Y chromosome is moving out of sex determination shadow

Abstract

Although sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.

Sex Dimorphic Effects of Bile Acid Metabolism in Liver Cancer in Mice

“…Sex dimorphism is an unavoidable feature in a plethora of diseases including HCC, and it can dictate susceptibility, severity, outcomes, and response to therapy. Data mining and case studies of HCC specimens have identified several Y-linked proto-oncogenes 41 and possible epigenetic modifications such as histone methylation 42 to discern sex differences. Sex-biased molecular signatures in HCC have focused on sex hormones, ie, androgen and estrogen.…”

Opt-in or out? Public perspectives on forensic DNA kinship investigations within the Dutch-speaking community

“…[ 21 ]One notable advantage of CSY stems from the Y-chromosome's classification as “the genetic wasteland” [ 44 ],referring to the perception that the Y-chromosome contains fewer genes compared to other chromosomes and is therefore less biologically significant [ 44 ]. Yet, recent research has shown that the Y-chromosome could still play a role in certain biological processes and disease susceptibility, albeit to a lesser extent than other chromosomes [ 45 ]. The concept of the Y-chromosome as a "genetic wasteland" may still hold true in terms of overall gene content, but specific genes could still have important effects on health and disease.…”

Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease

“…LOY is one of the most well-characterized mCA because it is large (~ 60 Mb) and relatively easy to detect in peripheral blood. For many years, LOY was thought to be part of normal male aging, but recent studies have shown that the Y chromosome plays a role beyond male development [ 46 ]. These functions may partially explain sex differences in disease and cancer predisposition [ 47 ].…”