Mosaic loss of human Y chromosome: what, how and why

Clonal chromosomal mosaicism and loss of chromosome Y in men are risk factors for SARS-CoV-2 vulnerability in the elderly

“…The numbers and proportions are likely to increase when individuals in aged care facilities are fully registered ( Figure S1). COVID-19 lethality in Italy and Spain and LOY prevalence in men, as reported in the UK biobank, 15 appear to increase exponentially with age ( Figure 1B). Sex-biased COVID-19 mortality, while heterogeneous across countries, is consistently higher for men ( Figure 1C).…”

“…[11][12][13][14] Genetic variation in multiple loci is involved in the inherited susceptibility to LOY, which can also be driven by smoking and other environmental exposures. 15 LOY is the most common copy number alteration in male leukocytes, estimated to occur in <2% men under 60 years of age, but exponentially increasing with aging to 15-40% in 70-85 year-old males and >50% at 93 years of age. 15 Extreme down-regulation of chromosome Y gene expression mainly driven by genes with X-chromosome homologs that escape X-inactivation seems to be the functional mediator of the reported association between LOY and disease.…”

“…15 LOY is the most common copy number alteration in male leukocytes, estimated to occur in <2% men under 60 years of age, but exponentially increasing with aging to 15-40% in 70-85 year-old males and >50% at 93 years of age. 15 Extreme down-regulation of chromosome Y gene expression mainly driven by genes with X-chromosome homologs that escape X-inactivation seems to be the functional mediator of the reported association between LOY and disease. 16,17 We, therefore, advance the hypothesis that XCM/LOY is an underlying factor for the increased severity and mortality of COVID-19 in aging men.…”

Loss of Chromosome Y and Its Potential Applications as Biomarker in Health and Forensic Sciences

“…Recently, a critical review on the origin and consequences of the Y chromosome's absence has gathered all the available information concerning the biological origins and clinical consequences of LOY. Guo et al [2020] highlight which pathologies have been associated with LOY, and there is an evaluation of the causal and consequence relationships that could connect this genetic aberration to pathogenic conditions. Nevertheless, functional studies that access interactions of the Y with the expression of immune system genes and LOYassociated variants in humans are needed to verify if LOY can have a depriving impact on human biological functions.…”

Y chromosome in health and diseases

“…androgen and estrogen receptors, could play important roles in such biological processes [1,3], genes on the male-specific Y chromosome could also contribute at the genetic levels to such differences between the sexes [9][10][11]. Recent studies on large populations with well-defined health information suggest that mosaic loss of the Y chromosome (mLOY) in the peripheral white blood cells predisposes men to various diseases, including cancers, cardiovascular and Alzheimer's diseases [12][13][14][15][16][17], suggesting that the Y chromosome could be essential in maintaining the homeostasis important for the health of men [11]. Despite such associations, it is uncertain how mLOY in small portion of the leukocytes could contribute to the genetic predisposition to diseases in men.…”