Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
Journal
Nature communications
Journal Volume
7
Journal Issue
1
Date Issued
2016-06-13
Author(s)
Machiela, Mitchell J
Zhou, Weiyin
Karlins, Eric
Sampson, Joshua N
Freedman, Neal D
Yang, Qi
Hicks, Belynda
Dagnall, Casey
Hautman, Christopher
Jacobs, Kevin B
Abnet, Christian C
Aldrich, Melinda C
Amos, Christopher
Amundadottir, Laufey T
Arslan, Alan A
Beane-Freeman, Laura E
Berndt, Sonja I
Black, Amanda
Blot, William J
Bock, Cathryn H
Bracci, Paige M
Brinton, Louise A
Bueno-de-Mesquita, H Bas
Burdett, Laurie
Buring, Julie E
Butler, Mary A
Canzian, Federico
Carreón, Tania
Chaffee, Kari G
Chang, I-Shou
Chatterjee, Nilanjan
Chen, Chu
Chen, Constance
Chen, Kexin
Chung, Charles C
Cook, Linda S
Crous Bou, Marta
Cullen, Michael
Davis, Faith G
De Vivo, Immaculata
Ding, Ti
Doherty, Jennifer
Duell, Eric J
Epstein, Caroline G
Fan, Jin-Hu
Figueroa, Jonine D
Fraumeni, Joseph F
Friedenreich, Christine M
Fuchs, Charles S
Gallinger, Steven
Gao, Yu-Tang
Gapstur, Susan M
Garcia-Closas, Montserrat
Gaudet, Mia M
Gaziano, J Michael
Giles, Graham G
Gillanders, Elizabeth M
Giovannucci, Edward L
Goldin, Lynn
Goldstein, Alisa M
Haiman, Christopher A
Hallmans, Goran
Hankinson, Susan E
Harris, Curtis C
Henriksson, Roger
Holly, Elizabeth A
Hong, Yun-Chul
Hoover, Robert N
Hsiung, Chao A
Hu, Nan
Hu, Wei
Hunter, David J
Hutchinson, Amy
Jenab, Mazda
Johansen, Christoffer
Khaw, Kay-Tee
Kim, Hee Nam
Kim, Yeul Hong
Kim, Young Tae
Klein, Alison P
Klein, Robert
Koh, Woon-Puay
Kolonel, Laurence N
Kooperberg, Charles
Kraft, Peter
Krogh, Vittorio
Kurtz, Robert C
LaCroix, Andrea
Lan, Qing
Landi, Maria Teresa
Marchand, Loic Le
Li, Donghui
Liang, Xiaolin
Liao, Linda M
Lin, Dongxin
Liu, Jianjun
Lissowska, Jolanta
Lu, Lingeng
Magliocco, Anthony M
Malats, Nuria
Matsuo, Keitaro
McNeill, Lorna H
McWilliams, Robert R
Melin, Beatrice S
Mirabello, Lisa
Moore, Lee
Olson, Sara H
Orlow, Irene
Park, Jae Yong
Patiño-Garcia, Ana
Peplonska, Beata
Peters, Ulrike
Petersen, Gloria M
Pooler, Loreall
Prescott, Jennifer
Prokunina-Olsson, Ludmila
Purdue, Mark P
Qiao, You-Lin
Rajaraman, Preetha
Real, Francisco X
Riboli, Elio
Risch, Harvey A
Rodriguez-Santiago, Benjamin
Ruder, Avima M
Savage, Sharon A
Schumacher, Fredrick
Schwartz, Ann G
Schwartz, Kendra L
Seow, Adeline
Wendy Setiawan, Veronica
Severi, Gianluca
Shen, Hongbing
Sheng, Xin
Shin, Min-Ho
Shu, Xiao-Ou
Silverman, Debra T
Spitz, Margaret R
Stevens, Victoria L
Stolzenberg-Solomon, Rachael
Stram, Daniel
Tang, Ze-Zhong
Taylor, Philip R
Teras, Lauren R
Tobias, Geoffrey S
Van Den Berg, David
Visvanathan, Kala
Wacholder, Sholom
Wang, Jiu-Cun
Wang, Zhaoming
Wentzensen, Nicolas
Wheeler, William
White, Emily
Wiencke, John K
Wolpin, Brian M
Wong, Maria Pik
Wu, Chen
Wu, Tangchun
Wu, Xifeng
Wu, Yi-Long
Wunder, Jay S
Xia, Lucy
Yang, Hannah P
Yu, Kai
Zanetti, Krista A
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Zhou, Baosen
Ziegler, Regina G
Perez-Jurado, Luis A
Caporaso, Neil E
Rothman, Nathaniel
Tucker, Margaret
Dean, Michael C
Yeager, Meredith
Chanock, Stephen J
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.
Subjects
DETECTABLE CLONAL MOSAICISM; SOMATIC MOSAICISM; BLOOD; METHYLATION; HEMATOPOIESIS; ANEUPLOIDIES; GENOME; RISK
SDGs
Publisher
NATURE RESEARCH
Type
journal article