconus biology from a gene expression and function point-of-view.

  11. 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.

  12. Analysis of gene expression in rabbit muscle

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    Alena Gálová

    2014-02-01

    Full Text Available Increasing consumer knowledge of the link between diet and health has raised the demand for high quality food. Meat and meat products may be considered as irreplaceable in human nutrition. Breeding livestock to higher content of lean meat and the use of modern hybrids entails problems with the quality of meat. Analysing of livestock genomes could get us a great deal of important information, which may significantly affect the improvement process. Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS, which utilizes high-density single-nucleotide polymorphism (SNP, provides a new way to tackle this issue. New technologies now allow producing microarrays containing thousands of hybridization probes on a single membrane or other solid support. We used microarray analysis to study gene expression in rabbit muscle during different developmental age stages. The outputs from GeneSpring GX sotware are presented in this work. After the evaluation of gene expression in rabbits, will be selected genes of interest in relation to meat quality parameters and will be further analyzed by the available methods of molecular biology and genetics.

  13. Moving Toward Integrating Gene Expression Profiling into ...

    Science.gov (United States)

    Microarray profiling of chemical-induced effects is being increasingly used in medium and high-throughput formats. In this study, we describe computational methods to identify molecular targets from whole-genome microarray data using as an example the estrogen receptor α (ERα), often modulated by potential endocrine disrupting chemicals. ERα biomarker genes were identified by their consistent expression after exposure to 7 structurally-diverse ERα agonists and 3 ERα antagonists in ERα-positive MCF-7 cells. Most of the biomarker genes were shown to be directly regulated by ERα as determined by ESR1 gene knockdown using siRNA as well as through ChIP-Seq analysis of ERα-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm by comparison to annotated gene expression data sets from experiments using MCF-7 cells, including those evaluating the transcriptional effects of hormones and chemicals. Using 141 comparisons from chemical- and hormone-treated cells, the biomarker gave a balanced accuracy for prediction of ERα activation or suppression of 94% and 93%, respectively. The biomarker was able to correctly classify 18 out of 21 (86%) ER reference chemicals including “very weak” agonists. Importantly, the biomarker predictions accurately replicated predictions based on 18 in vitro high-throughput screening assays that queried different steps in ERα signaling. For 114 chemicals,

  14. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

    DEFF Research Database (Denmark)

    Hustinx, Steven R; Cao, Dengfeng; Maitra, Anirban

    2004-01-01

    generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags....... Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify...

  15. 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.

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

    Science.gov (United States)

    Zhang, Meixian; Zhao, Xiaoyuan; Cheng, Hong; Wang, Liang; Xi, Bo; Shen, Yue; Hou, Dongqing; Mi, Jie

    2014-01-01

    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. 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. 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 (Pobesity (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. 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.

  17. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  18. Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

    2014-05-01

    Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  19. Gene Expression Profiling of Xeroderma Pigmentosum

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    Bowden Nikola A

    2006-05-01

    Full Text Available Abstract Xeroderma pigmentosum (XP is a rare recessive disorder that is characterized by extreme sensitivity to UV light. UV light exposure results in the formation of DNA damage such as cyclobutane dimers and (6-4 photoproducts. Nucleotide excision repair (NER orchestrates the removal of cyclobutane dimers and (6-4 photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups (XP-A to XP-G, which represent functional deficiencies in seven different genes, all of which are believed to be involved in NER. The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups. The relationship between NER and other types of DNA repair processes is now becoming evident but the exact relationships between the different complementation groups remains to be precisely determined. Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E and the severest form (XP-A of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G and without (XP-C, XP-E and XP-F were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.

  20. Cholinergic regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Kristensen, Bo; Georg, Birgitte; Fahrenkrug, Jan

    1997-01-01

    Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing......Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing...

  1. Gene expression in developing watermelon fruit

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    Hernandez Alvaro

    2008-06-01

    Full Text Available Abstract Background Cultivated watermelon form large fruits that are highly variable in size, shape, color, and content, yet have extremely narrow genetic diversity. Whereas a plethora of genes involved in cell wall metabolism, ethylene biosynthesis, fruit softening, and secondary metabolism during fruit development and ripening have been identified in other plant species, little is known of the genes involved in these processes in watermelon. A microarray and quantitative Real-Time PCR-based study was conducted in watermelon [Citrullus lanatus (Thunb. Matsum. & Nakai var. lanatus] in order to elucidate the flow of events associated with fruit development and ripening in this species. RNA from three different maturation stages of watermelon fruits, as well as leaf, were collected from field grown plants during three consecutive years, and analyzed for gene expression using high-density photolithography microarrays and quantitative PCR. Results High-density photolithography arrays, composed of probes of 832 EST-unigenes from a subtracted, fruit development, cDNA library of watermelon were utilized to examine gene expression at three distinct time-points in watermelon fruit development. Analysis was performed with field-grown fruits over three consecutive growing seasons. Microarray analysis identified three hundred and thirty-five unique ESTs that are differentially regulated by at least two-fold in watermelon fruits during the early, ripening, or mature stage when compared to leaf. Of the 335 ESTs identified, 211 share significant homology with known gene products and 96 had no significant matches with any database accession. Of the modulated watermelon ESTs related to annotated genes, a significant number were found to be associated with or involved in the vascular system, carotenoid biosynthesis, transcriptional regulation, pathogen and stress response, and ethylene biosynthesis. Ethylene bioassays, performed with a closely related watermelon

  2. Gene expression in first trimester preeclampsia placenta.

    Science.gov (United States)

    Founds, Sandra A; Terhorst, Lauren A; Conrad, Kirk P; Hogge, W Allen; Jeyabalan, Arun; Conley, Yvette P

    2011-04-01

    The goal of this study was to further validate eight candidate genes identified in a microarray analysis of first trimester placentas in preeclampsia. Surplus chorionic villus sampling (CVS) specimens of 4 women subsequently diagnosed with preeclampsia (PE) and 8 control women (C) without preeclampsia analyzed previously by microarray and 24 independent additional control samples (AS) were submitted for confirmatory studies by quantitative real-time polymerase chain reaction (qRT-PCR). Downregulation was significant in FSTL3 in PE as compared to C and AS (p = .04). PAEP was downregulated, but the difference was only significant between C and AS (p = .002) rather than between PE and either of the control groups. Expression levels for CFH, EPAS1, IGFBP1, MMP12, and SEMA3C were not statistically different among groups, but trends were consistent with microarray results; there was no anti-correlation. S100A8 was not measurable in all samples, probably because different probes and primers were needed. This study corroborates reduced FSTL3 expression in the first trimester of preeclampsia. Nonsignificant trends in the other genes may require follow-up in studies powered for medium or medium/large effect sizes. qRT-PCR verification of the prior microarray of CVS may support the placental origins of preeclampsia hypothesis. Replication is needed for the candidate genes as potential biomarkers of susceptibility, early detection, and/or individualized care of maternal-infant preeclampsia.

  3. Nuclear AXIN2 represses MYC gene expression

    International Nuclear Information System (INIS)

    Rennoll, Sherri A.; Konsavage, Wesley M.; Yochum, Gregory S.

    2014-01-01

    Highlights: •AXIN2 localizes to cytoplasmic and nuclear compartments in colorectal cancer cells. •Nuclear AXIN2 represses the activity of Wnt-responsive luciferase reporters. •β-Catenin bridges AXIN2 to TCF transcription factors. •AXIN2 binds the MYC promoter and represses MYC gene expression. -- Abstract: The β-catenin transcriptional coactivator is the key mediator of the canonical Wnt signaling pathway. In the absence of Wnt, β-catenin associates with a cytosolic and multi-protein destruction complex where it is phosphorylated and targeted for proteasomal degradation. In the presence of Wnt, the destruction complex is inactivated and β-catenin translocates into the nucleus. In the nucleus, β-catenin binds T-cell factor (TCF) transcription factors to activate expression of c-MYC (MYC) and Axis inhibition protein 2 (AXIN2). AXIN2 is a member of the destruction complex and, thus, serves in a negative feedback loop to control Wnt/β-catenin signaling. AXIN2 is also present in the nucleus, but its function within this compartment is unknown. Here, we demonstrate that AXIN2 localizes to the nuclei of epithelial cells within normal and colonic tumor tissues as well as colorectal cancer cell lines. In the nucleus, AXIN2 represses expression of Wnt/β-catenin-responsive luciferase reporters and forms a complex with β-catenin and TCF. We demonstrate that AXIN2 co-occupies β-catenin/TCF complexes at the MYC promoter region. When constitutively localized to the nucleus, AXIN2 alters the chromatin structure at the MYC promoter and directly represses MYC gene expression. These findings suggest that nuclear AXIN2 functions as a rheostat to control MYC expression in response to Wnt/β-catenin signaling

  4. Nuclear AXIN2 represses MYC gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Rennoll, Sherri A.; Konsavage, Wesley M.; Yochum, Gregory S., E-mail: gsy3@psu.edu

    2014-01-03

    Highlights: •AXIN2 localizes to cytoplasmic and nuclear compartments in colorectal cancer cells. •Nuclear AXIN2 represses the activity of Wnt-responsive luciferase reporters. •β-Catenin bridges AXIN2 to TCF transcription factors. •AXIN2 binds the MYC promoter and represses MYC gene expression. -- Abstract: The β-catenin transcriptional coactivator is the key mediator of the canonical Wnt signaling pathway. In the absence of Wnt, β-catenin associates with a cytosolic and multi-protein destruction complex where it is phosphorylated and targeted for proteasomal degradation. In the presence of Wnt, the destruction complex is inactivated and β-catenin translocates into the nucleus. In the nucleus, β-catenin binds T-cell factor (TCF) transcription factors to activate expression of c-MYC (MYC) and Axis inhibition protein 2 (AXIN2). AXIN2 is a member of the destruction complex and, thus, serves in a negative feedback loop to control Wnt/β-catenin signaling. AXIN2 is also present in the nucleus, but its function within this compartment is unknown. Here, we demonstrate that AXIN2 localizes to the nuclei of epithelial cells within normal and colonic tumor tissues as well as colorectal cancer cell lines. In the nucleus, AXIN2 represses expression of Wnt/β-catenin-responsive luciferase reporters and forms a complex with β-catenin and TCF. We demonstrate that AXIN2 co-occupies β-catenin/TCF complexes at the MYC promoter region. When constitutively localized to the nucleus, AXIN2 alters the chromatin structure at the MYC promoter and directly represses MYC gene expression. These findings suggest that nuclear AXIN2 functions as a rheostat to control MYC expression in response to Wnt/β-catenin signaling.

  5. Molecular mechanisms of curcumin action: gene expression.

    Science.gov (United States)

    Shishodia, Shishir

    2013-01-01

    Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  6. Studying the Complex Expression Dependences between Sets of Coexpressed Genes

    Directory of Open Access Journals (Sweden)

    Mario Huerta

    2014-01-01

    Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

  7. Changes in gene expression following androgen receptor blockade ...

    Indian Academy of Sciences (India)

    Madhu urs

    Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well- documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate, it is not clear whether all the gene expression changes ...

  8. Asthenoteratozoospermia in mice lacking testis expressed gene 18 (Tex18)

    NARCIS (Netherlands)

    Jaroszynski, L.; dev, A.; Li, M.; Meinhardt, A.; de rooij, D. G.; Mueller, Christian; Böhm, Detlef; Wolf, S.; Adham, I. M.; Wulf, G.; Engel, W.; Nayernia, K.

    2007-01-01

    Testis expressed gene 18 (Tex18) is a small gene with one exon of 240 bp, which is specifically expressed in male germ cells. The gene encodes for a protein of 80 amino acids with unknown domain. To investigate the function of (Tex18) gene, we generated mice with targeted disruption of the (Tex18)

  9. Effects of Emdogain on osteoblast gene expression.

    Science.gov (United States)

    Carinci, F; Piattelli, A; Guida, L; Perrotti, V; Laino, G; Oliva, A; Annunziata, M; Palmieri, A; Pezzetti, F

    2006-05-01

    Emdogain (EMD) is a protein extract purified from porcine enamel and has been introduced in clinical practice to obtain periodontal regeneration. EMD is composed mainly of amelogenins (90%), while the remaining 10% is composed of non-amelogenin enamel matrix proteins such as enamelins, tuftelin, amelin and ameloblastin. Enamel matrix proteins seem to be involved in root formation. EMD has been reported to promote proliferation, migration, adhesion and differentiation of cells associated with healing periodontal tissues in vivo. How this protein acts on osteoblasts is poorly understood. We therefore attempted to address this question by using a microarray technique to identify genes that are differently regulated in osteoblasts exposed to enamel matrix proteins. By using DNA microarrays containing 20,000 genes, we identified several upregulated and downregulated genes in the osteoblast-like cell line (MG-63) cultured with enamel matrix proteins (Emd). The differentially expressed genes cover a broad range of functional activities: (i) signaling transduction, (ii) transcription, (iii) translation, (iv) cell cycle regulation, proliferation and apoptosis, (v) immune system, (vi) vesicular transport and lysosome activity, and (vii) cytoskeleton, cell adhesion and extracellular matrix production. The data reported are the first genome-wide scan of the effect of enamel matrix proteins on osteoblast-like cells. These results can contribute to our understanding of the molecular mechanisms of bone regeneration and as a model for comparing other materials with similar clinical effects.

  10. The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

    Directory of Open Access Journals (Sweden)

    Jean-François Gout

    2010-05-01

    Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

  11. Body mass index, but not FTO genotype or major depressive disorder, influences brain structure.

    Science.gov (United States)

    Cole, J H; Boyle, C P; Simmons, A; Cohen-Woods, S; Rivera, M; McGuffin, P; Thompson, P M; Fu, C H Y

    2013-11-12

    Obesity and major depressive disorder (MDD) are highly prevalent and often comorbid health conditions. Both are associated with differences in brain structure and are genetically influenced. Yet, little is known about how obesity, MDD, and known risk genotypes might interact in the brain. Subjects were 81 patients with MDD (mean age 48.6 years) and 69 matched healthy controls (mean age 51.2 years). Subjects underwent 1.5T magnetic resonance imaging, genotyping for the fat mass and obesity associated (FTO) gene rs3751812 polymorphism, and measurements for body mass index (BMI). We conducted a whole brain voxelwise analysis using tensor-based morphometry (TBM) to examine the main and interaction effects of diagnosis, BMI and FTO genotype. Significant effects of BMI were observed across widespread brain regions, indicating reductions in predominantly subcortical and white matter areas associated with increased BMI, but there was no influence of MDD or FTO rs3751812 genotype. There were no significant interaction effects. Within MDD patients, there was no effect of current depressive symptoms; however the use of antidepressant medication was associated with reductions in brain volume in the frontal lobe and cerebellum. Obesity affects brain structure in both healthy participants and MDD patients; this influence may account for some of the brain changes previously associated with MDD. BMI and the use of medication should ideally be measured and controlled for when conducting structural brain imaging research in MDD. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.

    Science.gov (United States)

    Tan, Jonathan T; Dorajoo, Rajkumar; Seielstad, Mark; Sim, Xue Ling; Ong, Rick Twee-Hee; Chia, Kee Seng; Wong, Tien Yin; Saw, Seang Mei; Chew, Suok Kai; Aung, Tin; Tai, E-Shyong

    2008-10-01

    Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations. We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES). All nine SNPs exhibited strong linkage disequilibrium (r(2) = 0.6-0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m(2) (P Chinese, 0.65 to 0.91 kg/m(2) (P Malays, and 0.52 to 0.64 kg/m(2) (P Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17-1.22; P Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.

  14. Gene expression profiling of cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2007-02-01

    Full Text Available Abstract Background Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. Study Design This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days. 17.5K cDNA microarrays were utilized to profile the biopsy material. Results Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies and repair and angiogenesis genes in the later (4 to 8 days biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. Conclusion The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2

  15. Network Completion for Static Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Natsu Nakajima

    2014-01-01

    Full Text Available We tackle the problem of completing and inferring genetic networks under stationary conditions from static data, where network completion is to make the minimum amount of modifications to an initial network so that the completed network is most consistent with the expression data in which addition of edges and deletion of edges are basic modification operations. For this problem, we present a new method for network completion using dynamic programming and least-squares fitting. This method can find an optimal solution in polynomial time if the maximum indegree of the network is bounded by a constant. We evaluate the effectiveness of our method through computational experiments using synthetic data. Furthermore, we demonstrate that our proposed method can distinguish the differences between two types of genetic networks under stationary conditions from lung cancer and normal gene expression data.

  16. Inferring gene expression dynamics via functional regression analysis

    Directory of Open Access Journals (Sweden)

    Leng Xiaoyan

    2008-01-01

    Full Text Available Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

  17. Expression regulation of design process gene in product design

    DEFF Research Database (Denmark)

    Li, Bo; Fang, Lusheng; Li, Bo

    2011-01-01

    is proposed and analyzed, as well as its three categories i.e., the operator gene, the structural gene and the regulator gene. Second, the trigger mechanism that design objectives and constraints trigger the operator gene is constructed. Third, the expression principle of structural gene is analyzed...... with the example of design management gene. Last, the regulation mode that the regulator gene regulates the expression of the structural gene is established and it is illustrated by taking the design process management gene as an example. © (2011) Trans Tech Publications....

  18. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

  19. Prognostic Gene Expression Profiles in Breast Cancer

    DEFF Research Database (Denmark)

    Sørensen, Kristina Pilekær

    Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group and offe......Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group...... clinical courses, and they may be useful as novel prognostic biomarkers in breast cancer. The aim of the present project was to predict the development of metastasis in lymph node negative breast cancer patients by RNA profiling. We collected and analyzed 82 primary breast tumors from patients who...... developed metastasis and 82 primary breast tumors from patients who remained metastasis-free, by microarray gene expression profiling. We employed a nested case-control design, where samples were matched, in this study one-to-one, to exclude differences in gene expression based on tumor type, tumor size...

  20. The Effects of Hallucinogens on Gene Expression.

    Science.gov (United States)

    Martin, David A; Nichols, Charles D

    2018-01-01

    The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.

  1. Interactive visualization of gene regulatory networks with associated gene expression time series data

    NARCIS (Netherlands)

    Westenberg, Michel A.; Hijum, Sacha A.F.T. van; Lulko, Andrzej T.; Kuipers, Oscar P.; Roerdink, Jos B.T.M.; Linsen, L; Hagen, H; Hamann, B

    2008-01-01

    We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

  2. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  3. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  4. FlyTED: the Drosophila Testis Gene Expression Database

    OpenAIRE

    Zhao, Jun; Klyne, Graham; Benson, Elizabeth; Gudmannsdottir, Elin; White-Cooper, Helen; Shotton, David

    2009-01-01

    FlyTED, the Drosophila Testis Gene Expression Database, is a biological research database for gene expression images from the testis of the fruit fly Drosophila melanogaster. It currently contains 2762 mRNA in situ hybridization images and ancillary metadata revealing the patterns of gene expression of 817 Drosophila genes in testes of wild type flies and of seven meiotic arrest mutant strains in which spermatogenesis is defective. This database has been built by adapting a widely used digita...

  5. Sequence biases in large scale gene expression profiling data

    OpenAIRE

    Siddiqui, Asim S.; Delaney, Allen D.; Schnerch, Angelique; Griffith, Obi L.; Jones, Steven J. M.; Marra, Marco A.

    2006-01-01

    We present the results of a simple, statistical assay that measures the G+C content sensitivity bias of gene expression experiments without the requirement of a duplicate experiment. We analyse five gene expression profiling methods: Affymetrix GeneChip, Long Serial Analysis of Gene Expression (LongSAGE), LongSAGELite, ‘Classic’ Massively Parallel Signature Sequencing (MPSS) and ‘Signature’ MPSS. We demonstrate the methods have systematic and random errors leading to a different G+C content s...

  6. Analysis of multiplex gene expression maps obtained by voxelation

    Directory of Open Access Journals (Sweden)

    Smith Desmond J

    2009-04-01

    Full Text Available Abstract Background Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. Results To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in

  7. Effect of gene order in DNA constructs on gene expression upon integration into plant genome.

    Science.gov (United States)

    Aydın Akbudak, M; Srivastava, Vibha

    2017-06-01

    Several plant biotechnology applications are based on the expression of multiple genes located on a single transformation vector. The principles of stable expression of foreign genes in plant cells include integration of full-length gene fragments consisting of promoter and transcription terminator sequences, and avoiding converging orientation of the gene transcriptional direction. Therefore, investigators usually generate constructs in which genes are assembled in the same orientation. However, no specific information is available on the effect of the order in which genes should be assembled in the construct to support optimum expression of each gene upon integration in the genome. While many factors, including genomic position and the integration structure, could affect gene expression, the investigators judiciously design DNA constructs to avoid glitches. However, the gene order in a multigene assembly remains an open question. This study addressed the effect of gene order in the DNA construct on gene expression in rice using a simple design of two genes placed in two possible orders with respect to the genomic context. Transgenic rice lines containing green fluorescent protein (GFP) and β-glucuronidase (GUS) genes in two distinct orders were developed by Cre-lox-mediated site-specific integration. Gene expression analysis of transgenic lines showed that both genes were expressed at similar levels in either orientation, and different transgenic lines expressed each gene within 1-2× range. Thus, no significant effect of the gene order on gene expression was found in the transformed rice lines containing precise site-specific integrations and stable gene expression in plant cells could be obtained with altered gene orders. Therefore, gene orientation and integration structures are more important factors governing gene expression than gene orders in the genomic context.

  8. Classification across gene expression microarray studies

    Directory of Open Access Journals (Sweden)

    Kuner Ruprecht

    2009-12-01

    Full Text Available Abstract Background The increasing number of gene expression microarray studies represents an important resource in biomedical research. As a result, gene expression based diagnosis has entered clinical practice for patient stratification in breast cancer. However, the integration and combined analysis of microarray studies remains still a challenge. We assessed the potential benefit of data integration on the classification accuracy and systematically evaluated the generalization performance of selected methods on four breast cancer studies comprising almost 1000 independent samples. To this end, we introduced an evaluation framework which aims to establish good statistical practice and a graphical way to monitor differences. The classification goal was to correctly predict estrogen receptor status (negative/positive and histological grade (low/high of each tumor sample in an independent study which was not used for the training. For the classification we chose support vector machines (SVM, predictive analysis of microarrays (PAM, random forest (RF and k-top scoring pairs (kTSP. Guided by considerations relevant for classification across studies we developed a generalization of kTSP which we evaluated in addition. Our derived version (DV aims to improve the robustness of the intrinsic invariance of kTSP with respect to technologies and preprocessing. Results For each individual study the generalization error was benchmarked via complete cross-validation and was found to be similar for all classification methods. The misclassification rates were substantially higher in classification across studies, when each single study was used as an independent test set while all remaining studies were combined for the training of the classifier. However, with increasing number of independent microarray studies used in the training, the overall classification performance improved. DV performed better than the average and showed slightly less variance. In

  9. R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.

    Science.gov (United States)

    Su, Rui; Dong, Lei; Li, Chenying; Nachtergaele, Sigrid; Wunderlich, Mark; Qing, Ying; Deng, Xiaolan; Wang, Yungui; Weng, Xiaocheng; Hu, Chao; Yu, Mengxia; Skibbe, Jennifer; Dai, Qing; Zou, Dongling; Wu, Tong; Yu, Kangkang; Weng, Hengyou; Huang, Huilin; Ferchen, Kyle; Qin, Xi; Zhang, Bin; Qi, Jun; Sasaki, Atsuo T; Plas, David R; Bradner, James E; Wei, Minjie; Marcucci, Guido; Jiang, Xi; Mulloy, James C; Jin, Jie; He, Chuan; Chen, Jianjun

    2018-01-11

    R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N 6 -methyladenosine (m 6 A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways. Ectopically expressed mutant IDH1 and S-2HG recapitulate the effects of R-2HG. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. Collectively, while R-2HG accumulated in IDH1/2 mutant cancers contributes to cancer initiation, our work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m 6 A/MYC/CEBPA signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Codon usage and amino acid usage influence genes expression level.

