Search

Your search keyword '"Hackmann, Karl"' showing total 291 results
Start Over Author "Hackmann, Karl"
291 results on '"Hackmann, Karl"'

1. Limitations in next-generation sequencing-based genotyping of breast cancer polygenic risk score loci

Author

Baumann, Alexandra, Ruckert, Christian, Meier, Christoph, Hutschenreiter, Tim, Remy, Robert, Schnur, Benedikt, Döbel, Marvin, Fankep, Rudel Christian Nkouamedjo, Skowronek, Dariush, Kutz, Oliver, Arnold, Norbert, Katzke, Anna-Lena, Forster, Michael, Kobiela, Anna-Lena, Thiedig, Katharina, Zimmer, Andreas, Ritter, Julia, Weber, Bernhard H. F., Honisch, Ellen, Hackmann, Karl, Schmidt, Gunnar, Sturm, Marc, and Ernst, Corinna

Published
2024
Full Text
View/download PDF

4. Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis

Author

Verma, Divij, Kumar, Rahul, Pereira, Raquel S., Karantanou, Christina, Zanetti, Costanza, Minciacchi, Valentina R., Fulzele, Keertik, Kunz, Kathrin, Hoelper, Soraya, Zia-Chahabi, Sara, Jabagi, Marie-Joëlle, Emmerich, Joseph, Dray-Spira, Rosemary, Kuhlee, Franziska, Hackmann, Karl, Schroeck, Evelin, Wenzel, Philip, Müller, Stefan, Filmann, Natalie, Fontenay, Michaela, Pajevic, Paola Divieti, and Krause, Daniela S.

Published
2019
Full Text
View/download PDF

7. Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy

Author

Marrone, Lara, Poser, Ina, Casci, Ian, Japtok, Julia, Reinhardt, Peter, Janosch, Antje, Andree, Cordula, Lee, Hyun O., Moebius, Claudia, Koerner, Ellen, Reinhardt, Lydia, Cicardi, Maria Elena, Hackmann, Karl, Klink, Barbara, Poletti, Angelo, Alberti, Simon, Bickle, Marc, Hermann, Andreas, Pandey, Udai Bhan, Hyman, Anthony A., and Sterneckert, Jared L.

Published
2018
Full Text
View/download PDF

13. Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes

Author

Garcia-Pelaez, José, primary, Barbosa-Matos, Rita, additional, Lobo, Silvana, additional, Dias, Alexandre, additional, Garrido, Luzia, additional, Castedo, Sérgio, additional, Sousa, Sónia, additional, Pinheiro, Hugo, additional, Sousa, Liliana, additional, Monteiro, Rita, additional, Maqueda, Joaquin J, additional, Fernandes, Susana, additional, Carneiro, Fátima, additional, Pinto, Nádia, additional, Lemos, Carolina, additional, Pinto, Carla, additional, Teixeira, Manuel R, additional, Aretz, Stefan, additional, Bajalica-Lagercrantz, Svetlana, additional, Balmaña, Judith, additional, Blatnik, Ana, additional, Benusiglio, Patrick R, additional, Blanluet, Maud, additional, Bours, Vincent, additional, Brems, Hilde, additional, Brunet, Joan, additional, Calistri, Daniele, additional, Capellá, Gabriel, additional, Carrera, Sergio, additional, Colas, Chrystelle, additional, Dahan, Karin, additional, de Putter, Robin, additional, Desseignés, Camille, additional, Domínguez-Garrido, Elena, additional, Egas, Conceição, additional, Evans, D Gareth, additional, Feret, Damien, additional, Fewings, Eleanor, additional, Fitzgerald, Rebecca C, additional, Coulet, Florence, additional, Garcia-Barcina, María, additional, Genuardi, Maurizio, additional, Golmard, Lisa, additional, Hackmann, Karl, additional, Hanson, Helen, additional, Holinski-Feder, Elke, additional, Hüneburg, Robert, additional, Krajc, Mateja, additional, Lagerstedt-Robinson, Kristina, additional, Lázaro, Conxi, additional, Ligtenberg, Marjolijn J L, additional, Martínez-Bouzas, Cristina, additional, Merino, Sonia, additional, Michils, Geneviève, additional, Novaković, Srdjan, additional, Patiño-García, Ana, additional, Ranzani, Guglielmina Nadia, additional, Schröck, Evelin, additional, Silva, Inês, additional, Silveira, Catarina, additional, Soto, José L, additional, Spier, Isabel, additional, Steinke-Lange, Verena, additional, Tedaldi, Gianluca, additional, Tejada, María-Isabel, additional, Woodward, Emma R, additional, Tischkowitz, Marc, additional, Hoogerbrugge, Nicoline, additional, and Oliveira, Carla, additional

Published
2023
Full Text
View/download PDF

16. Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity

Author

Karpinski, Janet, Hauber, Ilona, Chemnitz, Jan, Schäfer, Carola, Paszkowski-Rogacz, Maciej, Chakraborty, Deboyoti, Beschorner, Niklas, Hofmann-Sieber, Helga, Lange, Ulrike C, Grundhoff, Adam, Hackmann, Karl, Schrock, Evelin, Abi-Ghanem, Josephine, Pisabarro, M Teresa, Surendranath, Vineeth, Schambach, Axel, Lindner, Christoph, van Lunzen, Jan, Hauber, Joachim, and Buchholz, Frank

Published
2016
Full Text
View/download PDF

17. Association Between Loss-of-Function Mutations Within the FANCM Gene and Early-Onset Familial Breast Cancer

Author

Neidhardt, Guido, Hauke, Jan, Ramser, Juliane, Groß, Eva, Gehrig, Andrea, Müller, Clemens R., Kahlert, Anne-Karin, Hackmann, Karl, Honisch, Ellen, Niederacher, Dieter, Heilmann-Heimbach, Stefanie, Franke, André, Lieb, Wolfgang, Thiele, Holger, Altmüller, Janine, Nürnberg, Peter, Klaschik, Kristina, Ernst, Corinna, Ditsch, Nina, Jessen, Frank, Ramirez, Alfredo, Wappenschmidt, Barbara, Engel, Christoph, Rhiem, Kerstin, Meindl, Alfons, Schmutzler, Rita K., and Hahnen, Eric

