Editing Germline (section)

==DNA damage, mutation and repair==

[[Reactive oxygen species]] (ROS) are produced as byproducts of metabolism.  In germline cells, ROS are likely a significant cause of [[DNA damage (naturally occurring)|DNA damage]]s that, upon [[DNA replication]], lead to [[mutation]]s.  [[8-Oxoguanine]], an oxidized derivative of [[guanine]], is produced by spontaneous oxidation in the germline cells of mice, and during the cell's DNA replication cause GC to TA [[transversion]] mutations.<ref name="pmid24732879">{{cite journal |vauthors=Ohno M, Sakumi K, Fukumura R, Furuichi M, Iwasaki Y, Hokama M, Ikemura T, Tsuzuki T, Gondo Y, Nakabeppu Y |title=8-oxoguanine causes spontaneous de novo germline mutations in mice |journal=Sci Rep |volume=4 |pages=4689 |year=2014 |pmid=24732879 |pmc=3986730 |doi=10.1038/srep04689 |bibcode=2014NatSR...4E4689O }}</ref>  Such mutations occur throughout the mouse [[chromosome]]s as well as during different stages of [[gametogenesis]].

The mutation frequencies for cells in different stages of gametogenesis are about 5 to 10-fold lower than in [[somatic cell]]s both for [[spermatogenesis]]<ref name="pmid9707592">{{cite journal |vauthors=Walter CA, Intano GW, McCarrey JR, McMahan CA, Walter RB |title=Mutation frequency declines during spermatogenesis in young mice but increases in old mice |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=17 |pages=10015–9 |year=1998 |pmid=9707592 |pmc=21453 |doi= 10.1073/pnas.95.17.10015|bibcode=1998PNAS...9510015W |doi-access=free }}</ref> and [[oogenesis]].<ref name="pmid23153565">{{cite journal |vauthors=Murphey P, McLean DJ, McMahan CA, Walter CA, McCarrey JR |title=Enhanced genetic integrity in mouse germ cells |journal=Biol. Reprod. |volume=88 |issue=1 |pages=6 |year=2013 |pmid=23153565 |pmc=4434944 |doi=10.1095/biolreprod.112.103481 }}</ref>  The lower frequencies of mutation in germline cells compared to somatic cells appears to be due to more efficient [[DNA repair]] of DNA damages, particularly [[homologous recombination]]al repair, during germline [[meiosis]].<ref>Bernstein H, Byerly HC, Hopf FA, Michod RE. Genetic damage, mutation, and the evolution of sex. Science. 1985 Sep 20;229(4719):1277-81. doi: 10.1126/science.3898363. PMID 3898363</ref>  Among humans, about five percent of live-born offspring have a genetic disorder, and of these, about 20% are due to newly arisen [[germline mutation]]s.<ref name="pmid9707592" />