Article
Author: Mehta, Heer ; Porubsky, David ; Shaffer, Tristan ; Hasson, Dan ; Doheny, Kim ; Berngruber, Chelsea ; Houlden, Henry ; Peter, Cyril ; Lichtenstein, Lee ; Sedeno-Cortes, Adriana ; Scriba, Carolin K. ; Pastinen, Tomi ; Hu, Jianhong ; Hall, Salina K. ; Dolzhenko, Egor ; Stevanovski, Igor ; Metcalf, Ginger ; Shifaw, Beri ; Hsieh, PingHsun ; Deveson, Ira W. ; Agarwal, Aman ; Bonnet, Céline ; Scott, Alan ; Jeong, Hyeonsoo ; Morina, Luke ; Usdin, Karen ; Timp, Winston ; Chen, Zhao ; Dicaire, Marie-Josée ; Bateman, Emily ; Schwartz, Sophie ; Laing, Nigel G. ; Maheshwari, Anant ; Spurdens, Guinevere ; Wang, Yuanyuan ; Prasad, Nripesh ; Renaud, Mathilde ; Matos-Rodrigues, Gabriel ; Paschall, Justin ; Frazar, Chris ; Levy, Shawn ; Weissenberger, George ; Kovaka, Sam ; Wandzel, Marion ; Sedlazeck, Fritz ; Muzny, Donna ; Hwang, James ; Shen, Hua ; Sanchis-Juan, Alba ; Lamont, Phillipa J. ; Rozanski, Allison N. ; Ravenscroft, Gianina ; Marosy, Beth ; Tsankova, Nadejda M. ; Gearhart, Jessica ; Wertz, Julie ; Soisangwan, Natthapon ; Nussenzweig, Andre ; LaPlante, Emily ; Huang, Yongqing ; Yoo, DongAhn ; Gupta, Namrata ; Zheng, Xinchang ; Brais, Bernard ; Eberle, Michael A. ; Nageshwaran, Sathiji K. ; Eichler, Evan E. ; Pellerin, David ; Smith, Joshua D. ; Schatz, Michael C. ; Zilka, Michelle ; Del Gobbo, Giulia F. ; Garimella, Kiran ; Wan, Evie ; Vee, Vanesa ; Neph, Shane ; Cunial, Fabio ; Jiang, Hong ; Han, Yi ; Stergachis, Andrew ; Hosea, Jess ; Kokosinski, Michelle ; Pionzio, Arianna ; Mohr, David ; Madmoud, Medhat ; Grimwood, Jane ; Lakatos, Rebecca ; Davis, Colleen P. ; Akbarian, Schahram ; Dugan-Perez, Shannon ; Musick, Anjene ; Dinh, Huyen ; Mostovoy, Yulia ; Doddapaneni, Harsha ; Su, Hang ; Lorig-Roach, Ryan ; Roth, Virginie ; Danzi, Matt C. ; Ashton, Catherine ; Gibbs, Richard ; Lennon, Niall ; Dewar, Ken ; Zuchner, Stephan ; Dutka, Tara ; Talkowski, Michael ; Harvey, William T. ; Li, Qiuhui ; Lee, Samuel K. ; Zhu, Yiming ; Kirkpatrick, Sarah ; Khan, Ziad ; Xu, Isaac R. L. ; Lord, Chris ; Izydorczyk, Michal ; Fazal, Sarah ; Napierala, Marek ; Kurtas, Edibe Nehir ; Couse, Madeline ; Patterson, Karynne ; Logsdon, Glennis A. ; Zaheri, Shadi ; Boycott, Kym M. ; Montano, Carolina ; Rebelo, Adriana ; Wheeler, Marsha ; Synofzik, Matthis ; Empey, Philip ; Cheung, Warren A. ; Whelan, Christopher
The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5'-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.