    Science.gov (United States)

    Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

    2018-02-01

    Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

  11. Comparative Analysis of Predicted Gene Expression among Crenarchaeal Genomes

    Directory of Open Access Journals (Sweden)

    Shibsankar Das

    2017-03-01

    Full Text Available Research into new methods for identifying highly expressed genes in anonymous genome sequences has been going on for more than 15 years. We presented here an alternative approach based on modified score of relative codon usage bias to identify highly expressed genes in crenarchaeal genomes. The proposed algorithm relies exclusively on sequence features for identifying the highly expressed genes. In this study, a comparative analysis of predicted highly expressed genes in five crenarchaeal genomes was performed using the score of Modified Relative Codon Bias Strength (MRCBS as a numerical estimator of gene expression level. We found a systematic strong correlation between Codon Adaptation Index and MRCBS. Additionally, MRCBS correlated well with other expression measures. Our study indicates that MRCBS can consistently capture the highly expressed genes.

  12. Genome polymorphism markers and stress genes expression for ...

    African Journals Online (AJOL)

    SAM

    2014-06-11

    Jun 11, 2014 ... peroxide (H2O2) and molecular oxygen in the cell (Luna et al., 2008). In this study, we investigated the levels of expression of two genes in eight turf species. The levels of expression of PAL and SOD genes varied with the type of turf. Based on the differences in band intensity as a measure of gene.

  13. Understanding gene expression in coronary artery disease through ...

    Indian Academy of Sciences (India)

    The most significant differentially expressed genes from microarray were independently validated by real time PCR in 97 cases and 97 controls. A total of 190 gene transcripts showed significant differential expression (fold change > 2, P < 0.05) between the cases and the controls of which 142 genes were upregulated and ...

  14. Gene expressions changes in bronchial epithelial cells

    DEFF Research Database (Denmark)

    Remy, S.; Verstraelen, S.; Van Den Heuvel, R.

    2014-01-01

    For the classification of respiratory sensitizing chemicals, no validated in vivo nor in vitro tests are currently available. In this study, we evaluated whether respiratory sensitizers trigger specific signals in human bronchial epithelial (BEAS-2B) cells at the level of the transcriptome...... oligonucleotide arrays. A limited number of 11 transcripts could be identified as potential biomarkers to identify respiratory sensitizers. Three of these transcripts are associated to immune system processes (HSPA5, UPP1, and SEPRINEI). In addition, the transcriptome was screened for transcripts....... The cells were exposed during 6, 10, and 24 h to 4 respiratory sensitizers and 6 non-respiratory sensitizers (3 skin sensitizers and 3 respiratory irritants) at a concentration inducing 20% cell viability loss after 24 h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4 x 44 K...

  15. Genetic Variants Contribute to Gene Expression Variability in Humans

    Science.gov (United States)

    Hulse, Amanda M.; Cai, James J.

    2013-01-01

    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

  16. Effect of Obesity-Linked FTO rs9939609 Variant on Physical Activity and Dietary Patterns in Physically Active Men and Women

    Directory of Open Access Journals (Sweden)

    Nathan R. West

    2018-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in the fat mass and obesity-associated (FTO locus are associated with obesity, but lifestyle factors may modulate the obesity risk related to FTO. This study examined the physical activity and dietary patterns of 528 physically active white men and women (mean (SD: 34.9 (9.5 years, 26.6 (4.3 kg·m−2 carrying different risk variants of FTO SNP rs9939609. Sex, age, and anthropometric measurements (stature, body mass, and waist circumference were self-reported using an online questionnaire, and body mass index and waist-to-height ratio were calculated. Physical activity and eating behaviour were assessed using the International Physical Activity Questionnaire (IPAQ and Three-Factor Eating Questionnaire (TFEQ, respectively. Body mass, body mass index (BMI, waist circumference, and waist-to-height ratio were not significantly different between individuals expressing different FTO rs9939609 risk variants (all P≥0.66. The cohort was physically active (4516 (3043 total MET min·week−1, although homozygous risk allele carriers (AA displayed higher TFEQ cognitive restraint compared with nonrisk allele carriers (TT (ES = 0.33 and P=0.03. In conclusion, obesity-related parameters were not different in physically active individuals expressing different risk variants of FTO rs9939609, although homozygous risk allele carriers exhibited higher cognitive restraint.

  17. Dissecting specific and global transcriptional regulation of bacterial gene expression

    NARCIS (Netherlands)

    Gerosa, Luca; Kochanowski, Karl; Heinemann, Matthias; Sauer, Uwe

    Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional-but often neglected-layer of complexity in gene expression. Here, we develop an

  18. Cloning and expression analysis of an anthocyanidin synthase gene ...

    Indian Academy of Sciences (India)

    Expression of ANS in leaves, embryo and seed coat was analysed, which provided a ... taneously amplify the 666-bp fragment of actin gene. The. ANS gene expression in leaves, 15 days after pollination ... ANS expression with shading treatment was evaluated by semiquantitive RT-PCR using B. carinata variety 3H008-6.

  19. Monoallelic expression of the human FOXP2 speech gene.

    Science.gov (United States)

    Adegbola, Abidemi A; Cox, Gerald F; Bradshaw, Elizabeth M; Hafler, David A; Gimelbrant, Alexander; Chess, Andrew

    2015-06-02

    The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations.

  20. Using RNA-Seq data to select refence genes for normalizing gene expression in apple roots

    Science.gov (United States)

    Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for t...

  1. CDX2 gene expression in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

    2014-01-01

    CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  2. Some statistical properties of gene expression clustering for array data

    DEFF Research Database (Denmark)

    Abreu, G C G; Pinheiro, A; Drummond, R D

    2010-01-01

    DNA arrays have been a rich source of data for the study of genomic expression of a wide variety of biological systems. Gene clustering is one of the paradigms quite used to assess the significance of a gene (or group of genes). However, most of the gene clustering techniques are applied to cDNA...

  3. Automated discovery of functional generality of human gene expression programs.

    Directory of Open Access Journals (Sweden)

    Georg K Gerber

    2007-08-01

    Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

  4. Gene expression profiling of breast tumours from New Zealand patients.

    Science.gov (United States)

    Muthukaruppan, Anita; Lasham, Annette; Blenkiron, Cherie; Woad, Kathryn J; Black, Michael A; Knowlton, Nicholas; McCarthy, Nicole; Findlay, Michael P; Print, Cristin G; Shelling, Andrew N

    2017-10-27

    New Zealand has one of the highest rates of breast cancer incidence in the world. We investigated the gene expression profiles of breast tumours from New Zealand patients, compared them to gene expression profiles of international breast cancer cohorts and identified any associations between altered gene expression and the clinicopathological features of the tumours. Affymetrix microarrays were used to measure the gene expression profiles of 106 breast tumours from New Zealand patients. Gene expression data from six international breast cancer cohorts were collated, and all the gene expression data were analysed using standard bioinformatic and statistical tools. Gene expression profiles associated with tumour ER and ERBB2 status, molecular subtype and selected gene expression signatures within the New Zealand cohort were consistent with those found in international cohorts. Significant differences in clinicopathological features such as tumour grade, tumour size and lymph node status were also observed between the New Zealand and international cohorts. Gene expression profiles, which are a sensitive indicator of tumour biology, showed no clear difference between breast tumours from New Zealand patients and those from non-New Zealand patients. This suggests that other factors may contribute to the high and increasing breast cancer incidence in New Zealand compared to international populations.

  5. The Effect of Statins on Blood Gene Expression in COPD.

    Directory of Open Access Journals (Sweden)

    Ma'en Obeidat

    Full Text Available COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS was used to process the expression data. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma package adjusting for propensity score and surrogate variables. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser.25 genes were differentially expressed between statin users and non-users at an FDR of 10%, including LDLR, CXCR2, SC4MOL, FAM108A1, IFI35, FRYL, ABCG1, MYLIP, and DHCR24. The 25 genes were significantly enriched in cholesterol homeostasis and metabolism pathways. The resulting gene signature showed correlation with Huntington's disease, Parkinson's disease and acute myeloid leukemia gene signatures.The blood gene signature of statins' use in COPD patients was enriched in cholesterol homeostasis pathways. Further studies are needed to delineate the role of these pathways in lung biology.

  6. 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 ob...... obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men.......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...

  7. Heterologous gene expression in filamentous fungi.

    Science.gov (United States)

    Su, Xiaoyun; Schmitz, George; Zhang, Meiling; Mackie, Roderick I; Cann, Isaac K O

    2012-01-01

    Filamentous fungi are critical to production of many commercial enzymes and organic compounds. Fungal-based systems have several advantages over bacterial-based systems for protein production because high-level secretion of enzymes is a common trait of their decomposer lifestyle. Furthermore, in the large-scale production of recombinant proteins of eukaryotic origin, the filamentous fungi become the vehicle of choice due to critical processes shared in gene expression with other eukaryotic organisms. The complexity and relative dearth of understanding of the physiology of filamentous fungi, compared to bacteria, have hindered rapid development of these organisms as highly efficient factories for the production of heterologous proteins. In this review, we highlight several of the known benefits and challenges in using filamentous fungi (particularly Aspergillus spp., Trichoderma reesei, and Neurospora crassa) for the production of proteins, especially heterologous, nonfungal enzymes. We review various techniques commonly employed in recombinant protein production in the filamentous fungi, including transformation methods, selection of gene regulatory elements such as promoters, protein secretion factors such as the signal peptide, and optimization of coding sequence. We provide insights into current models of host genomic defenses such as repeat-induced point mutation and quelling. Furthermore, we examine the regulatory effects of transcript sequences, including introns and untranslated regions, pre-mRNA (messenger RNA) processing, transcript transport, and mRNA stability. We anticipate that this review will become a resource for researchers who aim at advancing the use of these fascinating organisms as protein production factories, for both academic and industrial purposes, and also for scientists with general interest in the biology of the filamentous fungi. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. FARO server: Meta-analysis of gene expression by matching gene expression signatures to a compendium of public gene expression data

    DEFF Research Database (Denmark)

    Manijak, Mieszko P.; Nielsen, Henrik Bjørn

    2011-01-01

    circumvented by instead matching gene expression signatures to signatures of other experiments. FINDINGS: To facilitate this we present the Functional Association Response by Overlap (FARO) server, that match input signatures to a compendium of 242 gene expression signatures, extracted from more than 1700...... Arabidopsis microarray experiments. CONCLUSIONS: Hereby we present a publicly available tool for robust characterization of Arabidopsis gene expression experiments which can point to similar experimental factors in other experiments. The server is available at http://www.cbs.dtu.dk/services/faro/....

  9. Rhythmic diel pattern of gene expression in juvenile maize leaf.

    Directory of Open Access Journals (Sweden)

    Maciej Jończyk

    Full Text Available BACKGROUND: Numerous biochemical and physiological parameters of living organisms follow a circadian rhythm. Although such rhythmic behavior is particularly pronounced in plants, which are strictly dependent on the daily photoperiod, data on the molecular aspects of the diurnal cycle in plants is scarce and mostly concerns the model species Arabidopsis thaliana. Here we studied the leaf transcriptome in seedlings of maize, an important C4 crop only distantly related to A. thaliana, throughout a cycle of 10 h darkness and 14 h light to look for rhythmic patterns of gene expression. RESULTS: Using DNA microarrays comprising ca. 43,000 maize-specific probes we found that ca. 12% of all genes showed clear-cut diel rhythms of expression. Cluster analysis identified 35 groups containing from four to ca. 1,000 genes, each comprising genes of similar expression patterns. Perhaps unexpectedly, the most pronounced and most common (concerning the highest number of genes expression maxima were observed towards and during the dark phase. Using Gene Ontology classification several meaningful functional associations were found among genes showing similar diel expression patterns, including massive induction of expression of genes related to gene expression, translation, protein modification and folding at dusk and night. Additionally, we found a clear-cut tendency among genes belonging to individual clusters to share defined transcription factor-binding sequences. CONCLUSIONS: Co-expressed genes belonging to individual clusters are likely to be regulated by common mechanisms. The nocturnal phase of the diurnal cycle involves gross induction of fundamental biochemical processes and should be studied more thoroughly than was appreciated in most earlier physiological studies. Although some general mechanisms responsible for the diel regulation of gene expression might be shared among plants, details of the diurnal regulation of gene expression seem to differ

  10. Growth hormone receptor gene expression in puberty.

    Science.gov (United States)

    Pagani, S; Meazza, C; Gertosio, C; Bozzola, E; Bozzola, M

    2015-07-01

    The mechanisms regulating the synergic effect of growth hormone and other hormones during pubertal spurt are not completely clarified. We enrolled 64 females of Caucasian origin and normal height including 22 prepubertal girls, 26 pubertal girls, and 16 adults to evaluate the role of Growth Hormone/Insulin-like growth factor-I axis (GH/IGF-I) during the pubertal period. In these subjects both serum IGF-I and growth hormone binding protein levels, as well as quantitative growth hormone receptor (GHR) gene expression were evaluated in peripheral lymphocytes of all individuals by real-time PCR. Our results showed significantly lower IGF-I levels in women (148±10 ng/ml) and prepubertal girls (166.34±18.85 ng/ml) compared to pubertal girls (441.95±29.42 ng/ml; p<0.0001). Serum GHBP levels were significantly higher in prepubertal (127.02±20.76 ng/ml) compared to pubertal girls (16.63±2.97 ng/ml; p=0.0001) and adult women (19.95±6.65 ng/ml; p=0.0003). We also found higher GHR gene expression levels in pubertal girls [174.73±80.22 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)] compared with other groups of subjects [women: 42.52±7.66 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase); prepubertal girls: 58.45±0.18.12 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)], but the difference did not reach statistical significance. These results suggest that sexual hormones could positively influence GHR action, during the pubertal period, in a dual mode, that is, increasing GHR mRNA production and reducing GHR cleavage leading to GHBP variations. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Global gene expression analysis for evaluation and design of biomaterials

    Directory of Open Access Journals (Sweden)

    Nobutaka Hanagata, Taro Takemura and Takashi Minowa

    2010-01-01

    Full Text Available Comprehensive gene expression analysis using DNA microarrays has become a widespread technique in molecular biological research. In the biomaterials field, it is used to evaluate the biocompatibility or cellular toxicity of metals, polymers and ceramics. Studies in this field have extracted differentially expressed genes in the context of differences in cellular responses among multiple materials. Based on these genes, the effects of materials on cells at the molecular level have been examined. Expression data ranging from several to tens of thousands of genes can be obtained from DNA microarrays. For this reason, several tens or hundreds of differentially expressed genes are often present in different materials. In this review, we outline the principles of DNA microarrays, and provide an introduction to methods of extracting information which is useful for evaluating and designing biomaterials from comprehensive gene expression data.

  12. Genetic architecture of gene expression in ovine skeletal muscle

    DEFF Research Database (Denmark)

    Kogelman, Lisette Johanna Antonia; Byrne, Keren; Vuocolo, Tony

    2011-01-01

    weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing...... has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny......-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle.Results: The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing...

  13. Gene and enhancer trap tagging of vascular-expressed genes in poplar trees

    Science.gov (United States)

    Andrew Groover; Joseph R. Fontana; Gayle Dupper; Caiping Ma; Robert Martienssen; Steven Strauss; Richard Meilan

    2004-01-01

    We report a gene discovery system for poplar trees based on gene and enhancer traps. Gene and enhancer trap vectors carrying the β-glucuronidase (GUS) reporter gene were inserted into the poplar genome via Agrobacterium tumefaciens transformation, where they reveal the expression pattern of genes at or near the insertion sites. Because GUS...

  14. Transcriptomic analysis of gene expression in mice treated with troxerutin.

    Directory of Open Access Journals (Sweden)

    Yuerong Wang

    Full Text Available Troxerutin, a semi-synthetic derivative of the natural bioflavanoid rutin, has been reported to possess many beneficial effects in human bodies, such as vasoprotection, immune support, anti-inflammation and anti-aging. However, the effects of troxerutin on genome-wide transcription in blood cells are still unknown. In order to find out effects of troxerutin on gene transcription, a high-throughput RNA sequencing was employed to analysis differential gene expression in blood cells consisting of leucocytes, erythrocytes and platelets isolated from the mice received subcutaneous injection of troxerutin. Transcriptome analysis demonstrated that the expression of only fifteen genes was significantly changed by the treatment with troxerutin, among which 5 genes were up-regulated and 10 genes were down-regulated. Bioinformatic analysis of the fifteen differentially expressed genes was made by utilizing the Gene Ontology (GO, and the differential expression induced by troxerutin was further evaluated by real-time quantitative PCR (Q-PCR.

  15. Optimization of transient gene expression system in Gerbera jemosonii petals.

    Science.gov (United States)

    Hussein, Gihan M; Abu El-Heba, Ghada A; Abdou, Sara M; Abdallah, Naglaa A

    2013-01-01

    Low transformation efficiency and long generation time for production of transgenic Gerbera jemosonii plants leads to vulnerable gene function studies. Thus, transient expression of genes would be an efficient alternative. In this investigation, a transient expression system for gerbera petals based on the Agrobacterium infiltration protocol was developed using the reporter genes β-glucuronidase (gus) and green florescence protein (gfp). Results revealed the incapability of using the gfp gene as a reporter gene for transient expression study in gerbera flowers due to the detection of green fluorescent color in the non-infiltrated gerbera flower petals. However, the gus reporter gene was successfully utilized for optimizing and obtaining the suitable agroinfiltration system in gerbera flowers. The expression of GUS was detectable after three days of agroinfiltration in gerbera cultivars "Express" and "White Grizzly" with dark pink and white flower colors, respectively. The vacuum agroinfiltration protocol has been applied on the cultivar "Express" for evaluating the transient expression of the two genes involved in the anthocyanin pathway (iris-dfr and petunia-f3' 5'h), which is responsible for the color in flowers. In comparison to the control, transient expression results showed change in the anthocyanin pigment in all infiltrated flowers with color genes. Additionally, blue color was detected in the stigma and pollen grains in the infiltrated flowers. Moreover, blue colors with variant intensities were observed in produced calli during the routine work of stable transformation with f3' 5'h gene.

  16. Redox regulation of photosynthetic gene expression.

    Science.gov (United States)

    Queval, Guillaume; Foyer, Christine H

    2012-12-19

    Redox chemistry and redox regulation are central to the operation of photosynthesis and respiration. However, the roles of different oxidants and antioxidants in the regulation of photosynthetic or respiratory gene expression remain poorly understood. Leaf transcriptome profiles of a range of Arabidopsis thaliana genotypes that are deficient in either hydrogen peroxide processing enzymes or in low molecular weight antioxidant were therefore compared to determine how different antioxidant systems that process hydrogen peroxide influence transcripts encoding proteins targeted to the chloroplasts or mitochondria. Less than 10 per cent overlap was observed in the transcriptome patterns of leaves that are deficient in either photorespiratory (catalase (cat)2) or chloroplastic (thylakoid ascorbate peroxidase (tapx)) hydrogen peroxide processing. Transcripts encoding photosystem II (PSII) repair cycle components were lower in glutathione-deficient leaves, as were the thylakoid NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) dehydrogenases (NDH) mRNAs. Some thylakoid NDH mRNAs were also less abundant in tAPX-deficient and ascorbate-deficient leaves. Transcripts encoding the external and internal respiratory NDHs were increased by low glutathione and low ascorbate. Regulation of transcripts encoding specific components of the photosynthetic and respiratory electron transport chains by hydrogen peroxide, ascorbate and glutathione may serve to balance non-cyclic and cyclic electron flow pathways in relation to oxidant production and reductant availability.

  17. Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans

    Science.gov (United States)

    Mayne, Benjamin T.; Bianco-Miotto, Tina; Buckberry, Sam; Breen, James; Clifton, Vicki; Shoubridge, Cheryl; Roberts, Claire T.

    2016-01-01

    The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases. PMID:27790248

  18. Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

    Directory of Open Access Journals (Sweden)

    Benjamin Mayne

    2016-10-01

    Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

  19. Microarray gene expression profiling and analysis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  20. Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps.

    Science.gov (United States)

    An, Li; Obradovic, Zoran; Smith, Desmond; Bodenreider, Olivier; Megalooikonomou, Vasileios

    2009-11-01

    Association rules mining methods have been recently applied to gene expression data analysis to reveal relationships between genes and different conditions and features. However, not much effort has focused on detecting the relation between gene expression maps and related gene functions. Here we describe such an approach to mine association rules among gene functions in clusters of similar gene expression maps on mouse brain. The experimental results show that the detected association rules make sense biologically. By inspecting the obtained clusters and the genes having the gene functions of frequent itemsets, interesting clues were discovered that provide valuable insight to biological scientists. Moreover, discovered association rules can be potentially used to predict gene functions based on similarity of gene expression maps.

  1. A stochastic approach to multi-gene expression dynamics

    International Nuclear Information System (INIS)

    Ochiai, T.; Nacher, J.C.; Akutsu, T.

