Display options
Cite
Orta AH, Bush SJ, Gutiérrez-Mariscal M, et al. Rats exhibit age-related mosaic loss of chromosome Y. Commun Biol. 2021;4(1):1418doi: 10.1038/s42003-021-02936-y.
Orta, A. H., Bush, S. J., Gutiérrez-Mariscal, M., Castro-Obregón, S., Jaimes-Hoy, L., Grande, R., Vázquez, G., Gorostieta-Salas, E., Martínez-Pacheco, M., Díaz-Barba, K., Cornejo-Páramo, P., Sanchez-Flores, A., Székely, T., Urrutia, A. O., & Cortez, D. (2021). Rats exhibit age-related mosaic loss of chromosome Y. Communications biology, 4(1), 1418. https://doi.org/10.1038/s42003-021-02936-y
Orta, Alberto H, et al. "Rats exhibit age-related mosaic loss of chromosome Y." Communications biology vol. 4,1 (2021): 1418. doi: https://doi.org/10.1038/s42003-021-02936-y
Orta AH, Bush SJ, Gutiérrez-Mariscal M, Castro-Obregón S, Jaimes-Hoy L, Grande R, Vázquez G, Gorostieta-Salas E, Martínez-Pacheco M, Díaz-Barba K, Cornejo-Páramo P, Sanchez-Flores A, Székely T, Urrutia AO, Cortez D. Rats exhibit age-related mosaic loss of chromosome Y. Commun Biol. 2021 Dec 21;4(1):1418. doi: 10.1038/s42003-021-02936-y. PMID: 34934158.
Copy Download .nbib Format: NLM
Share it on

Commun Biol. 2021 Dec 21;4(1):1418. doi: 10.1038/s42003-021-02936-y.

Rats exhibit age-related mosaic loss of chromosome Y.

Communications biology

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

Affiliations

  1. Centro de Ciencias Genómicas, UNAM, CP62210, Cuernavaca, México.
  2. Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, Oxford, UK.
  3. Instituto de Biotecnología, UNAM, CP62210, Cuernavaca, México.
  4. Instituto de Fisiología Celular, UNAM, Ciudad Universitaria, CP04510, Ciudad de México, México.
  5. Unidad Universitaria de Secuenciación Masiva y Bioinformática, Instituto de Biotecnología, UNAM, CP62210, Cuernavaca, México.
  6. Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, CP76010, Querétaro, México.
  7. Instituto de Ecología, UNAM, Ciudad Universitaria, CP04510, Ciudad de México, México.
  8. Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, BA2 7AY, Bath, UK.
  9. Department of Evolutionary Zoology and Human Biology, University of Debrecen, H-4032, Debrecen, Hungary.
  10. Instituto de Ecología, UNAM, Ciudad Universitaria, CP04510, Ciudad de México, México. [email protected].
  11. Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, BA2 7AY, Bath, UK. [email protected].
  12. Centro de Ciencias Genómicas, UNAM, CP62210, Cuernavaca, México. [email protected].

PMID: 34934158 DOI: 10.1038/s42003-021-02936-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.

© 2021. The Author(s).

