4 results on '"Dahm S"'
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2. A meta-analysis of quantitative trait loci associated with body weight and adiposity in mice.
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Wuschke, S., Dahm, S., Schmidt, C., Joost, H-G., and Al-Hasani, H.
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OBESITY treatment , *BODY weight , *OBESITY , *LABORATORY mice , *OBESITY in animals , *METABOLIC disorders , *GENETICS - Abstract
Objective:Cross-breeding experiments with different mouse strains have successfully been used by many groups to identify genetic loci that predispose for obesity. In order to provide a statistical assessment of these quantitative trait loci (QTL) as a basis for a systematic investigation of candidate genes, we have performed a meta-analysis of genome-wide linkage scans for body weight and body fat.Data:From a total of 34 published mouse cross-breeding experiments, we compiled a list of 162 non-redundant QTL for body weight and 117 QTL for fat weight and body fat percentage. Collectively, these studies include data from 42 different parental mouse strains and >14 500 individual mice.Methods:The results of the studies were analyzed using the truncated product method (TPM).Results:The analysis revealed significant evidence (logarithm of odds (LOD) score >4.3) for linkage of body weight and adiposity to 49 different segments of the mouse genome. The most prominent regions with linkage for body weight and body fat (LOD scores 14.8–21.8) on chromosomes 1, 2, 7, 11, 15, and 17 contain a total of 58 QTL for body weight and body fat. At least 34 candidate genes and genetic loci, which have been implicated in regulation of body weight and body composition in rodents and/or humans, are found in these regions, including CCAAT/enhancer-binding protein alpha (C/EBPA), sterol regulatory element-binding transcription factor 1 (SREBP-1), peroxisome proliferator activator receptor delta (PPARD), and hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1). Our results demonstrate the presence of numerous distinct consensus QTL regions with highly significant LOD scores that control body weight and body composition. An interactive physical map of the QTL is available online at http://www.obesitygenes.org.International Journal of Obesity (2007) 31, 829–841. doi:10.1038/sj.ijo.0803473; published online 24 October 2006 [ABSTRACT FROM AUTHOR]
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- 2007
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3. A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis
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Heiko, Witt, Miklos Sahin Toth, Olfert, Landt, Jian Min Chen, Thilo, Kahne, Drenth, Joost P. H., Zoltan, Kukor, Edit, Szepessy, Walter, Halangk, Stefan, Dahm, Klaus, Rohde, Hans Ulrich Schulz, Cedric Le Marechal, Nejat, Akar, Ammann, Rudolf W., Kaspar, Truninger, Mario, Bargetzi, Eesh, Bhatia, Carlo, Castellani, Giulia Martina Cavestro, Milos, Cerny, DESTRO-BISOL, Giovanni, Spedini, Gabriella, Hans, Eiberg, Jansen, Jan B. M. J., Monika, Koudova, Eva, Rausova, Milan, Macek, Macek Jr, M., Nuria, Malats, Real, Francisco X., Hans Jurgen Menzel, Pedro, Moral, Roberta, Galavotti, Pier Franco Pignatti, Olga, Rickards, Julius, Spicak, Narcis Octavian Zarnescu, Wolfgang, Bock, Gress, Thomas M., Helmut, Friess, Johann, Ockenga, Hartmut, Schmidt, Roland, Pfutzer, Matthias, Lohr, Peter, Simon, Frank Ulrich Weiss, Lerch, Markus M., Niels, Teich, Volker, Keim, Thomas, Berg, Bertram, Wiedenmann, Werner, Luck, David Alexander Groneberg, Michael, Becker, Thomas, Keil, Andreas, Kage, Jana, Bernardova, Markus, Braun, Claudia, Guldner, Juliane, Halangk, Jonas, Rosendahl, Ulrike, Witt, Matthias, Treiber, Renate, Nickel, Claude, Ferec, Witt, H, SAHIN TOTH, M, Landt, O, Chen, Jm, Kahne, T, Drenth, Jp, Kukor, Z, Szepessy, E, Halangk, W, Dahm, S, Rohde, K, Schulz, Hu, LE MARECHAL, C, Akar, N, Ammann, Rw, Truninger, K, Bargetzi, M, Bhatia, E, Castellani, C, Cavestro, GIULIA MARTINA, Cerny, M, DESTRO BISOL, G, Spedini, G, Eiberg, H, Jansen, Jb, Koudova, M, Rausova, E, MACEK M., Jr, Malats, N, Real, Fx, Menzel, Hj, Moral, P, Galavotti, R, Pignatti, Pf, Rickards, O, Spicak, J, Zarnescu, No, Bock, W, Gress, Tm, Friess, H, Ockenga, J, Schmidt, H, Pfutzer, R, Lohr, M, Simon, P, Weiss, Fu, Lerch, Mm, Teich, N, Keim, V, Berg, T, Wiedenmann, B, Luck, W, Groneberg, Da, Becker, M, Keil, T, Kage, A, Bernardova, J, Braun, M, Guldner, C, Halangk, J, Rosendahl, J, Witt, U, Treiber, M, Nickel, R, and Ferec, C.
