Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Bethesda, Maryland 20892, USA.
Nat Commun. 2016 Jun 13;7:11843. doi: 10.1038/ncomms11843.
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.
为了研究 X 染色体的大型结构嵌合性,我们分析了来自癌症全基因组关联研究的 38303 名女性的 SNP 微阵列强度数据(20878 例病例和 17425 例对照),并在 97 名女性(0.25%)中检测到 124 个>2 Mb 的嵌合 X 事件。在这里,我们发现 X 染色体嵌合体的发生率是常染色体平均发生率的四倍;X 嵌合体事件更常包含整个染色体,并且具有 X 事件的参与者更可能携带常染色体嵌合体事件。X 嵌合体的频率随年龄增加而增加(50 岁时为 0.11%;75 岁时为 0.45%),正如 Y 染色体和常染色体所报道的那样。对 33 名 X 染色体嵌合体女性进行的甲基化阵列分析表明,事件优先涉及失活的 X 染色体。我们的结果进一步证明,性染色体比常染色体更容易发生嵌合体事件,这可能对理解嵌合体事件的潜在机制及其对慢性疾病风险的可能贡献具有重要意义。