    2005-01-01

    In the last years, tens of thousands gene expression profiles for cells of several organisms have been monitored. Gene expression is a complex transcriptional process where mRNA molecules are translated into proteins, which control most of the cell functions. In this process, the correlation among genes is crucial to determine the specific functions of genes. Here, we propose a novel multi-dimensional stochastic approach to deal with the gene correlation phenomena. Interestingly, our stochastic framework suggests that the study of the gene correlation requires only one theoretical assumption-Markov property-and the experimental transition probability, which characterizes the gene correlation system. Finally, a gene expression experiment is proposed for future applications of the model

  2. Lack of association between genetic polymorphism of FTO, AKT1 and AKTIP in childhood overweight and obesity.

    Science.gov (United States)

    Pereira, Patrícia de Araújo; Alvim-Soares, António Marcos; Sandrim, Valéria Cristina; Lanna, Carla Márcia Moreira; Souza-Costa, Débora Cristine; Belo, Vanessa de Almeida; de Paula, Jonas Jardim; Tanus-Santos, José Eduardo; Romano-Silva, Marco Aurélio; Miranda, Débora Marques de

    2016-01-01

    Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  3. Characterization of differentially expressed genes using high-dimensional co-expression networks

    DEFF Research Database (Denmark)

    Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

    2010-01-01

    We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

  4. Expression profiles for six zebrafish genes during gonadal sex differentiation

    Directory of Open Access Journals (Sweden)

    Rasmussen Lene J

    2008-06-01

    Full Text Available Abstract Background The mechanism of sex determination in zebrafish is largely unknown and neither sex chromosomes nor a sex-determining gene have been identified. This indicates that sex determination in zebrafish is mediated by genetic signals from autosomal genes. The aim of this study was to determine the precise timing of expression of six genes previously suggested to be associated with sex differentiation in zebrafish. The current study investigates the expression of all six genes in the same individual fish with extensive sampling dates during sex determination and -differentiation. Results In the present study, we have used quantitative real-time PCR to investigate the expression of ar, sox9a, dmrt1, fig alpha, cyp19a1a and cyp19a1b during the expected sex determination and gonadal sex differentiation period. The expression of the genes expected to be high in males (ar, sox9a and dmrt1a and high in females (fig alpha and cyp19a1a was segregated in two groups with more than 10 times difference in expression levels. All of the investigated genes showed peaks in expression levels during the time of sex determination and gonadal sex differentiation. Expression of all genes was investigated on cDNA from the same fish allowing comparison of the high and low expressers of genes that are expected to be highest expressed in either males or females. There were 78% high or low expressers of all three "male" genes (ar, sox9a and dmrt1 in the investigated period and 81% were high or low expressers of both "female" genes (fig alpha and cyp19a1a. When comparing all five genes with expected sex related expression 56% show expression expected for either male or female. Furthermore, the expression of all genes was investigated in different tissue of adult male and female zebrafish. Conclusion In zebrafish, the first significant peak in gene expression during the investigated period (2–40 dph was dmrt1 at 10 dph which indicates involvement of this gene

  5. Gene Expression Measurement Module (GEMM) - a fully automated, miniaturized instrument for measuring gene expression in space

    Science.gov (United States)

    Karouia, Fathi; Ricco, Antonio; Pohorille, Andrew; Peyvan, Kianoosh

    2012-07-01

    The capability to measure gene expression on board spacecrafts opens the doors to a large number of experiments on the influence of space environment on biological systems that will profoundly impact our ability to conduct safe and effective space travel, and might also shed light on terrestrial physiology or biological function and human disease and aging processes. Measurements of gene expression will help us to understand adaptation of terrestrial life to conditions beyond the planet of origin, identify deleterious effects of the space environment on a wide range of organisms from microbes to humans, develop effective countermeasures against these effects, determine metabolic basis of microbial pathogenicity and drug resistance, test our ability to sustain and grow in space organisms that can be used for life support and in situ resource utilization during long-duration space exploration, and monitor both the spacecraft environment and crew health. These and other applications hold significant potential for discoveries in space biology, biotechnology and medicine. Accordingly, supported by funding from the NASA Astrobiology Science and Technology Instrument Development Program, we are developing a fully automated, miniaturized, integrated fluidic system for small spacecraft capable of in-situ measuring microbial expression of thousands of genes from multiple samples. The instrument will be capable of (1) lysing bacterial cell walls, (2) extracting and purifying RNA released from cells, (3) hybridizing it on a microarray and (4) providing electrochemical readout, all in a microfluidics cartridge. The prototype under development is suitable for deployment on nanosatellite platforms developed by the NASA Small Spacecraft Office. The first target application is to cultivate and measure gene expression of the photosynthetic bacterium Synechococcus elongatus, i.e. a cyanobacterium known to exhibit remarkable metabolic diversity and resilience to adverse conditions

  6. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood.

    Science.gov (United States)

    Stamova, Boryana S; Apperson, Michelle; Walker, Wynn L; Tian, Yingfang; Xu, Huichun; Adamczy, Peter; Zhan, Xinhua; Liu, Da-Zhi; Ander, Bradley P; Liao, Isaac H; Gregg, Jeffrey P; Turner, Renee J; Jickling, Glen; Lit, Lisa; Sharp, Frank R

    2009-08-05

    Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  7. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

    Directory of Open Access Journals (Sweden)

    Turner Renee J

    2009-08-01

    Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  8. 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)

  9. Stably Expressed Genes Involved in Basic Cellular Functions.

    Directory of Open Access Journals (Sweden)

    Kejian Wang

    Full Text Available Stably Expressed Genes (SEGs whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age in both sexes of F344 rats (n = 4/group; 320 samples. Expression changes (calculated as the maximum expression / minimum expression for each gene of >19000 genes across organs, ages, and sexes ranged from 2.35 to >109-fold, with a median of 165-fold. The expression of 278 SEGs was found to vary ≤4-fold and these genes were significantly involved in protein catabolism (proteasome and ubiquitination, RNA transport, protein processing, and the spliceosome. Such stability of expression was further validated in human samples where the expression variability of the homologous human SEGs was significantly lower than that of other genes in the human genome. It was also found that the homologous human SEGs were generally less subject to non-synonymous mutation than other genes, as would be expected of stably expressed genes. We also found that knockout of SEG homologs in mouse models was more likely to cause complete preweaning lethality than non-SEG homologs, corroborating the fundamental roles played by SEGs in biological development. Such stably expressed genes and pathways across life-stages suggest that tight control of these processes is important in basic cellular functions and that perturbation by endogenous (e.g., genetics or exogenous agents (e.g., drugs, environmental factors may cause serious adverse effects.

  10. Effects of heat stress on gene expression in eggplant ( Solanum ...

    African Journals Online (AJOL)

    In order to identify differentially expressed genes involved in heat shock response, cDNA amplified fragment length polymorphism (cDNA-AFLP) and quantitative real-time polymerase chain reaction (QPCR) were used to study gene expression of eggplant seedlings subjected to 0, 6 and 12 h at 43°C. A total of 53 of over ...

  11. Long SAGE analysis of genes differentially expressed in the midgut ...

    African Journals Online (AJOL)

    There are great differences in silk production efficiency and quality between the male and female domestic silkworm (Bombyx mori). Many genes act together but are differentially expressed between the sexes during silk biosynthesis. Two long serial analyses of gene expression (SAGE) libraries were constructed from the ...

  12. Regulation of mitochondrial gene expression, the epigenetic enigma

    NARCIS (Netherlands)

    Mposhi, Archibold; van der Wijst, Monique G. P.; Faber, Klaas Nico; Rots, Marianne G.

    2017-01-01

    Epigenetics provides an important layer of information on top of the DNA sequence and is essential for establishing gene expression profiles. Extensive studies have shown that nuclear DNA methylation and histone modifications influence nuclear gene expression. However, it remains unclear whether

  13. The gene expressions of DNA methylation/demethylation enzymes ...

    African Journals Online (AJOL)

    A decrease in mRNA levels for cytochrome c oxidase (COX) subunits was observed in skeletal muscle of hypothyroid rats. However, the precise expression mechanisms of the related genes in hypothyroid state still remain unclear. This study investigated gene expressions of DNA methyltransferases (Dnmts), DNA ...

  14. Comparative genomics of the relationship between gene structure and expression

    NARCIS (Netherlands)

    Ren, X.

    2006-01-01

    The relationship between the structure of genes and their expression is a relatively new aspect of genome organization and regulation. With more genome sequences and expression data becoming available, bioinformatics approaches can help the further elucidation of the relationships between gene

  15. Gene expression profiles in adenosine-treated human mast cells ...

    African Journals Online (AJOL)

    The role of mast cells in allergic diseases and innate immunity has been widely researched and much is known about the expression profiles of immune-related genes in mast cells after bacterial challenges. However, little is known about the gene expression profiles of mast cells in response to adenosine. Herein, we ...

  16. Microarray analysis of the gene expression profile in triethylene ...

    African Journals Online (AJOL)

    Microarray analysis of the gene expression profile in triethylene glycol dimethacrylate-treated human dental pulp cells. ... Conclusions: Our results suggest that TEGDMA can change the many functions of hDPCs through large changes in gene expression levels and complex interactions with different signaling pathways.

  17. The gene expressions of DNA methylation/demethylation enzymes ...

    African Journals Online (AJOL)

    user

    2011-01-31

    Jan 31, 2011 ... A decrease in mRNA levels for cytochrome c oxidase (COX) subunits was observed in skeletal muscle of hypothyroid rats. However, the precise expression mechanisms of the related genes in hypothyroid state still remain unclear. This study investigated gene expressions of DNA methyltransferases.

  18. Genome organization and expression of the rat ACBP gene family

    DEFF Research Database (Denmark)

    Mandrup, S; Andreasen, P H; Knudsen, J

    1993-01-01

    pool former. We have molecularly cloned and characterized the rat ACBP gene family which comprises one expressed and four processed pseudogenes. One of these was shown to exist in two allelic forms. A comprehensive computer-aided analysis of the promoter region of the expressed ACBP gene revealed...

  19. Expression of KLK2 gene in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sajad Shafai

    2018-01-01

    Conclusion: The expression of KLK2 gene in people with prostate cancer is the higher than the healthy person; finally, according to the results, it could be mentioned that the KLK2 gene considered as a useful factor in prostate cancer, whose expression is associated with progression and development of the prostate cancer.

  20. Differential expressed genes in ECV304 Endothelial-like Cells ...

    African Journals Online (AJOL)

    Background: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. Objective: With the application of DNA microarrays, we could monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale.

  1. RNA preparation and characterization for gene expression studies

    DEFF Research Database (Denmark)

    Stangegaard, Michael

    2009-01-01

    Much information can be obtained from knowledge of the relative expression level of each gene in the transcriptome. With the current advances in technology as little as a single cell is required as starting material for gene expression experiments. The mRNA from a single cell may be linearly...

  2. Meta-analysis of differentially expressed genes in ankylosing spondylitis.

    Science.gov (United States)

    Lee, Y H; Song, G G

    2015-05-18

    The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in ankylosing spondylitis (AS). We performed a meta-analysis using the integrative meta-analysis of expression data program on publicly available microarray AS Gene Expression Omnibus (GEO) datasets. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using the Kyoto Encyclopedia of Genes and Genomes. Four GEO datasets, including 31 patients with AS and 39 controls, were available for the meta-analysis. We identified 65 genes across the studies that were consistently DE in patients with AS vs controls (23 upregulated and 42 downregulated). The upregulated gene with the largest effect size (ES; -1.2628, P = 0.020951) was integral membrane protein 2A (ITM2A), which is expressed by CD4+ T cells and plays a role in activation of T cells. The downregulated gene with the largest ES (1.2299, P = 0.040075) was mitochondrial ribosomal protein S11 (MRPS11). The most significant GO enrichment was in the respiratory electron transport chain category (P = 1.67 x 10-9). Therefore, our meta-analysis identified genes that were consistently DE as well as biological pathways associated with gene expression changes in AS.

  3. Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study.

    Science.gov (United States)

    Tabara, Y; Osawa, H; Guo, H; Kawamoto, R; Onuma, H; Shimizu, I; Takara, Y; Nishida, W; Yamamoto, M; Makino, H; Kohara, K; Miki, T

    2009-11-01

    Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284). FTO genotype is an independent risk factor for future development of obesity.

  4. Expression and clinical significance of Pax6 gene in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Hai-Dong Huang

    2013-07-01

    Full Text Available AIM: To discuss the expression and clinical significance of Pax6 gene in retinoblastoma(Rb. METHODS: Totally 15 cases of fresh Rb organizations were selected as observation group and 15 normal retinal organizations as control group. Western-Blot and reverse transcriptase polymerase chain reaction(RT-PCRmethods were used to detect Pax6 protein and Pax6 mRNA expressions of the normal retina organizations and Rb organizations. At the same time, Western Blot method was used to detect the Pax6 gene downstream MATH5 and BRN3b differentiation gene protein level expression. After the comparison between two groups, the expression and clinical significance of Pax6 gene in Rb were discussed. RESULTS: In the observation group, average value of mRNA expression of Pax6 gene was 0.99±0.03; average value of Pax6 gene protein expression was 2.07±0.15; average value of BRN3b protein expression was 0.195±0.016; average value of MATH5 protein expression was 0.190±0.031. They were significantly higher than the control group, and the differences were statistically significant(PCONCLUSION: Abnormal expression of Pax6 gene is likely to accelerate the occurrence of Rb.

  5. Fungal and plant gene expression in arbuscular mycorrhizal symbiosis.

    Science.gov (United States)

    Balestrini, Raffaella; Lanfranco, Luisa

    2006-11-01

    Arbuscular mycorrhizas (AMs) are a unique example of symbiosis between two eukaryotes, soil fungi and plants. This association induces important physiological changes in each partner that lead to reciprocal benefits, mainly in nutrient supply. The symbiosis results from modifications in plant and fungal cell organization caused by specific changes in gene expression. Recently, much effort has gone into studying these gene expression patterns to identify a wider spectrum of genes involved. We aim in this review to describe AM symbiosis in terms of current knowledge on plant and fungal gene expression profiles.

  6. Decoupling Linear and Nonlinear Associations of Gene Expression

    KAUST Repository

    Itakura, Alan

    2013-05-01

    The FANTOM consortium has generated a large gene expression dataset of different cell lines and tissue cultures using the single-molecule sequencing technology of HeliscopeCAGE. This provides a unique opportunity to investigate novel associations between gene expression over time and different cell types. Here, we create a MatLab wrapper for a powerful and computationally intensive set of statistics known as Maximal Information Coefficient, and then calculate this statistic for a large, comprehensive dataset containing gene expression of a variety of differentiating tissues. We then distinguish between linear and nonlinear associations, and then create gene association networks. Following this analysis, we are then able to identify clusters of linear gene associations that then associate nonlinearly with other clusters of linearity, providing insight to much more complex connections between gene expression patterns than previously anticipated.

  7. Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR

    Science.gov (United States)

    Silver, Nicholas; Best, Steve; Jiang, Jie; Thein, Swee Lay

    2006-01-01

    Background Control genes, which are often referred to as housekeeping genes, are frequently used to normalise mRNA levels between different samples. However, the expression level of these genes may vary among tissues or cells and may change under certain circumstances. Thus, the selection of housekeeping genes is critical for gene expression studies. To address this issue, 7 candidate housekeeping genes including several commonly used ones were investigated in isolated human reticulocytes. For this, a simple ΔCt approach was employed by comparing relative expression of 'pairs of genes' within each sample. On this basis, stability of the candidate housekeeping genes was ranked according to repeatability of the gene expression differences among 31 samples. Results Initial screening of the expression pattern demonstrated that 1 of the 7 genes was expressed at very low levels in reticulocytes and was excluded from further analysis. The range of expression stability of the other 6 genes was (from most stable to least stable): GAPDH (glyceraldehyde 3-phosphate dehydrogenase), SDHA (succinate dehydrogenase), HPRT1 (hypoxanthine phosphoribosyl transferase 1), HBS1L (HBS1-like protein) and AHSP (alpha haemoglobin stabilising protein), followed by B2M (beta-2-microglobulin). Conclusion Using this simple approach, GAPDH was found to be the most suitable housekeeping gene for expression studies in reticulocytes while the commonly used B2M should be avoided. PMID:17026756

  8. Local gene expression in nerve endings.

    Science.gov (United States)

    Crispino, Marianna; Chun, Jong Tai; Cefaliello, Carolina; Perrone Capano, Carla; Giuditta, Antonio

    2014-03-01

    At the Nobel lecture for physiology in 1906, Ramón y Cajal famously stated that "the nerve elements possess reciprocal relationships in contiguity but not in continuity," summing up the neuron doctrine. Sixty years later, by the time the central dogma of molecular biology formulated the axis of genetic information flow from DNA to mRNA, and then to protein, it became obvious that neurons with extensive ramifications and long axons inevitably incur an innate problem: how can the effect of gene expression be extended from the nucleus to the remote and specific sites of the cell periphery? The most straightforward solution would be to deliver soma-produced proteins to the target sites. The influential discovery of axoplasmic flow has supported this scheme of protein supply. Alternatively, mRNAs can be dispatched instead of protein, and translated locally at the strategic target sites. Over the past decades, such a local system of protein synthesis has been demonstrated in dendrites, axons, and presynaptic terminals. Moreover, the local protein synthesis in neurons might even involve intercellular trafficking of molecules. The innovative concept of glia-neuron unit suggests that the local protein synthesis in the axonal and presynaptic domain of mature neurons is sustained by a local supply of RNAs synthesized in the surrounding glial cells and transferred to these domains. Here, we have reviewed some of the evidence indicating the presence of a local system of protein synthesis in axon terminals, and have examined its regulation in various model systems. Copyright © 2013 Wiley Periodicals, Inc.

  9. Gene ordering in partitive clustering using microarray expressions

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    fibroblast data and showed that our approach improves the result quality of partitive clustering solution, by identifying subclusters within big clusters, grouping functionally correlated genes within clusters, minimization of summation of gene expression distances, and the maximization of biological gene ordering using MIPS ...

  10. Differentially expressed genes in white egg 2 mutant of silkworm ...

    African Journals Online (AJOL)

    In order to obtain an overall view on gene expression profiles at early embryo development stages, the white egg 2 near-isogenic line was constructed and the whole-genome of silkworm microarray system containing 21375 predicted genes from the silkworm whole genome sequence was employed to investigate gene ...

  11. Gene expression profile study on osteoinductive effect of natural hydroxyapatite.

    Science.gov (United States)

    Lü, Xiaoying; Wang, Jiandan; Li, Bin; Zhang, Zhiwei; Zhao, Lifeng

    2014-08-01

    The aim of this study was to investigate the osteoinductive effect of natural hydroxyapatite (NHA). NHA was extracted from pig bones and prepared into disk-like samples. Then, proliferation of mouse bone mesenchymal stem cells (MSCs) cultured on NHA was assessed by the methylthiazoltetrazolium (MTT) assay. Furthermore, microarray technology was applied to obtain the gene expression profiles of MSCs cultured on NHA at 24, 48, and 72 h. The gene expression profile was then comprehensively analyzed by clustering, Gene Ontology (GO), Gene Microarray Pathway Profiler (GenMAPP) and Ingenuity Pathway Analysis (IPA). According to the results of microarray experiment, 8992 differentially expressed genes were obtained. 90 differential expressed genes related to HA osteogenic differentiation were determined by GO analysis. These genes included not only 6 genes related to HA osteogenic differentiation as mentioned in the literatures but also newly discovered 84 genes. Some important signaling pathways (TGF-β, MAPK, Wnt, etc.) were influenced by these genes. Gene interaction networks were obtained by IPA software, in which the scoring values of two networks were highest, and their main functions were related to cell development. The comprehensive analysis of these results indicate that NHA regulate some crucial genes (e.g., Bmp2, Spp1) and then activate some pathways such as TGF-β signaling pathway, and ultimately osteogenic differentiation was induced. © 2013 Wiley Periodicals, Inc.

  12. DNA microarray analysis of genes differentially expressed in ...

    Indian Academy of Sciences (India)

    These genes may play a major role in promoting excessive proliferation and accumulation of lipid droplets, which contribute to the development of obesity. By using microarray-based technology, we examined differential gene expression in early differentiated adipocytes and late differentiated adipocytes. Validated genes ...

  13. Differentially expressed genes in the midgut of Silkworm infected ...

    African Journals Online (AJOL)

    In this report, we employed suppression subtractive hybridization to compare differentially expressed genes in the midguts of CPV-infected and normal silkworm larvae. 36 genes and 20 novel ESTs were obtained from 2 reciprocal subtractive libraries. Three up-regulated genes (ferritin, rpL11 and alkaline nuclease) and 3 ...

  14. Expression profiles of genes involved in tanshinone biosynthesis of ...

    Indian Academy of Sciences (India)

    Expression profiles of genes involved in tanshinone biosynthesis of two. Salvia miltiorrhiza genotypes with different tanshinone contents. Zhenqiao Song, Jianhua Wang and Xingfeng Li. J. Genet. 95, 433–439. Table 1. S. miltiorrhiza genes and primer pairs used for qRT-PCR. Gene. GenBank accession. Primer name.

  15. Identification of differentially expressed genes in seeds of two ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... the differentially expressed genes are related to metabolism and regulation. The possible role of these genes in seeds ..... genes are regulated by hormones such as insulin. (Moustaid et al., 1994), by dietary fatty .... Physiol. 99: 197-202. Heppard EP, Kinney AJ, Stecca KL, Miao GH (1996). Developmental.

  16. Molecular characterization, expression profile of the FSHR gene and ...

    Indian Academy of Sciences (India)

    JIGUO XU

    2017-06-17

    Jun 17, 2017 ... the expression pattern of FSHR mRNA in various mus- covy duck tissues, besides, identified the polymorphism of this gene and evaluated its association with muscovy duck egg production traits, by using methods of reverse transcription, gene cloning, PCR amplification, qPCR and gene sequencing.

  17. MASISH: a database for gene expression in maize seeds.

    Science.gov (United States)

    Miquel, M; López-Ribera, I; Ràmia, M; Casillas, S; Barbadilla, A; Vicient, C M

    2011-02-01

    Grass seeds are complex organs composed by multiple tissues and cell types that develop coordinately to produce a viable embryo. The identification of genes involved in seed development is of great interest, but systematic spatial analyses of gene expression on maize seeds at the cell level have not yet been performed. MASISH is an online database holding information for gene expression spatial patterns in maize seeds based on in situ hybridization experiments. The web-based query interface allows the execution of gene queries and provides hybridization images, published references and information of the analyzed genes. http://masish.uab.cat/.

  18. Adaptive differences in gene expression in European flounder ( Platichthys flesus )

    DEFF Research Database (Denmark)

    Larsen, Peter Foged; Eg Nielsen, Einar; Williams, T.D.

    2007-01-01

    levels of neutral genetic divergence, a high number of genes were significantly differentially expressed between North Sea and Baltic Sea flounders maintained in a long-term reciprocal transplantation experiment mimicking natural salinities. Several of the differentially regulated genes could be directly...... linked to fitness traits. These findings demonstrate that flounders, despite little neutral genetic divergence between populations, are differently adapted to local environmental conditions and imply that adaptation in gene expression could be common in other marine organisms with similar low levels...