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trypsin inhibitor ,Models, Molecular ,Enteropeptidase ,Pancreatic disease ,Membrane transport and intracellular motility [NCMLS 5] ,arginine ,genetic risk ,chemistry.chemical_compound ,Models ,proteinosis ,Trypsin ,Pancreatic Secretory Trypsin Inhibitor ,PRSS1 gene ,enteropeptidase ,medicine.diagnostic_test ,adult ,Hydrolysis ,cationic trypsinogen ,protection ,unclassified drug ,enzyme activity ,female ,priority journal ,risk factor ,CHRONIC PANCREATITIS ,protein degradation ,Trypsinogen ,medicine.drug ,medicine.medical_specialty ,anionic trypsinogen ,Proteolysis ,Biology ,Article ,male ,Internal medicine ,Genetics ,medicine ,Matrix-Assisted Laser Desorption-Ionization ,Humans ,PRSS2 ,controlled study ,human ,Molecular gastro-enterology and hepatology [IGMD 2] ,gene ,DNA Primers ,Genetic polymorphism ,catalysis ,Base Sequence ,Spectrometry ,disease predisposition ,Molecular ,cationic trypsinogen prss1 ,glycine ,pancreatic secretory trypsin inhibitor spink1 ,trypsin ,trypsinogen ,article ,chronic pancreatitis ,codon ,genetic susceptibility ,major clinical study ,nucleotide sequence ,Chronic Disease ,Haplotypes ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mass ,medicine.disease ,Tripsinogen ,Tripsina ,Settore BIO/18 - Genetica ,Endocrinology ,Genetic defects of metabolism [UMCN 5.1] ,Pancreatitis ,chemistry ,Genètica - Abstract
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis. The initial experiments were supported by the DFG (Wi 2036/1-1). This work was supported by the Sonnenfeld-Stiftung, Berlin, Germany (to H.W.), the US National Institutes of Health (NIH) (grant DK058088 to M.S.-T.), INSERM (Institut National de la Santé et de la Recherche Médicale) and the Programme Hospitalier de Recherche Clinique (grant PHRC R 08-04 to C.F.)
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- 2006
- Full Text
- View/download PDF
4. Haplotype-based analysis of common variation in the acetyl-coA carboxylase alpha gene and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition
- Author
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Eva Ardanaz, James McKay, Guillem Pera, Véronique Chajès, Carla H. van Gils, Miren Dorronsoro, H. Bas Bueno-de-Mesquita, Rudolf Kaaks, Federico Canzian, Petra H.M. Peeters, Göran Berglund, Lydie Gioia, Sean V. Tavtigian, Heiner Boeing, Göran Hallmans, Carine Biessy, Carmen Martinez Garcia, Anja Olsen, Sheila Bingham, Antonia Trichopoulou, Olga M. Sinilnikova, Eiliv Lund, Naomi E. Allen, Franco Berrino, Per Lenner, Françoise Clavel-Chapelon, Stephan Dahm, Majken K. Jensen, Jakob Linseisen, Deepika DeSilva, Elio Riboli, José Ramón Quirós, Jonas Manjer, Kim Overvad, Anne Tjønneland, Laure Dossus, Dimitrios Trichopoulos, Rosario Tumino, Virginie Joulin, Paolo Vineis, Kay-Tee Khaw, Salvatore Panico, Gilbert M. Lenoir, Domenico Palli, Stéphanie Monnier, Jenny Chang-Claude, María José Tormo, Maria Koliva, David J. Hughes, Catherine Boillot, Timothy J. Key, Sinilnikova, Om, Mckay, Jd, Tavtigian, Sv, Canzian, F, Desilva, D, Biessy, C, Monnier, S, Dossus, L, Boillot, C, Gioia, L, Hughes, Dj, Jensen, Mk, Overvad, K, Tjonneland, A, Olsen, A, CLAVEL CHAPELON, F, Chajes, V, Joulin, V, Linseisen, J, CHANG CLAUDE, J, Boeing, H, Dahm, S, Trichopoulou, A, Trichopoulos, D, Koliva, M, Khaw, Kt, Bingham, S, Allen, Ne, Key, T, Palli, D, Panico, Salvatore, Berrino, F, Tumino, R, Vineis, P, BUENO DE MESQUITA, Hb, Peeters, Ph, VAN GILS, Ch, Lund, E, Pera, G, Quiros, Jr, Dorronsoro, M, MARTINEZ GARCIA, C, Tormo, Mj, Ardanaz, E, Hallmans, G, Lenner, P, Berglund, G, Manjer, J, Riboli, E, Lenoir, Gm, and Kaaks, R.
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Oncology ,Adult ,medicine.medical_specialty ,Genotype ,Epidemiology ,Breast Neoplasms ,Biology ,Breast cancer ,Gene Frequency ,Polymorphism (computer science) ,Risk Factors ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Alleles ,Aged ,Genetics ,Chi-Square Distribution ,Haplotype ,Acetyl-CoA carboxylase ,Case-control study ,Genetic Variation ,Middle Aged ,medicine.disease ,European Prospective Investigation into Cancer and Nutrition ,Europe ,Logistic Models ,Haplotypes ,Case-Control Studies ,Female ,Acetyl-CoA Carboxylase - Abstract
A key fatty acid synthesis enzyme, acetyl-CoA carboxylase α (ACC-α), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-α common genetic variation (allele frequency >5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotype-tagging polymorphisms efficiently capturing common variation within 325 kb of ACC-α and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-α common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis. (Cancer Epidemiol Biomarkers Prev 2007;16(3):409–15)
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- 2007
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