Published
2017
Full Text
View/download PDF

18. HBOC multi-gene panel testing: comparison of two sequencing centers

Author

Schroeder, Christopher, Faust, Ulrike, Sturm, Marc, Hackmann, Karl, Grundmann, Kathrin, Harmuth, Florian, Bosse, Kristin, Kehrer, Martin, Benkert, Tanja, Klink, Barbara, Mackenroth, Luisa, Betcheva-Krajcir, Elitza, Wimberger, Pauline, Kast, Karin, Heilig, Mechthilde, Nguyen, Huu Phuc, Riess, Olaf, Schröck, Evelin, Bauer, Peter, and Rump, Andreas

Published
2015
Full Text
View/download PDF

19. Uncovering the Contribution of Moderate-Penetrance Susceptibility Genes to Breast Cancer by Whole-Exome Sequencing and Targeted Enrichment Sequencing of Candidate Genes in Women of European Ancestry

Author

Dumont, Martine, Weber-Lassalle, Nana, Joly-Beauparlant, Charles, Ernst, Corinna, Droit, Arnaud, Feng, Bing-Jian, Dubois, Stephane, Collin-Deschesnes, Annie-Claude, Soucy, Penny, Vallee, Maxime, Fournier, Frederic, Lemacon, Audrey, Adank, Muriel A., Allen, Jamie, Altmueller, Janine, Arnold, Norbert, Ausems, Margreet G. E. M., Berutti, Riccardo, Bolla, Manjeet K., Bull, Shelley, Carvalho, Sara, Cornelissen, Sten, Dufault, Michael R., Dunning, Alison M., Engel, Christoph, Gehrig, Andrea, Geurts-Giele, Willemina R. R., Gieger, Christian, Green, Jessica, Hackmann, Karl, Helmy, Mohamed, Hentschel, Julia, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hooning, Maartje J., Horvath, Judit, Ikram, M. Arf An, Kaulfuss, Silke, Keeman, Renske, Kuang, Da, Luccarini, Craig, Maier, Wolfgang, Martens, John W. M., Niederacher, Dieter, Nurnberg, Peter, Ott, Claus-Eric, Peters, Annette, Pharoah, Paul D. P., Ramirez, Alfredo, Ramser, Juliane, Riedel-Heller, Steffi, Schmidt, Gunnar, Shah, Mitul, Scherer, Martin, Stabler, Antje, Strom, Tim M., Sutter, Christian, Thiele, Holger, van Asperen, Christi J., van der Kolk, Lizet, van der Luijt, Rob B., Volk, Alexander E., Wagner, Michael, Waisfisz, Quinten, Wang, Qin, Wang-Gohrke, Shan, Weber, Bernhard H. F., Devilee, Peter, Tavtigian, Sean, Bader, Gary D., Meindl, Alfons, Goldgar, David E., Andrulis, Irene L., Schmutzler, Rita K., Easton, Douglas F., Schmidt, Marjanka K., Hahnen, Eric, Simard, Jacques, Dumont, Martine, Weber-Lassalle, Nana, Joly-Beauparlant, Charles, Ernst, Corinna, Droit, Arnaud, Feng, Bing-Jian, Dubois, Stephane, Collin-Deschesnes, Annie-Claude, Soucy, Penny, Vallee, Maxime, Fournier, Frederic, Lemacon, Audrey, Adank, Muriel A., Allen, Jamie, Altmueller, Janine, Arnold, Norbert, Ausems, Margreet G. E. M., Berutti, Riccardo, Bolla, Manjeet K., Bull, Shelley, Carvalho, Sara, Cornelissen, Sten, Dufault, Michael R., Dunning, Alison M., Engel, Christoph, Gehrig, Andrea, Geurts-Giele, Willemina R. R., Gieger, Christian, Green, Jessica, Hackmann, Karl, Helmy, Mohamed, Hentschel, Julia, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hooning, Maartje J., Horvath, Judit, Ikram, M. Arf An, Kaulfuss, Silke, Keeman, Renske, Kuang, Da, Luccarini, Craig, Maier, Wolfgang, Martens, John W. M., Niederacher, Dieter, Nurnberg, Peter, Ott, Claus-Eric, Peters, Annette, Pharoah, Paul D. P., Ramirez, Alfredo, Ramser, Juliane, Riedel-Heller, Steffi, Schmidt, Gunnar, Shah, Mitul, Scherer, Martin, Stabler, Antje, Strom, Tim M., Sutter, Christian, Thiele, Holger, van Asperen, Christi J., van der Kolk, Lizet, van der Luijt, Rob B., Volk, Alexander E., Wagner, Michael, Waisfisz, Quinten, Wang, Qin, Wang-Gohrke, Shan, Weber, Bernhard H. F., Devilee, Peter, Tavtigian, Sean, Bader, Gary D., Meindl, Alfons, Goldgar, David E., Andrulis, Irene L., Schmutzler, Rita K., Easton, Douglas F., Schmidt, Marjanka K., Hahnen, Eric, and Simard, Jacques

Abstract

Simple Summary Genetic variants explaining approximately 40% of familial breast cancer risk have been identified, thus leaving a significant fraction of the heritability of this disease still unexplained. The exact nature of this missing fraction is unknown; more extensive sequencing efforts could potentially identify new moderate-penetrance breast cancer risk alleles. The aim of this study was to perform a large-scale whole-exome sequencing study, followed by a targeted validation, in breast cancer patients and healthy women of European descent. We identified 20 novel genes with modest evidence of association (p-value < 0.05) for either overall or subtype-specific breast cancer; however, much larger studies are needed to confirm the exact role of these genes in susceptibility to breast cancer. Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical p

