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

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Listed:
  • Mitchell J. Machiela

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Weiyin Zhou

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Eric Karlins

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Joshua N. Sampson

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Neal D. Freedman

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Qi Yang

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Belynda Hicks

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Casey Dagnall

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Christopher Hautman

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Kevin B. Jacobs

    (Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.
    Bioinformed, LLC)

  • Christian C. Abnet

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Melinda C. Aldrich

    (Vanderbilt University School of Medicine
    Vanderbilt Epidemiology Center, Vanderbilt University Medical Center)

  • Christopher Amos

    (The University of Texas MD Anderson Cancer Center)

  • Laufey T. Amundadottir

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Alan A. Arslan

    (New York University School of Medicine
    New York University School of Medicine
    New York University Cancer Institute)

  • Laura E. Beane-Freeman

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Sonja I. Berndt

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Amanda Black

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • William J. Blot

    (Vanderbilt Epidemiology Center, Vanderbilt University Medical Center
    International Epidemiology Institute)

  • Cathryn H. Bock

    (Wayne State University School of Medicine)

  • Paige M. Bracci

    (University of California San Francisco)

  • Louise A. Brinton

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • H Bas Bueno-de-Mesquita

    (National Institute for Public Health and the Environment (RIVM)
    University Medical Center
    The School of Public Health, Imperial College London
    Faculty of Medicine, University of Malaya)

  • Laurie Burdett

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Julie E. Buring

    (Brigham and Women’s Hospital)

  • Mary A. Butler

    (National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Tania Carreón

    (National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention)

  • Kari G. Chaffee

    (Mayo Clinic)

  • I-Shou Chang

    (National Institute of Cancer Research, National Health Research Institutes)

  • Nilanjan Chatterjee

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Chu Chen

    (Fred Hutchinson Cancer Research Center)

  • Constance Chen

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health)

  • Kexin Chen

    (Tianjin Medical University Cancer Institute and Hospital)

  • Charles C. Chung

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Linda S. Cook

    (University of New Mexico)

  • Marta Crous Bou

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health
    Brigham and Women's Hospital and Harvard Medical School)

  • Michael Cullen

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Faith G. Davis

    (School of Public Health, University of Alberta)

  • Immaculata De Vivo

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health
    Brigham and Women's Hospital and Harvard Medical School)

  • Ti Ding

    (Shanxi Cancer Hospital)

  • Jennifer Doherty

    (Geisel School of Medicine, Dartmouth College)

  • Eric J. Duell

    (Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology (ICO-IDIBELL))

  • Caroline G. Epstein

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Jin-Hu Fan

    (Shanghai Cancer Institute)

  • Jonine D. Figueroa

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Joseph F. Fraumeni

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Christine M. Friedenreich

    (Cancer Control Alberta, Alberta Health Services)

  • Charles S. Fuchs

    (Brigham and Women's Hospital and Harvard Medical School
    Dana-Farber Cancer Institute)

  • Steven Gallinger

    (Fred A Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute)

  • Yu-Tang Gao

    (Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotaong University School of Medicine)

  • Susan M. Gapstur

    (Epidemiology Research Program, American Cancer Society)

  • Montserrat Garcia-Closas

    (and Breakthrough Breast Cancer Centre, Institute for Cancer Research)

  • Mia M. Gaudet

    (Epidemiology Research Program, American Cancer Society)

  • J. Michael Gaziano

    (Brigham and Women’s Hospital and Harvard Medical School
    Massachusetts Veterans Epidemiology Research and Information Center/VA Cooperative Studies Programs, Veterans Affairs Boston Healthcare System)

  • Graham G. Giles

    (Cancer Epidemiology Centre, Cancer Council Victoria & Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne)

  • Elizabeth M. Gillanders

    (National Cancer Institute)

  • Edward L. Giovannucci

    (Brigham and Women's Hospital and Harvard Medical School
    Harvard School of Public Health)

  • Lynn Goldin

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Alisa M. Goldstein

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Christopher A. Haiman

    (Keck School of Medicine at the University of Southern California)

  • Goran Hallmans

    (Umeå University)

