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

Authors:
Dr. Michael Dean, PhD
Dr. Michael Dean, PhD
National Cancer Institute
Sr. Scientist, LTG, DCEG
Human Genetics
Gaithersburg, MD | United States
Loreall Pooler
Loreall Pooler
University of Southern California
United States
Dr. Jonine Figueroa, PhD
Dr. Jonine Figueroa, PhD
Usher Institute of Population Health Sciences and Informatics
Chancellor's Fellow
Molecular epidemiology
Edinburgh, Scotland | United Kingdom
Yun-Chul Hong
Yun-Chul Hong
Seoul National University College of Medicine
Professor
Environmental Epidemiology
Seoul | Korea, Republic of
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 Bock Paige 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 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 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

Nat Commun 2016 06 13;7:11843. Epub 2016 Jun 13.

Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms11843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909985PMC
June 2016
116 Reads
10 Citations
10.742 Impact Factor

Publication Analysis

Top Keywords

mosaic events
20
events
7
mosaic
5
mosaicism
5
mosaicism frequency
4
frequency increases
4
events mosaicism
4
autosomal mosaic
4
harbour autosomal
4
increases age
4
50-year olds
4
045% 75-year
4
75-year olds
4
olds 045%
4
events harbour
4
011% 50-year
4
age 011%
4
entire chromosome
4
x-chromosome mosaicism
4
mosaicism times
4

Altmetric Statistics

References

(Supplied by CrossRef)

G Genovese et al.
N. Engl. J. Med. 2014

KB Jacobs et al.
Nat. Genet. 2012

S Jaiswal et al.
N. Engl. J. Med. 2014

CC Laurie et al.
Nat. Genet. 2012

A Bonnefond et al.
Nat. Genet. 2013

H Youssoufian et al.
Nat. Rev. Genet. 2002

MJ Machiela et al.
Semin. Hematol. 2013

LG Biesecker et al.
Nat. Rev. Genet. 2013

LA Forsberg et al.
Am. J. Hum. Genet. 2012

B Rodriguez-Santiago et al.
Am. J. Hum. Genet. 2010

Similar Publications