Rats exhibit age-related mosaic loss of chromosome Y

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.

Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease

“…There is evidence from animal models that the rate of Y chromosome loss is tissue-dependent. By 2 years of age, rats develop LOY in the blood, brain, kidney, testis, and liver, but they do not develop LOY in the lung, muscle, pancreas, skin, or spleen [ 54 ]. Importantly, this study used qPCR of bulk tissue, which may miss LOY in underrepresented cell types.…”

First Cytogenomic Characterization of the Murine Testicular Tumor Cell Line I-10

“…The loss of Y-chromosome has been previously reported in other murine cell lines but never in a testicular-derived murine cell line. However, Y-chromosome instability has been found in rat and human testicular tumors [26][27][28], while the loss of the Y-chromosome was reported in the human testicular cell lines JKT-1 and TCam-2 [29,30], as well. The reason for this tumor-associated sex-chromosome loss remains undetermined.…”

Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease

“…This common post-zygotic structural mutation shows a robust association with AD [151,152], contributing to disease through immune system dysfunction [150,153,154]. It has been hypothesized that as microglia proliferate, they could be more prone to LOY accumulation [155]. A recent study showed LOY is enriched in microglia from AD patients, resulting in dysregulation of many genes associated with aging and inflammation [156].…”