Published
2022

21. Erratum: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease (PLoS Genetics (2021) 17:7 (e1009679) DOI: 10.1371/journal.pgen.1009679)

Author

Audain, Enrique, Wilsdon, Anna, Breckpot, Jeroen, Izarzugaza, Jose M. G., Fitzgerald, Tomas W., Kahlert, Anne-Karin, Sifrim, Alejandro, Wunnemann, Florian, Perez-Riverol, Yasset, Abdul-Khaliq, Hashim, Bak, Mads, Bassett, Anne S., Benson, D. Woodrow, Berger, Felix, Daehnert, Ingo, Devriendt, Koenraad, Dittrich, Sven, Daubeney, Piers Ef, Garg, Vidu, Hackmann, Karl, Hoff, Kirstin, Hofmann, Philipp, Dombrowsky, Gregor, Pickardt, Thomas, Bauer, Ulrike, Keavney, Bernard D., Klaassen, Sabine, Kramer, Hans-Heiner, Marshall, Christian R., Milewicz, Dianna M., Lemaire, Scott, Coselli, Joseph S., Mitchell, Michael E., Tomita-Mitchell, Aoy, Prakash, Siddharth K., Stamm, Karl, Stewart, Alexandre F. R., Silversides, Candice K., Siebert, Reiner, Stiller, Brigitte, Rosenfeld, Jill A., Vater, Inga, Postma, Alex V., Caliebe, Almuth, Brook, J. David, Andelfinger, Gregor, Hurles, Matthew E., Thienpont, Bernard, Larsen, Lars Allan, Hitz, Marc-Phillip, Human Genetics, Medical Biology, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Amsterdam Cardiovascular Sciences, and Amsterdam Reproduction & Development (AR&D)

Abstract

The thirteenth author's name is spelled incorrectly. The correct name is: D. Woodrow Benson.

Published
2021

24. Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Author

Audain, Enrique, primary, Wilsdon, Anna, additional, Breckpot, Jeroen, additional, Izarzugaza, Jose M. G., additional, Fitzgerald, Tomas W., additional, Kahlert, Anne-Karin, additional, Sifrim, Alejandro, additional, Wünnemann, Florian, additional, Perez-Riverol, Yasset, additional, Abdul-Khaliq, Hashim, additional, Bak, Mads, additional, Bassett, Anne S., additional, Benson, D. Woodrow, additional, Berger, Felix, additional, Daehnert, Ingo, additional, Devriendt, Koenraad, additional, Dittrich, Sven, additional, Daubeney, Piers EF, additional, Garg, Vidu, additional, Hackmann, Karl, additional, Hoff, Kirstin, additional, Hofmann, Philipp, additional, Dombrowsky, Gregor, additional, Pickardt, Thomas, additional, Bauer, Ulrike, additional, Keavney, Bernard D., additional, Klaassen, Sabine, additional, Kramer, Hans-Heiner, additional, Marshall, Christian R., additional, Milewicz, Dianna M., additional, Lemaire, Scott, additional, Coselli, Joseph S., additional, Mitchell, Michael E., additional, Tomita-Mitchell, Aoy, additional, Prakash, Siddharth K., additional, Stamm, Karl, additional, Stewart, Alexandre F. R., additional, Silversides, Candice K., additional, Siebert, Reiner, additional, Stiller, Brigitte, additional, Rosenfeld, Jill A., additional, Vater, Inga, additional, Postma, Alex V., additional, Caliebe, Almuth, additional, Brook, J. David, additional, Andelfinger, Gregor, additional, Hurles, Matthew E., additional, Thienpont, Bernard, additional, Larsen, Lars Allan, additional, and Hitz, Marc-Phillip, additional

Published
2021
Full Text
View/download PDF

25. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Author

Audain, Enrique, primary, Wilsdon, Anna, additional, Breckpot, Jeroen, additional, Izarzugaza, Jose M. G., additional, Fitzgerald, Tomas W., additional, Kahlert, Anne-Karin, additional, Sifrim, Alejandro, additional, Wünnemann, Florian, additional, Perez-Riverol, Yasset, additional, Abdul-Khaliq, Hashim, additional, Bak, Mads, additional, Bassett, Anne S., additional, Benson, Woodrow D., additional, Berger, Felix, additional, Daehnert, Ingo, additional, Devriendt, Koenraad, additional, Dittrich, Sven, additional, Daubeney, Piers EF, additional, Garg, Vidu, additional, Hackmann, Karl, additional, Hoff, Kirstin, additional, Hofmann, Philipp, additional, Dombrowsky, Gregor, additional, Pickardt, Thomas, additional, Bauer, Ulrike, additional, Keavney, Bernard D., additional, Klaassen, Sabine, additional, Kramer, Hans-Heiner, additional, Marshall, Christian R., additional, Milewicz, Dianna M., additional, Lemaire, Scott, additional, Coselli, Joseph S., additional, Mitchell, Michael E., additional, Tomita-Mitchell, Aoy, additional, Prakash, Siddharth K., additional, Stamm, Karl, additional, Stewart, Alexandre F. R., additional, Silversides, Candice K., additional, Siebert, Reiner, additional, Stiller, Brigitte, additional, Rosenfeld, Jill A., additional, Vater, Inga, additional, Postma, Alex V., additional, Caliebe, Almuth, additional, Brook, J. David, additional, Andelfinger, Gregor, additional, Hurles, Matthew E., additional, Thienpont, Bernard, additional, Larsen, Lars Allan, additional, and Hitz, Marc-Phillip, additional