  19. Gene Expression and the Diversity of Identified Neurons

    OpenAIRE

    Buck, L.; Stein, R.; Palazzolo, M.; Anderson, D. J.; Axel, R.

    1983-01-01

    Nervous systems consist of diverse populations of neurons that are anatomically and functionally distinct. The diversity of neurons and the precision with which they are interconnected suggest that specific genes or sets of genes are activated in some neurons but not expressed in others. Experimentally, this problem may be considered at two levels. First, what is the total number of genes expressed in the brain, and how are they distributed among the different populations of neurons? Second, ...

  20. Binary gene induction and protein expression in individual cells

    Directory of Open Access Journals (Sweden)

    Conolly Rory B

    2006-04-01

    Full Text Available Abstract Background Eukaryotic gene transcription is believed to occur in either a binary or a graded fashion. With binary induction, a transcription activator (TA regulates the probability with which a gene template is switched from the inactive to the active state without affecting the rate at which RNA molecules are produced from the template. With graded, also called rheostat-like, induction the gene template has continuously varying levels of transcriptional activity, and the TA regulates the rate of RNA production. Support for each of these two mechanisms arises primarily from experimental studies measuring reporter proteins in individual cells, rather than from direct measurement of induction events at the gene template. Methods and results In this paper, using a computational model of stochastic gene expression, we have studied the biological and experimental conditions under which a binary induction mode operating at the gene template can give rise to differentially expressed "phenotypes" (i.e., binary, hybrid or graded at the protein level. We have also investigated whether the choice of reporter genes plays a significant role in determining the observed protein expression patterns in individual cells, given the diverse properties of commonly-used reporter genes. Our simulation confirmed early findings that the lifetimes of active/inactive promoters and half-lives of downstream mRNA/protein products are important determinants of various protein expression patterns, but showed that the induction time and the sensitivity with which the expressed genes are detected are also important experimental variables. Using parameter conditions representative of reporter genes including green fluorescence protein (GFP and β-galactosidase, we also demonstrated that graded gene expression is more likely to be observed with GFP, a longer-lived protein with low detection sensitivity. Conclusion The choice of reporter genes may determine whether protein

  1. Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

    Directory of Open Access Journals (Sweden)

    Tintle Nathan L

    2012-08-01

    Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

  2. Radiolabeled PNAs for imaging gene expression

    Directory of Open Access Journals (Sweden)

    Eric Wickstrom

    2002-09-01

    Full Text Available Scintigraphic imaging of gene expression in vivo by non-invasive means could precisely direct physicians to appropriate intervention at the onset of disease and could contribute extensively to the management of patients. However, no method is currently available to image specific overexpressed oncogene mRNAs in vivo by scintigraphic imaging. Nevertheless, we have observed that Tc-99m-peptides can delineate tumors, and that PNA-peptides are specific for receptors on malignant cells and are taken up specifically and concentrated in nuclei. We hypothesize that antisense Tc-99m-PNA-peptides will be taken up by human breast cancer cells, hybridize to complementary mRNA targets, and permit imaging of oncogene mRNAs in human breast cancer xenografts in a mouse model, providing a proof-of-principle for non-invasive detection of precancerous and invasive breast cancer. Oncogenes cyclin D1, erbB-2, c-MYC, and tumor suppressor p53 will be probed. If successful, this technique will be useful for diagnostic imaging of other solid tumors as well.Imagens cintigráficas da expressão genética in vivo por metódos não invasivos poderiam orientar mais precisamente as intervenções médicas para o local definido da doença e poderia contribuir para melhor tratamento dos pacientes. Entretanto, nenhum método está atualmente disponível para a imagem específica da intensa expressão de um oncogene de RNAm (s in vivo por imagem cintigráfica. Contudo, nós temos observado que peptídeos marcados Tc-99m podem delinear tumores, e que peptídeos PNA são específicos para receptores em células malignas e são captados e concentrados no núcleo. Nós sugerimos que peptideos PNA nonsense marcados com Tc-99m serão capturados pelas células neoplásicas de mama humana, hibridizarão com sequências complementares de alvos de RNAm e permitirão imagen de oncogenes de RNAm em câncer de mama humana com enxerto em modelo animal, provendo um prova do princípio de detec

  3. Expression of MAGE and BAGE genes in Japanese breast cancers.

    Science.gov (United States)

    Fujie, T; Mori, M; Ueo, H; Sugimachi, K; Akiyoshi, T

    1997-04-01

    The MAGE and BAGE genes code for distinct antigens, which are recognized on melanoma cells as well as on other various tumor cells by autologous cytolytic T lymphocytes. These antigens may thus constitute useful targets for specific immunotherapy, since no expression of MAGE or BAGE genes has been recognized in normal tissue except for the testis. We studied the MAGE-1, MAGE-3, and BAGE gene expression observed in 49 Japanese breast cancers. Gene expression was evaluated by reverse transcription polymerase chain reaction. Out of 49 tumor tissue specimens of primary breast cancers, the expression of MAGE-1, -3 and BAGE was recognized in 15 (31%), 12 (24%), and 4 (8%) tumors, respectively. The expression of MAGE and BAGE genes is not recognized in normal breast tissue. The expression of the MAGE-3 gene was frequently recognized in tumors with lymphatic and/or vascular vessel permeations. Either MAGE-1 or -3 gene expressions were induced in 1 of 3 MAGE-1 negative breast cell lines or 1 of 3 MAGE-3 negative breast cell lines by the treatment with 5-aza-2'-deoxycytidine. These findings suggest that: 1) the identification of such antigens coded by MAGE or BAGE genes may thus offer the possibility of using specific immunotherapy, and 2) the use of a demethylating agent may increase the number of patients who might be candidates for MAGE specific immunotherapy.

  4. 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.

  5. Clustering Algorithms: Their Application to Gene Expression Data.

    Science.gov (United States)

    Oyelade, Jelili; Isewon, Itunuoluwa; Oladipupo, Funke; Aromolaran, Olufemi; Uwoghiren, Efosa; Ameh, Faridah; Achas, Moses; Adebiyi, Ezekiel

    2016-01-01

    Gene expression data hide vital information required to understand the biological process that takes place in a particular organism in relation to its environment. Deciphering the hidden patterns in gene expression data proffers a prodigious preference to strengthen the understanding of functional genomics. The complexity of biological networks and the volume of genes present increase the challenges of comprehending and interpretation of the resulting mass of data, which consists of millions of measurements; these data also inhibit vagueness, imprecision, and noise. Therefore, the use of clustering techniques is a first step toward addressing these challenges, which is essential in the data mining process to reveal natural structures and identify interesting patterns in the underlying data. The clustering of gene expression data has been proven to be useful in making known the natural structure inherent in gene expression data, understanding gene functions, cellular processes, and subtypes of cells, mining useful information from noisy data, and understanding gene regulation. The other benefit of clustering gene expression data is the identification of homology, which is very important in vaccine design. This review examines the various clustering algorithms applicable to the gene expression data in order to discover and provide useful knowledge of the appropriate clustering technique that will guarantee stability and high degree of accuracy in its analysis procedure.

  6. Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.

    Science.gov (United States)

    Baek, Eseul; Yoon, Ju-Yeon; Palukaitis, Peter

    2017-10-01

    To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Salicin regulates the expression of functional 'youth gene clusters' to reflect a more youthful gene expression profile.

    Science.gov (United States)

    Gopaul, R; Knaggs, H E; Lephart, J

    2011-10-01

    There are a variety of biological mechanisms that contribute to specific characteristics of ageing skin; for example, the loss of skin structure proteins, increased susceptibility to UV-induced pigmentation and/or loss of hydration. Each of these biological processes is influenced by specific groups of genes. In this research, we have identified groups of genes associated with specific clinical signs of skin ageing and refer to these as functional 'youth gene clusters'. In this study, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the effects of topical application of salicin in regulating the expression of functional 'youth gene clusters' to reflect a more youthful skin profile and reduce the appearance of attributes associated with skin ageing. Results showed that salicin significantly influences the gene expression profiles of treated human equivalent full-thickness skin, by regulating the expression of genes associated with various biological processes involving skin structure, skin hydration, pigmentation and cellular differentiation. Based on the findings from this experiment, salicin was identified as a key ingredient that may regulate functional 'youth gene clusters' to reflect a more youthful gene expression profile by increasing the expression of genes responsible for youthful skin and decreasing the expression of genes responsible for the appearance of aged skin. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  8. With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies.

    Science.gov (United States)

    Chapman, Joanne R; Waldenström, Jonas

    2015-01-01

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

  9. Using PCR to Target Misconceptions about Gene Expression

    Directory of Open Access Journals (Sweden)

    Leslie K. Wright

    2013-02-01

    Full Text Available We present a PCR-based laboratory exercise that can be used with first- or second-year biology students to help overcome common misconceptions about gene expression. Biology students typically do not have a clear understanding of the difference between genes (DNA and gene expression (mRNA/protein and often believe that genes exist in an organism or cell only when they are expressed. This laboratory exercise allows students to carry out a PCR-based experiment designed to challenge their misunderstanding of the difference between genes and gene expression. Students first transform E. coli with an inducible GFP gene containing plasmid and observe induced and un-induced colonies. The following exercise creates cognitive dissonance when actual PCR results contradict their initial (incorrect predictions of the presence of the GFP gene in transformed cells. Field testing of this laboratory exercise resulted in learning gains on both knowledge and application questions on concepts related to genes and gene expression.

  10. Sequence biases in large scale gene expression profiling data.

    Science.gov (United States)

    Siddiqui, Asim S; Delaney, Allen D; Schnerch, Angelique; Griffith, Obi L; Jones, Steven J M; Marra, Marco A

    2006-07-13

    We present the results of a simple, statistical assay that measures the G+C content sensitivity bias of gene expression experiments without the requirement of a duplicate experiment. We analyse five gene expression profiling methods: Affymetrix GeneChip, Long Serial Analysis of Gene Expression (LongSAGE), LongSAGELite, 'Classic' Massively Parallel Signature Sequencing (MPSS) and 'Signature' MPSS. We demonstrate the methods have systematic and random errors leading to a different G+C content sensitivity. The relationship between this experimental error and the G+C content of the probe set or tag that identifies each gene influences whether the gene is detected and, if detected, the level of gene expression measured. LongSAGE has the least bias, while Signature MPSS shows a strong bias to G+C rich tags and Affymetrix data show different bias depending on the data processing method (MAS 5.0, RMA or GC-RMA). The bias in the Affymetrix data primarily impacts genes expressed at lower levels. Despite the larger sampling of the MPSS library, SAGE identifies significantly more genes (60% more RefSeq genes in a single comparison).

  11. Validation of housekeeping genes for studying differential gene expression in the bovine myometrium.

    Science.gov (United States)

    Rekawiecki, Robert; Kowalik, Magdalena K; Kotwica, Jan

    2013-12-01

    The aim of this study was to determine the steady-state expression of 13 selected housekeeping genes in the myometrium of cyclic and pregnant cows. Cells taken from bovine myometrium on days 1-5, 6-10, 11-16 and 17-20 of the oestrous cycle and in weeks 3-5, 6-8 and 9-12 of pregnancy were used. Reverse transcribed RNA was amplified in real-time PCR using designed primers. Reaction efficiency was determined with the Linreg programme. The geNorm and NormFinder programmes were used to select the best housekeeping genes. They calculate the expression stability factor for each used housekeeping gene with the smallest value for most stably expressed genes. According to geNorm, the most stable housekeeping genes in the myometrium were C2orf29, TPB and TUBB2B, while the least stably expressed genes were 18S RNA, HPRT1 and GAPDH. NormFinder identified the best genes in the myometrium as C2orf29, MRPL12 and TBP, while the worst genes were 18S RNA, B2M and SF3A1. Differences in stability factors between the two programmes may also indicate that the physiological status of the female, e.g. pregnancy, affects the stability of expression of housekeeping genes. The different expression stability of housekeeping genes did not affect progesterone receptor expression but it could be important if small differences in gene expression were measured between studies.

  12. Dynamic association rules for gene expression data analysis.

    Science.gov (United States)

    Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

    2015-10-14

    The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed

  13. 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.

  14. Epigenetic regulation on the gene expression signature in esophagus adenocarcinoma.

    Science.gov (United States)

    Xi, Ting; Zhang, Guizhi

    2017-02-01

    Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS. In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis between NOS and controls was performed in terms of gene expression, miRNA expression, and DNA methylation. Bioinformatic analysis was followed to explore the regulation mechanisms of miRNA and DNA methylationon gene expression. Totally, up to 1320 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs were identified. 240 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. 101 DEGs were found to be highlymethylated in CpG islands. Then, 8 differentially methylated genes (DMGs) were selected, which showed down-regulated expression in NOS. Among of these genes, 6 genes including ADHFE1, DPP6, GRIA4, CNKSR2, RPS6KA6 and ZNF135 were target genes of differentially expressed miRNAs (hsa-mir-335, hsa-mir-18a, hsa-mir-93, hsa-mir-106b and hsa-mir-21). The identified altered miRNA, genes and DNA methylation site may be applied as biomarkers for diagnosis and prognosis of NOS. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Green Fluorescent Protein as a Marker for Gene Expression

    Science.gov (United States)

    Chalfie, Martin; Tu, Yuan; Euskirchen, Ghia; Ward, William W.; Prasher, Douglas C.

    1994-02-01

    A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic (Escherichia coli) or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms.

  16. Paralogous Genes as a Tool to Study the Regulation of Gene Expression

    DEFF Research Database (Denmark)

    Hoffmann, Robert D

    their duplicate were found to be under less purifying selection. A gene ontology (GO) term enrichment analysis showed that paralogs with similar expression levels were enriched in GO terms related to macromolecular complexes, whereas paralogs with different expression levels were enriched in terms associated...... new functions, or their gene products are in a dosage balance. Regulatory DNA elements - some of which are conserved across species and hence called conserved non-coding sequences (CNSs) - that control expression of duplicated genes are thus under similar purifying selection. In the present study, I...... have performed in-depth analyses of paralogous genes in Arabidopsis thaliana, their expression profile, their sequence conservation, and their functions, in order to investigate the relationship between gene expression and retention of paralogous genes. Paralogs with lower expression than...

  17. Identifying the optimal gene and gene set in hepatocellular carcinoma based on differential expression and differential co-expression algorithm.

    Science.gov (United States)

    Dong, Li-Yang; Zhou, Wei-Zhong; Ni, Jun-Wei; Xiang, Wei; Hu, Wen-Hao; Yu, Chang; Li, Hai-Yan

    2017-02-01

    The objective of this study was to identify the optimal gene and gene set for hepatocellular carcinoma (HCC) utilizing differential expression and differential co-expression (DEDC) algorithm. The DEDC algorithm consisted of four parts: calculating differential expression (DE) by absolute t-value in t-statistics; computing differential co-expression (DC) based on Z-test; determining optimal thresholds on the basis of Chi-squared (χ2) maximization and the corresponding gene was the optimal gene; and evaluating functional relevance of genes categorized into different partitions to determine the optimal gene set with highest mean minimum functional information (FI) gain (Δ*G). The optimal thresholds divided genes into four partitions, high DE and high DC (HDE-HDC), high DE and low DC (HDE-LDC), low DE and high DC (LDE‑HDC), and low DE and low DC (LDE-LDC). In addition, the optimal gene was validated by conducting reverse transcription-polymerase chain reaction (RT-PCR) assay. The optimal threshold for DC and DE were 1.032 and 1.911, respectively. Using the optimal gene, the genes were divided into four partitions including: HDE-HDC (2,053 genes), HED-LDC (2,822 genes), LDE-HDC (2,622 genes), and LDE-LDC (6,169 genes). The optimal gene was microtubule‑associated protein RP/EB family member 1 (MAPRE1), and RT-PCR assay validated the significant difference between the HCC and normal state. The optimal gene set was nucleoside metabolic process (GO\\GO:0009116) with Δ*G = 18.681 and 24 HDE-HDC partitions in total. In conclusion, we successfully investigated the optimal gene, MAPRE1, and gene set, nucleoside metabolic process, which may be potential biomarkers for targeted therapy and provide significant insight for revealing the pathological mechanism underlying HCC.

  18. Utilizing evolutionary information and gene expression data for estimating gene networks with bayesian network models.

    Science.gov (United States)

    Tamada, Yoshinori; Bannai, Hideo; Imoto, Seiya; Katayama, Toshiaki; Kanehisa, Minoru; Miyano, Satoru

    2005-12-01

    Since microarray gene expression data do not contain sufficient information for estimating accurate gene networks, other biological information has been considered to improve the estimated networks. Recent studies have revealed that highly conserved proteins that exhibit similar expression patterns in different organisms, have almost the same function in each organism. Such conserved proteins are also known to play similar roles in terms of the regulation of genes. Therefore, this evolutionary information can be used to refine regulatory relationships among genes, which are estimated from gene expression data. We propose a statistical method for estimating gene networks from gene expression data by utilizing evolutionarily conserved relationships between genes. Our method simultaneously estimates two gene networks of two distinct organisms, with a Bayesian network model utilizing the evolutionary information so that gene expression data of one organism helps to estimate the gene network of the other. We show the effectiveness of the method through the analysis on Saccharomyces cerevisiae and Homo sapiens cell cycle gene expression data. Our method was successful in estimating gene networks that capture many known relationships as well as several unknown relationships which are likely to be novel. Supplementary information is available at http://bonsai.ims.u-tokyo.ac.jp/~tamada/bayesnet/.

  19. Using RNA-seq data to select reference genes for normalizing gene expression in apple roots.

    Directory of Open Access Journals (Sweden)

    Zhe Zhou

    Full Text Available Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for their potential use as reliable reference genes. These genes were selected based on their low variance of gene expression in apple root tissues from a recent RNA-seq data set, and a few previously reported apple reference genes for other tissue types. Four methods, Delta Ct, geNorm, NormFinder and BestKeeper, were used to evaluate their stability in apple root tissues of various genotypes and under different experimental conditions. A small panel of stably expressed genes, MDP0000095375, MDP0000147424, MDP0000233640, MDP0000326399 and MDP0000173025 were recommended for normalizing quantitative gene expression data in apple roots under various abiotic or biotic stresses. When the most stable and least stable reference genes were used for data normalization, significant differences were observed on the expression patterns of two target genes, MdLecRLK5 (MDP0000228426, a gene encoding a lectin receptor like kinase and MdMAPK3 (MDP0000187103, a gene encoding a mitogen-activated protein kinase. Our data also indicated that for those carefully validated reference genes, a single reference gene is sufficient for reliable normalization of the quantitative gene expression. Depending on the experimental conditions, the most suitable reference genes can be specific to the sample of interest for more reliable RT-qPCR data normalization.

  20. Insert sequence length determines transfection efficiency and gene expression levels in bicistronic mammalian expression vectors

    OpenAIRE

    Payne, Andrew J; Gerdes, Bryan C; Kaja, Simon; Koulen, Peter

    2013-01-01

    Bicistronic expression vectors have been widely used for co-expression studies since the initial discovery of the internal ribosome entry site (IRES) about 25 years ago. IRES sequences allow the 5’ cap-independent initiation of translation of multiple genes on a single messenger RNA strand. Using a commercially available mammalian expression vector containing an IRES sequence with a 3’ green fluorescent protein fluorescent marker, we found that sequence length of the gene of interest expresse...

  1. Noise in gene expression is coupled to growth rate.

    Science.gov (United States)

    Keren, Leeat; van Dijk, David; Weingarten-Gabbay, Shira; Davidi, Dan; Jona, Ghil; Weinberger, Adina; Milo, Ron; Segal, Eran

    2015-12-01

    Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle-regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications. © 2015 Keren et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE)

    OpenAIRE

    P?rez-Plasencia, Carlos; Riggins, Gregory; V?zquez-Ortiz, Guelaguetza; Moreno, Jos?; Arreola, Hugo; Hidalgo, Alfredo; Pi?a-Sanchez, Patricia; Salcedo, Mauricio

    2005-01-01

    Abstract Background Serial Analysis of Gene Expression (SAGE) is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE), useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mai...

  3. 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.

  4. Mutation of the miaA gene of Agrobacterium tumefaciens results in reduced vir gene expression.

    OpenAIRE

    Gray, J; Wang, J; Gelvin, S B

    1992-01-01

    vir regulon expression in Agrobacterium tumefaciens involves both chromosome- and Ti-plasmid-encoded gene products. We have isolated and characterized a new chromosomal gene that when mutated results in a 2- to 10-fold reduction in the induced expression of vir genes by acetosyringone. This reduced expression occurs in AB minimal medium (pH 5.5) containing either sucrose or glucose and containing phosphate at high or low concentrations. The locus was cloned and used to complement A. tumefacie...

  5. 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.

  6. Expression profiles for six zebrafish genes during gonadal sex differentiation

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Morthorst, Jane E.; Andersen, Ole

    2008-01-01

    the precise timing of expression of six genes previously suggested to be associated with sex differentiation in zebrafish. The current study investigates the expression of all six genes in the same individual fish with extensive sampling dates during sex determination and -differentiation. RESULTS......BACKGROUND: The mechanism of sex determination in zebrafish is largely unknown and neither sex chromosomes nor a sex-determining gene have been identified. This indicates that sex determination in zebrafish is mediated by genetic signals from autosomal genes. The aim of this study was to determine......: In the present study, we have used quantitative real-time PCR to investigate the expression of ar, sox9a, dmrt1, fig alpha, cyp19a1a and cyp19a1b during the expected sex determination and gonadal sex differentiation period. The expression of the genes expected to be high in males (ar, sox9a and dmrt1a) and high...