References

  1. Cortez, D. et al. Origins and functional evolution of Y chromosomes across mammals. Nature 508, 488–493 (2014). - PubMed
  2. Bachtrog, D. Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration. Nat. Rev. Genet 14, 113–124 (2013). - PubMed
  3. Colaco, S. & Modi, D. Genetics of the human Y chromosome and its association with male infertility. Reprod. Biol. Endocrinol. 16, 14 (2018). - PubMed
  4. Liu, W. S. Mammalian sex chromosome structure, gene content, and function in male fertility. Annu Rev. Anim. Biosci. 7, 103–124 (2019). - PubMed
  5. Forsberg, L. A. et al. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat. Genet 46, 624–628 (2014). - PubMed
  6. Zhou, W. et al. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat. Genet 48, 563–568 (2016). - PubMed
  7. Thompson, D. J. et al. Genetic predisposition to mosaic Y chromosome loss in blood. Nature 575, 652–657 (2019). - PubMed
  8. Lin, S. H. et al. Incident disease associations with mosaic chromosomal alterations on autosomes, X and Y chromosomes: insights from a phenome-wide association study in the UK Biobank. Cell Biosci. 11, 143 (2021). - PubMed
  9. Lin, S. H. et al. Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men. Sci. Rep. 10, 3655 (2020). - PubMed
  10. Loftfield, E. et al. Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank. Sci. Rep. 8, 12316 (2018). - PubMed
  11. Forsberg, L. A. et al. Mosaic loss of chromosome Y in leukocytes matters. Nat. Genet 51, 4–7 (2019). - PubMed
  12. Hachiya, T. et al. Evaluation of the usefulness of saliva for mosaic loss of chromosome Y analysis. Sci. Rep. 11, 3769 (2021). - PubMed
  13. Danielsson, M. et al. Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals. Eur. J. Hum. Genet 28, 349–357 (2020). - PubMed
  14. Forsberg, L. A. Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men. Hum. Genet 136, 657–663 (2017). - PubMed
  15. Wright, D. J. et al. Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility. Nat. Genet 49, 674–679 (2017). - PubMed
  16. Machiela, M. J. et al. Mosaic chromosome Y loss and testicular germ cell tumor risk. J. Hum. Genet 62, 637–640 (2017). - PubMed
  17. Noveski, P. et al. Loss of Y chromosome in peripheral blood of colorectal and prostate cancer patients. PLoS One 11, e0146264 (2016). - PubMed
  18. Grassmann, F., International, A. M. D. G. C., Weber, B. H. F. & Veitia, R. A. Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data. Hum. Genet 139, 401–407 (2020). - PubMed
  19. Grassmann, F. et al. Y chromosome mosaicism is associated with age-related macular degeneration. Eur. J. Hum. Genet 27, 36–41 (2019). - PubMed
  20. Dumanski, J. P. et al. Mosaic loss of chromosome Y in blood is associated with Alzheimer disease. Am. J. Hum. Genet 98, 1208–1219 (2016). - PubMed
  21. Haitjema, S. et al. Loss of Y chromosome in blood is associated with major cardiovascular events during follow-up in men after carotid endarterectomy. Circ. Cardiovasc Genet 10, e001544 (2017). - PubMed
  22. Wong, J. Y. Y. et al. Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study. Environ. Int 116, 239–247 (2018). - PubMed
  23. Kimura, A. et al. Loss of chromosome Y in blood, but not in brain, of suicide completers. PLoS One 13, e0190667 (2018). - PubMed
  24. Bellott, D. W. et al. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature 508, 494–499 (2014). - PubMed
  25. Terao, C. et al. GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation. Nat. Commun. 10, 4719 (2019). - PubMed
  26. Terao, C. et al. Chromosomal alterations among age-related haematopoietic clones in Japan. Nature 584, 130–135 (2020). - PubMed
  27. Graham, E. J. et al. Somatic mosaicism of sex chromosomes in the blood and brain. Brain Res 1721, 146345 (2019). - PubMed
  28. Dumanski, J. P. et al. Immune cells lacking Y chromosome show dysregulation of autosomal gene expression. Cell Mol. Life Sci. 78, 4019–4033 (2021). - PubMed
  29. Tacutu, R. et al. Human Ageing Genomic Resources: new and updated databases. Nucleic Acids Res 46, D1083–D1090 (2018). - PubMed
  30. Dumanski, J. P. et al. Mutagenesis. Smoking is associated with mosaic loss of chromosome Y. Science 347, 81–83 (2015). - PubMed
  31. Muzinic, V., Ramic, S. & Zeljezic, D. Chromosome missegregation and aneuploidy induction in human peripheral blood lymphocytes in vitro by low concentrations of chlorpyrifos, imidacloprid and alpha-cypermethrin. Environ. Mol. Mutagen 60, 72–84 (2019). - PubMed
  32. Guo, X. et al. Mosaic loss of human Y chromosome: what, how and why. Hum. Genet 139, 421–446 (2020). - PubMed
  33. Oluwole, O. A. et al. Highly dynamic temporal changes of TSPY gene copy number in aging bulls. PLoS One 12, e0178558 (2017). - PubMed
  34. Faggioli, F., Wang, T., Vijg, J. & Montagna, C. Chromosome-specific accumulation of aneuploidy in the aging mouse brain. Hum. Mol. Genet 21, 5246–5253 (2012). - PubMed
  35. Treangen, T. J. & Salzberg, S. L. Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat. Rev. Genet 13, 36–46 (2011). - PubMed
  36. Ramirez-Tortosa, C. L. et al. Longevity and cause of death in male wistar rats fed lifelong diets based on virgin olive oil, sunflower oil, or fish oil. J. Gerontol. A Biol. Sci. Med Sci. 75, 442–451 (2020). - PubMed
  37. Sengupta, P. The laboratory rat: relating its age with human’s. Int J. Prev. Med 4, 624–630 (2013). - PubMed
  38. Machiela, M. J. et al. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat. Commun. 7, 11843 (2016). - PubMed
  39. Zhou, W. et al. Detectable chromosome X mosaicism in males is rarely tolerated in peripheral leukocytes. Sci. Rep. 11, 1193 (2021). - PubMed
  40. Mattisson, J. et al. Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99. Sci. Rep. 11, 15160 (2021). - PubMed
  41. Chow, H. M. & Herrup, K. Genomic integrity and the ageing brain. Nat. Rev. Neurosci. 16, 672–684 (2015). - PubMed
  42. Rehen, S. K. et al. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc. Natl Acad. Sci. USA 98, 13361–13366 (2001). - PubMed
  43. Pipoly, I. et al. The genetic sex-determination system predicts adult sex ratios in tetrapods. Nature 527, 91–94 (2015). - PubMed
  44. Marais, G. A. B. et al. Sex gap in aging and longevity: can sex chromosomes play a role? Biol. Sex. Differ. 9, 33 (2018). - PubMed
  45. Wong, H. Y. et al. TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer. Oncotarget 6, 44927–44940 (2015). - PubMed
  46. Arseneault, M. et al. Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma. Sci. Rep. 7, 44876 (2017). - PubMed
  47. Jangravi, Z. et al. Two splice variants of Y chromosome-located lysine-specific demethylase 5D have distinct function in prostate cancer cell line (DU-145). J. Proteome Res 14, 3492–3502 (2015). - PubMed
  48. Martinez-Pacheco, M. et al. Expression evolution of ancestral XY gametologs across all major groups of placental mammals. Genome Biol. Evol. 12, 2015–2028 (2020). - PubMed
  49. Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014). - PubMed
  50. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012). - PubMed
  51. Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, https://doi.org/10.1093/gigascience/giab008 (2021). - PubMed
  52. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990). - PubMed

Publication Types