Role of an Atypical Cadherin Gene, Cdh23 in Prepulse Inhibition and Implication of CDH23 in Schizophrenia
作者： Yasuko Hisano , Shusuke Numata , Manabu Toyoshima , Hisako Ohba , Tetsuro Ohmori
DOI: 10.1101/2020.10.29.360180
关键词:
摘要: Abstract We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from analysis F2 mice inbred strains with high (C57BL/6N; B6) low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the QTLs increased marker density. The highest LOD score (26.66) peaked at synonymous coding splice-site variant, c.753G>A (rs257098870), in Cdh23 10; c.753G (C3H) allele showed PPI-lowering effect. Bayesian multiple QTL mapping also supported same variant posterior probability 1. Thus, engineered into B6 genetic background, which led to dampened PPI. revealed e-QTL (expression-QTL) effect imparted by expression brain. In human study, homologous (c.753G>A; rs769896655) CDH23 nominally significant enrichment individuals schizophrenia. potentially deleterious variants Collectively, present study reveals PPI-regulating possible contribution schizophrenia susceptibility.
sci-hub.st 参考文章(57)
Panos Roussos, Stella G. Giakoumaki, Chrysoula Zouraraki, John F. Fullard, Vasiliki-Eirini Karagiorga, Eva-Maria Tsapakis, Zoe Petraki, Larry J. Siever, Todd Lencz, Anil Malhotra, Cleanthe Spanaki, Panos Bitsios, The Relationship of Common Risk Variants and Polygenic Risk for Schizophrenia to Sensorimotor Gating Biological Psychiatry. ,vol. 79, pp. 988- 996 ,(2016) , 10.1016/J.BIOPSYCH.2015.06.019
Federica Di Palma, Ralph H. Holme, Elizabeth C. Bryda, Inna A. Belyantseva, Richard Pellegrino, Bechara Kachar, Karen P. Steel, Konrad Noben-Trauth, Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nature Genetics. ,vol. 27, pp. 103- 107 ,(2001) , 10.1038/83660
Atsushi Umemura, Yuichi Oka, Kenji Okita, Noriyuki Matsukawa, Kazuo Yamada, Subthalamic nucleus stimulation for Parkinson disease with severe medication-induced hallucinations or delusions. Journal of Neurosurgery. ,vol. 114, pp. 1701- 1705 ,(2011) , 10.3171/2011.2.JNS101261
Greta Glover, Stephan C.F. Neuhauss, Christian Söllner, Teresa Nicolson, Kaspar P. Mueller, The Usher gene cadherin 23 is expressed in the zebrafish brain and a subset of retinal amacrine cells Molecular Vision. ,vol. 18, pp. 2309- 2322 ,(2012) , 10.5167/UZH-64868
Takako Kita, Pavel Osten, Hitoshi Kita, Rat subthalamic nucleus and zona incerta share extensively overlapped representations of cortical functional territories. The Journal of Comparative Neurology. ,vol. 522, pp. 4043- 4056 ,(2014) , 10.1002/CNE.23655
Brian J. O’Roak, Laura Vives, Santhosh Girirajan, Emre Karakoc, Niklas Krumm, Bradley P. Coe, Roie Levy, Arthur Ko, Choli Lee, Joshua D. Smith, Emily H. Turner, Ian B. Stanaway, Benjamin Vernot, Maika Malig, Carl Baker, Beau Reilly, Joshua M. Akey, Elhanan Borenstein, Mark J. Rieder, Deborah A. Nickerson, Raphael Bernier, Jay Shendure, Evan E. Eichler, Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations Nature. ,vol. 485, pp. 246- 250 ,(2012) , 10.1038/NATURE10989
Thomas Insel, Bruce Cuthbert, Marjorie Garvey, Robert Heinssen, Daniel S. Pine, Kevin Quinn, Charles Sanislow, Philip Wang, Research domain criteria (RDoC): toward a new classification framework for research on mental disorders American Journal of Psychiatry. ,vol. 167, pp. 748- 751 ,(2010) , 10.1176/APPI.AJP.2010.09091379
F Ann Ran, Patrick D Hsu, Jason Wright, Vineeta Agarwala, David A Scott, Feng Zhang, Genome engineering using the CRISPR-Cas9 system Nature Protocols. ,vol. 8, pp. 2281- 2308 ,(2013) , 10.1038/NPROT.2013.143
Larry J. Seidman, Gerhard Hellemann, Keith H. Nuechterlein, Tiffany A. Greenwood, David L. Braff, Kristin S. Cadenhead, Monica E. Calkins, Robert Freedman, Raquel E. Gur, Ruben C. Gur, Laura C. Lazzeroni, Gregory A. Light, Ann Olincy, Allen D. Radant, Larry J. Siever, Jeremy M. Silverman, Joyce Sprock, William S. Stone, Catherine Sugar, Neal R. Swerdlow, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Michael F. Green, Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1) Schizophrenia Research. ,vol. 163, pp. 73- 79 ,(2015) , 10.1016/J.SCHRES.2015.01.027
Charles Watson, Christopher R. P. Lind, Meghan G. Thomas, The anatomy of the caudal zona incerta in rodents and primates Journal of Anatomy. ,vol. 224, pp. 95- 107 ,(2014) , 10.1111/JOA.12132