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.
| Original language | English |
|---|---|
| Article number | 11843 |
| Journal | Nature Communications |
| Volume | 7 |
| Number of pages | 9 |
| ISSN | 2041-1723 |
| DOIs | |
| Publication status | Published - Jun 2016 |
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- 10.1038/ncomms11843Licence: CC BY
- Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosomeFinal published version, 456 KBLicence: CC BY
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. / Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D; Yang, Qi; Hicks, Belynda D; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B; Abnet, Christian C; Aldrich, Melinda C.; Amos, Christopher I; 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 Ann; 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; García-Closas, Montserrat; Gaudet, Mia; Gaziano, J Michael; Giles, Graham; 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, Zhuo-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 J; Koh, Woon-Puay; Kolonel, Laurence N; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea Z; 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, Núria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S; Mirabello, Lisa; Moore, Lee; Olson, Sara H; Orlow, Irene; Park, Jae Yong; Patinõ-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall C; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A; Rodríguez-Santiago, Benjamín; 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 O; 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; Yang, Pan Chyr; 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 A; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.
In: Nature Communications, Vol. 7, 11843, 06.2016.Research output: Contribution to journal › Journal article › Research › peer-review
}
TY - JOUR
T1 - Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
AU - Machiela, Mitchell J
AU - Zhou, Weiyin
AU - Karlins, Eric
AU - Sampson, Joshua N.
AU - Freedman, Neal D
AU - Yang, Qi
AU - Hicks, Belynda D
AU - Dagnall, Casey
AU - Hautman, Christopher
AU - Jacobs, Kevin B
AU - Abnet, Christian C
AU - Aldrich, Melinda C.
AU - Amos, Christopher I
AU - Amundadottir, Laufey T.
AU - Arslan, Alan A.
AU - Beane-Freeman, Laura E.
AU - Berndt, Sonja I
AU - Black, Amanda
AU - Blot, William J
AU - Bock, Cathryn H.
AU - Bracci, Paige M.
AU - Brinton, Louise A
AU - Bueno-de-Mesquita, H Bas
AU - Burdett, Laurie
AU - Buring, Julie E
AU - Butler, Mary Ann
AU - Canzian, Federico
AU - Carreón, Tania
AU - Chaffee, Kari G.
AU - Chang, I-Shou
AU - Chatterjee, Nilanjan
AU - Chen, Chu
AU - Chen, Constance
AU - Chen, Kexin
AU - Chung, Charles C
AU - Cook, Linda S
AU - Crous Bou, Marta
AU - Cullen, Michael
AU - Davis, Faith G
AU - De Vivo, Immaculata
AU - Ding, Ti
AU - Doherty, Jennifer
AU - Duell, Eric J
AU - Epstein, Caroline G.
AU - Fan, Jin Hu
AU - Figueroa, Jonine D
AU - Fraumeni, Joseph F.
AU - Friedenreich, Christine M.
AU - Fuchs, Charles S.
AU - Gallinger, Steven
AU - Gao, Yu Tang
AU - Gapstur, Susan M
AU - García-Closas, Montserrat
AU - Gaudet, Mia
AU - Gaziano, J Michael
AU - Giles, Graham
AU - Gillanders, Elizabeth M
AU - Giovannucci, Edward L
AU - Goldin, Lynn
AU - Goldstein, Alisa M
AU - Haiman, Christopher A
AU - Hallmans, Goran
AU - Hankinson, Susan E
AU - Harris, Curtis C
AU - Henriksson, Roger
AU - Holly, Elizabeth A.
AU - Hong, Yun Chul
AU - Hoover, Robert N
AU - Hsiung, Chao A
AU - Hu, Nan
AU - Hu, Zhuo-Wei
AU - Hunter, David J
AU - Hutchinson, Amy
AU - Jenab, Mazda
AU - Johansen, Christoffer
AU - Khaw, Kay-Tee
AU - Kim, Hee Nam
AU - Kim, Yeul Hong
AU - Kim, Young Tae
AU - Klein, Alison P.
AU - Klein, Robert J
AU - Koh, Woon-Puay
AU - Kolonel, Laurence N
AU - Kooperberg, Charles
AU - Kraft, Peter
AU - Krogh, Vittorio
AU - Kurtz, Robert C.
AU - LaCroix, Andrea Z
AU - Lan, Qing
AU - Landi, Maria Teresa
AU - Marchand, Loic Le
AU - Li, Donghui
AU - Liang, Xiaolin
AU - Liao, Linda M.
AU - Lin, Dongxin
AU - Liu, Jianjun
AU - Lissowska, Jolanta
AU - Lu, Lingeng
AU - Magliocco, Anthony M
AU - Malats, Núria
AU - Matsuo, Keitaro
AU - McNeill, Lorna H.
AU - McWilliams, Robert R.
AU - Melin, Beatrice S
AU - Mirabello, Lisa
AU - Moore, Lee
AU - Olson, Sara H
AU - Orlow, Irene
AU - Park, Jae Yong
AU - Patinõ-Garcia, Ana
AU - Peplonska, Beata
AU - Peters, Ulrike
AU - Petersen, Gloria M.
AU - Pooler, Loreall C
AU - Prescott, Jennifer
AU - Prokunina-Olsson, Ludmila
AU - Purdue, Mark P.
AU - Qiao, You Lin
AU - Rajaraman, Preetha
AU - Real, Francisco X.
AU - Riboli, Elio
AU - Risch, Harvey A
AU - Rodríguez-Santiago, Benjamín
AU - Ruder, Avima M
AU - Savage, Sharon A
AU - Schumacher, Fredrick
AU - Schwartz, Ann G.
AU - Schwartz, Kendra L.
AU - Seow, Adeline
AU - Wendy Setiawan, Veronica
AU - Severi, Gianluca
AU - Shen, Hongbing
AU - Sheng, Xin
AU - Shin, Min Ho
AU - Shu, Xiao-Ou
AU - Silverman, Debra T.
AU - Spitz, Margaret R
AU - Stevens, Victoria L
AU - Stolzenberg-Solomon, Rachael
AU - Stram, Daniel O
AU - Tang, Ze Zhong
AU - Taylor, Philip R.
AU - Teras, Lauren R.
AU - Tobias, Geoffrey S.
AU - Van Den Berg, David
AU - Visvanathan, Kala
AU - Wacholder, Sholom
AU - Wang, Jiu Cun
AU - Wang, Zhaoming
AU - Wentzensen, Nicolas
AU - Wheeler, William
AU - White, Emily
AU - Wiencke, John K
AU - Wolpin, Brian M.
AU - Wong, Maria Pik
AU - Wu, Chen
AU - Wu, Tangchun
AU - Wu, Xifeng
AU - Wu, Yi Long
AU - Wunder, Jay S.
AU - Xia, Lucy
AU - Yang, Hannah P
AU - Yang, Pan Chyr
AU - Yu, Kai
AU - Zanetti, Krista A.
AU - Zeleniuch-Jacquotte, Anne
AU - Zheng, Wei
AU - Zhou, Baosen
AU - Ziegler, Regina G
AU - Perez-Jurado, Luis A.
AU - Caporaso, Neil E.
AU - Rothman, Nathaniel
AU - Tucker, Margaret A
AU - Dean, Michael C.
AU - Yeager, Meredith
AU - Chanock, Stephen J
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms11843
DO - 10.1038/ncomms11843
M3 - Journal article
C2 - 27291797
AN - SCOPUS:84974736225
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 11843
ER -