A decade of studies on the Loss of Y chromosome

3.01.2025

Prof. Jan Dumański, Natalia Filipowicz, Ph.D. and Edyta Rychlicka-Buniowska, Ph.D. from 3P-Medicine Laboratory, International Research Agenda MUG, along with collaborators from Uppsala University, authored the recently published review The effects of loss of Y chromosome on male health, which was released recently in renowned Nature Reviews Genetics (Impact Factor: 39.1).

The primary research focus of the 3P-Medicine Laboratory is the relatively poorly explored area of genetics involving post-zygotic mutations (PZMs), which can predispose to various diseases. Among these mutations, the loss of the Y chromosome (LOY) stands out as the most prevalent. The first reports of LOY in normal cells were published over 60 years ago, but got little attention before 2014 when the group of Jan Dumański published three papers highlighting LOY as an significant factor associated with all-cause mortality, increased risk for non-haematological cancer and Alzheimer disease. Moreover, their findings revealed that cigarette smoking can induce LOY. Since then more than 160 papers have reported various findings on causes, mechanisms and consequences of LOY.

In the published article the authors made an effort to review and summarize a decade of successful research documenting the effects of LOY in somatic cells on the health of male individuals, with emphasis on genetic and environmental factors that predispose to LOY as well as pleiotropic and cell-specific effects of LOY. The article stresses causal effects of LOY on increased mortality through disturbed homeostasis of immune system in males in the context of cardiac fibrosis, bladder cancer and Alzheimer disease. The comprehensive review of the literature reveals that the Y chromosome requires greater research attention, challenging the widespread belief that its contribution to phenotype is limited to sex differentiation and sperm production.

It is worth to stress that Professor Dumanski, in collaboration with his collegues from Uppsala University and Medical University of Gdańsk, has authored of 15 articles devoted to the phenomenon of LOY. However, his work in this field is far from over—several projects on LOY are currently ongoing. These include the National Science Center OPUS 25 project Functional consequences of loss of chromosome Y (LOY) in immune cells in the context of cancer – ex vivo and in vitro studies of human cells, led by Prof. Arkadiusz Piotrowski and Prof. Dumański at the Medical University of Gdańsk.

The article is available here.