Published
2021
Full Text
View/download PDF

26. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Author

Audain, Enrique, Wilsdon, Anna, Breckpot, Jeroen, Izarzugaza, Jose M.G., Fitzgerald, Tomas W., Kahlert, Anne Karin, Sifrim, Alejandro, Wünnemann, Florian, Perez-Riverol, Yasset, Abdul-Khaliq, Hashim, Bak, Mads, Bassett, Anne S., Benson, Woodrow D., Berger, Felix, Daehnert, Ingo, Devriendt, Koenraad, Dittrich, Sven, Daubeney, Piers E.F., Garg, Vidu, Hackmann, Karl, Hoff, Kirstin, Hofmann, Philipp, Dombrowsky, Gregor, Pickardt, Thomas, Bauer, Ulrike, Keavney, Bernard D., Klaassen, Sabine, Kramer, Hans Heiner, Marshall, Christian R., Milewicz, Dianna M., Lemaire, Scott, Coselli, Joseph S., Mitchell, Michael E., Tomita-Mitchell, Aoy, Prakash, Siddharth K., Stamm, Karl, Stewart, Alexandre F.R., Silversides, Candice K., Siebert, Reiner, Stiller, Brigitte, Rosenfeld, Jill A., Vater, Inga, Postma, Alex V., Caliebe, Almuth, Brook, J. David, Andelfinger, Gregor, Hurles, Matthew E., Thienpont, Bernard, Larsen, Lars Allan, Hitz, Marc Phillip, Audain, Enrique, Wilsdon, Anna, Breckpot, Jeroen, Izarzugaza, Jose M.G., Fitzgerald, Tomas W., Kahlert, Anne Karin, Sifrim, Alejandro, Wünnemann, Florian, Perez-Riverol, Yasset, Abdul-Khaliq, Hashim, Bak, Mads, Bassett, Anne S., Benson, Woodrow D., Berger, Felix, Daehnert, Ingo, Devriendt, Koenraad, Dittrich, Sven, Daubeney, Piers E.F., Garg, Vidu, Hackmann, Karl, Hoff, Kirstin, Hofmann, Philipp, Dombrowsky, Gregor, Pickardt, Thomas, Bauer, Ulrike, Keavney, Bernard D., Klaassen, Sabine, Kramer, Hans Heiner, Marshall, Christian R., Milewicz, Dianna M., Lemaire, Scott, Coselli, Joseph S., Mitchell, Michael E., Tomita-Mitchell, Aoy, Prakash, Siddharth K., Stamm, Karl, Stewart, Alexandre F.R., Silversides, Candice K., Siebert, Reiner, Stiller, Brigitte, Rosenfeld, Jill A., Vater, Inga, Postma, Alex V., Caliebe, Almuth, Brook, J. David, Andelfinger, Gregor, Hurles, Matthew E., Thienpont, Bernard, Larsen, Lars Allan, and Hitz, Marc Phillip

Abstract

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parentoffspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Published
2021

29. Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment

Author

Fiordaliso, Sarah K., Iwata-Otsubo, Aiko, Ritter, Alyssa L., Quesnel-Vallières, Mathieu, Fujiki, Katsunori, Nishi, Eriko, Hancarova, Miroslava, Miyake, Noriko, Morton, Jenny E.V., Lee, Sangmoon, Hackmann, Karl, Bando, Masashige, Masuda, Koji, Nakato, Ryuichiro, Arakawa, Michiko, Bhoj, Elizabeth, Li, Dong, Hakonarson, Hakon, Takeda, Ryojun, Harr, Margaret, Keena, Beth, Zackai, Elaine H., Okamoto, Nobuhiko, Mizuno, Seiji, Ko, Jung Min, Valachova, Alica, Prchalova, Darina, Vlckova, Marketa, Pippucci, Tommaso, Seiler, Christoph, Choi, Murim, Matsumoto, Naomichi, Di Donato, Nataliya, Barash, Yoseph, Sedlacek, Zdenek, Shirahige, Katsuhiko, and Izumi, Kosuke

Published
2019
Full Text
View/download PDF

31. Correction: Diagnostic value of partial exome sequencing in developmental disorders

Author

Gieldon, Laura, primary, Mackenroth, Luisa, additional, Kahlert, Anne-Karin, additional, Lemke, Johannes R., additional, Porrmann, Joseph, additional, Schallner, Jens, additional, von der Hagen, Maja, additional, Markus, Susanne, additional, Weidensee, Sabine, additional, Novotna, Barbara, additional, Soerensen, Charlotte, additional, Klink, Barbara, additional, Wagner, Johannes, additional, Tzschach, Andreas, additional, Jahn, Arne, additional, Kuhlee, Franziska, additional, Hackmann, Karl, additional, Schrock, Evelin, additional, Di Donato, Nataliya, additional, and Rump, Andreas, additional

Published
2020
Full Text
View/download PDF

33. Characterization of the binding protein-dependent cellobiose and cellotriose transport system of the cellulose degrader Streptomyces reticuli

Author

Schlosser, Andreas, Jantos, Jens, Hackmann, Karl, and Schrempf, Hildgund

Subjects
Streptomyces -- Research, Cellulose -- Research, Biological transport -- Research, Carrier proteins -- Research, Biodegradation -- Research, Biological sciences
Abstract

Streptomyces reticuli has an inducible ATP-dependent uptake system specific for cellobiose and cellotriose. Transcription of polycistronic ceb operon for the cellubiose binding protein (CebE), integral membrane protein and intracellular beta-glucosidase mRNAs is induced by cellobiose, whereas the ceb regulatory protein gene is transcribed independently. Immunological experiments showed that CebE is synthesized during growth with cellobiose and that ATP binding protein MsiK is produced in the presence of several sugars at high or moderate levels.

