Research Group: Loss of chromosome Y and human disease

The main research focus of the group is the loss of chromosome Y (LOY) occurring in the leukocytes of aging men, which is the most common post-zygotic human mutation and perhaps the most common human mutation of all categories. This mutation was first reported by cytogenetic analysis over 50 years ago. It has been shown in recent years by our group and other scientists that LOY is associated with earlier mortality and higher morbidity from many diseases in men, including multiple common forms of cancer, Alzheimer’s disease and cardiovascular diseases. LOY represents lack of nearly 2% of the haploid nuclear genome and is the most common post-zygotic mutation as shown by analyses of bulk DNA and single-cells from peripheral blood. The research on LOY in our group is focused on the identification of leukocyte subpopulation(s) primarily responsible for disease development. We use Fluorescent Activated Cell Sorter (FACS) to isolate specific types of leukocytes to analyze LOY in the blood of patients diagnosed with colorectal, prostate and bladder carcinoma as well as with Alzheimer’s disease. As the control we use the blood of healthy males at the age of ≥ 65 years. We apply SNP microarrays and whole exome sequencing to study the spectrum of post-zygotic changes accompanied by LOY. We are also studying functional influence of LOY on disease development by the examination of changes in the RNA and protein levels, as well as applying single cell transcriptomics methods.

Projects in progress:

• Correlation between loss of chromosome Y (LOY) and clonal hematopoiesis of indeterminate potential (CHIP) mutations in selected populations of sorted peripheral blood leukocytes; study of Alzheimer’s disease (AD) cohort and controls
• Mosaic loss of chromosome Y (LOY) might predispose males to severe course of COVID-19
• Integrating experimental and computational studies to investigate LOY in tumor microenviroment of colorectal cancer patients
• Analysis of early predisposing post-zygotic variation in prostate, colorectal, and bladder cancer