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Characterization of large structural genetic mosaicism in human autosomes.

  • Author(s): Machiela, Mitchell J
  • Zhou, Weiyin
  • Sampson, Joshua N
  • Dean, Michael C
  • Jacobs, Kevin B
  • Black, Amanda
  • Brinton, Louise A
  • Chang, I-Shou
  • Chen, Chu
  • Chen, Constance
  • Chen, Kexin
  • Cook, Linda S
  • Crous Bou, Marta
  • De Vivo, Immaculata
  • Doherty, Jennifer
  • Friedenreich, Christine M
  • Gaudet, Mia M
  • Haiman, Christopher A
  • Hankinson, Susan E
  • Hartge, Patricia
  • Henderson, Brian E
  • Hong, Yun-Chul
  • Hosgood, H Dean
  • Hsiung, Chao A
  • Hu, Wei
  • Hunter, David J
  • Jessop, Lea
  • Kim, Hee Nam
  • Kim, Yeul Hong
  • Kim, Young Tae
  • Klein, Robert
  • Kraft, Peter
  • Lan, Qing
  • Lin, Dongxin
  • Liu, Jianjun
  • Le Marchand, Loic
  • Liang, Xiaolin
  • Lissowska, Jolanta
  • Lu, Lingeng
  • Magliocco, Anthony M
  • Matsuo, Keitaro
  • Olson, Sara H
  • Orlow, Irene
  • Park, Jae Yong
  • Pooler, Loreall
  • Prescott, Jennifer
  • Rastogi, Radhai
  • Risch, Harvey A
  • Schumacher, Fredrick
  • Seow, Adeline
  • Setiawan, Veronica Wendy
  • Shen, Hongbing
  • Sheng, Xin
  • Shin, Min-Ho
  • Shu, Xiao-Ou
  • VanDen Berg, David
  • Wang, Jiu-Cun
  • Wentzensen, Nicolas
  • Wong, Maria Pik
  • Wu, Chen
  • Wu, Tangchun
  • Wu, Yi-Long
  • Xia, Lucy
  • Yang, Hannah P
  • Yang, Pan-Chyr
  • Zheng, Wei
  • Zhou, Baosen
  • Abnet, Christian C
  • Albanes, Demetrius
  • Aldrich, Melinda C
  • Amos, Christopher
  • Amundadottir, Laufey T
  • Berndt, Sonja I
  • Blot, William J
  • Bock, Cathryn H
  • Bracci, Paige M
  • Burdett, Laurie
  • Buring, Julie E
  • Butler, Mary A
  • Carreón, Tania
  • Chatterjee, Nilanjan
  • Chung, Charles C
  • Cook, Michael B
  • Cullen, Michael
  • Davis, Faith G
  • Ding, Ti
  • Duell, Eric J
  • Epstein, Caroline G
  • Fan, Jin-Hu
  • Figueroa, Jonine D
  • Fraumeni, Joseph F
  • Freedman, Neal D
  • Fuchs, Charles S
  • Gao, Yu-Tang
  • Gapstur, Susan M
  • Patiño-Garcia, Ana
  • Garcia-Closas, Montserrat
  • Gaziano, J Michael
  • Giles, Graham G
  • Gillanders, Elizabeth M
  • Giovannucci, Edward L
  • Goldin, Lynn
  • Goldstein, Alisa M
  • Greene, Mark H
  • Hallmans, Goran
  • Harris, Curtis C
  • Henriksson, Roger
  • Holly, Elizabeth A
  • Hoover, Robert N
  • Hu, Nan
  • Hutchinson, Amy
  • Jenab, Mazda
  • Johansen, Christoffer
  • Khaw, Kay-Tee
  • Koh, Woon-Puay
  • Kolonel, Laurence N
  • Kooperberg, Charles
  • Krogh, Vittorio
  • Kurtz, Robert C
  • LaCroix, Andrea
  • Landgren, Annelie
  • Landi, Maria Teresa
  • Li, Donghui
  • Liao, Linda M
  • Malats, Nuria
  • McGlynn, Katherine A
  • McNeill, Lorna H
  • McWilliams, Robert R
  • Melin, Beatrice S
  • Mirabello, Lisa
  • Peplonska, Beata
  • Peters, Ulrike
  • Petersen, Gloria M
  • Prokunina-Olsson, Ludmila
  • Purdue, Mark
  • Qiao, You-Lin
  • Rabe, Kari G
  • Rajaraman, Preetha
  • Real, Francisco X
  • Riboli, Elio
  • Rodríguez-Santiago, Benjamín
  • Rothman, Nathaniel
  • Ruder, Avima M
  • Savage, Sharon A
  • Schwartz, Ann G
  • Schwartz, Kendra L
  • Sesso, Howard D
  • Severi, Gianluca
  • Silverman, Debra T
  • Spitz, Margaret R
  • Stevens, Victoria L
  • Stolzenberg-Solomon, Rachael
  • Stram, Daniel
  • Tang, Ze-Zhong
  • Taylor, Philip R
  • Teras, Lauren R
  • Tobias, Geoffrey S
  • Viswanathan, Kala
  • Wacholder, Sholom
  • Wang, Zhaoming
  • Weinstein, Stephanie J
  • Wheeler, William
  • White, Emily
  • Wiencke, John K
  • Wolpin, Brian M
  • Wu, Xifeng
  • Wunder, Jay S
  • Yu, Kai
  • Zanetti, Krista A
  • Zeleniuch-Jacquotte, Anne
  • Ziegler, Regina G
  • de Andrade, Mariza
  • Barnes, Kathleen C
  • Beaty, Terri H
  • Bierut, Laura J
  • Desch, Karl C
  • Doheny, Kimberly F
  • Feenstra, Bjarke
  • Ginsburg, David
  • Heit, John A
  • Kang, Jae H
  • Laurie, Cecilia A
  • Li, Jun Z
  • Lowe, William L
  • Marazita, Mary L
  • Melbye, Mads
  • Mirel, Daniel B
  • Murray, Jeffrey C
  • Nelson, Sarah C
  • Pasquale, Louis R
  • Rice, Kenneth
  • Wiggs, Janey L
  • Wise, Anastasia
  • Tucker, Margaret
  • Pérez-Jurado, Luis A
  • Laurie, Cathy C
  • Caporaso, Neil E
  • Yeager, Meredith
  • Chanock, Stephen J
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375431/
No data is associated with this publication.
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.

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