Straub, Richard E
Mayo Clinic
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Citations 2
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Bae, Taejeong , Fasching, Liana , Wang, Yifan , Shin, Joo Heon , Šuvakov, Milovan , Jang, Yeongjun , Norton, Scott , Dias, Caroline , Mariani, Jessica , Jourdon, Alexandre , Wu, Feinan , Panda, Arijit , Pattni, Reenal , Chahine, Yasmine, Yeh, Rebecca C., Roberts, Rosalinda C. , Hüttner, Anita , Straub, Richard E. , Walsh, Christopher A. , Network§, Brain Somatic Mosaicism, Urban, Alexander E. , Weinberger, Daniel R. , Vaccarino, Flora M. , Abyzov, Alexej , Šestan, Nenad , Moran, John V. , Gleeson, Joseph G. , Mathern, Gary W. , Courchesne, Eric, Chess, Andrew , Bizzotto, Sara , D’Gama, Alissa M. , Hill, Robert , Kim, Sonia , Miller, Michael , Borges-Monroy, Rebeca , Bohrson, Craig L. , Galor, Alon , Kwon, Min‐Seok , Luquette, Joe, Sherman, Maxwell A. , Rosenbluh, Chaggai , Cho, Sean, Thorpe, Jeremy , McConnell, Michael J. , Narurkar, Rujuta, Paquola, Apuã C.M. , Shin, Jooheon, Molitor, Cindy, Peters, Mette A. , Linker, Sara B. , Reed, Patrick , Wang, Meiyan , Zhou, Bo , Amero, Aitor Serres, Lobón, Irene , Moruno, Manuel Solis, Pérez, Raquel García, Povolotskaya, Inna , Soriano, Eduardo , Antaki, Danny , Averbuj, Dan, Ball, Laurel, Yang, Xiaoxu , Chung, Changuk , Emery, Sarah B., Flasch, Diane A. , Sun, Chen , Zhao, Xuefang , Zhou, Weichen , Frisbie, Trenton J., Cherskov, Adriana , Pochareddy, Sirisha , Kleinman, Joel E , Hyde, Thomas M , Straub, Richard E , Walsh, Christopher A , Urban, Alexander E , Leckman, James F , Weinberger, Daniel R , Vaccarino, Flora M , Abyzov, Alexej , Shin, Joo Heon , Zhou, Bo , Šuvakov, Milovan , Bae, Taejeong , Wang, Yifan , Jang, Yeongjun , Network§, Brain Somatic Mosaicism, Leckman, James F. , Park, Peter J. , Gage, Fred H , Gleeson, Joseph G. , Courchesne, Eric, Roy, Subhojit , Akbarian, Schahram , Coulter, Michael E. , Ganz, Javier , Hill, Robert, Huang, August Yue , Khoshkhoo, Sattar , Lee, Alice , Lodato, Michael A. , Maury, Eduardo A. , Rodin, Rachel E. , Zhou, Zinan , Chu, Chong , Cortés‐Ciriano, Isidro , Dou, Yanmei , Gulhan, D. , Viswanadham, Vinay , Jones, Attila , Langmead, Ben , Erwin, Jennifer A. , Jaffe, Andrew E. , Zhu, Xiaowei , Juan, David , Marquès‐Bonet, Tomàs , Breuss, Martin W. , Kidd, Jeffrey M. , Kopera, Huira C. , Kwan, Kenneth Y , Mills, Ryan E. , Moldovan, John B. , Scuderi, Soraya
Science | July 28, 2022 | Volume: 377 | Issue: 6605 | Pages: 511-517
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network
McConnell, Michael J. , Moran, John V. , Abyzov, Alexej , Akbarian, Schahram , Bae, Taejeong , Cortés‐Ciriano, Isidro , Erwin, Jennifer A. , Fasching, Liana , Flasch, Diane A. , Freed, Donald , Ganz, Javier , Jaffe, Andrew E. , Kwon, Min‐Seok , Lodato, Michael A. , Mills, Ryan E. , Paquola, Apuã C.M. , Rodin, Rachel E. , Rosenbluh, Chaggai , Šestan, Nenad , Sherman, Maxwell A. , Shin, Joo Heon , Song, Saera , Straub, Richard E. , Thorpe, Jeremy , Weinberger, Daniel R. , Urban, Alexander E. , Zhou, Bo , Lehner, Thomas , Senthil, Geetha , Chess, Andrew , Courchesne, Eric , Gleeson, Joseph G. , Kidd, Jeffrey M. , Park, Peter J., Pevsner, Jonathan , Vaccarino, Flora M. , Network, Brain Somatic Mosaicism, Bekiranov, Stefan , Bohrson, Craig L. , Burbulis, Ian , Chronister, William D., Coppola, Gianfilippo , Daily, Kenneth , D’Gama, Alissa M. , Emery, Sarah B., Frisbie, Trenton J., Gao, Tianliuyun , Gulyás-Kovács, Attila, Haakenson, Mark F., Keil, Jason M. , Lam, Mandy M. , Mathern, Gary W. , Omberg, Larsson , Peters, Mette A. , Pochareddy, Sirisha , Pramparo, Tiziano , Sanavia, Tiziana , Wang, Meiyan , Wierman, Margaret E. , Wolpert, Matthew J., Woodworth, Mollie B. , Zhao, Xuefang , Zhou, Weichen , Kwan, Kenneth Y , Lodato, Michael A , Mills, Ryan E , Paquola, Apua C M , Rodin, Rachel E , Rosenbluh, Chaggai , Sestan, Nenad , Shin, Joo Heon , Song, Saera , Straub, Richard E , Urban, Alexander E , Zhou, Bo , Gage, Fred H , Lehner, Thomas , Senthil, Geetha , Chess, Andrew , Courchesne, Eric , Kidd, Jeffrey M , Pevsner, Jonathan , Vaccarino, Flora M , McConnell, Michael J. , Walsh, Christopher A. , Gleeson, Joseph G. , Network, Brain Somatic Mosaicism, Barton, Alison R. , Kopera, Huira C. , Lee, Eunjung A , Marquès‐Bonet, Tomàs , Moldovan, John B. , Oetjens, Matthew T. , Ratan, Aakrosh , Shi, Lei , Škarica, Mario , Wang, Jia , Wang, Yifan , Abyzov, Alexej , Bae, Taejeong , Akbarian, Schahram
Science | April 27, 2017 | Volume: 356 | Issue: 6336 | Pages: No page available
Single-cell diversity in the brain The cells that make up an organism may all start from one genome, but somatic mutations mean that somewhere along the line of development, an organism's individual cellular genomes diverge. McConnell et al. review the implications and causes of single-cell genomic diversity for brain function. Somatic mutations caused by mobile genetic elements or errors in DNA repair may underlie certain neuropsychiatric disorders. Science , this issue p. eaal1641