  • Susan E. Hankinson

    (Brigham and Women's Hospital and Harvard Medical School
    University of Massachusetts School of Public Health and Health Sciences)

  • Curtis C. Harris

    (Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute)

  • Roger Henriksson

    (Oncology, Umeå University)

  • Elizabeth A. Holly

    (University of California San Francisco)

  • Yun-Chul Hong

    (Seoul National University College of Medicine)

  • Robert N. Hoover

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Chao A. Hsiung

    (Institute of Population Health Sciences, National Health Research Institutes)

  • Nan Hu

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Wei Hu

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • David J. Hunter

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health
    Brigham and Women's Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Amy Hutchinson

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Mazda Jenab

    (International Agency for Research on Cancer (IARC-WHO))

  • Christoffer Johansen

    (Oncology, Finsen Centre
    Unit of Survivorship Research, The Danish Cancer Society Research Centre)

  • Kay-Tee Khaw

    (School of Clinical Medicine, University of Cambridge)

  • Hee Nam Kim

    (Center for Creative Biomedical Scientists, Chonnam National University)

  • Yeul Hong Kim

    (College of Medicine, Korea University Anam Hospital)

  • Young Tae Kim

    (Cancer Research Institute, Seoul National University College of Medicine)

  • Alison P. Klein

    (The Johns Hopkins University School of Medicine)

  • Robert Klein

    (Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center)

  • Woon-Puay Koh

    (Duke-NUS Graduate Medical School
    Saw Swee Hock School of Public Health, National University of Singapore)

  • Laurence N. Kolonel

    (Epidemiology Program, University of Hawaii Cancer Center)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Peter Kraft

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health)

  • Vittorio Krogh

    (Fondazione IRCCS Istituto Nazionale dei Tumori)

  • Robert C. Kurtz

    (Memorial Sloan-Kettering Cancer Center)

  • Andrea LaCroix

    (Fred Hutchinson Cancer Research Center)

  • Qing Lan

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Maria Teresa Landi

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Loic Le Marchand

    (Epidemiology Program, University of Hawaii Cancer Center)

  • Donghui Li

    (The University of Texas MD Anderson Cancer Center)

  • Xiaolin Liang

    (Memorial Sloan-Kettering Cancer Center)

  • Linda M. Liao

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Dongxin Lin

    (Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jianjun Liu

    (Genome Institute of Singapore
    School of Life Sciences, Anhui Medical University)

  • Jolanta Lissowska

    (Maria Sklodowska-Curie Cancer Center and Institute of Oncology)

  • Lingeng Lu

    (Yale School of Public Health)

  • Anthony M. Magliocco

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Nuria Malats

    (Spanish National Cancer Research Centre (CNIO))

  • Keitaro Matsuo

    (Aichi Cancer Center Research Institute)

  • Lorna H. McNeill

    (Cancer Prevention and Population Sciences, and Center for Community-Engaged Translational Research, Duncan Family Institute, The University of Texas MD Anderson Cancer Center)

  • Robert R. McWilliams

    (Mayo Clinic)

  • Beatrice S. Melin

    (Oncology, Umeå University)

  • Lisa Mirabello

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Lee Moore

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Sara H. Olson

    (Memorial Sloan-Kettering Cancer Center)

  • Irene Orlow

    (Memorial Sloan-Kettering Cancer Center)

  • Jae Yong Park

    (Lung Cancer Center, Kyungpook National University Medical Center)

  • Ana Patiño-Garcia

    (University Clinic of Navarra, Universidad de Navarra, IdiSNA, Navarra Institute for Health Research)

  • Beata Peplonska

    (Nofer Institute of Occupational Medicine)

  • Ulrike Peters

    (Fred Hutchinson Cancer Research Center)

  • Gloria M. Petersen

    (Mayo Clinic)

  • Loreall Pooler

    (University of Southern California)

  • Jennifer Prescott

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health
    Brigham and Women's Hospital and Harvard Medical School)

  • Ludmila Prokunina-Olsson

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Mark P. Purdue

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • You-Lin Qiao

    (Cancer Institute (Hospital), Chinese Academy of Medical Sciences)

