Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Mitchell J Machiela, Weiyin Zhou, Eric Karlins, Joshua N Sampson, Neal D Freedman, Qi Yang, Belynda Hicks, Casey Dagnall, Christopher Hautman, Kevin B Jacobs, Christian C Abnet, Melinda C Aldrich, Christopher Amos, Laufey T Amundadottir, Alan A Arslan, Laura E Beane-Freeman, Sonja I Berndt, Amanda Black, William J Blot, Cathryn H Bock, Paige M Bracci, Louise A Brinton, H Bas Bueno-de-Mesquita, Laurie Burdett, Julie E Buring, Mary A Butler, Federico Canzian, Tania Carreón, Kari G Chaffee, I-Shou Chang, Nilanjan Chatterjee, Chu Chen, Constance Chen, Kexin Chen, Charles C Chung, Linda S Cook, Marta Crous Bou, Michael Cullen, Faith G Davis, Immaculata De Vivo, Ti Ding, Jennifer Doherty, Eric J Duell, Caroline G Epstein, Jin-Hu Fan, Jonine D Figueroa, Joseph F Fraumeni, Christine M Friedenreich, Charles S Fuchs, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Mia M Gaudet, J Michael Gaziano, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Lynn Goldin, Alisa M Goldstein, Christopher A Haiman, Goran Hallmans, Susan E Hankinson, Curtis C Harris, Roger Henriksson, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, Chao A Hsiung, Nan Hu, Wei Hu, David J Hunter, Amy Hutchinson, Mazda Jenab, Christoffer Johansen, Kay-Tee Khaw, Hee Nam Kim, Yeul Hong Kim, Young Tae Kim, Alison P Klein, Robert Klein, Woon-Puay Koh, Laurence N Kolonel, Charles Kooperberg, Peter Kraft, Vittorio Krogh, Robert C Kurtz, Andrea LaCroix, Qing Lan, Maria Teresa Landi, Loic Le Marchand, Donghui Li, Xiaolin Liang, Linda M Liao, Dongxin Lin, Jianjun Liu, Jolanta Lissowska, Lingeng Lu, Anthony M Magliocco, Nuria Malats, Keitaro Matsuo, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Lisa Mirabello, Lee Moore, Sara H Olson, Irene Orlow, Jae Yong Park, Ana Patiño-Garcia, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Loreall Pooler, Jennifer Prescott, Ludmila Prokunina-Olsson, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Francisco X Real, Elio Riboli, Harvey A Risch, Benjamin Rodriguez-Santiago, Avima M Ruder, Sharon A Savage, Fredrick Schumacher, Ann G Schwartz, Kendra L Schwartz, Adeline Seow, Veronica Wendy Setiawan, Gianluca Severi, Hongbing Shen, Xin Sheng, Min-Ho Shin, Xiao-Ou Shu, Debra T Silverman, Margaret R Spitz, Victoria L Stevens, Rachael Stolzenberg-Solomon, Daniel Stram, Ze-Zhong Tang, Philip R Taylor, Lauren R Teras, Geoffrey S Tobias, David Van Den Berg, Kala Visvanathan, Sholom Wacholder, Jiu-Cun Wang, Zhaoming Wang, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Brian M Wolpin, Maria Pik Wong, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Lucy Xia, Hannah P Yang, Pan-Chyr Yang, Kai Yu, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Regina G Ziegler, Luis A Perez-Jurado, Neil E Caporaso, Nathaniel Rothman, Margaret Tucker, Michael C Dean, Meredith Yeager, Stephen J ChanockTo investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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