Published
1999

34. Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches

Author

Gieldon, Laura, William, Doreen, Hackmann, Karl, Jahn, Winnie, Jahn, Arne, Wagner, Johannes, Rump, Andreas, Bechmann, Nicole, Nölting, Svenja, Knösel, Thomas, Gudziol, Volker, Constantinescu, Georgiana, Masjkur, Jimmy, Beuschlein, Felix, Timmers, Henri J L M, Canu, Letizia, Pacak, Karel, Robledo, Mercedes, Aust, Daniela, Schröck, Evelin, Eisenhofer, Graeme, Richter, Susan, Klink, Barbara, Deutsche Forschungsgemeinschaft (Alemania), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), University of Zurich, and Klink, Barbara

Subjects
10265 Clinic for Endocrinology and Diabetology, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], 610 Medicine & health, Pheochromocytoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Sporadic, pheochromocytoma, lcsh:RC254-282, Article, Paraganglioma, paraganglioma, Hereditary, CNV detection, sporadic, Next-generation sequencing, next-generation sequencing, 2730 Oncology, 1306 Cancer Research, hereditary
Abstract

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in IDH2, ATRX and HRAS. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making. Acknowledgments: We thank the patients and their families who have made this research possible. We want to thank JacquesW. Lenders for his support. We further thank Alexander Krüger, Lydia Rossow and Franziska Stübner for technical support as well as Katharina Langton and Uwe Siemon for their assistance in patient administration. Sí

Published
2019

36. Additional file 1: of Targeted capture-based NGS is superior to multiplex PCR-based NGS for hereditary BRCA1 and BRCA2 gene analysis in FFPE tumor samples

Author

Zakrzewski, Falk, Gieldon, Laura, Rump, Andreas, Seifert, Michael, GrĂźtzmann, Konrad, KrĂźger, Alexander, Loos, Sina, Zeugner, Silke, Hackmann, Karl, Porrmann, Joseph, Wagner, Johannes, Kast, Karin, Wimberger, Pauline, Baretton, Gustavo, SchrĂśck, Evelin, Aust, Daniela, and Klink, Barbara

Abstract

Figure S1. Comparison of normalized coverage of targeted capture-based NGS to multiplex PCR-based NGS applied to FFPE tumor samples. A: Normalized coverage (y-axis) of targeted capture-based and multiplex PCR-based NGS of FFPE samples from patient 1 to 13 (Additional file 3: Table S2, P01 to P13) at single-base resolution along all concatenated BRCA1/2 targets (x-axis). Samples P01 to P13 are color-coded in blue. B: Normalized coverage (y-axis) of targeted capture-based and multiplex PCR-based NGS of FFPE samples from patient P14-P15 (Additional file 3: Table S2, P14 to P15) of FFPE samples from patient P14-P15 (Additional file 3: Table S2, P14 to P15) of FFPE samples from patient P14-P15 (Additional file 3: Table S2, P14 to P15) of FFPE samples from patient P14-P15 (Additional file 3: Table S2, P14 to P15) at single-base resolution along all concatenated BRCA1/2 targets (x-axis). Samples are color-coded in red and represent highly fragmented DNA. Exemplary, randomly chosen capture target dropouts and amplicon dropouts are marked by a red arrow. The vertical green line indicates the end of BRCA2 targets (target number is increasing from left to right which corresponds to five to three prime orientation of the gene) and the start of BRCA1 targets (target number is decreasing from left to right which corresponds to five to three prime orientation of the gene). The horizontal green line displays normalized coverage of 1.0. All target exons are separated by gray dotted vertical lines. Selected exons are marked. (PDF 2100 kb)

Published
2019
Full Text
View/download PDF

37. Diagnostic value of partial exome sequencing in developmental disorders

Author

Gieldon, Laura, Mackenroth, Luisa, Kahlert, Anne-Karin, Lemke, Johannes R., Porrmann, Joseph, Schallner, Jens, von der Hagen, Maja, Markus, Susanne, Weidensee, Sabine, Novotna, Barbara, Soerensen, Charlotte, Klink, Barbara, Wagner, Johannes, Tzschach, Andreas, Jahn, Arne, Kuhlee, Franziska, Hackmann, Karl, Schrock, Evelin, Di Donato, Nataliya, and Rump, Andreas

Subjects
Male, Molecular biology, Imaging Techniques, Developmental Disabilities, DNA Mutational Analysis, Gene Identification and Analysis, lcsh:Medicine, Gene Sequencing, Genes, Recessive, Nervous System Malformations, Research and Analysis Methods, Diagnostic Radiology, Cohort Studies, Sequencing techniques, Autosomal Recessive Diseases, Pregnancy, Diagnostic Medicine, Intellectual Disability, Exome Sequencing, Medicine and Health Sciences, Genetics, Humans, Abnormalities, Multiple, Exome, DNA sequencing, lcsh:Science, Child, Mutation Detection, Clinical Genetics, Biology and life sciences, Radiology and Imaging, lcsh:R, Genetic Variation, Human Genetics, Sequence Analysis, DNA, Syndrome, Magnetic Resonance Imaging, Phenotype, Molecular biology techniques, Genetic Diseases, Face, Mutation, lcsh:Q, Female, Anatomy, Head, Research Article
Abstract

Although intellectual disability is one of the major indications for genetic counselling, there are no homogenous diagnostic algorithms for molecular testing. While whole exome sequencing is increasingly applied, we questioned whether analyzing a partial exome, enriched for genes associated with Mendelian disorders, might be a valid alternative approach that yields similar detection rates but requires less sequencing capacities. Within this context 106 patients with different intellectual disability forms were analyzed for mutations in 4.813 genes after pre-exclusion of copy number variations by array-CGH. Subsequent variant interpretation was performed in accordance with the ACMG guidelines. By this, a molecular diagnosis was established in 34% of cases and candidate mutations were identified in additional 24% of patients. Detection rates of causative mutations were above 30%, regardless of further symptoms, except for patients with seizures (23%). We did not detect an advantage from partial exome sequencing for patients with severe intellectual disability (36%) as compared to those with mild intellectual disability (44%). Specific clinical diagnoses pre-existed for 20 patients. Of these, 5 could be confirmed and an additional 6 cases could be solved, but showed mutations in other genes than initially suspected. In conclusion partial exome sequencing solved >30% of intellectual disability cases, which is similar to published rates obtained by whole exome sequencing. The approach therefore proved to be a valid alternative to whole exome sequencing for molecular diagnostics in this cohort. The method proved equally suitable for both syndromic and non-syndromic intellectual disability forms of all severity grades.

