Abstract
The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.
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Acknowledgements
This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique and from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757).
Funding
This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique, from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757) and by institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (Contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1X01HG006934-01 (to Gonçalo R. Abecasis, University of Michigan, Department of Biostatistics).
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Grassmann, F., International AMD Genomics Consortium (IAMDGC)., Weber, B.H.F. et al. 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). https://doi.org/10.1007/s00439-019-02029-1
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DOI: https://doi.org/10.1007/s00439-019-02029-1