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

  title={Mosaic loss of human Y chromosome: what, how and why},
  author={Xihan Guo and Xueqin Dai and Tao Zhou and Han Wang and Juan Ni and Jing-lun Xue and Xu Wang},
  journal={Human Genetics},
Y chromosome (ChrY), the male-specific sex chromosome, has been considered as a genetic wasteland. Aging-related mosaic loss of ChrY (LOY) has been known for more than half a century, but it was constantly considered as a neutral karyotype related to normal aging. These views have been challenged with genome-wide association studies identifying mosaic LOY in human somatic cells is the most commonly acquired mutation in male’s genome and is associated with a wide spectrum of human diseases… 

Rats exhibit age-related mosaic loss of chromosome Y

This is the first report, to the authors' knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and it is concluded that LOY may be a natural process in placental mammals.

Mosaic loss of the Y chromosome and men's health

Y chromosomes in men can be lost at every life stage and Y chromosomal loss is associated with various health problems.

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

The potential application of LOY as biomarker highlights the necessity to clarify the molecular mechanism behind its occurrence and its possible applications in both health and forensic studies.

Genetics of autosomal mosaic chromosomal alteration (mCA).

This concise review briefly introduced mCA, its link with cancer and aging, and the emerging genetic mechanisms of this phenomenon, and highlighted the following aspects: the interplay between somatic and inherited germline mutations in generating mosaicism; monogenic and polygenic architectures of mCA; and population-specific profiles of m CA.

Mosaic loss of chromosome Y in aged human microglia

To the knowledge, the first evidence of LOY in the microglia is provided, highlighting its potential roles in aging and the pathogenesis of neurodegenerative disorders such as AD.

A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells

It is suggested that a PRS for LOY could become a useful tool for risk prediction and targeted intervention for common disease in men.

The Y chromosome and its impact on health and disease.

The literature is reviewed, focusing on the last two years, for recent evidence of the role of the Y chromosome in protecting from or contributing to disease, and current technology and methods for analyzing Y chromosome variation.

Y chromosome in health and diseases

This mini review discusses the nature of the genes on the human Y chromosome and identifies two general categories of genes: those sharing dosage-sensitivity functions with their X homologues and those with testis-specific expression and functions.

Repetitive DNA Sequences in the Human Y Chromosome and Male Infertility

  • Yong XuQ. Pang
  • Biology
    Frontiers in Cell and Developmental Biology
  • 2022
The structure and repetitive sequence of the Y chromosome is introduced, the correlation between Y chromosome various sequence deletions and male infertility is summarized, and research motivation is provided for further explore of the molecules mechanism of Y-deletion andmale infertility.



Genetic predisposition to mosaic Y chromosome loss in blood

A genome-wide association study of mosaic loss of chromosome Y in UK Biobank participants identifies 156 genetic determinants of LOY, showing that LOY is associated with cancer and non-haematological health outcomes and supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues.

The Y chromosome: a blueprint for men’s health?

The UTY (Ubiquitously Transcribed Tetratricopeptide Repeat Containing, Y-Linked) gene is emerging as a promising candidate underlying the associations between Y-chromosome variants and the immunity-driven susceptibility to complex disease.

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events.

Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease

Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility

The results demonstrate that genotype-array-intensity data enables a measure of cell cycle efficiency at population scale and identifies genes implicated in aneuploidy, genome instability and cancer susceptibility, in addition to inferring a causal effect of smoking on mLOY.

Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

Observed associations between LOY in blood and various diseases in aging men and known risk factors for LOY are focused on, and mechanisms that could possibly explain how an acquired mutation in blood cells can be associated with disease processes in other organs are discussed.

Genetics of the human Y chromosome and its association with male infertility

Screening for Yq microdeletions would aid the clinician in determining the cause of male infertility and decide a rational management strategy for the patient, as these deletions are transmitted to 100% of male offspring born through assisted reproduction, testing of Yq deletions will allow the couples to make an informed choice regarding the perpetuation ofmale infertility in future generations.

Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals

A formula to transform mLRRY-values to percentage of LOY that is a more comprehensible unit is presented and could be applied for analyses of the vast amount of SNP-array data already generated in the scientific community, allowing further discoveries of LOy associated diseases and outcomes.

Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes

These findings support the hypothesis that altered immune function in leukocytes is a mechanism directly linking LOY to disease and highlight a surprisingly broad role for chromosome Y challenging the view of it as a “genetic wasteland”.