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

Mitchell J Machiela; Weiyin Zhou; Eric Karlins; Joshua N. Sampson; Neal D Freedman; Qi Yang; Belynda D Hicks; Casey Dagnall; Christopher Hautman; Kevin B Jacobs; Christian C Abnet; Melinda C. Aldrich; Christopher I 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 Ann 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 García-Closas; Mia Gaudet; J Michael Gaziano; Graham 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; Yun Chul Hong; Robert N Hoover; Chao A Hsiung; Nan Hu; Zhuo-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 J Klein; Woon-Puay Koh; Laurence N Kolonel; Charles Kooperberg; Peter Kraft; Vittorio Krogh; Robert C. Kurtz; Andrea Z 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; Núria 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 Patinõ-Garcia; Beata Peplonska; Ulrike Peters; Gloria M. Petersen; Loreall C Pooler; Jennifer Prescott; Ludmila Prokunina-Olsson; Mark P. Purdue; You Lin Qiao; Preetha Rajaraman; Francisco X. Real; Elio Riboli; Harvey A Risch; Benjamín Rodríguez-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 O 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 A Tucker; Michael C. Dean; Meredith Yeager; Stephen J Chanock

doi:10.1038/ncomms11843

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

Mitchell J Machiela, Weiyin Zhou, Eric Karlins, Joshua N. Sampson, Neal D Freedman, Qi Yang, Belynda D Hicks, Casey Dagnall, Christopher Hautman, Kevin B Jacobs, Christian C Abnet, Melinda C. Aldrich, Christopher I Amos, Laufey T. Amundadottir, Alan A. Arslan, Laura E. Beane-Freeman, Sonja I Berndt, Amanda Black, William J Blot, Cathryn H. BockPaige M. Bracci, Louise A Brinton, H Bas Bueno-de-Mesquita, Laurie Burdett, Julie E Buring, Mary Ann 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 García-Closas, Mia Gaudet, J Michael Gaziano, Graham 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, Yun Chul Hong, Robert N Hoover, Chao A Hsiung, Nan Hu, Zhuo-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 J Klein, Woon-Puay Koh, Laurence N Kolonel, Charles Kooperberg, Peter Kraft, Vittorio Krogh, Robert C. Kurtz, Andrea Z 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, Núria 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 Patinõ-Garcia, Beata Peplonska, Ulrike Peters, Gloria M. Petersen, Loreall C Pooler, Jennifer Prescott, Ludmila Prokunina-Olsson, Mark P. Purdue, You Lin Qiao, Preetha Rajaraman, Francisco X. Real, Elio Riboli, Harvey A Risch, Benjamín Rodríguez-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 O 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 A Tucker, Michael C. Dean, Meredith Yeager, Stephen J Chanock

Department of Clinical Medicine

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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	https://doi.org/10.1038/ncomms11843
Publication status	Published - Jun 2016

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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosomeFinal published version, 456 KBLicence: CC BY

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Machiela, M. J., Zhou, W., Karlins, E., Sampson, J. N., Freedman, N. D., Yang, Q., Hicks, B. D., Dagnall, C., Hautman, C., Jacobs, K. B., Abnet, C. C., Aldrich, M. C., Amos, C. I., Amundadottir, L. T., Arslan, A. A., Beane-Freeman, L. E., Berndt, S. I., Black, A., Blot, W. J., ... Chanock, S. J. (2016). Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nature Communications, 7, [11843]. https://doi.org/10.1038/ncomms11843

Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, BD, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, CI, 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, C, Chen, K, Chung, CC, Cook, LS, Crous Bou, M, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, JH, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, YT, Gapstur, SM, García-Closas, M, Gaudet, M, Gaziano, JM, Giles, G, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, YC, Hoover, RN, Hsiung, CA, Hu, N, Hu, Z-W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, RJ, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, AZ, Lan, Q, Landi, MT, Marchand, LL, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patinõ-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, LC, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, YL, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodríguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Wendy Setiawan, V, Severi, G, Shen, H, Sheng, X, Shin, MH, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, DO, Tang, ZZ, Taylor, PR, Teras, LR, Tobias, GS, Van Den Berg, D, Visvanathan, K, Wacholder, S, Wang, JC, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, YL, Wunder, JS, Xia, L, Yang, HP, Yang, PC, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, MA, Dean, MC, Yeager, M & Chanock, SJ 2016, 'Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome', Nature Communications, vol. 7, 11843. https://doi.org/10.1038/ncomms11843

