Characterization of large structural genetic mosaicism in human autosomes
Journal
American journal of human genetics
Journal Volume
96
Journal Issue
3
Pages
487
Date Issued
2015-03-05
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
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
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.
Subjects
DETECTABLE CLONAL MOSAICISM; COPY-NUMBER-VARIATION; SOMATIC MOSAICISM; MAFFUCCI SYNDROME; OLLIER DISEASE; HUMAN GENOME; MUTATIONS; CANCER; CELLS; IDENTIFICATION
SDGs
Publisher
CELL PRESS
Type
journal article