Correlation found between loss of chromosome Y and genetic instability

In an international collaboration, researchers from Uppsala University have shown that loss of chromosome Y in the blood in men can function as an indicator of genetic instability, which in turn can affect the susceptibility for cancer in other parts of the body. The study has been published in the journal Nature.

In men, almost all cells have one Y chromosome and one X chromosome. In recent years researchers have discovered that it is relatively common in older men that some of the white blood cells no longer contain a Y chromosome. This loss of the Y chromosome, LOY, has been associated with diseases such as cancer, autoimmune conditions, Alzheimer’s disease and cardiovascular disease. However, the association has not been clarified: Does LOY in blood cells have a direct functional effect on the diseases or does LOY in the blood reflect a broader genomic instability which in turn affects the diseases?

In the present study the researchers show both processes are of importance. They could identify a large group of genes that are associated with LOY in blood cells. The function of these genes show that they are involved in genomic instability and cancer susceptibility or tumour growth. Other genes have a role in different aspects of cell cycle regulation and DNA damage response.

“Our findings indicate that LOY in white blood cells is a result of a common mechanism that leads to genomic instability, and that predisposes cells also in other tissues to cancer,” says Lars Forsberg, researcher at the Department of Immunology, Genetics and Pathology, who has led the study at Uppsala University.

Furthermore, the researchers show that LOY could have a direct effect on disease risk by influencing immune cell functions.

“By comparison of the gene expression of single cells from blood with and without a Y chromosome, we can see that LOY has an impact on immune cell functions. We hope that future studies may build on these observations, yielding further insights into mechanisms behind cancers and other ageing-related diseases,” says Lars Forsberg.

Collaborators in the study were Lars Forsberg’s and Jan Dumanski’s research groups at the Department of Immunology, Genetics and Pathology, Uppsala University, and international researchers and research consortiums.

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