  7. Gene expression profiles of Nitrosomonas europaea, an obligate chemolitotroph

    Energy Technology Data Exchange (ETDEWEB)

    Daniel J Arp

    2005-06-15

    Nitrosomonas europaea is an aerobic lithoautotrophic bacterium that uses ammonia (NH3) as its energy source. As a nitrifier, it is an important participant in the nitrogen cycle, which can also influence the carbon cycle. The focus of this work was to explore the genetic structure and mechanisms underlying the lithoautotrophic growth style of N. europaea. Whole genome gene expression. The gene expression profile of cells in exponential growth and during starvation was analyzed using microarrays. During growth, 98% of the genes increased in expression at least two fold compared to starvation conditions. In growing cells, approximately 30% of the genes were expressed eight fold higher, Approximately 10% were expressed more than 15 fold higher. Approximately 3% (91 genes) were expressed to more than 20 fold of their levels in starved cells. Carbon fixation gene expression. N. europaea fixes carbon via the Calvin-Benson-Bassham (CBB) cycle via a type I ribulose bisphosphate carboxylase/oxygenase (RubisCO). This study showed that transcription of cbb genes was up-regulated when the carbon source was limited, while amo, hao and other energy harvesting related genes were down-regulated. Iron related gene expression. Because N. europaea has a relatively high content of hemes, sufficient Fe must be available in the medium for it to grow. The genome revealed that approximately 5% of the coding genes in N. europaea are dedicated to Fe transport and assimilation. Nonetheless, with the exception of citrate biosynthesis genes, N. europaea lacks genes for siderophore production. The Fe requirements for growth and the expression of the putative membrane siderophore receptors were determined. The N. europaea genome has over 100 putative genes ({approx}5% of the coding genes) related to Fe uptake and its siderophore receptors could be grouped phylogenetically in four clusters. Fe related genes, such as a number of TonB-dependent Fe-siderophore receptors for ferrichrome and

  8. Gene expression profiles of Nitrosomonas europaea, an obligate chemolitotroph

    Energy Technology Data Exchange (ETDEWEB)

    Daniel J. Arp

    2005-05-25

    Nitrosomonas europaea is an aerobic lithoautotrophic bacterium that uses ammonia (NH3) as its energy source. As a nitrifier, it is an important participant in the nitrogen cycle, which can also influence the carbon cycle. The focus of this work was to explore the genetic structure and mechanisms underlying the lithoautotrophic growth style of N. europaea. Whole genome gene expression: The gene expression profile of cells in exponential growth and during starvation was analyzed using microarrays. During growth, 98% of the genes increased in expression at least two fold compared to starvation conditions. In growing cells, approximately 30% of the genes were expressed eight fold higher, Approximately 10% were expressed more than 15 fold higher. Approximately 3% (91 genes) were expressed to more than 20 fold of their levels in starved cells. Carbon fixation gene expression: N. europaea fixes carbon via the Calvin-Benson-Bassham (CBB) cycle via a type I ribulose bisphosphate carboxylase/oxygenase (RubisCO). This study showed that transcription of cbb genes was up-regulated when the carbon source was limited, while amo, hao and other energy harvesting related genes were down-regulated. Iron related gene expression: Because N. europaea has a relatively high content of hemes, sufficient Fe must be available in the medium for it to grow. The genome revealed that approximately 5% of the coding genes in N. europaea are dedicated to Fe transport and assimilation. Nonetheless, with the exception of citrate biosynthesis genes, N. europaea lacks genes for siderophore production. The Fe requirements for growth and the expression of the putative membrane siderophore receptors were determined. The N. europaea genome has over 100 putative genes ({approx}5% of the coding genes) related to Fe uptake and its siderophore receptors could be grouped phylogenetically in four clusters. Fe related genes, such as a number of TonB-dependent Fe-siderophore receptors for ferrichrome and

  9. An Interactive Database of Cocaine-Responsive Gene Expression

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman

    2002-01-01

    Full Text Available The postgenomic era of large-scale gene expression studies is inundating drug abuse researchers and many other scientists with findings related to gene expression. This information is distributed across many different journals, and requires laborious literature searches. Here, we present an interactive database that combines existing information related to cocaine-mediated changes in gene expression in an easy-to-use format. The database is limited to statistically significant changes in mRNA or protein expression after cocaine administration. The Flash-based program is integrated into a Web page, and organizes changes in gene expression based on neuroanatomical region, general function, and gene name. Accompanying each gene is a description of the gene, links to the original publications, and a link to the appropriate OMIM (Online Mendelian Inheritance in Man entry. The nature of this review allows for timely modifications and rapid inclusion of new publications, and should help researchers build second-generation hypotheses on the role of gene expression changes in the physiology and behavior of cocaine abuse. Furthermore, this method of organizing large volumes of scientific information can easily be adapted to assist researchers in fields outside of drug abuse.

  10. Detecting microRNA activity from gene expression data.

    LENUS (Irish Health Repository)

    Madden, Stephen F

    2010-01-01

    BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. RESULTS: Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. CONCLUSIONS: We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

  11. Detecting microRNA activity from gene expression data

    LENUS (Irish Health Repository)

    Madden, Stephen F

    2010-05-18

    Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. Results Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. Conclusions We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

  12. MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas.

    Science.gov (United States)

    Dalerba, P; Frascella, E; Macino, B; Mandruzzato, S; Zambon, A; Rosolen, A; Carli, M; Ninfo, V; Zanovello, P

    2001-07-01

    MAGE, BAGE and GAGE genes encode tumor-associated antigens that are presented by HLA class I molecules and recognized by CD8(+) cytolytic T lymphocytes. These antigens are currently regarded as promising targets for active, specific tumor immunotherapy because MAGE, BAGE and GAGE genes are expressed in many human cancers of different histotype and are silent in normal tissues, with the exception of spermatogonia and placental cells. MAGE, BAGE and GAGE gene expression has been extensively studied in different tumors of adults but is largely unknown in many forms of pediatric solid cancer. Using RT-PCR, we analyzed MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-6, BAGE, GAGE-1,-2 or -8 and GAGE-3,-4,-5,-6 or -7b gene expression in 31 samples of pediatric rhabdomyosarcoma, the most frequent form of malignant soft tissue tumor in children. MAGE genes were expressed in a substantial proportion of patients (MAGE-1, 38%; MAGE-2, 51%; MAGE-3, 35%; MAGE-4, 22%; MAGE-6, 35%), while expression of BAGE (6%); GAGE-1, GAGE-2 and GAGE-8 (9%); and GAGE-3, GAGE-4, GAGE-5, GAGE-6 and GAGE-7B (16%) was less frequent. Overall, 58% of tumors expressed at least 1 gene, and 35% expressed 3 or more genes simultaneously. Our data suggest that a subset of rhabdomyosarcoma patients could be eligible for active, specific immunotherapy directed against MAGE, BAGE and GAGE antigens. Copyright 2001 Wiley-Liss, Inc.

  13. A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

    Directory of Open Access Journals (Sweden)

    Emond Mary

    2007-09-01

    Full Text Available Abstract Background Marfan syndrome (MFS is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusion Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value -6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status. An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.

  14. Interplay of bistable kinetics of gene expression during cellular growth

    International Nuclear Information System (INIS)

    Zhdanov, Vladimir P

    2009-01-01

    In cells, the bistable kinetics of gene expression can be observed on the level of (i) one gene with positive feedback between protein and mRNA production, (ii) two genes with negative mutual feedback between protein and mRNA production, or (iii) in more complex cases. We analyse the interplay of two genes of type (ii) governed by a gene of type (i) during cellular growth. In particular, using kinetic Monte Carlo simulations, we show that in the case where gene 1, operating in the bistable regime, regulates mutually inhibiting genes 2 and 3, also operating in the bistable regime, the latter genes may eventually be trapped either to the state with high transcriptional activity of gene 2 and low activity of gene 3 or to the state with high transcriptional activity of gene 3 and low activity of gene 2. The probability to get to one of these states depends on the values of the model parameters. If genes 2 and 3 are kinetically equivalent, the probability is equal to 0.5. Thus, our model illustrates how different intracellular states can be chosen at random with predetermined probabilities. This type of kinetics of gene expression may be behind complex processes occurring in cells, e.g., behind the choice of the fate by stem cells

  15. Novel redox nanomedicine improves gene expression of polyion complex vector

    Directory of Open Access Journals (Sweden)

    Kazuko Toh, Toru Yoshitomi, Yutaka Ikeda and Yukio Nagasaki

    2011-01-01

    Full Text Available Gene therapy has generated worldwide attention as a new medical technology. While non-viral gene vectors are promising candidates as gene carriers, they have several issues such as toxicity and low transfection efficiency. We have hypothesized that the generation of reactive oxygen species (ROS affects gene expression in polyplex supported gene delivery systems. The effect of ROS on the gene expression of polyplex was evaluated using a nitroxide radical-containing nanoparticle (RNP as an ROS scavenger. When polyethyleneimine (PEI/pGL3 or PEI alone was added to the HeLa cells, ROS levels increased significantly. In contrast, when (PEI/pGL3 or PEI was added with RNP, the ROS levels were suppressed. The luciferase expression was increased by the treatment with RNP in a dose-dependent manner and the cellular uptake of pDNA was also increased. Inflammatory cytokines play an important role in ROS generation in vivo. In particular, tumor necrosis factor (TNF-α caused intracellular ROS generation in HeLa cells and decreased gene expression. RNP treatment suppressed ROS production even in the presence of TNF-α and increased gene expression. This anti-inflammatory property of RNP suggests that it may be used as an effective adjuvant for non-viral gene delivery systems.

  16. Biasogram: visualization of confounding technical bias in gene expression data

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Szallasi, Zoltan Imre; Eklund, Aron Charles

    2013-01-01

    Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors...... such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined...... by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may...

  17. Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

  18. Bioluminescence Imaging of Period1 Gene Expression in Utero

    Directory of Open Access Journals (Sweden)

    Meera T. Saxena

    2007-01-01

    Full Text Available The use of real-time reporters has accelerated our understanding of gene expression in vivo. This study examined the feasibility of a luciferase-based reporter to image spatiotemporal changes in fetal gene expression in utero. We chose to monitor Period1 (Per1 because it is expressed broadly in the body and plays a role in circadian rhythmicity. Using rats carrying a Per1::luc transgene, we repetitively imaged fetuses in utero throughout gestation. We found that bioluminescence was specific to transgenic pups, increased dramatically on embryonic day 10 (10 days after successful mating, and continued to increase logarithmically until birth. Diurnal fluctuations in Per1 expression were apparent several days prior to birth. These results demonstrate the feasibility of in utero imaging of mammalian gene expression, tracking of fetal gene expression from the same litter, and early detection of mammalian clock gene expression. We conclude that luciferase-based reporters can provide a sensitive, noninvasive measure of in utero gene expression.

  19. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  20. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    International Nuclear Information System (INIS)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T.

    2004-01-01

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  1. Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.

    Science.gov (United States)

    Gerashchenko, Dmitry; Pasumarthi, Ravi K; Kilduff, Thomas S

    2017-07-01

    Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  2. Molecular subsets in the gene expression signatures of scleroderma skin.

    Directory of Open Access Journals (Sweden)

    Ausra Milano

    2008-07-01

    Full Text Available Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production.We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc with diffuse scleroderma (dSSc, 7 patients with SSc with limited scleroderma (lSSc, 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of 'intrinsic' genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p<0.001 and each has been mapped to clinical covariates of modified Rodnan skin score, interstitial lung disease, gastrointestinal involvement, digital ulcers, Raynaud's phenomenon and disease duration. We report a 177-gene signature that is associated with severity of skin disease in dSSc.Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays. The diversity in gene expression demonstrates multiple distinct gene expression programs in the skin of patients with scleroderma.

  3. Blood cell gene expression profiling in rheumatoid arthritis. Discriminative genes and effect of rheumatoid factor

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Rieneck, Klaus; Workman, Christopher

    2004-01-01

    To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA...... patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays. The analyses showed no significant differences in PBMC expression patterns from RF-positive and RF-negative patients. However, comparisons of gene expression patterns...

  4. Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.

    Science.gov (United States)

    Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav

    2018-04-16

    Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.

  5. Gene expression profiling predicts survival in conventional renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hongjuan Zhao

    2006-01-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  6. Gene Expression Profiling Predicts Survival in Conventional Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  7. Os odontoideum in identical twins: Comparative gene expression analysis.

    Science.gov (United States)

    Straus, David; Xu, Shunbin; Traynelis, Vincent C

    2014-01-01

    Os odontoideum is a well identified anomaly of the craniovertebral junction. Since its initial description, there has been a continuous debate regarding the nature of its etiology: Whether congenital or traumatic. We sought to compare the gene expression profiles in patients with congenital os odontoideum, those with traumatic os odontoideum and controls. We have evaluated a pair of identical twins both with os odontoideum. We identified two additional patients with and four subjects without os odontoideum. We analyzed the gene expression profiles in these patients using a custom TaqMan microarray and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The relative gene expression profiles in the two identical twins, the two nontwin patients with os odontoideum and the controls were assessed. A total of 213 genes with significantly different expression between the twin os odontoideum patients and the subjects without os odontoideum were detected. CACNG6, PHEX, CACNAD3, IL2, FAS, TUFT1, KIT, TGFBR2, and IGF2 were expressed at levels greater than 100-fold more in the twins. There were six genes with significantly different expression profiles in the twins as compared with the nontwin os odontoideum patients: CMK4, ATF1, PLCG1, TAB1, E2F3, and ATF4. There were no statistically significant differences in gene expression in the four patients with os odontoideum and the subjects without. Trends, however, were noted in MMP8, KIT, HIF1A, CREB3, PWHAZ, TGFBR1, NFKB2, FGFR1, IPO8, STAT1, COL1A1, and BMP3. Os odontoideum has multiple etiologies, both traumatic and congenital and perhaps some represent a combination of the two. This work has identified a number of genes that show increased expression in a pair of twins with congenital os odontoideum and also demonstrates trends in gene expression profiles between a larger group of os odontoideum patients and non-os patients. A number of these genes are related to bone morphogenesis and maintenance.

  8. A deep auto-encoder model for gene expression prediction.

    Science.gov (United States)

    Xie, Rui; Wen, Jia; Quitadamo, Andrew; Cheng, Jianlin; Shi, Xinghua

    2017-11-17

    Gene expression is a key intermediate level that genotypes lead to a particular trait. Gene expression is affected by various factors including genotypes of genetic variants. With an aim of delineating the genetic impact on gene expression, we build a deep auto-encoder model to assess how good genetic variants will contribute to gene expression changes. This new deep learning model is a regression-based predictive model based on the MultiLayer Perceptron and Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked denoising auto-encoder for feature selection and a multilayer perceptron framework for backpropagation. We further improve the model by introducing dropout to prevent overfitting and improve performance. To demonstrate the usage of this model, we apply MLP-SAE to a real genomic datasets with genotypes and gene expression profiles measured in yeast. Our results show that the MLP-SAE model with dropout outperforms other models including Lasso, Random Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with dropout, we show that gene expression quantifications predicted by the model solely based on genotypes, align well with true gene expression patterns. We provide a deep auto-encoder model for predicting gene expression from SNP genotypes. This study demonstrates that deep learning is appropriate for tackling another genomic problem, i.e., building predictive models to understand genotypes' contribution to gene expression. With the emerging availability of richer genomic data, we anticipate that deep learning models play a bigger role in modeling and interpreting genomics.

  9. Bovine Mammary Gene Expression Profiling during the Onset of Lactation

    Science.gov (United States)

    Gao, Yuanyuan; Lin, Xueyan; Shi, Kerong; Yan, Zhengui; Wang, Zhonghua

    2013-01-01

    Background Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. Methodology/Principal Findings To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE) on bovine mammary tissue at three time points (on approximately day 35 before parturition (−35 d), day 7 before parturition (−7 d) and day 3 after parturition (+3 d)). Approximately 6.2 million (M), 5.8 million (M) and 6.1 million (M) 21-nt cDNA tags were sequenced in the three cDNA libraries (−35 d, −7 d and +3 d), respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥2 or ≤−2 and a false discovery rate (FDR) of ≤0.001, a total of 812 genes were significantly differentially expressed at −7 d compared with −35 d (stage I). Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with −7 d (stage II), and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with −35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. Conclusions The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation. PMID:23990904

  10. Bovine mammary gene expression profiling during the onset of lactation.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Gao

    Full Text Available BACKGROUND: Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE on bovine mammary tissue at three time points (on approximately day 35 before parturition (-35 d, day 7 before parturition (-7 d and day 3 after parturition (+3 d. Approximately 6.2 million (M, 5.8 million (M and 6.1 million (M 21-nt cDNA tags were sequenced in the three cDNA libraries (-35 d, -7 d and +3 d, respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥ 2 or ≤-2 and a false discovery rate (FDR of ≤ 0.001, a total of 812 genes were significantly differentially expressed at -7 d compared with -35 d (stage I. Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with -7 d (stage II, and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with -35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. CONCLUSIONS: The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation.

  11. Assays for noninvasive imaging of reporter gene expression

    International Nuclear Information System (INIS)

    Gambhir, S.S.; Barrio, J.R.; Herschman, H.R.; Phelps, M.E.

    1999-01-01

    Repeated, noninvasive imaging of reporter gene expression is emerging as a valuable tool for monitoring the expression of genes in animals and humans. Monitoring of organ/cell transplantation in living animals and humans, and the assessment of environmental, behavioral, and pharmacologic modulation of gene expression in transgenic animals should soon be possible. The earliest clinical application is likely to be monitoring human gene therapy in tumors transduced with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene. Several candidate assays for imaging reporter gene expression have been studied, utilizing cytosine deaminase (CD), HSV1-tk, and dopamine 2 receptor (D2R) as reporter genes. For the HSV1-tk reporter gene, both uracil nucleoside derivatives (e.g., 5-iodo-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil [FIAU] labeled with 124 I, 131 I ) and acycloguanosine derivatives {e.g., 8-[ 18 F]fluoro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (8-[ 18 F]-fluoroganciclovir) ([ 18 F]FGCV), 9-[(3-[ 18 F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG)} have been investigated as reporter probes. For the D2R reporter gene, a derivative of spiperone {3-(2'-[ 18 F]-Fluoroethyl)spiperone ([ 18 F]FESP)} has been used with positron emission tomography (PET) imaging. In this review, the principles and specific assays for imaging reporter gene expression are presented and discussed. Specific examples utilizing adenoviral-mediated delivery of a reporter gene as well as tumors expressing reporter genes are discussed

  12. In plants, expression breadth and expression level distinctly and non-linearly correlate with gene structure

    Directory of Open Access Journals (Sweden)

    Yang Hangxing

    2009-11-01

    Full Text Available Abstract Background Compactness of highly/broadly expressed genes in human has been explained as selection for efficiency, regional mutation biases or genomic design. However, highly expressed genes in flowering plants were shown to be less compact than lowly expressed ones. On the other hand, opposite facts have also been documented that pollen-expressed Arabidopsis genes tend to contain shorter introns and highly expressed moss genes are compact. This issue is important because it provides a chance to compare the selectionism and the neutralism views about genome evolution. Furthermore, this issue also helps to understand the fates of introns, from the angle of gene expression. Results In this study, I used expression data covering more tissues and employ new analytical methods to reexamine the correlations between gene expression and gene structure for two flowering plants, Arabidopsis thaliana and Oryza sativa. It is shown that, different aspects of expression pattern correlate with different parts of gene sequences in distinct ways. In detail, expression level is significantly negatively correlated with gene size, especially the size of non-coding regions, whereas expression breadth correlates with non-coding structural parameters positively and with coding region parameters negatively. Furthermore, the relationships between expression level and structural parameters seem to be non-linear, with the extremes of structural parameters possibly scale as power-laws or logrithmic functions of expression levels. Conclusion In plants, highly expressed genes are compact, especially in the non-coding regions. Broadly expressed genes tend to contain longer non-coding sequences, which may be necessary for complex regulations. In combination with previous studies about other plants and about animals, some common scenarios about the correlation between gene expression and gene structure begin to emerge. Based on the functional relationships between

  13. A longitudinal study of gene expression in healthy individuals

    Directory of Open Access Journals (Sweden)

    Tessier Michel

    2009-06-01

    Full Text Available Abstract Background The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years and gender. Methods Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR, as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Results Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF, 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. Conclusion This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated

  14. Selection and validation of reference genes for gene expression analysis in apomictic and sexual Cenchrus ciliaris

    Science.gov (United States)

    2013-01-01

    Background Apomixis is a naturally occurring asexual mode of seed reproduction resulting in offspring genetically identical to the maternal plant. Identifying differential gene expression patterns between apomictic and sexual plants is valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a popular method for analyzing gene expression. Normalizing gene expression data using proper reference genes which show stable expression under investigated conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE, GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9 accessions of C. ciliaris. Findings Among tissue types evaluated, EF1alpha showed the highest level of expression while TUBA showed the lowest. When all tissue types were evaluated and compared between genotypes, EIF4A was the most stable reference gene. Gene expression stability for specific ovary stages of B-2S and B-12-9 was also determined. Except for TUBA, all other tested reference genes could be used for any stage-specific ovary tissue normalization, irrespective of the mode of reproduction. Conclusion Our gene expression stability assay using six reference genes, in sexual and apomictic accessions of C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types analyzed. All other tested reference genes, with the exception of TUBA, could be used for gene expression comparison studies between sexual and apomictic ovaries over multiple developmental stages. This reference gene validation data in C. ciliaris will serve as an important base for future apomixis-related transcriptome data validation. PMID:24083672

  15. Scaling of gene expression with transcription-factor fugacity.

    Science.gov (United States)

    Weinert, Franz M; Brewster, Robert C; Rydenfelt, Mattias; Phillips, Rob; Kegel, Willem K

    2014-12-19

    The proteins associated with gene regulation are often shared between multiple pathways simultaneously. By way of contrast, models in regulatory biology often assume these pathways act independently. We demonstrate a framework for calculating the change in gene expression for the interacting case by decoupling repressor occupancy across the cell from the gene of interest by way of a chemical potential. The details of the interacting regulatory architecture are encompassed in an effective concentration, and thus, a single scaling function describes a collection of gene expression data from diverse regulatory situations and collapses it onto a single master curve.

  16. The Role of Nuclear Bodies in Gene Expression and Disease

    Science.gov (United States)

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  17. Dihydrotestostenone increase the gene expression of androgen ...

    African Journals Online (AJOL)

    HNTEP cells were grown in basal medium and treated with DHT in different conditions. HNTEP cells under treatment with DHT (10-13 M) induced an increase in FHL-2 expression. In turn, high DHT concentrations (10-8 M) induced an increase in the expression SHP-1. The present data suggest that the SHP-1 and FHL-2 ...

  18. Cloning and selection of reference genes for gene expression ...

    African Journals Online (AJOL)

    Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...

  19. Differentially Expressed Genes in Human Prostatic Carcinoma

    National Research Council Canada - National Science Library

    Dong, Jin-Tang

    2001-01-01

    Unlike other major common cancers, no major tumor genes have been reported in prostate cancer, although this disease is the most frequently diagnosed cancer and the second leading cause of cancer death in American men...

