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

Details

• Personal Author:
  Abnet CC ; Aldrich MC ; Amos C ; Amundadottir LT ; Arslan AA ; Beane-Freeman LE ; Berndt SI ; Black A ; Blot WJ ; Bock CH ; Bracci PM ; Brinton LA ; Bueno De Mesquita HB ; Burdett L ; Buring JE ; Butler MA ; Canzian F ; Carreón T ; Chaffee KG ; Chang I-S ; Chatterjee N ; Chen C ; Chen K ; Chung CC ; Cook LS ; Crous Bou M ; Cullen M ; Dagnall C ; Davis FG ; De Vivo I ; Ding T ; Doherty J ; Duell EJ ; Epstein CG ; Fan J-H ; Figueroa JD ; Fraumeni JF ; Freedman ND ; Friedenreich CM ; Fuchs CS ; Gallinger S ; Gao Y-T ; Gapstur SM ; Garcia-Closas M ; Gaudet MM ; Gaziano JM ; Giles GG ; Gillanders EM ; Giovannucci EL ; Goldin L ; Goldstein AM ; Haiman CA ; Hallmans G ; Hankinson SE ; Harris CC ; Hautman C ; Henriksson R ; Hicks B ; Holly EA ; Hong Y-C ; Hoover RN ; Hsiung CA ; Hu N ; Hu W ; Hunter DJ ; Hutchinson A ; Jacobs KB ; Jenab M ; Johansen C ; Karlins E ; Khaw K-T ; Kim HN ; Kim YH ; Kim YT ; Klein AP ; Klein R ; Koh W-P ; Machiela MJ ; Sampson JN ; Yang Q ; Zhou W
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Age Factors Chronic Disease Microbiology Neoplasms Occupational Health Risk Assessment Risk Factors Safety Sex Characteristics Women
• Keywords:
  Age Factors Cancer Cell Differentiation Cell Type Chromosome Disorders Chronic Diseases Deoxyribonucleic Acids DNA DNA Microarrays Gender Factors Genomics Genotype Microscopic Analysis Risk Factors

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• ISSN:
  2041-1723
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; Florida ; Maryland ; Massachusetts ; Michigan ; Minnesota ; New Hampshire ; New York ; Ohio ; OSHA Region 1 ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; OSHA Region 9 ; Tennessee ; Texas ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• NIOSHTIC Number:
  nn:20048300
• Citation:
  Nat Commun 2016 Jun; 7:11843
• Contact Point Address:
  Stephen J. Chanock, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA
• Email:
  chanocks@mail.nih.gov
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nature Communications
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ba3d8171824c6417652cb4888475cde1da907b8e0582d493e9c6661edb310eeeb574080da9e25f341993efe53cb0fd94f1bf57b325485789ba0fdefef1a23699
• Download URL:
  https://stacks.cdc.gov/view/cdc/203079/cdc_203079_DS1.pdf
• File Type:
  [PDF - 429.22 KB ]