| Title: | MosCoverY: A method to estimate mosaic loss of Y chromosome from sequencing coverage data |
| Journal: | American Journal of Human Genetics |
| Published: | 11 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40939594/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2025.08.016 |
| URL: | https://www.cell.com/ajhg/pdf/S0002-9297(25)00326-X.pdf |
Publication 19519
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Mosaic loss of the Y chromosome (mLOY) is the most common somatic event in men, strongly associated with aging and various health conditions. Current methods for detecting mLOY primarily rely on DNA genotyping arrays. Here, we present MosCoverY, a method for estimating mLOY from exome or whole-genome sequencing data. MosCoverY addresses the challenges posed by the structure of the Y chromosome by focusing on single-copy genes and normalizing their coverage against autosomal exons matched by length and GC content. We validated it using data from 212,062 male participants in the UK Biobank, comparing the results to those obtained using genotyping- or whole-genome-sequencing-based methods. MosCoverY identified mLOY in 5.6% of men, demonstrating performance that was comparable to the other methods. We validated our approach by replicating known mLOY associations with age, smoking, all-cause mortality, and germline genetic loci. We further confirmed the robustness of our method at lower sequencing depth and demonstrated its applicability in single-sample analysis. Finally, we used data from The Cancer Genome Atlas to demonstrate that MosCoverY can also reliably detect variable mLOY in tumoral genomes. MosCoverY offers a valuable tool for detecting mLOY from exome or genome data in population-scale studies.</p>
11 Keywords
- Adult
- Aged
- Chromosome Deletion
- Chromosomes, Human, Y
- Exome
- Humans
- Male
- Middle Aged
- Mosaicism
- Sequence Analysis, DNA
- Whole Genome Sequencing
5 Authors
- Valeriia Timonina
- Astrid Marchal
- Laurent Abel
- Aurélie Cobat
- Jacques Fellay
1 Application
| Application ID | Title |
|---|---|
| 84415 | The influence of germline and somatic genetic variation on susceptibility to infectious diseases |
Enabling scientific discoveries that improve human health