  20. Reference genes for gene expression studies in wheat flag leaves grown under different farming conditions

    Directory of Open Access Journals (Sweden)

    Cordeiro Raposo Fernando

    2011-09-01

    Full Text Available Abstract Background Internal control genes with highly uniform expression throughout the experimental conditions are required for accurate gene expression analysis as no universal reference genes exists. In this study, the expression stability of 24 candidate genes from Triticum aestivum cv. Cubus flag leaves grown under organic and conventional farming systems was evaluated in two locations in order to select suitable genes that can be used for normalization of real-time quantitative reverse-transcription PCR (RT-qPCR reactions. The genes were selected among the most common used reference genes as well as genes encoding proteins involved in several metabolic pathways. Findings Individual genes displayed different expression rates across all samples assayed. Applying geNorm, a set of three potential reference genes were suitable for normalization of RT-qPCR reactions in winter wheat flag leaves cv. Cubus: TaFNRII (ferredoxin-NADP(H oxidoreductase; AJ457980.1, ACT2 (actin 2; TC234027, and rrn26 (a putative homologue to RNA 26S gene; AL827977.1. In addition of these three genes that were also top-ranked by NormFinder, two extra genes: CYP18-2 (Cyclophilin A, AY456122.1 and TaWIN1 (14-3-3 like protein, AB042193 were most consistently stably expressed. Furthermore, we showed that TaFNRII, ACT2, and CYP18-2 are suitable for gene expression normalization in other two winter wheat varieties (Tommi and Centenaire grown under three treatments (organic, conventional and no nitrogen and a different environment than the one tested with cv. Cubus. Conclusions This study provides a new set of reference genes which should improve the accuracy of gene expression analyses when using wheat flag leaves as those related to the improvement of nitrogen use efficiency for cereal production.

  1. Differential testicular gene expression in seasonal fertility

    OpenAIRE

    Maywood, Elizabeth S.; Chahad-Ehlers, Samira; Garabette, Martine L.; Pritchard, Claire; Underhill, Phillip; Greenfield, Andrew; Ebling, Francis J. P.; Kyriacou, Charalambos P.; Hastings, Michael H.; Reddy, Akhilesh B.

    2009-01-01

    Spermatogenesis is an essential precursor for successful sexual reproduction. Recently, there has been an expansion in our knowledge of the genes associated with particular stages of normal, physiological testicular development and pubertal activation. What has been lacking, however, is an understanding of those genes that are involved in specifically regulating sperm production, rather than in maturation and elaboration of the testis as an organ. By utilising the reversible (seasonal) fertil...

  2. Gene expression profiling of Drosophila tracheal fusion cells.

    Science.gov (United States)

    Chandran, Rachana R; Iordanou, Ekaterini; Ajja, Crystal; Wille, Michael; Jiang, Lan

    2014-07-01

    The Drosophila trachea is a premier genetic system to investigate the fundamental mechanisms of tubular organ formation. Tracheal fusion cells lead the branch fusion process to form an interconnected tubular network. Therefore, fusion cells in the Drosophila trachea will be an excellent model to study branch fusion in mammalian tubular organs, such as kidneys and blood vessels. The fusion process is a dynamic cellular process involving cell migration, adhesion, vesicle trafficking, cytoskeleton rearrangement, and membrane fusion. To understand how these cellular events are coordinated, we initiated the critical step to assemble a gene expression profile of fusion cells. For this study, we analyzed the expression of 234 potential tracheal-expressed genes in fusion cells during fusion cell development. 143 Tracheal genes were found to encode transcription factors, signal proteins, cytoskeleton and matrix proteins, transporters, and proteins with unknown function. These genes were divided into four subgroups based on their levels of expression in fusion cells compared to neighboring non-fusion cells revealed by in situ hybridization: (1) genes that have relative high abundance in fusion cells, (2) genes that are dynamically expressed in fusion cells, (3) genes that have relative low abundance in fusion cells, and (4) genes that are expressed at similar levels in fusion cells and non-fusion tracheal cells. This study identifies the expression profile of fusion cells and hypothetically suggests genes which are necessary for the fusion process and which play roles in distinct stages of fusion, as indicated by the location and timing of expression. These data will provide the basis for a comprehensive understanding of the molecular and cellular mechanisms of branch fusion. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The CK1 gene family: expression patterning in zebrafish development

    Directory of Open Access Journals (Sweden)

    AMELINA ALBORNOZ

    2007-01-01

    Full Text Available Protein kinase CK1 is a ser/thr protein kinase family which has been identified in the cytosol cell fraction, associated with membranes as well as in the nucleus. Several isoforms of this gene family have been described in various organisms: CK1á, CK1ß, CK1δ, CK1å and CK1γ. Over the last decade, several members of this family have been involved in development processes related to wnt and sonic hedgehog signalling pathways. However, there is no detailed temporal information on the CK1 family in embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe for the first time the cloning and detailed expression pattern of five CK1 zebrafish genes. Sequence analysis revealed that zebrafish CK1 proteins are highly homologous to other vertebrate orthologues. Zebrafish CK1 genes are expressed throughout development in common and different territories. All the genes studied in development show maternal and zygotic expression with the exception of CK1å. This last gene presents only a zygotic component of expression. In early stages of development CK1 genes are ubiquitously expressed with the exception of CK1å. In later stages the five CK1 genes are expressed in the brain but not in the same way. This observation probably implicates the CK1 family genes in different and also in redundant functions. This is the first time that a detailed comparison of the expression of CK1 family genes is directly assessed in a vertebrate system throughout development

  4. Integrated olfactory receptor and microarray gene expression databases

    Directory of Open Access Journals (Sweden)

    Crasto Chiquito J

    2007-06-01

    Full Text Available Abstract Background Gene expression patterns of olfactory receptors (ORs are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB, which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction. Description ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data. Conclusion ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

  5. Global Gene Expression Analysis for the Assessment of Nanobiomaterials.

    Science.gov (United States)

    Hanagata, Nobutaka

    2015-01-01

    Using global gene expression analysis, the effects of biomaterials and nanomaterials can be analyzed at the genetic level. Even though information obtained from global gene expression analysis can be useful for the evaluation and design of biomaterials and nanomaterials, its use for these purposes is not widespread. This is due to the difficulties involved in data analysis. Because the expression data of about 20,000 genes can be obtained at once with global gene expression analysis, the data must be analyzed using bioinformatics. A method of bioinformatic analysis called gene ontology can estimate the kinds of changes on cell functions caused by genes whose expression level is changed by biomaterials and nanomaterials. Also, by applying a statistical analysis technique called hierarchical clustering to global gene expression data between a variety of biomaterials, the effects of the properties of materials on cell functions can be estimated. In this chapter, these theories of analysis and examples of applications to nanomaterials and biomaterials are described. Furthermore, global microRNA analysis, a method that has gained attention in recent years, and its application to nanomaterials are introduced. © 2015 S. Karger AG, Basel.

  6. Gene expression for carbonic anhydrase isoenzymes in human nasal mucosa.

    Science.gov (United States)

    Tarun, Alice S; Bryant, Bruce; Zhai, Wenwu; Solomon, Colin; Shusterman, Dennis

    2003-09-01

    Carbonic anhydrase (CA) is physiologically important in the reversible hydration reaction of CO(2); it is expressed in a number of isoforms (CA I-XIV) with varying degrees of enzymatic activity. In nasal chemesthesis, CA inhibition decreases the electrophysiologic response to CO(2), a common irritant test compound. CA enzymatic activity has been demonstrated in the human nasal mucosa using enzyme histochemical methods, but no systematic study of nasal mucosal CA isoenzyme gene expression has been published. We examined CA gene expression in superficial nasal mucosal scrapings from 15 subjects (6 females; 6 allergic rhinitics; age range, 21-56 years). Both non-quantitative and quantitative reverse transcription polymerase chain reaction (RT-PCR) were performed using primers for each gene coding for the 11 catalytically active CA isoenzymes and the housekeeping gene GADPH. Amplification products of GADPH and 10 of the 11 CA genes were detected in the specimens (CA VA was not detected). Relative expression of the CA genes was quantified using real-time PCR. Averaged across subjects, the relative abundance of the CA isoenzyme transcripts is as follows: CA XII > CA II > CA VB > CA IV > CA IX > CA III > CA XIV > CA I > CA VI > CA VII. Limited qualitative validation of gene expression was obtained by immunohistochemistry for CA I, CA II and CA IV. We also observed inter-individual variability in the expression of CA isoenzymes in human nasal mucosa, potentially contributing to differences in nasal chemosensitivity to CO(2) between individuals

  7. Carbon Catabolite Repression Regulates Glyoxylate Cycle Gene Expression in Cucumber.

    Science.gov (United States)

    Graham, I. A.; Denby, K. J.; Leaver, C. J.

    1994-01-01

    We have previously proposed that metabolic status is important in the regulation of cucumber malate synthase (MS) and isocitrate lyase (ICL) gene expression during plant development. In this article, we used a cell culture system to demonstrate that intracellular metabolic status does influence expression of both of these genes. Starvation of cucumber cell cultures resulted in the coordinate induction of the expression of MS and ICL genes, and this effect was reversed when sucrose was returned to the culture media. The induction of gene expression was closely correlated with a drop in intracellular sucrose, glucose, and fructose below threshold concentrations, but it was not correlated with a decrease in respiration rate. Glucose, fructose, or raffinose in the culture media also resulted in repression of MS and ICL. Both 2-deoxyglucose and mannose, which are phosphorylated by hexokinase but not further metabolized, specifically repressed MS and ICL gene expression relative to a third glyoxylate cycle gene, malate dehydrogenase. However, the addition of 3-methylglucose, an analog of glucose that is not phosphorylated, did not result in repression of either MS or ICL. It is proposed that the signal giving rise to a change in gene expression originates from the intracellular concentration of hexose sugars or the flux of hexose sugars into glycolysis. PMID:12244257

  8. A comparative study of three different gene expression analysis methods.

    Science.gov (United States)

    Choe, Jae Young; Han, Hyung Soo; Lee, Seon Duk; Lee, Hanna; Lee, Dong Eun; Ahn, Jae Yun; Ryoo, Hyun Wook; Seo, Kang Suk; Kim, Jong Kun

    2017-12-04

    TNF-α regulates immune cells and acts as an endogenous pyrogen. Reverse transcription polymerase chain reaction (RT-PCR) is one of the most commonly used methods for gene expression analysis. Among the alternatives to PCR, loop-mediated isothermal amplification (LAMP) shows good potential in terms of specificity and sensitivity. However, few studies have compared RT-PCR and LAMP for human gene expression analysis. Therefore, in the present study, we compared one-step RT-PCR, two-step RT-LAMP and one-step RT-LAMP for human gene expression analysis. We compared three gene expression analysis methods using the human TNF-α gene as a biomarker from peripheral blood cells. Total RNA from the three selected febrile patients were subjected to the three different methods of gene expression analysis. In the comparison of three gene expression analysis methods, the detection limit of both one-step RT-PCR and one-step RT-LAMP were the same, while that of two-step RT-LAMP was inferior. One-step RT-LAMP takes less time, and the experimental result is easy to determine. One-step RT-LAMP is a potentially useful and complementary tool that is fast and reasonably sensitive. In addition, one-step RT-LAMP could be useful in environments lacking specialized equipment or expertise.

  9. SIGNATURE: A workbench for gene expression signature analysis

    Directory of Open Access Journals (Sweden)

    Chang Jeffrey T

    2011-11-01

    Full Text Available Abstract Background The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. Results We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. Conclusions SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/.

  10. Gene Expression in Human Accessory Lacrimal Glands of Wolfring

    Science.gov (United States)

    Ubels, John L.; Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Van Dyken, Rachel E.; Hatton, Mark P.

    2012-01-01

    Purpose. The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Methods. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Results. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. Conclusions. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs. PMID:22956620

  11. Changes in gene expression during male meiosis in Petunia hybrida.

    Science.gov (United States)

    Cnudde, Filip; Hedatale, Veena; de Jong, Hans; Pierson, Elisabeth S; Rainey, Daphne Y; Zabeau, Marc; Weterings, Koen; Gerats, Tom; Peters, Janny L

    2006-01-01

    We analyzed changes in gene expression during male meiosis in Petunia by combining the meiotic staging of pollen mother cells from a single anther with cDNA-AFLP transcript profiling of mRNA from the synchronously developing sister anthers. The transcript profiling experiments focused on the identification of genes with a modulated expression profile during meiosis, while premeiotic archesporial cells and postmeiotic microspores served as a reference. About 8000 transcript tags, estimated at 30% of the total transcriptome, were generated, of which around 6% exhibited a modulated gene expression pattern at meiosis. Cluster analysis revealed a transcriptional cascade that coincides with the initiation and progression through all stages of the two meiotic divisions. Fragments that exhibited high expression specifically during meiosis I were characterized further by sequencing; 90 out of the 293 sequenced fragments showed homology with known genes, belonging to a wide range of gene classes, including previously characterized meiotic genes. In-situ hybridization experiments were performed to determine the spatial expression pattern for five selected transcript tags. Its concurrence with cDNA-AFLP transcript profiles indicates that this is an excellent approach to study genes involved in specialized processes such as meiosis. Our data set provides the potential to unravel unique meiotic genes that are as yet elusive to reverse genetics approaches.

  12. GESearch: An Interactive GUI Tool for Identifying Gene Expression Signature

    Directory of Open Access Journals (Sweden)

    Ning Ye

    2015-01-01

    Full Text Available The huge amount of gene expression data generated by microarray and next-generation sequencing technologies present challenges to exploit their biological meanings. When searching for the coexpression genes, the data mining process is largely affected by selection of algorithms. Thus, it is highly desirable to provide multiple options of algorithms in the user-friendly analytical toolkit to explore the gene expression signatures. For this purpose, we developed GESearch, an interactive graphical user interface (GUI toolkit, which is written in MATLAB and supports a variety of gene expression data files. This analytical toolkit provides four models, including the mean, the regression, the delegate, and the ensemble models, to identify the coexpression genes, and enables the users to filter data and to select gene expression patterns by browsing the display window or by importing knowledge-based genes. Subsequently, the utility of this analytical toolkit is demonstrated by analyzing two sets of real-life microarray datasets from cell-cycle experiments. Overall, we have developed an interactive GUI toolkit that allows for choosing multiple algorithms for analyzing the gene expression signatures.

  13. GESearch: An Interactive GUI Tool for Identifying Gene Expression Signature.

    Science.gov (United States)

    Ye, Ning; Yin, Hengfu; Liu, Jingjing; Dai, Xiaogang; Yin, Tongming

    2015-01-01

    The huge amount of gene expression data generated by microarray and next-generation sequencing technologies present challenges to exploit their biological meanings. When searching for the coexpression genes, the data mining process is largely affected by selection of algorithms. Thus, it is highly desirable to provide multiple options of algorithms in the user-friendly analytical toolkit to explore the gene expression signatures. For this purpose, we developed GESearch, an interactive graphical user interface (GUI) toolkit, which is written in MATLAB and supports a variety of gene expression data files. This analytical toolkit provides four models, including the mean, the regression, the delegate, and the ensemble models, to identify the coexpression genes, and enables the users to filter data and to select gene expression patterns by browsing the display window or by importing knowledge-based genes. Subsequently, the utility of this analytical toolkit is demonstrated by analyzing two sets of real-life microarray datasets from cell-cycle experiments. Overall, we have developed an interactive GUI toolkit that allows for choosing multiple algorithms for analyzing the gene expression signatures.

  14. Differential gene-expression profiles associated with gastric adenoma.

    Science.gov (United States)

    Takenawa, H; Kurosaki, M; Enomoto, N; Miyasaka, Y; Kanazawa, N; Sakamoto, N; Ikeda, T; Izumi, N; Sato, C; Watanabe, M

    2004-01-12

    Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The purpose of the present study was to identify gene-expression profiles linked to the heterogeneous nature of gastric adenoma as compared to adenocarcinoma. Suppression subtractive hybridisation analysis was performed to extract relevant genes from two cases of low- and high-grade gastric adenomas. The identified genes were quantified by RT-PCR in 14 low-grade adenoma, nine high-grade adenoma and nine adenocarcinoma samples, followed by hierarchical clustering analysis to separate tumours into groups according to their gene-expression profiles. Nine genes previously implicated in carcinogenesis in a variety of organs, including three genes related to gastric adenocarcinoma, were identified. The overexpression of these genes in gastric adenoma has not been reported previously. The clustering analysis of these nine genes across 32 cases identified three groups, one of which consisted primarily of adenocarcinomas, whereas the other two groups consisted of adenomas. One group of adenomas, characterised by larger tumour size, exhibited gene-expression profiles of an intestinal cell lineage implicated in the pathogenesis of an intestinal-type gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas with smaller tumour size exhibited a unique expression profile. In conclusion, clustering analysis of expression profiles using a limited number of genes may serve as molecular markers for gastric adenoma with different biological properties. Although the prognostic values of these gene-expression profiles need to be evaluated in further follow-up study of adenoma cases, these findings add new insights to (a) our understanding of the pathogenesis of gastric tumours, (b) the development of specific tumour markers for clinical practice, and (c) the design of novel therapeutic targets.

  15. Estradiol-induced gene expression in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Bowman, C.J.; Kroll, K.J.; Gross, T.G.; Denslow, N.D.

    2002-01-01

    Vitellogenin (Vtg) and estrogen receptor (ER) gene expression levels were measured in largemouth bass to evaluate the activation of the ER-mediated pathway by estradiol (E2). Single injections of E2 ranging from 0.0005 to 5 mg/kg up-regulated plasma Vtg in a dose-dependent manner. Vtg and ER mRNAs were measured using partial cDNA sequences corresponding to the C-terminal domain for Vtg and the ligand-binding domain of ER?? sequences. After acute E2-exposures (2 mg/kg), Vtg and ER mRNAs and plasma Vtg levels peaked after 2 days. The rate of ER mRNA accumulation peaked 36-42 h earlier than Vtg mRNA. The expression window for ER defines the primary response to E2 in largemouth bass and that for Vtg a delayed primary response. The specific effect of E2 on other estrogen-regulated genes was tested during these same time windows using differential display RT-PCR. Specific up-regulated genes that are expressed in the same time window as Vtg were ERp72 (a membrane-bound disulfide isomerase) and a gene with homology to an expressed gene identified in zebrafish. Genes that were expressed in a pattern that mimics the ER include the gene for zona radiata protein ZP2, and a gene with homology to an expressed gene found in winter flounder. One gene for fibrinogen ?? was down-regulated and an unidentified gene was transiently up-regulated after 12 h of exposure and returned to basal levels by 48 h. Taken together these studies indicate that the acute molecular response to E2 involves a complex network of responses over time. ?? 2002 Elsevier Science Ireland Ltd. All rights reserved.

  16. Domestication rewired gene expression and nucleotide diversity patterns in tomato.

    Science.gov (United States)

    Sauvage, Christopher; Rau, Andrea; Aichholz, Charlotte; Chadoeuf, Joël; Sarah, Gautier; Ruiz, Manuel; Santoni, Sylvain; Causse, Mathilde; David, Jacques; Glémin, Sylvain

    2017-08-01

    Plant domestication has led to considerable phenotypic modifications from wild species to modern varieties. However, although changes in key traits have been well documented, less is known about the underlying molecular mechanisms, such as the reduction of molecular diversity or global gene co-expression patterns. In this study, we used a combination of gene expression and population genetics in wild and crop tomato to decipher the footprints of domestication. We found a set of 1729 differentially expressed genes (DEG) between the two genetic groups, belonging to 17 clusters of co-expressed DEG, suggesting that domestication affected not only individual genes but also regulatory networks. Five co-expression clusters were enriched in functional terms involving carbohydrate metabolism or epigenetic regulation of gene expression. We detected differences in nucleotide diversity between the crop and wild groups specific to DEG. Our study provides an extensive profiling of the rewiring of gene co-expression induced by the domestication syndrome in one of the main crop species. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Prolactin Upregulates Female-Predominant P450 Gene Expressions and Downregulates Male-Predominant Gene Expressions in Mouse Liver.

    Science.gov (United States)

    Sato, Yuya; Kaneko, Yoshikatsu; Cho, Takamasa; Goto, Kei; Otsuka, Tadashi; Yamamoto, Suguru; Goto, Shin; Maruyama, Hiroki; Narita, Ichiei

    2017-06-01

    Prolactin is a polypeptide hormone with over 300 separate biologic activities. Its serum level is increased during pregnancy and lactation, and it has been reported that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (P450) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver P450 expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of expression of liver sex-predominant genes, including P450s. To investigate the role of prolactin in the hepatic gene expressions, pCAGGS expression vector containing mouse prolactin cDNA was transfected by hydrodynamic injection into both male and female mice. Hyperprolactinemia phosphorylated signal transducer and activator of transcription 5 in the liver and augmented female mouse liver mRNA expression of Cyp3a16 , Cyp3a41 , Cyp3a44 , Cyp2b9 , and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expression of male-predominant genes such as Cyp2d9 , Cyp7b1 , Mup1 , and Alas2 were reduced in male mice with hyperprolactinemia. The serum levels of conventional regulators of hepatic gene expressions, growth hormone, and testosterone were not affected by hyperprolactinemia. We demonstrated that prolactin upregulated female-predominant genes in female mice and downregulated male-predominant genes in male mice. We conjecture that higher concentration of prolactin would alter steroid and xenobiotic metabolisms by modulating hepatic P450 gene expressions during pregnancy and lactation. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Multiscale Embedded Gene Co-expression Network Analysis.

    Directory of Open Access Journals (Sweden)

    Won-Min Song

    2015-11-01

    Full Text Available Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3, the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA by: i introducing quality control of co-expression similarities, ii parallelizing embedded network construction, and iii developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs. We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA. MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  19. Multiscale Embedded Gene Co-expression Network Analysis.

    Science.gov (United States)

    Song, Won-Min; Zhang, Bin

    2015-11-01

    Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  20. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Kruhøffer, Mogens; Andersen, Thomas Thykjær

    2004-01-01

    The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (s...... in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present...

  1. The evolution of gene expression levels in mammalian organs

    DEFF Research Database (Denmark)

    Brawand, David; Soumillon, Magali; Necsulea, Anamaria

    2011-01-01

    Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across...... ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages...... and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped...

  2. Enhancement of plasmid-mediated stable gene expression by ...

    African Journals Online (AJOL)

    WPRE) is a possible enhancer of gene expression in mammalian cells that promotes efficient export of unspliced (RNA) into the cytoplasm, as has been proved in transient transfection. In this study, WPRE was evaluated for enhancing stable ...

  3. State-related alterations of gene expression in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Berk, Michael

    2012-01-01

    on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications. Results:  A total of 17......Munkholm K, Vinberg M, Berk M, Kessing LV. State-related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684-696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective:  Alterations in gene expression in bipolar disorder...... have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate...

  4. Gene expression, neurogenesis, and healing: psychosocial genomics of therapeutic hypnosis.

    Science.gov (United States)

    Rossi, Ernest L

    2003-01-01

    The historical lineage of therapeutic hypnosis in James Braid's "psychophysiology", Pierre Janet's "physiological modification", and Milton Erickson's "neuro-psycho-physiology" is extended to include current neuroscience research on activity-dependent gene expression, neurogenesis, and stem cells in memory, learning, behavior change, and healing. Three conditions that optimize gene expression and neurogenesis--novelty, environmental enrichment, and exercise--could integrate fundamentals of the theory, research, and practice of therapeutic hypnosis. Continuing research on immediate-early, activity-dependent, behavior state-related, and clock gene expression could enhance our understanding of how relaxation, sleep, dreaming, consciousness, arousal, stress and trauma are modulated by therapeutic hypnosis. It is speculated that therapeutic and post-hypnotic suggestion could be focused more precisely with the time parameters of gene expression and neurogenesis that range from minutes and hours for synthesizing new synapses to weeks and months for the generation and maturation of new, functioning neurons in the adult brain.