  • Preetha Rajaraman

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Francisco X. Real

    (Spanish National Cancer Research Centre (CNIO)
    Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra)

  • Elio Riboli

    (School of Public Health, Imperial College London)

  • Harvey A. Risch

    (Yale School of Public Health)

  • Benjamin Rodriguez-Santiago

    (Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
    Quantitative Genomic Medicine Laboratory, qGenomics)

  • Avima M. Ruder

    (National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention)

  • Sharon A. Savage

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Fredrick Schumacher

    (Keck School of Medicine at the University of Southern California)

  • Ann G. Schwartz

    (Wayne State University School of Medicine)

  • Kendra L. Schwartz

    (Wayne State University School of Medicine)

  • Adeline Seow

    (Saw Swee Hock School of Public Health, National University of Singapore)

  • Veronica Wendy Setiawan

    (Keck School of Medicine at the University of Southern California)

  • Gianluca Severi

    (Cancer Epidemiology Centre, Cancer Council Victoria & Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
    Human Genetics Foundation (HuGeF))

  • Hongbing Shen

    (Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University
    Nanjing Medical University School of Public Health)

  • Xin Sheng

    (University of Southern California)

  • Min-Ho Shin

    (Chonnam National University Medical School)

  • Xiao-Ou Shu

    (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center)

  • Debra T. Silverman

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Margaret R. Spitz

    (Baylor College of Medicine)

  • Victoria L. Stevens

    (Epidemiology Research Program, American Cancer Society)

  • Rachael Stolzenberg-Solomon

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Daniel Stram

    (Keck School of Medicine at the University of Southern California)

  • Ze-Zhong Tang

    (Shanxi Cancer Hospital)

  • Philip R. Taylor

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Lauren R. Teras

    (Epidemiology Research Program, American Cancer Society)

  • Geoffrey S. Tobias

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • David Van Den Berg

    (Keck School of Medicine at the University of Southern California)

  • Kala Visvanathan

    (Johns Hopkins Bloomberg School of Public Health)

  • Sholom Wacholder

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Jiu-Cun Wang

    (Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University)

  • Zhaoming Wang

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Nicolas Wentzensen

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • William Wheeler

    (Information Management Services Inc.)

  • Emily White

    (Fred Hutchinson Cancer Research Center)

  • John K. Wiencke

    (University of California San Francisco)

  • Brian M. Wolpin

    (Brigham and Women's Hospital and Harvard Medical School
    Dana-Farber Cancer Institute)

  • Maria Pik Wong

    (Li Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Chen Wu

    (Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Tangchun Wu

    (Institute of Occupational Medicine and Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Huazhong University of Science and Technology)

  • Xifeng Wu

    (The University of Texas MD Anderson Cancer Center)

  • Yi-Long Wu

    (Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences)

  • Jay S. Wunder

    (Washington University School of Medicine)

  • Lucy Xia

    (University of Southern California)

  • Hannah P. Yang

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Pan-Chyr Yang

    (National Taiwan University College of Medicine)

  • Kai Yu

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Krista A. Zanetti

    (National Cancer Institute)

  • Anne Zeleniuch-Jacquotte

    (New York University Cancer Institute
    New York University School of Medicine)

  • Wei Zheng

    (Vanderbilt Epidemiology Center, Vanderbilt University Medical Center)

  • Baosen Zhou

    (School of Public Health, China Medical University)

  • Regina G. Ziegler

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Luis A. Perez-Jurado

    (Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER))

  • Neil E. Caporaso

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Nathaniel Rothman

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Margaret Tucker

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Michael C. Dean

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Meredith Yeager

    (National Cancer Institute (NCI), National Institutes of Health (NIH)
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Stephen J. Chanock

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

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.

Suggested Citation

  • 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 & Melind, 2016. "Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11843
    DOI: 10.1038/ncomms11843
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    Cited by:

    1. Weiyin Zhou & Anja Fischer & Martin D. Ogwang & Wen Luo & Patrick Kerchan & Steven J. Reynolds & Constance N. Tenge & Pamela A. Were & Robert T. Kuremu & Walter N. Wekesa & Nestory Masalu & Esther Kaw, 2023. "Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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