Published in

Cell Press, American Journal of Human Genetics, 3(96), p. 487-497, 2015

DOI: 10.1016/j.ajhg.2015.01.011

Links

Tools

Export citation

Search in Google Scholar

Characterization of large structural genetic mosaicism in human autosomes

Journal article published in 2015 by Mitchell J. Machiela, Mitchell J Machiela, Weiyin Zhou, I. Shou Chang, Joshua N. Sampson, Michael C. Dean, Kevin B. Jacobs, Amanda Black, Louise A. Brinton, Is-Shou Chang, Chu Chen, Constance Chen, Kexin Chen ORCID, Loic Le Marchand, Linda S. Cook and other authors.
This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Orange circle
Postprint: archiving restricted
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

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.