  5. Visually Relating Gene Expression and in vivo DNA Binding Data

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Min-Yu; Mackey, Lester; Ker?,; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  6. Cloning, expression and characterisation of a novel gene encoding ...

    African Journals Online (AJOL)

    微软用户

    2012-01-12

    families. The recombinant BtabCSP was successfully expressed in Escherichia coli cells. This is the first report on the existence of chemosensory protein-coding gene in whiteflies. It will help us to elucidate the molecular.

  7. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  8. Visual sensitivities tuned by heterochronic shifts in opsin gene expression

    Directory of Open Access Journals (Sweden)

    McFarland William N

    2008-05-01

    Full Text Available Abstract Background Cichlid fishes have radiated into hundreds of species in the Great Lakes of Africa. Brightly colored males display on leks and vie to be chosen by females as mates. Strong discrimination by females causes differential male mating success, rapid evolution of male color patterns and, possibly, speciation. In addition to differences in color pattern, Lake Malawi cichlids also show some of the largest known shifts in visual sensitivity among closely related species. These shifts result from modulated expression of seven cone opsin genes. However, the mechanisms for this modulated expression are unknown. Results In this work, we ask whether these differences might result from changes in developmental patterning of cone opsin genes. To test this, we compared the developmental pattern of cone opsin gene expression of the Nile tilapia, Oreochromis niloticus, with that of several cichlid species from Lake Malawi. In tilapia, quantitative polymerase chain reaction showed that opsin gene expression changes dynamically from a larval gene set through a juvenile set to a final adult set. In contrast, Lake Malawi species showed one of two developmental patterns. In some species, the expressed gene set changes slowly, either retaining the larval pattern or progressing only from larval to juvenile gene sets (neoteny. In the other species, the same genes are expressed in both larvae and adults but correspond to the tilapia adult genes (direct development. Conclusion Differences in visual sensitivities among species of Lake Malawi cichlids arise through heterochronic shifts relative to the ontogenetic pattern of the tilapia outgroup. Heterochrony has previously been shown to be a powerful mechanism for change in morphological evolution. We found that altering developmental expression patterns is also an important mechanism for altering sensory systems. These resulting sensory shifts will have major impacts on visual communication and could help

  9. Semi-supervised consensus clustering for gene expression data analysis

    OpenAIRE

    Wang, Yunli; Pan, Youlian

    2014-01-01

    Background Simple clustering methods such as hierarchical clustering and k-means are widely used for gene expression data analysis; but they are unable to deal with noise and high dimensionality associated with the microarray gene expression data. Consensus clustering appears to improve the robustness and quality of clustering results. Incorporating prior knowledge in clustering process (semi-supervised clustering) has been shown to improve the consistency between the data partitioning and do...

  10. Microarray analysis of gene expression during bacteriophage T4 infection.

    Science.gov (United States)

    Luke, Kimberly; Radek, Agnes; Liu, XiuPing; Campbell, John; Uzan, Marc; Haselkorn, Robert; Kogan, Yakov

    2002-08-01

    Genomic microarrays were used to examine the complex temporal program of gene expression exhibited by bacteriophage T4 during the course of development. The microarray data confirm the existence of distinct early, middle, and late transcriptional classes during the bacteriophage replicative cycle. This approach allows assignment of previously uncharacterized genes to specific temporal classes. The genomic expression data verify many promoter assignments and predict the existence of previously unidentified promoters.

  11. Gene structure, phylogeny and expression profile of the sucrose ...

    Indian Academy of Sciences (India)

    The Sus genes exhibited distinct but partially redundant expression profiles in cacao, with TcSus1, TcSus5 and TcSus6, being the predominant genes in the bark with phloem, TcSus2 predominantly expressing in the seed during the stereotype stage. TcSus3 and TcSus4 were significantly detected more in the pod husk and ...

  12. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  13. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes.

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B; Rivkees, Scott A; Wendler, Christopher C

    2014-12-15

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20-60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3-65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. Copyright © 2014 the American Physiological Society.

  14. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  15. [Gene expression profile of spinal ventral horn in ALS].

    Science.gov (United States)

    Yamamoto, Masahiko; Tanaka, Fumiaki; Sobue, Gen

    2007-10-01

    The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons as well as spinal ventral horn from autopsied patients with sporadic ALS were examined. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were significantly downregulated, and 1% were upregulated in motor neurons. In contrast with motor neurons, the total spinal ventral horn homogenates demonstrated 0.7% and 0.2% significant upregulation and downregulation of gene expression, respectively. Downregulated genes in motor neurons included those associated with cytoskeleton/axonal transport, transcription and cell surface antigens/receptors, such as dynactin 1 (DCTN1) and early growth response 3 (EGR3). In particular, DCTN1 was markedly downregulated in most residual motor neurons prior to the accumulation of pNF-H and ubiquitylated protein. Promoters for cell death pathway, death receptor 5 (DR5), cyclins C (CCNC) and A1 (CCNA), and caspases were upregulated, whereas cell death inhibitors, acetyl-CoA transporter (ACATN) and NF-kappaB (NFKB) were also upregulated. In terms of spinal ventral horn, the expression of genes related to cell surface antigens/receptors, transcription and cell adhesion/ECM were increased. The gene expression resulting in neurodegenerative and neuroprotective changes were both present in spinal motor neurons and ventral horn. Moreover, Inflammation-related genes, such as belonging to the cytokine family were not, however, significantly upregulated in either motor neurons or ventral horn. The sequence of motor neuron-specific gene expression changes from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death, and are helpful

  16. Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes.

    NARCIS (Netherlands)

    Kok, J.B. de; Roelofs, R.W.; Giesendorf, B.A.J.; Pennings, J.L.; Waas, E.T.; Feuth, A.B.; Swinkels, D.W.; Span, P.N.

    2005-01-01

    For interpretation of quantitative gene expression measurements in clinical tumor samples, a normalizer is necessary to correct expression data for differences in cellular input, RNA quality, and RT efficiency between samples. In many studies, a single housekeeping gene is used for normalization.

  17. Changes in skeletal muscle gene expression following clenbuterol administration

    Science.gov (United States)

    Spurlock, Diane M; McDaneld, Tara G; McIntyre, Lauren M

    2006-01-01

    Background Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P clenbuterol treatment. A total of 22,605 probesets were evaluated with 52 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signalling pathways, and genes involved in polyamine metabolism. Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for

  18. Digital Gene Expression Profiling to Explore Differentially Expressed Genes Associated with Terpenoid Biosynthesis during Fruit Development in Litsea cubeba

    Directory of Open Access Journals (Sweden)

    Ming Gao

    2016-09-01

    Full Text Available Mountain pepper (Litsea cubeba (Lour. Pers. (Lauraceae is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil.

  19. Microspatial gene expression patterns in the Amazon River Plume.

    Science.gov (United States)

    Satinsky, Brandon M; Crump, Byron C; Smith, Christa B; Sharma, Shalabh; Zielinski, Brian L; Doherty, Mary; Meng, Jun; Sun, Shulei; Medeiros, Patricia M; Paul, John H; Coles, Victoria J; Yager, Patricia L; Moran, Mary Ann

    2014-07-29

    We investigated expression of genes mediating elemental cycling at the microspatial scale in the ocean's largest river plume using, to our knowledge, the first fully quantitative inventory of genes and transcripts. The bacterial and archaeal communities associated with a phytoplankton bloom in Amazon River Plume waters at the outer continental shelf in June 2010 harbored ∼ 1.0 × 10(13) genes and 4.7 × 10(11) transcripts per liter that mapped to several thousand microbial genomes. Genomes from free-living cells were more abundant than those from particle-associated cells, and they generated more transcripts per liter for carbon fixation, heterotrophy, nitrogen and phosphorus uptake, and iron acquisition, although they had lower expression ratios (transcripts ⋅ gene(-1)) overall. Genomes from particle-associated cells contributed more transcripts for sulfur cycling, aromatic compound degradation, and the synthesis of biologically essential vitamins, with an overall twofold up-regulation of expression compared with free-living cells. Quantitatively, gene regulation differences were more important than genome abundance differences in explaining why microenvironment transcriptomes differed. Taxa contributing genomes to both free-living and particle-associated communities had up to 65% of their expressed genes regulated differently between the two, quantifying the extent of transcriptional plasticity in marine microbes in situ. In response to patchiness in carbon, nutrients, and light at the micrometer scale, Amazon Plume microbes regulated the expression of genes relevant to biogeochemical processes at the ecosystem scale.

  20. Random Subspace Aggregation for Cancer Prediction with Gene Expression Profiles

    Directory of Open Access Journals (Sweden)

    Liying Yang

    2016-01-01

    Full Text Available Background. Precisely predicting cancer is crucial for cancer treatment. Gene expression profiles make it possible to analyze patterns between genes and cancers on the genome-wide scale. Gene expression data analysis, however, is confronted with enormous challenges for its characteristics, such as high dimensionality, small sample size, and low Signal-to-Noise Ratio. Results. This paper proposes a method, termed RS_SVM, to predict gene expression profiles via aggregating SVM trained on random subspaces. After choosing gene features through statistical analysis, RS_SVM randomly selects feature subsets to yield random subspaces and training SVM classifiers accordingly and then aggregates SVM classifiers to capture the advantage of ensemble learning. Experiments on eight real gene expression datasets are performed to validate the RS_SVM method. Experimental results show that RS_SVM achieved better classification accuracy and generalization performance in contrast with single SVM, K-nearest neighbor, decision tree, Bagging, AdaBoost, and the state-of-the-art methods. Experiments also explored the effect of subspace size on prediction performance. Conclusions. The proposed RS_SVM method yielded superior performance in analyzing gene expression profiles, which demonstrates that RS_SVM provides a good channel for such biological data.

  1. Blood gene expression profiling of an early acetaminophen response.

    Science.gov (United States)

    Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

    2017-06-01

    Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

  2. Differential endometrial gene expression in pregnant and nonpregnant sows

    DEFF Research Database (Denmark)

    Østrup, Esben; Bauersachs, Stefan; Blum, Helmut

    2010-01-01

    obtained from the endometrium of pregnant sows and sows inseminated with inactivated semen. Analysis of the microarray data revealed 263 genes to be significantly differentially expressed between the pregnant and nonpregnant sows. Most gene ontology terms significantly enriched at pregnancy had allocated......In an attempt to unveil molecular processes controlling the porcine placentation, we have investigated the pregnancy-induced gene expression in the endometrium using the Affymetrix GeneChip Porcine Genome Array. At Day 14 after insemination, at the time of initial placentation, samples were...... more up-regulated genes than down-regulated genes. These terms included developmental process, transporter activity, calcium ion binding, apoptosis, cell motility, enzyme-linked receptor protein signaling pathway, positive regulation of cell proliferation, ion homeostasis, and hormone activity. Only...

  3. Drosophila Myc is required for normal DREF gene expression

    International Nuclear Information System (INIS)

    Dang Thi Phuong Thao; Seto, Hirokazu; Yamaguchi, Masamitsu

    2008-01-01

    The Drosophila DNA replication-related element-binding factor (dDREF) is required for the expression of many proliferation-related genes carrying the DRE sequence, 5'-TATCGATA. Finding a canonical E-box, 5'-CACGTG, in the dDREF gene promoter prompted us to explore the possibility that the dDREF gene is a target of Drosophila Myc (dMyc). Luciferase transient expression assays combined with RNA interference in Drosophila S2 cells revealed that knockdown of dmyc reduced dDREF gene promoter activity by 35% to 82%, an effect at least partly mediated by the E-box in the promoter. dm 4 /Y hemizygous mutant larvae demonstrated no maternal dMyc and severe impairment of dDREF mRNA transcription. dMyc loss of function in dm 2 /dm 2 homozygous mutant follicle cell clones also resulted in loss of anti-dDREF immunostaining in nuclei. In contrast, co-expression of dMyc-dMax up-regulated dDREF promoter activity in S2 cells. Furthermore, dMyc over-expressing clones exhibited a high level of dDREF gene expression in wing and eye discs. These results taken together indicate that dMyc is indeed required for dDREF gene expression

  4. Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue

    Directory of Open Access Journals (Sweden)

    Dunner Susana

    2008-09-01

    Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.

  5. Expression of conserved signalling pathway genes during ...

    Indian Academy of Sciences (India)

    However, though ES cells of different origins are regarded as equally pluripotent, their in vitro differentiation potential varies, suggesting that their response to developmental signals is different. The R1 cell line is widely used for gene manipulation due to its good growth characteristics and highly efficient germline ...

  6. Plant gene transfer and expression protocols

    National Research Council Canada - National Science Library

    Jones, Heddwyn

    1995-01-01

    ... proteins in plants can often lead to a better understanding of biochemical and physiological processes. Fourth, gene transfer technology has allowed the improvement of plant agricultural productivity. For example, plants have been engineered with improved viral resistance or the ability to withstand herbicide attack, therefore allowing a more eff...

  7. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    -based gene-lookup webservices, called HemaExplorer and BloodSpot. These web-services support the aim of making data and analysis of haematopoietic cells from mouse and human accessible for researchers without bioinformatics expertise. Finally, in order to aid the analysis of the very limited number...

  8. Classification and expression analyses of homeobox genes

    Indian Academy of Sciences (India)

    We present here the first genome-wide classification and comparative genomic analysis of the 14 homeobox genes present in D. discoideum. Based on the structural alignment of the homeodomains, they ... Himanshu Mishra1 Shweta Saran1. School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India ...

  9. Molecular characterization, expression profile of the FSHR gene and ...

    Indian Academy of Sciences (India)

    JIGUO XU

    2017-06-17

    Jun 17, 2017 ... Quantitative real-time PCR (RT-qPCR) results showed that the FSHR gene was expressed in all the 14 tested tissues, and the ... and could be potential markers that can be used for marker-assisted selection programmes to increase egg production ... ancestors of protein kinase gene (B and C could also be.

  10. Research Article Gene expression profiling for coronary artery ...

    Indian Academy of Sciences (India)

    Shiridhar Kashyap

    Keywords. 19. Coronary artery disease; atherosclerosis; severity of lesion; gene expression; candidate genes; biological processes; north Indian population ..... to distinguish distinct two severities of CAD, thereby overcoming the skewed effect transition between control subjects to less severe CAD and to. 11 higher CAD.

  11. Gene ordering in partitive clustering using microarray expressions

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    the new hybrid approach, finds comparable or sometimes superior biological gene order in less computation time than those obtained by optimal leaf ordering in hierarchical clustering solution. Ray S S, Bandyopadhyay S and Pal S K 2007 Gene ordering in partitive clustering using microarray expressions; J. Biosci.

  12. Genomewide identification and expression analysis of the ARF gene ...

    Indian Academy of Sciences (India)

    Genomewide identification and expression analysis of the ARF gene family in apple. Xiao-Cui Luo, Mei-Hong Sun, Rui-Rui Xu, Huai-Rui Shu, Jia-Wei Wang and Shi-Zhong Zhang. J. Genet. 93, 785–797. Figure 1. Phylogenetic relation of apple ARF genes. The phylogenetic tree was constructed based on a complete protein ...

  13. Gene expression profiling of chicken intestinal host responses

    NARCIS (Netherlands)

    Hemert, van S.

    2007-01-01

    Chicken lines differ in genetic disease susceptibility. The scope of the research described in this thesis was to identify genes involved in genetic disease resistance in the chicken intestine. Therefore gene expression in the jejunum was investigated using a microarray approach. An intestine

  14. Different patterns of gene expression in rice varieties undergoing a ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... The rice line carrying the nonhost gene Rxo1, which was cloned from maize, exhibits a rapid hypersensitive response (HR) to Xanthomonas oryzae pv. oryzicola (Xoc). In this study, a microarray experiment was carried out to analyze the genome-wide gene expression responses to Xoc at the early stage in ...

  15. Scaling of gene expression with transcription-factor fugacity

    NARCIS (Netherlands)

    Weinert, Franz M; Brewster, Robert C; Rydenfelt, Mattias; Phillips, Rob; Kegel, Willem K

    2014-01-01

    The proteins associated with gene regulation are often shared between multiple pathways simultaneously. By way of contrast, models in regulatory biology often assume these pathways act independently. We demonstrate a framework for calculating the change in gene expression for the interacting case by

  16. Microarray analysis of adipose tissue gene expression profiles ...

    Indian Academy of Sciences (India)

    Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In order to visualize the mechanisms involved in the gene expression and regulation of lipid metabolism in adipose tissue, cDNA microarray containing 9 024 cDNA was used to construct gene ...

  17. A Critical Perspective On Microarray Breast Cancer Gene Expression Profiling

    NARCIS (Netherlands)

    Sontrop, H.M.J.

    2015-01-01

    Microarrays offer biologists an exciting tool that allows the simultaneous assessment of gene expression levels for thousands of genes at once. At the time of their inception, microarrays were hailed as the new dawn in cancer biology and oncology practice with the hope that within a decade diseases

  18. Diet induced gene expression in rat peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Caimari, A.; Oliver, P.; Rodenburg, W.; Keijer, Jaap; Palou, A.

    2009-01-01

    Gene expression of rat peripheral blood mononuclear cells was analyzed by microarray analysis in normoweight and in diet-induced obese rats (cafeteria rats). The aim of this study was to identify genes involved in energy homeostasis that are altered in the obese state.

  19. Importance of globin gene order for correct developmental expression.

    NARCIS (Netherlands)

    O. Hanscombe (Olivia); D. Whyatt (David); P.J. Fraser (Peter); N. Yannoutsos (Nikos); D.R. Greaves (David); N.O. Dillon (Niall); F.G. Grosveld (Frank)

    1991-01-01

    textabstractWe have used transgenic mice to study the influence of position of the human globin genes relative to the locus control region (LCR) on their expression pattern during development. The LCR, which is located 5' of the globin gene cluster, is normally required for the activation of all the

  20. Comparison of gene expression profiles in Bacillus megaterium ...

    African Journals Online (AJOL)

    Abstract. The MP agent, prepared from Bacillus megaterium isolated from the soil near tobacco fields, can improve metabolic products, and hence the aroma, of tobacco (Nicotiana tabacum) leaf. To explore genes regulating metabolic responses in tobacco leaf, we used microarrays to analyze differentially expressed genes ...

  1. Differential expressions of putative genes in various floral organs of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... Full Length Research Paper. Differential expressions of putative genes in various floral organs of the Pigeon orchid (Dendrobium crumenatum) using GeneFishing. Faridah, Q. Z.1, 2, Ng, B. Z.3, Raha, A. R.4, Umi, K. A. B.5 and Khosravi, A. R.2*. 1Department of Biology, Faculty Science, University Putra ...

  2. Identification of salt-stress induced differentially expressed genes in ...

    African Journals Online (AJOL)

    Identification of salt-stress induced differentially expressed genes in barley leaves using the annealingcontrol- primer-based GeneFishing technique. S Lee, K Lee, K Kim, GJ Choi, SH Yoon, HC Ji, S Seo, YC Lim, N Ahsan ...

  3. Genes differentially expressed in medulloblastoma and fetal brain

    NARCIS (Netherlands)

    Michiels, E. M.; Oussoren, E.; van Groenigen, M.; Pauws, E.; Bossuyt, P. M.; Voûte, P. A.; Baas, F.

    1999-01-01

    Serial analysis of gene expression (SAGE) was used to identify genes that might be involved in the development or growth of medulloblastoma, a childhood brain tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were determined. The distributions of sequence tags in each

  4. Different patterns of gene expression in rice varieties undergoing a ...

    African Journals Online (AJOL)

    Different patterns of gene expression in rice varieties undergoing a resistant or susceptible interaction with the bacterial leaf streak pathogen. ... rice line and its wild type were distinctly different: 92.00% of the DRGs were up-regulated in inoculated 9804-Rxo1 and 48.22% of the DRGs were sorted as defense-related genes.

  5. Evaluation of Appropriate Reference Genes for Gene Expression Normalization during Watermelon Fruit Development.

    Directory of Open Access Journals (Sweden)

    Qiusheng Kong

    Full Text Available Gene expression analysis in watermelon (Citrullus lanatus fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC, β-actin (ClACT, and alpha tubulin 5 (ClTUA5 as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1, a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.

  6. Evaluation of Appropriate Reference Genes for Gene Expression Normalization during Watermelon Fruit Development.

    Science.gov (United States)

    Kong, Qiusheng; Yuan, Jingxian; Gao, Lingyun; Zhao, Liqiang; Cheng, Fei; Huang, Yuan; Bie, Zhilong

    2015-01-01

    Gene expression analysis in watermelon (Citrullus lanatus) fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR) is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC), β-actin (ClACT), and alpha tubulin 5 (ClTUA5) as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND) was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1), a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.

  7. Probabilistic estimation of microarray data reliability and underlying gene expression

    Directory of Open Access Journals (Sweden)

    Sigvardsson Mikael

    2003-09-01

    Full Text Available Abstract Background The availability of high throughput methods for measurement of mRNA concentrations makes the reliability of conclusions drawn from the data and global quality control of samples and hybridization important issues. We address these issues by an information theoretic approach, applied to discretized expression values in replicated gene expression data. Results Our approach yields a quantitative measure of two important parameter classes: First, the probability P(σ|S that a gene is in the biological state σ in a certain variety, given its observed expression S in the samples of that variety. Second, sample specific error probabilities which serve as consistency indicators of the measured samples of each variety. The method and its limitations are tested on gene expression data for developing murine B-cells and a t-test is used as reference. On a set of known genes it performs better than the t-test despite the crude discretization into only two expression levels. The consistency indicators, i.e. the error probabilities, correlate well with variations in the biological material and thus prove efficient. Conclusions The proposed method is effective in determining differential gene expression and sample reliability in replicated microarray data. Already at two discrete expression levels in each sample, it gives a good explanation of the data and is comparable to standard techniques.

  8. Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis.

