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Characterization of large structural genetic mosaicism in human autosomes.
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.
Affiliation
  • Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Zhou W; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Leidos Biomedical Research Inc., Bethesda, MD 20892, USA.
  • Sampson JN; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Dean MC; Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
  • Jacobs KB; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Leidos Biomedical Research Inc., Bethesda, MD 20892, USA; BioInformed LLC, Gaithersburg, MD 20877, USA.
  • Black A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Brinton LA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Chang IS; National Institute of Cancer Research, National Health Research Institutes, Zhunan 35053, Taiwan, ROC.
  • Chen C; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Chen C; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA.
  • Chen K; Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300040, People's Republic of China.
  • Cook LS; University of New Mexico, Albuquerque, NM 87131, USA.
  • Crous Bou M; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • De Vivo I; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Doherty J; Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA.
  • Friedenreich CM; Department of Population Health Research, CancerControl Alberta, Alberta Health Services, Calgary, AB T2N 2T9, Canada.
  • Gaudet MM; Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.
  • Haiman CA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Hankinson SE; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA.
  • Hartge P; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Henderson BE; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Hong YC; Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
  • Hosgood HD; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Hsiung CA; Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan, ROC.
  • Hu W; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Hunter DJ; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambrid
  • Jessop L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Kim HN; Center for Creative Biomedical Scientists, Chonnam National University, Gwangju 500-757, Republic of Korea.
  • Kim YH; Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul 151-742, Republic of Korea.
  • Kim YT; Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, College of Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
  • Klein R; Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Kraft P; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA.
  • Lan Q; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Lin D; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China; State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Liu J; Department of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore; School of Life Sciences, Anhui Medical University, Hefei 230032, People's Republic of China.
  • Le Marchand L; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
  • Liang X; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Lissowska J; Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
  • Lu L; Yale School of Public Health, New Haven, CT 06510, USA.
  • Magliocco AM; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • Matsuo K; Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 819-0395, Japan.
  • Olson SH; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Orlow I; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Park JY; Lung Cancer Center, Kyungpook National University Medical Center, Daegu 101, Republic of Korea.
  • Pooler L; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90007, USA.
  • Prescott J; Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Rastogi R; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Risch HA; Yale School of Public Health, New Haven, CT 06510, USA.
  • Schumacher F; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Seow A; Saw Swee Hock School of Public Health, National University of Singapore, Singapore 119077, Singapore.
Am J Hum Genet ; 96(3): 487-97, 2015 Mar 05.
Article in En | MEDLINE | ID: mdl-25748358
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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Full text: 1 Database: MEDLINE Main subject: Genome, Human / Chromosome Aberrations / Mosaicism Type of study: Systematic_reviews Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Am J Hum Genet Year: 2015 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Genome, Human / Chromosome Aberrations / Mosaicism Type of study: Systematic_reviews Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Am J Hum Genet Year: 2015 Type: Article Affiliation country: United States