Published
2018

38. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., primary, Tudini, Emma, additional, Li, Hongyan, additional, Hahnen, Eric, additional, Wappenschmidt, Barbara, additional, Feliubadaló, Lidia, additional, Aalfs, Cora M., additional, Agata, Simona, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Alonso‐Cerezo, María Concepción, additional, Arnold, Norbert, additional, Auber, Bernd, additional, Austin, Rachel, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barbieri, Elena, additional, Bartram, Claus R., additional, Blanco, Ana, additional, Blümcke, Britta, additional, Bonache, Sandra, additional, Bonanni, Bernardo, additional, Borg, Åke, additional, Bortesi, Beatrice, additional, Brunet, Joan, additional, Bruzzone, Carla, additional, Bucksch, Karolin, additional, Cagnoli, Giulia, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Capone, Gabriele L., additional, Caputo, Sandrine M., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Caux‐Moncoutier, Virginie, additional, Cavalli, Pietro, additional, Cini, Giulia, additional, Clarke, Edward M., additional, Concolino, Paola, additional, Cops, Elisa J., additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Darder, Esther, additional, Hoya, Miguel, additional, Dean, Michael, additional, Debatin, Irmgard, additional, Del Valle, Jesús, additional, Delnatte, Capucine, additional, Derive, Nicolas, additional, Diez, Orland, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Dutrannoy, Véronique, additional, Eccles, Diana M., additional, Ehrencrona, Hans, additional, Enders, Ute, additional, Evans, D. Gareth, additional, Farra, Chantal, additional, Faust, Ulrike, additional, Felbor, Ute, additional, Feroce, Irene, additional, Fine, Miriam, additional, Foulkes, William D., additional, Galvao, Henrique C.R., additional, Gambino, Gaetana, additional, Gehrig, Andrea, additional, Gensini, Francesca, additional, Gerdes, Anne‐Marie, additional, Germani, Aldo, additional, Giesecke, Jutta, additional, Gismondi, Viviana, additional, Gómez, Carolina, additional, Garcia, Encarna B., additional, González, Sara, additional, Grau, Elia, additional, Grill, Sabine, additional, Gross, Eva, additional, Guerrieri‐Gonzaga, Aliana, additional, Guillaud‐Bataille, Marine, additional, Gutiérrez‐Enríquez, Sara, additional, Haaf, Thomas, additional, Hackmann, Karl, additional, Hansen, Thomas V.O., additional, Harris, Marion, additional, Hauke, Jan, additional, Heinrich, Tilman, additional, Hellebrand, Heide, additional, Herold, Karen N., additional, Honisch, Ellen, additional, Horvath, Judit, additional, Houdayer, Claude, additional, Hübbel, Verena, additional, Iglesias, Silvia, additional, Izquierdo, Angel, additional, James, Paul A., additional, Janssen, Linda A.M., additional, Jeschke, Udo, additional, Kaulfuß, Silke, additional, Keupp, Katharina, additional, Kiechle, Marion, additional, Kölbl, Alexandra, additional, Krieger, Sophie, additional, Kruse, Torben A., additional, Kvist, Anders, additional, Lalloo, Fiona, additional, Larsen, Mirjam, additional, Lattimore, Vanessa L., additional, Lautrup, Charlotte, additional, Ledig, Susanne, additional, Leinert, Elena, additional, Lewis, Alexandra L., additional, Lim, Joanna, additional, Loeffler, Markus, additional, López‐Fernández, Adrià, additional, Lucci‐Cordisco, Emanuela, additional, Maass, Nicolai, additional, Manoukian, Siranoush, additional, Marabelli, Monica, additional, Matricardi, Laura, additional, Meindl, Alfons, additional, Michelli, Rodrigo D., additional, Moghadasi, Setareh, additional, Moles‐Fernández, Alejandro, additional, Montagna, Marco, additional, Montalban, Gemma, additional, Monteiro, Alvaro N., additional, Montes, Eva, additional, Mori, Luigi, additional, Moserle, Lidia, additional, Müller, Clemens R., additional, Mundhenke, Christoph, additional, Naldi, Nadia, additional, Nathanson, Katherine L., additional, Navarro, Matilde, additional, Nevanlinna, Heli, additional, Nichols, Cassandra B., additional, Niederacher, Dieter, additional, Nielsen, Henriette R., additional, Ong, Kai‐ren, additional, Pachter, Nicholas, additional, Palmero, Edenir I., additional, Papi, Laura, additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Perez‐Segura, Pedro, additional, Pfeifer, Katharina, additional, Pineda, Marta, additional, Pohl‐Rescigno, Esther, additional, Poplawski, Nicola K., additional, Porfirio, Berardino, additional, Quante, Anne S., additional, Ramser, Juliane, additional, Reis, Rui M., additional, Revillion, Françoise, additional, Rhiem, Kerstin, additional, Riboli, Barbara, additional, Ritter, Julia, additional, Rivera, Daniela, additional, Rofes, Paula, additional, Rump, Andreas, additional, Salinas, Monica, additional, Sánchez de Abajo, Ana María, additional, Schmidt, Gunnar, additional, Schoenwiese, Ulrike, additional, Seggewiß, Jochen, additional, Solanes, Ares, additional, Steinemann, Doris, additional, Stiller, Mathias, additional, Stoppa‐Lyonnet, Dominique, additional, Sullivan, Kelly J., additional, Susman, Rachel, additional, Sutter, Christian, additional, Tavtigian, Sean V., additional, Teo, Soo H., additional, Teulé, Alex, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tornero, Eva, additional, Törngren, Therese, additional, Torres‐Esquius, Sara, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tucker, Katherine M., additional, Asperen, Christi J., additional, Mackelenbergh, Marion T., additional, Varesco, Liliana, additional, Vargas‐Parra, Gardenia, additional, Varon, Raymonda, additional, Vega, Ana, additional, Velasco, Ángela, additional, Vesper, Anne‐Sophie, additional, Viel, Alessandra, additional, Vreeswijk, Maaike P. G., additional, Wagner, Sebastian A., additional, Waha, Anke, additional, Walker, Logan C., additional, Walters, Rhiannon J., additional, Wang‐Gohrke, Shan, additional, Weber, Bernhard H. F., additional, Weichert, Wilko, additional, Wieland, Kerstin, additional, Wiesmüller, Lisa, additional, Witzel, Isabell, additional, Wöckel, Achim, additional, Woodward, Emma R., additional, Zachariae, Silke, additional, Zampiga, Valentina, additional, Zeder‐Göß, Christine, additional, Investigators, KConFab, additional, Lázaro, Conxi, additional, Nicolo, Arcangela, additional, Radice, Paolo, additional, Engel, Christoph, additional, Schmutzler, Rita K., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional

Published
2019
Full Text
View/download PDF

39. Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

Author

Ullmann Reinhard, Tinschert Sigrid, Prott Eva, Nagl Sandra, Maystadt Isabelle, Kohlhase Jürgen, Klapecki Jakub, Hoyer Juliane, Horn Denise, Hackmann Karl, Engels Hartmut, Ekici Arif B, Bijlsma Emilia K, Bader Ingrid, Albrecht Beate, Gregor Anne, Wohlleber Eva, Woods Geoffrey, Reis André, Rauch Anita, and Zweier Christiane

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. Methods 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. Results By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. Conclusions We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.

Published
2011
Full Text
View/download PDF

40. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

41. Universal Tre (uTre) recombinase specifically targets the majority of HIV‐1 isolates

Author

Karpinski, Janet, Chemnitz, Jan, Hauber, Ilona, Abi?Ghanem, Josephine, Paszkowski?Rogacz, Maciej, Surendranath, Vineeth, Chakrabort, Debojyoti, Hackmann, Karl, Schröck, Evelin, Pisabarro, María Teresa, Hauber, Joachim, and Buchholz, Frank

Subjects
Recombinases -- Genetic aspects, Drug resistance -- Genetic aspects, HIV infection -- Drug therapy -- Genetic aspects, Enzyme engineering -- Methods, Health
Abstract

Current drugs against HIV can suppress the progression to AIDS but cannot clear the patient from the virus. Because of potential side effects of these drugs and the possible development of drug resistance, finding a cure for HIV infection remains a high priority of HIV/AIDS research. We recently generated a recombinase (termed Tre) tailored to efficiently eradicate the provirus from the host genome of HIV‐1 infected cells by specifically targeting a sequence that is present in the long terminal repeats (LTRs) of the viral DNA [1]. In vivo analyses in HIV‐infected humanized mice demonstrated highly significant antiviral effects of Tre recombinase [2]. However, the fact that Tre recognizes a particular HIV‐1 subtype A strain may limit its broad therapeutic application. To advance our Tre‐based strategy towards a universally efficient cure, we have engineered a new, universal recombinase (uTre) applicable to the majority of HIV‐1 infections by the various virus strains and subtypes. We employed the search tool SeLOX [3] in order to find a well‐conserved HIV‐1 proviral sequence that could serve as target site for a universal Tre from sequences compiled in the Los Alamos HIV Sequence Database. We selected a candidate (termed loxLTRu) with a mean conservation rate of 94% throughout the major HIV‐1 subtype groups A, B and C. We applied loxLTRu as substrate in our established substrate‐linked protein evolution (SLiPE) process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly specific enzymatic activity on loxLTRu is demonstrated for uTre in both Escherichia coli and human cells. Naturally occurring viral variants with single mutations within the loxLTRu sequence are also shown to be efficiently targeted by uTre, further increasing the range of applicability of the recombinase. Potential off‐target sites in the human genome are not recombined by uTre. Furthermore, uTre expression in primary human T cells shows no obvious Tre‐related cytopathic or genotoxic effects. Finally, uTre expressing mice show no undesired phenotypes during their normal lifespan. We have developed a broad‐range HIV‐1 LTR specific recombinase that has the potential to be effective against the vast majority of HIV‐1 strains and to cure HIV‐1 infected cells from the infection. These results strongly encouraged us in our confidence that a Tre recombinase‐mediated HIV eradication strategy may become a valuable component of a future therapy for HIV‐infected patients., References Sarkar I, Hauber I, Hauber J, Buchholz F. HIV‐1 proviral DNA excision using an evolved recombinase. Science. 2007;316(5833): 1912–5. Hauber I, Hofmann‐Sieber H, Chemnitz J, et al. Highly Significant [...]

Published
2014
Full Text
View/download PDF

42. Additional file 4: of Breast cancer patients suggestive of Li-Fraumeni syndrome: mutational spectrum, candidate genes, and unexplained heredity

Author

Penkert, Judith, Schmidt, Gunnar, Hofmann, Winfried, Schubert, Stephanie, Schieck, Maximilian, Auber, Bernd, Ripperger, Tim, Hackmann, Karl, Sturm, Marc, Prokisch, Holger, Hille-Betz, Ursula, Mark, Dorothea, Illig, Thomas, Schlegelberger, Brigitte, and Steinemann, Doris

Abstract

Total list of TP53 (NM_000546.5) variants detected via NGS-based sequencing (entire list of all detected TP53 variants in our collective). (DOCX 35Â kb)