    Science.gov (United States)

    Hu, Yao Fei; Caron, Marc G; Sieber-Blum, Maya

    2009-04-08

    We have identified a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET) gene. NET is the target of psychotropic substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET mutations have been implicated in depression, anxiety, orthostatic intolerance and attention deficit hyperactivity disorder (ADHD). NET function in adult noradrenergic neurons of the peripheral and central nervous systems is to internalize norepinephrine from the synaptic cleft. By contrast, during embryogenesis norepinephrine (NE) transport promotes differentiation of neural crest stem cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors block noradrenergic differentiation. While the structure of NET und the regulation of NET function are well described, little is known about downstream target genes of norepinephrine (NE) transport. We have prepared gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) mouse neural crest cells using long serial analysis of gene expression (LongSAGE). Comparison analyses have identified a number of important differentially expressed genes, including genes relevant to neural crest formation, noradrenergic neuron differentiation and the phenotype of NETKO mice. Examples of differentially expressed genes that affect noradrenergic cell differentiation include genes in the bone morphogenetic protein (BMP) signaling pathway, the Phox2b binding partner Tlx2, the ubiquitin ligase Praja2, and the inhibitor of Notch signaling, Numbl. Differentially expressed genes that are likely to contribute to the NETKO phenotype include dopamine-beta-hydroxylase (Dbh), tyrosine hydroxylase (Th), the peptide transmitter 'cocaine and amphetamine regulated transcript' (Cart), and the serotonin receptor subunit Htr3a. Real-time PCR confirmed differential expression of key genes not only in neural

  9. Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis

    Directory of Open Access Journals (Sweden)

    Sieber-Blum Maya

    2009-04-01

    Full Text Available Abstract Background We have identified a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET gene. NET is the target of psychotropic substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET mutations have been implicated in depression, anxiety, orthostatic intolerance and attention deficit hyperactivity disorder (ADHD. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is to internalize norepinephrine from the synaptic cleft. By contrast, during embryogenesis norepinephrine (NE transport promotes differentiation of neural crest stem cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors block noradrenergic differentiation. While the structure of NET und the regulation of NET function are well described, little is known about downstream target genes of norepinephrine (NE transport. Results We have prepared gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO mouse neural crest cells using long serial analysis of gene expression (LongSAGE. Comparison analyses have identified a number of important differentially expressed genes, including genes relevant to neural crest formation, noradrenergic neuron differentiation and the phenotype of NETKO mice. Examples of differentially expressed genes that affect noradrenergic cell differentiation include genes in the bone morphogenetic protein (BMP signaling pathway, the Phox2b binding partner Tlx2, the ubiquitin ligase Praja2, and the inhibitor of Notch signaling, Numbl. Differentially expressed genes that are likely to contribute to the NETKO phenotype include dopamine-β-hydroxylase (Dbh, tyrosine hydroxylase (Th, the peptide transmitter 'cocaine and amphetamine regulated transcript' (Cart, and the serotonin receptor subunit Htr3a. Real-time PCR confirmed differential expression

  10. Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Kuramochi, Hidekazu; Crüger, Dorthe Gylling

    2011-01-01

    Microsatellite instability (MSI) is caused by defective mismatch repair (MMR) and is one of the very few molecular markers with proven clinical importance in colorectal cancer with respect to heredity, prognosis, and treatment effect. The gene expression of the MMR gene MSH2 may be a quantitative...... marker for the level of MMR and a potential molecular marker with clinical relevance. The aim was to investigate the gene expression of MSH2 in primary operable colorectal cancer in correlation with MSI, protein expression, and promoter hypermethylation. In a cohort of 210 patients, the primary tumor...... and lymphnode metastases were analyzed with immunohistochemistry, methylation and MSI analyses, and quantitative polymerase chain reaction (PCR). The median gene expression of MSH2 was 1.00 (range 0.16-11.2, quartiles 0.70-1.51) and there was good agreement between the gene expression in primary tumor and lymph...

  11. The Medicago truncatula gene expression atlas web server

    Directory of Open Access Journals (Sweden)

    Tang Yuhong

    2009-12-01

    Full Text Available Abstract Background Legumes (Leguminosae or Fabaceae play a major role in agriculture. Transcriptomics studies in the model legume species, Medicago truncatula, are instrumental in helping to formulate hypotheses about the role of legume genes. With the rapid growth of publically available Affymetrix GeneChip Medicago Genome Array GeneChip data from a great range of tissues, cell types, growth conditions, and stress treatments, the legume research community desires an effective bioinformatics system to aid efforts to interpret the Medicago genome through functional genomics. We developed the Medicago truncatula Gene Expression Atlas (MtGEA web server for this purpose. Description The Medicago truncatula Gene Expression Atlas (MtGEA web server is a centralized platform for analyzing the Medicago transcriptome. Currently, the web server hosts gene expression data from 156 Affymetrix GeneChip® Medicago genome arrays in 64 different experiments, covering a broad range of developmental and environmental conditions. The server enables flexible, multifaceted analyses of transcript data and provides a range of additional information about genes, including different types of annotation and links to the genome sequence, which help users formulate hypotheses about gene function. Transcript data can be accessed using Affymetrix probe identification number, DNA sequence, gene name, functional description in natural language, GO and KEGG annotation terms, and InterPro domain number. Transcripts can also be discovered through co-expression or differential expression analysis. Flexible tools to select a subset of experiments and to visualize and compare expression profiles of multiple genes have been implemented. Data can be downloaded, in part or full, in a tabular form compatible with common analytical and visualization software. The web server will be updated on a regular basis to incorporate new gene expression data and genome annotation, and is accessible

  12. The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.

    Science.gov (United States)

    Samaan, Z; Anand, S S; Anand, S; Zhang, X; Desai, D; Rivera, M; Pare, G; Thabane, L; Xie, C; Gerstein, H; Engert, J C; Craig, I; Cohen-Woods, S; Mohan, V; Diaz, R; Wang, X; Liu, L; Corre, T; Preisig, M; Kutalik, Z; Bergmann, S; Vollenweider, P; Waeber, G; Yusuf, S; Meyre, D

    2013-12-01

    Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

  13. Analysis of gene expression during neurite outgrowth and regeneration

    Directory of Open Access Journals (Sweden)

    Tai Yu

    2007-11-01

    Full Text Available Abstract Background The ability of a neuron to regenerate functional connections after injury is influenced by both its intrinsic state and also by extrinsic cues in its surroundings. Investigations of the transcriptional changes undergone by neurons during in vivo models of injury and regeneration have revealed many transcripts associated with these processes. Because of the complex milieu of interactions in vivo, these results include not only expression changes directly related to regenerative outgrowth and but also unrelated responses to surrounding cells and signals. In vitro models of neurite outgrowth provide a means to study the intrinsic transcriptional patterns of neurite outgrowth in the absence of extensive extrinsic cues from nearby cells and tissues. Results We have undertaken a genome-wide study of transcriptional activity in embryonic superior cervical ganglia (SCG and dorsal root ganglia (DRG during a time course of neurite outgrowth in vitro. Gene expression observed in these models likely includes both developmental gene expression patterns and regenerative responses to axotomy, which occurs as the result of tissue dissection. Comparison across both models revealed many genes with similar gene expression patterns during neurite outgrowth. These patterns were minimally affected by exposure to the potent inhibitory cue Semaphorin3A, indicating that this extrinsic cue does not exert major effects at the level of nuclear transcription. We also compared our data to several published studies of DRG and SCG gene expression in animal models of regeneration, and found the expression of a large number of genes in common between neurite outgrowth in vitro and regeneration in vivo. Conclusion Many gene expression changes undergone by SCG and DRG during in vitro outgrowth are shared between these two tissue types and in common with in vivo regeneration models. This suggests that the genes identified in this in vitro study may represent new

  14. Expression of T4 Lysozyme Gene (gene e) in Streptococcus ...

    African Journals Online (AJOL)

    GREGO

    2007-04-16

    Apr 16, 2007 ... cloning and inserting Streptococcal replication origin of pTRW10 vector into pL1. pL2 plasmid isolated from E. coli was introduced into S. salivarius subsp. thermophilus and Lactococcus lactis cells by electro-transformation. The lysozyme enzymes expressing by these bacteria were found to be active on.

  15. Expression of T4 Lysozyme Gene (gene e) in Streptococcus ...

    African Journals Online (AJOL)

    pL2 plasmid isolated from E. coli was introduced into S. salivarius subsp. thermophilus and Lactococcus lactis cells by electro-transformation. The lysozyme enzymes expressing by these bacteria were found to be active on Micrococcus luteus cells and thereby preventing their growth on assay plates. Thermostability of ...

  16. pH but not hypoxia affects neonatal gene expression: relevance for housekeeping gene selection.

    Science.gov (United States)

    Maron, Jill L; Arya, Michelle A; Seefeld, Kimberly J; Peter, Inga; Bianchi, Diana W; Johnson, Kirby L

    2008-07-01

    To identify a candidate neonatal housekeeping gene and to determine the effects of pH and PaO(2) on the stability of newborn gene expression in physiologically hypoxic and acidotic newborn blood. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) amplification was performed for four commonly used housekeeping genes (GAPDH, beta-actin, cyclophilin, 28S rRNA) on extracted RNA. Blood gas analyses determined pH and PaO(2) levels. Beta-Actin was the least variable and GAPDH the most variable housekeeping gene studied. pH negatively correlated with gene expression levels. PaO(2) levels did not significantly affect gene expression. These results inform selection of housekeeping genes for neonatal mRNA research.

  17. Relative expression of genes related with cold tolerance in ...

    African Journals Online (AJOL)

    Low temperature is one of the main abiotic stresses affecting rice yield in Chile. Alterations in phenology and physiology of the crop are observed after a cold event. The objective of this work was to study the relative expression of genes related with cold stress in Chilean cultivars of rice. For this, we analyzed the expression ...

  18. Gene-expression Classifier in Papillary Thyroid Carcinoma

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Jespersen, Marie Louise; Krogdahl, Annelise

    2016-01-01

    BACKGROUND: No reliable biomarker for metastatic potential in the risk stratification of papillary thyroid carcinoma exists. We aimed to develop a gene-expression classifier for metastatic potential. MATERIALS AND METHODS: Genome-wide expression analyses were used. Development cohort: freshly...

  19. Ferritin reporter used for gene expression imaging by magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Kenji; Fuma, Kazuya; Tabata, Kaori [Department of Brain Functions, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi 464-8601 (Japan); Sawada, Makoto, E-mail: msawada@riem.nagoya-u.ac.jp [Department of Brain Functions, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi 464-8601 (Japan)

    2009-10-23

    Magnetic resonance imaging (MRI) is a minimally invasive way to provide high spatial resolution tomograms. However, MRI has been considered to be useless for gene expression imaging compared to optical imaging. In this study, we used a ferritin reporter, binding with biogenic iron, to make it a powerful tool for gene expression imaging in MRI studies. GL261 mouse glioma cells were over-expressed with dual-reporter ferritin-DsRed under {beta}-actin promoter, then gene expression was observed by optical imaging and MRI in a brain tumor model. GL261 cells expressing ferritin-DsRed fusion protein showed enhanced visualizing effect by reducing T2-weighted signal intensity for in vitro and in vivo MRI studies, as well as DsRed fluorescence for optical imaging. Furthermore, a higher contrast was achieved on T2-weighted images when permeating the plasma membrane of ferritin-DsRed-expressing GL261. Thus, a ferritin expression vector can be used as an MRI reporter to monitor in vivo gene expression.

  20. VESPUCCI: exploring patterns of gene expression in grapevine

    Directory of Open Access Journals (Sweden)

    Marco eMoretto

    2016-05-01

    Full Text Available Large-scale transcriptional studies aim to decipher the dynamic cellular responses to a stimulus, like different environmental conditions. In the era of high-throughput omics biology, the most used technologies for these purposes are microarray and RNA-Seq, whose data are usually required to be deposited in public repositories upon publication. Such repositories have the enormous potential to provide a comprehensive view of how different experimental conditions lead to expression changes, by comparing gene expression across all possible measured conditions. Unfortunately, this task is greatly impaired by differences among experimental platforms that make direct comparisons difficult.In this paper we present the Vitis Expression Studies Platform Using COLOMBOS Compendia Instances (VESPUCCI, a gene expression compendium for grapevine which was built by adapting an approach originally developed for bacteria, and show how it can be used to investigate complex gene expression patterns. We integrated nearly all publicly available microarray and RNA-Seq expression data: 1608 gene expression samples from 10 different technological platforms. Each sample has been manually annotated using a controlled vocabulary developed ad hoc to ensure both human readability and computational tractability. Expression data in the compendium can be visually explored using several tools provided by the web interface or can be programmatically accessed using the REST interface. VESPUCCI is freely accessible at http://vespucci.colombos.fmach.it.

  1. Subcloning and expression of human alpha-fetoprotein gene in ...

    African Journals Online (AJOL)

    Subcloning and expression of human alpha-fetoprotein gene in Pichia pastoris. ... in inducing protein production in auxotrophic media lacking histidine. This protein could be useful in monoclonal antibody production and in diagnostic kit preparations. Keywords: Alpha-fetoprotein, Pichia pastoris, cloning, expression ...

  2. Genetic effects on gene expression across human tissues

    NARCIS (Netherlands)

    Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan; Hormozdiari, Farhad; Howald, Cedric; Kyung Im, Hae; Jo, Brian; Yong Kang, Eun; Kim, Yungil; Kim-Hellmuth, Sarah; Lappalainen, Tuuli; Li, Gen; Li, Xin; Liu, Boxiang; Mangul, Serghei; McCarthy, Mark I.; McDowell, Ian C.; Mohammadi, Pejman; Monlong, Jean; Muñoz-Aguirre, Manuel; Ndungu, Anne W.; Nicolae, Dan L.; Nobel, Andrew B.; Oliva, Meritxell; Ongen, Halit; Palowitch, John J.; Panousis, Nikolaos; Papasaikas, Panagiotis; Park, Yoson; Parsana, Princy; Payne, Anthony J.; Peterson, Christine B.; Quan, Jie; Reverter, Ferran; Sabatti, Chiara; Saha, Ashis; Sammeth, Michael; Scott, Alexandra J.; Shabalin, Andrey A.; Sodaei, Reza; Stephens, Matthew; Stranger, Barbara E.; Strober, Benjamin J.; Sul, Jae Hoon; Tsang, Emily K.; Urbut, Sarah; van de Bunt, Martijn; Wang, Gao; Wen, Xiaoquan; Wright, Fred A.; Xi, Hualin S.; Yeger-Lotem, Esti; Zappala, Zachary; Zaugg, Judith B.; Zhou, Yi-Hui; Akey, Joshua M.; Bates, Daniel; Chan, Joanne; Claussnitzer, Melina; Demanelis, Kathryn; Diegel, Morgan; Doherty, Jennifer A.; Feinberg, Andrew P.; Fernando, Marian S.; Halow, Jessica; Hansen, Kasper D.; Haugen, Eric; Hickey, Peter F.; Hou, Lei; Jasmine, Farzana; Jian, Ruiqi; Jiang, Lihua; Johnson, Audra; Kaul, Rajinder; Kellis, Manolis; Kibriya, Muhammad G.; Lee, Kristen; Billy Li, Jin; Li, Qin; Lin, Jessica; Lin, Shin; Linder, Sandra; Linke, Caroline; Liu, Yaping; Maurano, Matthew T.; Molinie, Benoit; Nelson, Jemma; Neri, Fidencio J.; Park, Yongjin; Pierce, Brandon L.; Rinaldi, Nicola J.; Rizzardi, Lindsay F.; Sandstrom, Richard; Skol, Andrew; Smith, Kevin S.; Snyder, Michael P.; Stamatoyannopoulos, John; Tang, Hua; Wang, Li; Wang, Meng; van Wittenberghe, Nicholas; Wu, Fan; Zhang, Rui; Nierras, Concepcion R.; Branton, Philip A.; Carithers, Latarsha J.; Guan, Ping; Moore, Helen M.; Rao, Abhi; Vaught, Jimmie B.; Gould, Sarah E.; Lockart, Nicole C.; Martin, Casey; Struewing, Jeffery P.; Volpi, Simona; Addington, Anjene M.; Koester, Susan E.; Little, A. Roger; Brigham, Lori E.; Hasz, Richard; Hunter, Marcus; Johns, Christopher; Johnson, Mark; Kopen, Gene; Leinweber, William F.; Lonsdale, John T.; McDonald, Alisa; Mestichelli, Bernadette; Myer, Kevin; Roe, Brian; Salvatore, Michael; Shad, Saboor; Thomas, Jeffrey A.; Walters, Gary; Washington, Michael; Wheeler, Joseph; Bridge, Jason; Foster, Barbara A.; Gillard, Bryan M.; Karasik, Ellen; Kumar, Rachna; Miklos, Mark; Moser, Michael T.; Jewell, Scott D.; Montroy, Robert G.; Rohrer, Daniel C.; Valley, Dana R.; Davis, David A.; Mash, Deborah C.; Undale, Anita H.; Smith, Anna M.; Tabor, David E.; Roche, Nancy V.; McLean, Jeffrey A.; Vatanian, Negin; Robinson, Karna L.; Sobin, Leslie; Barcus, Mary E.; Valentino, Kimberly M.; Qi, Liqun; Hunter, Steven; Hariharan, Pushpa; Singh, Shilpi; Um, Ki Sung; Matose, Takunda; Tomaszewski, Maria M.; Barker, Laura K.; Mosavel, Maghboeba; Siminoff, Laura A.; Traino, Heather M.; Flicek, Paul; Juettemann, Thomas; Ruffier, Magali; Sheppard, Dan; Taylor, Kieron; Trevanion, Stephen J.; Zerbino, Daniel R.; Craft, Brian; Goldman, Mary; Haeussler, Maximilian; Kent, W. James; Lee, Christopher M.; Paten, Benedict; Rosenbloom, Kate R.; Vivian, John; Zhu, Jingchun; Brown, Andrew A.; Nguyen, Duyen Y.; Sullivan, Timothy J.; Addington, Anjene; Koester, Susan; Lockhart, Nicole C.; Roe, Bryan; Valley, Dana; He, Amy Z.; Kang, Eun Yong; Quon, Gerald; Ripke, Stephan; Shimko, Tyler C.; Teran, Nicole A.; Zhang, Hailei; Bustamante, Carlos D.; Guigó, Roderic

    2017-01-01

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

  3. Comparison of gene expression patterns between porcine cumulus ...

    African Journals Online (AJOL)

    These results suggest that the aberrant of gene expression patterns detected in the oocytes of NOs compared with COCs explains their reduced quality in terms of development and maturation. In conclusion, these differentially expressed mRNAs may be involved in cellular interactions between oocytes and cumulus cells ...

  4. Expression of bgt gene in transgenic birch (Betula platyphylla Suk ...

    African Journals Online (AJOL)

    Study on the characteristics of integration and expression is the basis of genetic stability of foreign genes in transgenic trees. To obtain insight into the relationship of transgene copy number and expression level, we screened 22 transgenic birch lines. Southern blot analysis of the transgenic birch plants indicated that the ...

  5. A fuzzy network module extraction technique for gene expression data

    Indian Academy of Sciences (India)

    2014-05-01

    May 1, 2014 ... tion. Therefore, in this study, the structural properties of the co-expression network inferred from gene expression microarray data were compared with the topological prop- erties of the known, well-established network data of the same organism. We use a Web application called. topoGSA (Glaab et al.

  6. Expression of bgt gene in transgenic birch (Betula platyphylla Suk.)

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... Study on the characteristics of integration and expression is the basis of genetic stability of foreign genes in transgenic trees. To obtain insight into the relationship of transgene copy number and expression level, we screened 22 transgenic birch lines. Southern blot analysis of the transgenic birch.

  7. Induction of gene expression in bacteria at optimal growth temperatures.

    Science.gov (United States)

    Jiang, Xinglin; Zhang, Haibo; Yang, Jianming; Liu, Min; Feng, Hongru; Liu, Xiaobin; Cao, Yujin; Feng, Dexin; Xian, Mo

    2013-06-01

    Traditional temperature-sensitive systems use either heat shock (40-42 °C) or cold shock (15-23 °C) to induce gene expression at temperatures that are not the optimal temperature for host cell growth (37 °C). This impacts the overall productivity and yield by disturbing cell growth and cellular metabolism. Here, we have developed a new system which controls gene expression in Escherichia coli at more permissive temperatures. The temperature-sensitive cI857-P L system and the classic lacI-P lacO system were connected in series to control the gene of interest. When the culture temperature was lowered, the thermolabile cI857 repressor was activated and blocked the expression of lacI from P L. Subsequently, the decrease of LacI derepressed the expression of gene of interest from P lacO . Using a green fluorescent protein marker, we demonstrated that (1) gene expression was tightly regulated at 42 °C and strongly induced by lowering temperature to 25-37 °C; (2) different levels of gene expression can be induced by varying culture temperature; and (3) gene expression after induction was sustained until the end of the log phase. We then applied this system in the biosynthesis of acetoin and demonstrated that high yield and production could be achieved using temperature induction. The ability to express proteins at optimal growth temperatures without chemical inducers is advantageous for large-scale and industrial fermentations.

  8. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  9. Novel gene expression tools for rice biotechnology

    Science.gov (United States)

    Biotechnology is an effective and important method of improving both quality and agronomic traits in rice. We are developing novel molecular tools for genetic engineering, with a focus on developing novel transgene expression control elements (i.e. promoters) for rice. A suite of monocot grass promo...

  10. Gene Expression in the Human Endolymphatic Sac

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2015-01-01

    a1 sodium-bicarbonate transporter, SLC9a2 sodium-hydrogen transporter, SLC12a3 thiazide-sensitive Na-Cl transporter, and SLC34a2 sodium-phosphate transporter. CONCLUSIONS: Several important ion transporters of the SLC family are expressed in the human endolymphatic sac, including Pendrin...

  11. Real-time PCR gene expression profiling

    Czech Academy of Sciences Publication Activity Database

    Kubista, Mikael; Sjögreen, B.; Forootan, A.; Šindelka, Radek; Jonák, Jiří; Andrade, J.M.

    2007-01-01

    Roč. 1, - (2007), s. 56-60 ISSN 1360-8606 R&D Projects: GA AV ČR KJB500520601 Institutional research plan: CEZ:AV0Z50520514 Keywords : real - time PCR, * expression profiling * statistical analysis Subject RIV: EB - Genetics ; Molecular Biology

  12. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Lipopolysaccharide (LPS) is a predominant glycolipid in the outer membranes of gam-negative bacteria that stimulates monocytes, macrophages, and neutrophils to produce cytokines. The aim was to study the expression profile of TLRs and cytokines and determine the role of LPS in the peripheral blood lymphocytes.

  13. 4 gene expression in hepatocellular carcinoma (HCC)

    African Journals Online (AJOL)

    Gamalat El Gedawy

    2016-06-06

    Jun 6, 2016 ... showed that overexpression of miRNA-21 was associated with advanced clinical stage and lymph node metastasis in breast cancer, colorectal cancer, laryngeal squamous cell carcinoma and HCC respectively. Furthermore, they indicated that patients with high miRNA-21 expression had poor prognosis.

  14. Patterns of expression of cell wall related genes in sugarcane

    Directory of Open Access Journals (Sweden)

    Lima D.U.

    2001-01-01

    Full Text Avail