Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes
Jan P. Dumanski,
Behrooz Torabi Moghadam,
Piotr L. Chłosta,
John R B Perry,
Lars A. Forsberg
Posted 18 Jun 2019
bioRxiv DOI: 10.1101/673459
Posted 18 Jun 2019
Mosaic loss of chromosome Y (LOY) in leukocytes has been associated with many diseases, yet it remains unclear whether this form of clonal mosaicism exerts a direct physiological effect. Here we perform single-cell and bulk RNA sequencing in leukocytes, observing considerable variation in the rate of LOY across individuals, cell types and disease state. Cells with LOY demonstrated a profound degree of transcriptional dysregulation impacting ∼500 autosomal genes. These genes are preferentially involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y challenging the view of it as a “genetic wasteland”. Furthermore, they support the hypothesis that altered immune function in leukocytes is a mechanism directly linking LOY to disease.
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