Dataset Information

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.

SUBMITTER: Machiela MJ

PROVIDER: S-EPMC4375431 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Characterization of large structural genetic mosaicism in human autosomes.

Machiela Mitchell J MJ Zhou Weiyin W Sampson Joshua N JN Dean Michael C MC Jacobs Kevin B KB Black Amanda A Brinton Louise A LA Chang I-Shou IS Chen Chu C Chen Constance C Chen Kexin K Cook Linda S LS Crous Bou Marta M De Vivo Immaculata I Doherty Jennifer J Friedenreich Christine M CM Gaudet Mia M MM Haiman Christopher A CA Hankinson Susan E SE Hartge Patricia P Henderson Brian E BE Hong Yun-Chul YC Hosgood H Dean HD Hsiung Chao A CA Hu Wei W Hunter David J DJ Jessop Lea L Kim Hee Nam HN Kim Yeul Hong YH Kim Young Tae YT Klein Robert R Kraft Peter P Lan Qing Q Lin Dongxin D Liu Jianjun J Le Marchand Loic L Liang Xiaolin X Lissowska Jolanta J Lu Lingeng L Magliocco Anthony M AM Matsuo Keitaro K Olson Sara H SH Orlow Irene I Park Jae Yong JY Pooler Loreall L Prescott Jennifer J Rastogi Radhai R Risch Harvey A HA Schumacher Fredrick F Seow Adeline A Setiawan Veronica Wendy VW Shen Hongbing H Sheng Xin X Shin Min-Ho MH Shu Xiao-Ou XO VanDen Berg David D Wang Jiu-Cun JC Wentzensen Nicolas N Wong Maria Pik MP Wu Chen C Wu Tangchun T Wu Yi-Long YL Xia Lucy L Yang Hannah P HP Yang Pan-Chyr PC Zheng Wei W Zhou Baosen B Abnet Christian C CC Albanes Demetrius D Aldrich Melinda C MC Amos Christopher C Amundadottir Laufey T LT Berndt Sonja I SI Blot William J WJ Bock Cathryn H CH Bracci Paige M PM Burdett Laurie L Buring Julie E JE Butler Mary A MA Carreón Tania T Chatterjee Nilanjan N Chung Charles C CC Cook Michael B MB Cullen Michael M Davis Faith G FG Ding Ti T Duell Eric J EJ Epstein Caroline G CG Fan Jin-Hu JH Figueroa Jonine D JD Fraumeni Joseph F JF Freedman Neal D ND Fuchs Charles S CS Gao Yu-Tang YT Gapstur Susan M SM Patiño-Garcia Ana A Garcia-Closas Montserrat M Gaziano J Michael JM Giles Graham G GG Gillanders Elizabeth M EM Giovannucci Edward L EL Goldin Lynn L Goldstein Alisa M AM Greene Mark H MH Hallmans Goran G Harris Curtis C CC Henriksson Roger R Holly Elizabeth A EA Hoover Robert N RN Hu Nan N Hutchinson Amy A Jenab Mazda M Johansen Christoffer C Khaw Kay-Tee KT Koh Woon-Puay WP Kolonel Laurence N LN Kooperberg Charles C Krogh Vittorio V Kurtz Robert C RC LaCroix Andrea A Landgren Annelie A Landi Maria Teresa MT Li Donghui D Liao Linda M LM Malats Nuria N McGlynn Katherine A KA McNeill Lorna H LH McWilliams Robert R RR Melin Beatrice S BS Mirabello Lisa L Peplonska Beata B Peters Ulrike U Petersen Gloria M GM Prokunina-Olsson Ludmila L Purdue Mark M Qiao You-Lin YL Rabe Kari G KG Rajaraman Preetha P Real Francisco X FX Riboli Elio E Rodríguez-Santiago Benjamín B Rothman Nathaniel N Ruder Avima M AM Savage Sharon A SA Schwartz Ann G AG Schwartz Kendra L KL Sesso Howard D HD Severi Gianluca G Silverman Debra T DT Spitz Margaret R MR Stevens Victoria L VL Stolzenberg-Solomon Rachael R Stram Daniel D Tang Ze-Zhong ZZ Taylor Philip R PR Teras Lauren R LR Tobias Geoffrey S GS Viswanathan Kala K Wacholder Sholom S Wang Zhaoming Z Weinstein Stephanie J SJ Wheeler William W White Emily E Wiencke John K JK Wolpin Brian M BM Wu Xifeng X Wunder Jay S JS Yu Kai K Zanetti Krista A KA Zeleniuch-Jacquotte Anne A Ziegler Regina G RG de Andrade Mariza M Barnes Kathleen C KC Beaty Terri H TH Bierut Laura J LJ Desch Karl C KC Doheny Kimberly F KF Feenstra Bjarke B Ginsburg David D Heit John A JA Kang Jae H JH Laurie Cecilia A CA Li Jun Z JZ Lowe William L WL Marazita Mary L ML Melbye Mads M Mirel Daniel B DB Murray Jeffrey C JC Nelson Sarah C SC Pasquale Louis R LR Rice Kenneth K Wiggs Janey L JL Wise Anastasia A Tucker Margaret M Pérez-Jurado Luis A LA Laurie Cathy C CC Caporaso Neil E NE Yeager Meredith M Chanock Stephen J SJ

American journal of human genetics 20150301 3

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 s ...[more]

PMID: 25748358

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Dataset Information

Characterization of large structural genetic mosaicism in human autosomes.

Publications

Characterization of large structural genetic mosaicism in human autosomes.

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