@article{021637babf4842018223d4f51bba8814,

title = "Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome",

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.",

author = "Machiela, {Mitchell J} and Weiyin Zhou and Eric Karlins and Sampson, {Joshua N.} and Freedman, {Neal D} and Qi Yang and Hicks, {Belynda D} and Casey Dagnall and Christopher Hautman and Jacobs, {Kevin B} and Abnet, {Christian C} and Aldrich, {Melinda C.} and Amos, {Christopher I} and Amundadottir, {Laufey T.} and Arslan, {Alan A.} and Beane-Freeman, {Laura E.} and Berndt, {Sonja I} and Amanda Black and Blot, {William J} and Bock, {Cathryn H.} and Bracci, {Paige M.} and Brinton, {Louise A} and Bueno-de-Mesquita, {H Bas} and Laurie Burdett and Buring, {Julie E} and Butler, {Mary Ann} and Federico Canzian and Tania Carre{\'o}n and Chaffee, {Kari G.} and I-Shou Chang and Nilanjan Chatterjee and Chu Chen and Constance Chen and Kexin Chen and Chung, {Charles C} and Cook, {Linda S} and {Crous Bou}, Marta and Michael Cullen and Davis, {Faith G} and {De Vivo}, Immaculata and Ti Ding and Jennifer Doherty and Duell, {Eric J} and Epstein, {Caroline G.} and Fan, {Jin Hu} and Figueroa, {Jonine D} and Fraumeni, {Joseph F.} and Friedenreich, {Christine M.} and Fuchs, {Charles S.} and Steven Gallinger and Gao, {Yu Tang} and Gapstur, {Susan M} and Montserrat Garc{\'i}a-Closas and Mia Gaudet and Gaziano, {J Michael} and Graham Giles and Gillanders, {Elizabeth M} and Giovannucci, {Edward L} and Lynn Goldin and Goldstein, {Alisa M} and Haiman, {Christopher A} and Goran Hallmans and Hankinson, {Susan E} and Harris, {Curtis C} and Roger Henriksson and Holly, {Elizabeth A.} and Hong, {Yun Chul} and Hoover, {Robert N} and Hsiung, {Chao A} and Nan Hu and Zhuo-Wei Hu and Hunter, {David J} and Amy Hutchinson and Mazda Jenab and Christoffer Johansen and Kay-Tee Khaw and Kim, {Hee Nam} and Kim, {Yeul Hong} and Kim, {Young Tae} and Klein, {Alison P.} and Klein, {Robert J} and Woon-Puay Koh and Kolonel, {Laurence N} and Charles Kooperberg and Peter Kraft and Vittorio Krogh and Kurtz, {Robert C.} and LaCroix, {Andrea Z} and Qing Lan and Landi, {Maria Teresa} and Marchand, {Loic Le} and Donghui Li and Xiaolin Liang and Liao, {Linda M.} and Dongxin Lin and Jianjun Liu and Jolanta Lissowska and Lingeng Lu and Magliocco, {Anthony M} and N{\'u}ria Malats and Keitaro Matsuo and McNeill, {Lorna H.} and McWilliams, {Robert R.} and Melin, {Beatrice S} and Lisa Mirabello and Lee Moore and Olson, {Sara H} and Irene Orlow and Park, {Jae Yong} and Ana Patin{\~o}-Garcia and Beata Peplonska and Ulrike Peters and Petersen, {Gloria M.} and Pooler, {Loreall C} and Jennifer Prescott and Ludmila Prokunina-Olsson and Purdue, {Mark P.} and Qiao, {You Lin} and Preetha Rajaraman and Real, {Francisco X.} and Elio Riboli and Risch, {Harvey A} and Benjam{\'i}n Rodr{\'i}guez-Santiago and Ruder, {Avima M} and Savage, {Sharon A} and Fredrick Schumacher and Schwartz, {Ann G.} and Schwartz, {Kendra L.} and Adeline Seow and {Wendy Setiawan}, Veronica and Gianluca Severi and Hongbing Shen and Xin Sheng and Shin, {Min Ho} and Xiao-Ou Shu and Silverman, {Debra T.} and Spitz, {Margaret R} and Stevens, {Victoria L} and Rachael Stolzenberg-Solomon and Stram, {Daniel O} and Tang, {Ze Zhong} and Taylor, {Philip R.} and Teras, {Lauren R.} and Tobias, {Geoffrey S.} and {Van Den Berg}, David and Kala Visvanathan and Sholom Wacholder and Wang, {Jiu Cun} and Zhaoming Wang and Nicolas Wentzensen and William Wheeler and Emily White and Wiencke, {John K} and Wolpin, {Brian M.} and Wong, {Maria Pik} and Chen Wu and Tangchun Wu and Xifeng Wu and Wu, {Yi Long} and Wunder, {Jay S.} and Lucy Xia and Yang, {Hannah P} and Yang, {Pan Chyr} and Kai Yu and Zanetti, {Krista A.} and Anne Zeleniuch-Jacquotte and Wei Zheng and Baosen Zhou and Ziegler, {Regina G} and Perez-Jurado, {Luis A.} and Caporaso, {Neil E.} and Nathaniel Rothman and Tucker, {Margaret A} and Dean, {Michael C.} and Meredith Yeager and Chanock, {Stephen J}",

year = "2016",

month = jun,

doi = "10.1038/ncomms11843",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

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

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11843

ER -

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

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