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. BockPaige 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 Patinõ-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. Chanock

Research output: Contribution to journalArticle

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Abstract

To 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.

Original languageEnglish (US)
Article number11843
JournalNature communications
Volume7
DOIs
StatePublished - Jun 13 2016

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

MacHiela, M. J., Zhou, W., Karlins, E., Sampson, J. N., Freedman, N. D., Yang, Q., Hicks, B., Dagnall, C., Hautman, C., Jacobs, K. B., Abnet, C. C., Aldrich, M. C., Amos, C., Amundadottir, L. T., Arslan, A. A., Beane-Freeman, L. E., Berndt, S. I., Black, A., Blot, W. J., ... Chanock, S. J. (2016). Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nature communications, 7, [11843]. https://doi.org/10.1038/ncomms11843