Published
2018
Full Text
View/download PDF

43. Additional file 1: Table S1. of BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer

Author

Weber-Lassalle, Nana, Hauke, Jan, Ramser, Juliane, Richters, Lisa, Groß, Eva, Blümcke, Britta, Gehrig, Andrea, Anne-Karin Kahlert, Müller, Clemens, Hackmann, Karl, Honisch, Ellen, Weber-Lassalle, Konstantin, Niederacher, Dieter, Borde, Julika, Thiele, Holger, Ernst, Corinna, Altmüller, Janine, Neidhardt, Guido, Nürnberg, Peter, Klaschik, Kristina, Schroeder, Christopher, Platzer, Konrad, Volk, Alexander, Wang-Gohrke, Shan, Just, Walter, Auber, Bernd, Kubisch, Christian, Schmidt, Gunnar, Horvath, Judit, Wappenschmidt, Barbara, Engel, Christoph, Arnold, Norbert, Dworniczak, Bernd, Rhiem, Kerstin, Meindl, Alfons, Schmutzler, Rita, and Hahnen, Eric

Abstract

Inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for BRCA1 and BRCA2 germline testing. Table S2. Heterozygous protein-truncating mutations identified in the BRIP1 gene. Figure S1. Characterization of the c.507G > A variant within the BRIP1 gene (rs876660937) on transcript level. Table S3. Genotypes and phenotypes of heterozygous BRIP1 mutation carriers identified within the BC/OC index patient cohorts. Table S4. Potentially damaging missense variants identified in the BRIP1 gene. (PDF 215 kb)

Published
2018
Full Text
View/download PDF

44. Additional file 1: of Breast cancer patients suggestive of Li-Fraumeni syndrome: mutational spectrum, candidate genes, and unexplained heredity

Author

Penkert, Judith, Schmidt, Gunnar, Hofmann, Winfried, Schubert, Stephanie, Schieck, Maximilian, Auber, Bernd, Ripperger, Tim, Hackmann, Karl, Sturm, Marc, Prokisch, Holger, Hille-Betz, Ursula, Mark, Dorothea, Illig, Thomas, Schlegelberger, Brigitte, and Steinemann, Doris

Subjects
mental disorders
Abstract

TruSight Cancer Target Genes and SNPs (a list of all 94 investigated genes) (Illumina). (DOCX 15Â kb)

Published
2018
Full Text
View/download PDF

45. Additional file 2: of Breast cancer patients suggestive of Li-Fraumeni syndrome: mutational spectrum, candidate genes, and unexplained heredity

Author

Penkert, Judith, Schmidt, Gunnar, Hofmann, Winfried, Schubert, Stephanie, Schieck, Maximilian, Auber, Bernd, Ripperger, Tim, Hackmann, Karl, Sturm, Marc, Prokisch, Holger, Hille-Betz, Ursula, Mark, Dorothea, Illig, Thomas, Schlegelberger, Brigitte, and Steinemann, Doris

Abstract

Definitions of Li-Fraumeni criteria (official definitions of available clinical criteria, including classic LFS criteria, LFL criteria of Eeles and Birch, and 3 versions of Chompret criteria). (DOCX 18Â kb)

Published
2018
Full Text
View/download PDF

46. The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants

Author

Schubert, Stephanie, primary, Luttikhuizen, Jana L., additional, Auber, Bernd, additional, Schmidt, Gunnar, additional, Hofmann, Winfried, additional, Penkert, Judith, additional, Davenport, Colin F., additional, Hille‐Betz, Ursula, additional, Wendeburg, Lena, additional, Bublitz, Janin, additional, Tauscher, Marcel, additional, Hackmann, Karl, additional, Schröck, Evelin, additional, Scholz, Caroline, additional, Wallaschek, Hannah, additional, Schlegelberger, Brigitte, additional, Illig, Thomas, additional, and Steinemann, Doris, additional

Published
2019
Full Text
View/download PDF

49. Abstract 1410: Pedigree analysis equally identifies cases of pancreatic cancer in families with BRCA1 and BRCA2 mutations

Author

Schrock, Evelin, primary, Hackmann, Karl, additional, Kuhlee, Franziska, additional, Jahn, Arne, additional, Wagner, Johannes, additional, Kahlert, Anne-Karin, additional, Porrmann, Joseph, additional, Tzschach, Andreas, additional, Aust, Daniela, additional, Baretton, Gustavo, additional, Kast, Karin, additional, Wimberger, Pauline, additional, Laniado, Michael, additional, Kahlert, Christoph, additional, Welsch, Thilo, additional, Weitz, Jürgen, additional, Klink, Barbara, additional, Rump, Andreas, additional, and Gieldon, Laura, additional

Published
2018
Full Text
View/download PDF

50. Gene panel testing of 5589 BRCA1/2 -negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Hauke, Jan, primary, Horvath, Judit, additional, Groß, Eva, additional, Gehrig, Andrea, additional, Honisch, Ellen, additional, Hackmann, Karl, additional, Schmidt, Gunnar, additional, Arnold, Norbert, additional, Faust, Ulrike, additional, Sutter, Christian, additional, Hentschel, Julia, additional, Wang-Gohrke, Shan, additional, Smogavec, Mateja, additional, Weber, Bernhard H. F., additional, Weber-Lassalle, Nana, additional, Weber-Lassalle, Konstantin, additional, Borde, Julika, additional, Ernst, Corinna, additional, Altmüller, Janine, additional, Volk, Alexander E., additional, Thiele, Holger, additional, Hübbel, Verena, additional, Nürnberg, Peter, additional, Keupp, Katharina, additional, Versmold, Beatrix, additional, Pohl, Esther, additional, Kubisch, Christian, additional, Grill, Sabine, additional, Paul, Victoria, additional, Herold, Natalie, additional, Lichey, Nadine, additional, Rhiem, Kerstin, additional, Ditsch, Nina, additional, Ruckert, Christian, additional, Wappenschmidt, Barbara, additional, Auber, Bernd, additional, Rump, Andreas, additional, Niederacher, Dieter, additional, Haaf, Thomas, additional, Ramser, Juliane, additional, Dworniczak, Bernd, additional, Engel, Christoph, additional, Meindl, Alfons, additional, Schmutzler, Rita K., additional, and Hahnen, Eric, additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results