Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Machiela MJ., Zhou W., Karlins E., Sampson JN., Freedman ND., Yang Q., Hicks B., Dagnall C., Hautman C., Jacobs KB., 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 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 J-H., Figueroa JD., Fraumeni JF., 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., Henriksson R., Holly EA., Hong Y-C., Hoover RN., Hsiung CA., Hu N., Hu W., Hunter DJ., Hutchinson A., Jenab M., Johansen C., Khaw K-T., Kim HN., Kim YH., Kim YT., Klein AP., Klein R., Koh W-P., Kolonel LN., Kooperberg C., Kraft P., Krogh V., Kurtz RC., LaCroix A., 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., Patiño-Garcia A., Peplonska B., Peters U., Petersen GM., Pooler L., Prescott J., Prokunina-Olsson L., Purdue MP., Qiao Y-L., Rajaraman P., Real FX., Riboli E., Risch HA., Rodriguez-Santiago B., Ruder AM., Savage SA., Schumacher F., Schwartz AG., Schwartz KL., Seow A., Wendy Setiawan V., Severi G., Shen H., Sheng X., Shin M-H., Shu X-O., Silverman DT., Spitz MR., Stevens VL., Stolzenberg-Solomon R., Stram D., Tang Z-Z., Taylor PR., Teras LR., Tobias GS., Van Den Berg D., Visvanathan K., Wacholder S., Wang J-C., Wang Z., Wentzensen N., Wheeler W., White E., Wiencke JK., Wolpin BM., Wong MP., Wu C., Wu T., Wu X., Wu Y-L., Wunder JS., Xia L., Yang HP., Yang P-C., Yu K., Zanetti KA., Zeleniuch-Jacquotte A., Zheng W., Zhou B., Ziegler RG., Perez-Jurado LA., Caporaso NE., Rothman N., Tucker M., Dean MC., Yeager M., Chanock SJ.
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.