Rats exhibit age-related mosaic loss of chromosome Y

Alberto H. Orta, Stephen J. Bush, Mariana Gutiérrez-Mariscal, Susana Castro-Obregón, Lorraine Jaimes-Hoy, Ricardo Grande, Gloria Vázquez, Elisa Gorostieta-Salas, Mónica Martínez-Pacheco, Karina Díaz-Barba, Paola Cornejo-Páramo, Alejandro Sanchez-Flores, Tamas Székely, Araxi O. Urrutia, Diego Cortez

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6 Citations (SciVal)

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.

Original languageEnglish
Article number1418
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 21 Dec 2021

Bibliographical note

Funding Information:
We thank Manuel Villa Herrera, Sergio González Trujillo, M.V.z. Graciela Margarita Cabeza Pérez and M.V.z. Maria Elena Elizabeth Mata Moreno for their work in the animal facility monitoring and taking care of the rats. This study was supported by a CONACYT Fronteras en la Ciencia grant (no. FC-2016/1682), a CONACYT Ciencia de Frontera grant (no. 682142) and a Royal Society Newton Advanced Fellowship (no. NA160564) to DC, TS and AOU; a NERC grant (no. NE/P004121/1) and PAPIIT-DGAPA-UNAM grant (no. IA204020) to AOU; travel grants SEP-UNAM-FUNAM Programa de Capacitación en Métodos de Investigación to PCP and KDB; a special grant from the Undergraduate Program on Genomic Sciences – UNAM to PCP; the Korner Traveling Fellowship Fund and TELMEX foundation fellowship to KDB.

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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