With respect to reproductive biology, mtDNA sequences encoding RNR1, RNR2 and ND4 as well as the D-loop region have been found significantly hypermethylated in porcine oocytes in association with PCOS, indicating that abnormal activation of one-carbon metabolism and hypermethylation of mtDNA may contribute substantially to mitochondrial malfunction and decreased oocyte quality40. The gene discussed is MT-ND4; the disease is polycystic ovary syndrome.