@article{ZahoGhirlandoAlfonsoetal.2015, author = {Zaho, Huaying and Ghirlando, Rodolfo and Alfonso, Carlos and Arisaka, Fumio and Attali, Ilan and Bain, David L. and Bakhtina, Marina M. and Becker, Donald F. and Bedwell, Gregory J. and Bekdemir, Ahmet and Besong, Tabot M. D. and Birck, Catherine and Brautigam, Chad A. and Brennerman, William and Byron, Olwyn and Bzowska, Agnieszka and Chaires, Jonathan B. and Chaton, Catherine T. and Coelfen, Helmbut and Connaghan, Keith D. and Crowley, Kimberly A. and Curth, Ute and Daviter, Tina and Dean, William L. and Diez, Ana I. and Ebel, Christine and Eckert, Debra M. and Eisele, Leslie E. and Eisenstein, Edward and England, Patrick and Escalante, Carlos and Fagan, Jeffrey A. and Fairman, Robert and Finn, Ron M. and Fischle, Wolfgang and Garcia de la Torre, Jose and Gor, Jayesh and Gustafsson, Henning and Hall, Damien and Harding, Stephen E. and Hernandez Cifre, Jose G. and Herr, Andrew B. and Howell, Elizabeth E. and Isaac, Richard S. and Jao, Shu-Chuan and Jose, Davis and Kim, Soon-Jong and Kokona, Bashkim and Kornblatt, Jack A. and Kosek, Dalibor and Krayukhina, Elena and Krzizike, Daniel and Kusznir, Eric A. and Kwon, Hyewon and Larson, Adam and Laue, Thomas M. and Le Roy, Aline and Leech, Andrew P. and Lilie, Hauke and Luger, Karolin and Luque-Ortega, Juan R. and Ma, Jia and May, Carrie A. and Maynard, Ernest L. and Modrak-Wojcik, Anna and Mok, Yee-Foong and M{\"u}cke, Norbert and Nagel-Steger, Luitgard and Narlikar, Geeta J. and Noda, Masanori and Nourse, Amanda and Obsil, Thomas and Park, Chad K and Park, Jin-Ku and Pawelek, Peter D. and Perdue, Erby E. and Perkins, Stephen J. and Perugini, Matthew A. and Peterson, Craig L. and Peverelli, Martin G. and Piszczek, Grzegorz and Prag, Gali and Prevelige, Peter E. and Raynal, Bertrand D. E. and Rezabkova, Lenka and Richter, Klaus and Ringel, Alison E. and Rosenberg, Rose and Rowe, Arthur J. and Rufer, Arne C. and Scott, David J. and Seravalli, Javier G. and Solovyova, Alexandra S. and Song, Renjie and Staunton, David and Stoddard, Caitlin and Stott, Katherine and Strauss, Holder M. and Streicher, Werner W. and Sumida, John P. and Swygert, Sarah G. and Szczepanowski, Roman H. and Tessmer, Ingrid and Toth, Ronald T. and Tripathy, Ashutosh and Uchiyama, Susumu and Uebel, Stephan F. W. and Unzai, Satoru and Gruber, Anna Vitlin and von Hippel, Peter H. and Wandrey, Christine and Wang, Szu-Huan and Weitzel, Steven E and Wielgus-Kutrowska, Beata and Wolberger, Cynthia and Wolff, Martin and Wright, Edward and Wu, Yu-Sung and Wubben, Jacinta M. and Schuck, Peter}, title = {A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0126420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151903}, pages = {e0126420}, year = {2015}, abstract = {Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4\%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7\%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.}, language = {en} } @article{DavisYuKeenanetal.2013, author = {Davis, Lea K. and Yu, Dongmei and Keenan, Clare L. and Gamazon, Eric R. and Konkashbaev, Anuar I. and Derks, Eske M. and Neale, Benjamin M. and Yang, Jian and Lee, S. Hong and Evans, Patrick and Barr, Cathy L. and Bellodi, Laura and Benarroch, Fortu and Berrio, Gabriel Bedoya and Bienvenu, Oscar J. and Bloch, Michael H. and Blom, Rianne M. and Bruun, Ruth D. and Budman, Cathy L. and Camarena, Beatriz and Campbell, Desmond and Cappi, Carolina and Cardona Silgado, Julio C. and Cath, Danielle C. and Cavallini, Maria C. and Chavira, Denise A. and Chouinard, Sylvian and Conti, David V. and