Abstract
Sex differences are prevalent in normal development, physiology and disease pathogeneses. Recent studies have demonstrated that mosaic loss of Y chromosome and aberrant activation of its genes could modify the disease processes in male biased manners. This mini review discusses the nature of the genes on the human Y chromosome and identifies two general categories of genes: those sharing dosage-sensitivity functions with their X homologues and those with testis-specific expression and functions. Mosaic loss of the former disrupts the homeostasis important for the maintenance of health while aberrant activation of the latter promotes pathogenesis in non-gonadal tissues, thereby contributing to genetic predispositions to diseases in men.