Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

• DOI: 10.1038/ncomms11843
• Publication Date: 2016-06-13T10:10:58Z
• Authors: 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. Amundad...; Alan A. Arslan; Laura E. Beane-Fr...; Sonja I. Berndt; Amanda Black; William J. Blot; Cathryn H. Bock; Paige M. Bracci; Louise A. Brinton; H Bas Bueno-de-Me...; 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. Frie...; Charles S. Fuchs; Steven Gallinger; Yu-Tang Gao; Susan M. Gapstur; Montserrat Garcia...; Mia M. Gaudet; J. Michael Gaziano; Graham G. Giles; Elizabeth M. Gill...; Edward L. Giovann...; Lynn Goldin; Alisa M. Goldstein; Christopher A. Ha...; 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...; Mark P. Purdue; You-Lin Qiao; Preetha Rajaraman; Francisco X. Real; Elio Riboli; Harvey A. Risch; Benjamin Rodrigue...; Avima M. Ruder; Sharon A. Savage; Fredrick Schumacher; Ann G. Schwartz; Kendra L. Schwartz; Adeline Seow; Veronica Wendy Se...; Gianluca Severi; Hongbing Shen; Xin Sheng; Min-Ho Shin; Xiao-Ou Shu; Debra T. Silverman; Margaret R. Spitz; Victoria L. Stevens; Rachael Stolzenbe...; 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-Ja...; 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
• Keywords: Male; 0301 basic medicine; Aging; BLOOD; SOMATIC MOSAICISM; Science; 610; HEMATOPOIESIS; Polymerase Chain Reaction; Article; 03 medical and health sciences; X Chromosome Inactivation; 616; MD Multidisciplinary; HUMAN GENOME; Humans; MUTATION; Cancer genetics; Chromosomes, Human, X; Science & Technology; ANEUPLOIDIES; Mosaicism; 9. Industry and infrastructure; genetic mosaicism, X chromosome; 4. Education; Q; METHYLATION; Reproducibility of Results; DNA Methylation; 16. Peace & justice; CANCER; 3. Good health; Multidisciplinary Sciences; DETECTABLE CLONAL MOSAICISM; CELLS; Science & Technology - Other Topics; Female

Abstract To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here show rates for X-chromosome are four times higher than mean autosomal rates; more often include entire participants with likely harbour events. frequency increases age (0.11% 50-year olds; 0.45% 75-year olds), as reported Y autosomes. Methylation array analyses 33 indicate preferentially involve inactive chromosome. Our results provide further evidence that sex chromosomes undergo frequently autosomes, which could have implications understanding underlying mechanisms their possible contribution to risk chronic diseases.