Faculty, Staff and Student Publications
Publication Date
2-6-2025
Journal
American Journal of Human Genetics
Abstract
Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones.
Keywords
Humans, Chromosomes, Human, Y, Mosaicism, Male, Phenotype, Haplotypes, Whole Genome Sequencing, Genomics, Chromosome Deletion, Alleles
DOI
10.1016/j.ajhg.2024.12.014
PMID
39809269
PMCID
PMC11866972
PubMedCentral® Posted Date
1-13-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
