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

@article{Guo2020MosaicLO,
  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},
  year={2020},
  volume={139},
  pages={421 - 446},
  url={https://api.semanticscholar.org/CorpusID:211036885}
}
The micronucleation hypothesis and centromere-dysfunction and telomere-attrition models are proposed to explain how mosaic LOY occurs and why ChrY is prone to lose and an improved understanding of mosaic LOy will open new pathways to modify and increase healthy aging in males.
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86 Citations
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86 Citations

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141 References

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

Examination of women with cancer and cancer-free controls shows that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk.

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.

Somatic mosaicism of sex chromosomes in the blood and brain

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”.
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