Cook, Edwin H. and Coric, Vladimir and Cullen, Bernadette A. and Deforce, Dieter and Delorme, Richard and Dion, Yves and Edlund, Christopher K. and Egberts, Karin and Falkai, Peter and Fernandez, Thomas V. and Gallagher, Patience J. and Garrido, Helena and Geller, Daniel and Girard, Simon L. and Grabe, Hans J. and Grados, Marco A. and Greenberg, Benjamin D. and Gross-Tsur, Varda and Haddad, Stephen and Heiman, Gary A. and Hemmings, Sian M. J. and Hounie, Ana G. and Illmann, Cornelia and Jankovic, Joseph and Jenike, Micheal A. and Kennedy, James L. and King, Robert A. and Kremeyer, Barbara and Kurlan, Roger and Lanzagorta, Nuria and Leboyer, Marion and Leckman, James F. and Lennertz, Leonhard and Liu, Chunyu and Lochner, Christine and Lowe, Thomas L. and Macciardi, Fabio and McCracken, James T. and McGrath, Lauren M. and Restrepo, Sandra C. Mesa and Moessner, Rainald and Morgan, Jubel and Muller, Heike and Murphy, Dennis L. and Naarden, Allan L. and Ochoa, William Cornejo and Ophoff, Roel A. and Osiecki, Lisa and Pakstis, Andrew J. and Pato, Michele T. and Pato, Carlos N. and Piacentini, John and Pittenger, Christopher and Pollak, Yehunda and Rauch, Scott L. and Renner, Tobias J. and Reus, Victor I. and Richter, Margaret A. and Riddle, Mark A. and Robertson, Mary M. and Romero, Roxana and Ros{\`a}rio, Maria C. and Rosenberg, David and Rouleau, Guy A. and Ruhrmann, Stephan and Ruiz-Linares, Andreas and Sampaio, Aline S. and Samuels, Jack and Sandor, Paul and Sheppard, Broke and Singer, Harvey S. and Smit, Jan H. and Stein, Dan J. and Strengman, E. and Tischfield, Jay A. and Valencia Duarte, Ana V. and Vallada, Homero and Van Nieuwerburgh, Flip and Veenstra-VanderWeele, Jeremy and Walitza, Susanne and Wang, Ying and Wendland, Jens R. and Westenberg, Herman G. M. and Shugart, Yin Yao and Miguel, Euripedes C. and McMahon, William and Wagner, Michael and Nicolini, Humberto and Posthuma, Danielle and Hanna, Gregory L. and Heutink, Peter and Denys, Damiaan and Arnold, Paul D. and Oostra, Ben A. and Nestadt, Gerald and Freimer, Nelson B. and Pauls, David L. and Wray, Naomi R. and Stewart, S. Evelyn and Mathews, Carol A. and Knowles, James A. and Cox, Nancy J. and Scharf, Jeremiah M.}, title = {Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture}, series = {PLoS Genetics}, volume = {9}, journal = {PLoS Genetics}, number = {10}, issn = {1553-7390}, doi = {10.1371/journal.pgen.1003864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127377}, pages = {e1003864}, year = {2013}, abstract = {The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5\% accounted for 21\% of the TS heritability and 0\% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.}, language = {en} } @article{WeisschuhMayerStrometal.2016, author = {Weisschuh, Nicole and Mayer, Anja K. and Strom, Tim M. and Kohl, Susanne and Gl{\"o}ckle, Nicola and Schubach, Max and Andreasson, Sten and Bernd, Antje and Birch, David G. and Hamel, Christian P. and Heckenlively, John R. and Jacobson, Samuel G. and Kamme, Christina and Kellner, Ulrich and Kunstmann, Erdmute and Maffei, Pietro and Reiff, Charlotte M. and Rohrschneider, Klaus and Rosenberg, Thomas and Rudolph, G{\"u}nther and V{\´a}mos, Rita and Vars{\´a}nyi, Bal{\´a}zs and Weleber, Richard G. and Wissinger, Bernd}, title = {Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0145951}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167398}, pages = {e0145951}, year = {2016}, abstract = {Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61\% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.}, language = {en} }