Characterization of large structural genetic mosaicism in human autosomes.
| Authors | |
| Keywords | |
| 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. |
| Year of Publication | 2015
|
| Journal | Am J Hum Genet
|
| Volume | 96
|
| Issue | 3
|
| Pages | 487-97
|
| Date Published | 2015 Mar 05
|
| ISSN | 1537-6605
|
| URL | |
| DOI | 10.1016/j.ajhg.2015.01.011
|
| PubMed ID | 25748358
|
| PubMed Central ID | PMC4375431
|
| Links | |
| Grant list | P30 CA016672 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
K05 CA154337 / CA / NCI NIH HHS / United States
R01 CA092447 / CA / NCI NIH HHS / United States
UM1 CA182934 / CA / NCI NIH HHS / United States
G1000143 / Medical Research Council / United Kingdom
K07 CA172294 / CA / NCI NIH HHS / United States
R01 HL039693 / HL / NHLBI NIH HHS / United States
P30 CA023108 / CA / NCI NIH HHS / United States
R25 CA174664 / CA / NCI NIH HHS / United States
R01 CA124908 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 DE016148 / DE / NIDCR NIH HHS / United States
G0401527 / Medical Research Council / United Kingdom
R01 EY022305 / EY / NEI NIH HHS / United States
R01 EY015473 / EY / NEI NIH HHS / United States
P30 EY014104 / EY / NEI NIH HHS / United States
R01 HL112642 / HL / NHLBI NIH HHS / United States
|