Characterization of large structural genetic mosaicism in human autosomes Journal Article
| Authors: | Machiela, M. J.; Zhou, W.; Sampson, J. N.; Dean, M. C.; Jacobs, K. B.; Black, A.; Brinton, L. A.; Chang, I. S.; Chen, C.; Chen, C.; Chen, K.; Cook, L. S.; Crous Bou, M.; De Vivo, I.; Doherty, J.; Friedenreich, C. M.; Gaudet, M. M.; Haiman, C. A.; Hankinson, S. E.; Hartge, P.; Henderson, B. E.; Hong, Y. C.; Hosgood, H. D. 3rd; Hsiung, C. A.; Hu, W.; Hunter, D. J.; Jessop, L.; Kim, H. N.; Kim, Y. H.; Kim, Y. T.; Klein, R.; Kraft, P.; Lan, Q.; Lin, D.; Liu, J.; Le Marchand, L.; Liang, X.; Lissowska, J.; Lu, L.; Magliocco, A. M.; Matsuo, K.; Olson, S. H.; Orlow, I.; Park, J. Y.; Pooler, L.; Prescott, J.; Rastogi, R.; Risch, H. A.; Schumacher, F.; Seow, A.; Setiawan, V. W.; Shen, H.; Sheng, X.; Shin, M. H.; Shu, X. O.; VanDen Berg, D.; Wang, J. C.; Wentzensen, N.; Wong, M. P.; Wu, C.; Wu, T.; Wu, Y. L.; Xia, L.; Yang, H. P.; Yang, P. C.; Zheng, W.; Zhou, B.; Abnet, C. C.; Albanes, D.; Aldrich, M. C.; Amos, C.; Amundadottie, L. T.; Berndt, S. I.; Blot, W. J.; Bock, C. H.; Bracci, P. M.; Burdett, L.; Buring, J. E.; Butler, M. A.; Carreon, T.; Chaterjee, N.; Chung, C. C.; Cook, M. B.; Cullen, M.; Davis, F. G.; Ding, T.; Duell, E. J.; Epstein, C. G.; Fan, J. H.; Figueroa, J. D.; Fraumeni, J. F. Jr; Freedman, N. D.; Fuchs, C. S.; Gao, Y. T.; Gapstur, S. M.; Patino-Garcia, A.; Garcia-Closas, M.; Gaziano, J. M.; Giles, G. G.; Gillanders, E. M.; Giovannucci, E. L.; Goldin, L.; Goldstein, A. M.; Greene, M. H.; Hallmans, G.; Harris, C. C.; Henriksson, R.; Holly, E. A.; Hoover, R. N.; Hu, N.; Hutchinson, A.; Jenab, M.; Johansen, C.; Khaw, K. T.; Koh, W. P.; Kolonel, L. N.; Kopperberg, C.; Krogh, V.; Kurtz, R. C.; LaCroix, A.; Landgren, A.; Landi, M. T.; Li, D.; Liao, L. M.; Malats, N.; McGlynn, K. A.; McNeill, L. H.; McWilliams, R. R.; Melin, B. S.; Mirabello, L.; Peplonska, B.; Peters, U.; Petersen, G. M.; Prokunin-Olsson, L.; Purdue, M.; Qiao, Y. L.; Rabe, K. G.; Rajaraman, P.; Real, F. X.; Riboli, E.; Rodriguez-Santiago, B.; Rothman, N.; Ruder, A. M.; Savage, S. A.; Schwartz, A. G.; Schwartz, K. L.; Sesso, H. D.; Severi, G.; Silverman, D. T.; Spitz, M. R.; Stevens, V. L.; Stolzenberg-Solomon, R.; Stram, D.; Tang, Z. Z.; Taylor, P. R.; Teras, L. R.; Tobias, G. S.; Viswanathan, K.; Wacholder, S.; Wang, Z.; Weinstein, S. J.; Wheeler, W.; White, E.; Wiencke, J. K.; Wolpin, B. M.; Wu, X.; Wunder, J. S.; Yu, K.; Zanetti, K. A.; Zeleniuch-Jacquotte, A.; Ziegler, R. G.; de Andrade, M.; Barnes, K. C.; Beaty, T. H.; Bierut, L. J.; Desch, K. C.; Doheny, K. F.; Feenstra, B.; Ginsburg, D.; Heit, J. A.; Kang, J. H.; Laurie, C. A.; Li, J. Z.; Lowe, W. L.; Marazita, M. L.; Melbye, M.; Mirel, D. B.; Murray, J. C.; Nelson, S. C.; Pasquale, L. R.; Rice, K.; Wiggs, J. L.; Wise, A.; Tucker, M.; Perez-Jurado, L. A.; Laurie, C. C.; Caporaso, N. E.; Yeager, M.; Chanock, S. J. |
| Article Title: | Characterization of large structural genetic mosaicism in human autosomes |
| Abstract: | Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10-31) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. © 2015 The American Society of Human Genetics. |
| Keywords: | controlled study; major clinical study; single nucleotide polymorphism; genetic association; genotype; dna; genome; aging; autosome; african; environment; mosaicism; ancestry group; human; priority journal; article; autosome mosaicism |
| Journal Title: | American Journal of Human Genetics |
| Volume: | 96 |
| Issue: | 3 |
| ISSN: | 0002-9297 |
| Publisher: | Cell Press |
| Date Published: | 2015-03-05 |
| Start Page: | 487 |
| End Page: | 497 |
| Language: | English |
| DOI: | 10.1016/j.ajhg.2015.01.011 |
| PROVIDER: | scopus |
| PMCID: | PMC4375431 |
| PUBMED: | 25748358 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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