Abstract
Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. To date, studies of LOY have only been performed in humans, and so it is unclear whether LOY is a natural consequence of our relatively long lifespan or due to exposure to human-specific external stressors. Here, we explored whether LOY could be detected in rats. We applied a locus-specific PCR and target sequencing approach that we used as a proxy to estimate LOY in 339 samples covering eleven tissues from young and old individuals. We detected LOY in four tissues of older rats. To confirm the results from the PCR screening, we re-sequenced 60 full genomes from old rats, which revealed that the Y chromosome is the sole chromosome with low copy numbers. Finally, our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome. This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and conclude that LOY may be a natural process in placental mammals.
Highlights
Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease
Old rats showed significant LOY in blood, brain, kidney, liver, and testis (Fig. 1b; Mann–Whitney U test against a distribution with a fixed median of 0, P < 0.05)
We found no difference in the testis between young and old rats (Fig. 1a, b; Mann–Whitney U test, P < 0.05), meaning the observed LOY in younger rats did not increase over time
Summary
Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. Our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are present in a rodent, and conclude that LOY may be a natural process in placental mammals. LOY has been associated with the increased prevalence of several diseases including several types of cancer[5,10,16,17], macular degeneration[18,19], Alzheimer’s disease[20], cardiovascular diseases[21,22], type 2 diabetes[10] as well as obesity[10] and harmful behaviors such as suicide completion[23] The results from these large association studies suggest that genes found on
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