Machiela, Mitchell J.Real, Francisco X.Rodríguez Santiago, BenjamínPérez Jurado, Luis AlbertoChanock, Stephen J.2016-02-222016-02-222015Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A et al. Characterization of large structural genetic mosaicism in human autosomes. American Journal of Human Genetics. 2015;96(3):487-97. DOI 10.1016/j.ajhg.2015.01.0110002-9297http://hdl.handle.net/10230/25923Analyses 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.application/pdfeng© Elsevier. This is the published version of an article http://dx.doi.org/10.1016/j.ajhg.2015.01.011 that appeared in the journal American Journal of Human Genetics. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseGenoma humàCromosomes humansinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ajhg.2015.01.011info:eu-repo/semantics/openAccess