Editing Genomic imprinting (section)

==Human disorders associated with imprinting==
{{Anchor|disorders}}Imprinting may cause problems in [[cloning]], with clones having DNA that is not [[DNA methylation|methylated]] in the correct positions. It is possible that this is due to a lack of time for reprogramming to be completely achieved. When a [[cell nucleus|nucleus]] is added to an egg during [[somatic cell nuclear transfer]], the egg starts dividing in minutes, as compared to the days or months it takes for reprogramming during [[embryo]]nic development. If time is the responsible factor, it may be possible to delay cell division in clones, giving time for proper reprogramming to occur.{{cn|date=July 2019}}

[[In vitro fertilisation]], including [[Intracytoplasmic sperm injection|ICSI]], is associated with an increased risk of imprinting disorders, with an [[odds ratio]] of 3.7 (95% [[confidence interval]] 1.4 to 9.7).<ref name="LazaraviciuteKauser2014">{{cite journal | vauthors = Lazaraviciute G, Kauser M, Bhattacharya S, Haggarty P, Bhattacharya S | title = A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously | journal = Human Reproduction Update | volume = 20 | issue = 6 | pages = 840–852 | year = 2014 | pmid = 24961233 | doi = 10.1093/humupd/dmu033 | doi-access = free }}</ref>

===Male infertility===
Epigenetic deregulations at [[H19 (gene)|H19]] imprinted gene in sperm have been observed associated with male [[infertility]].<ref name="H19">{{cite journal | vauthors = Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F | title = Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males | journal = Epigenetics | volume = 8 | issue = 9 | pages = 990–997 | date = September 2013 | pmid = 23975186 | pmc = 3883776 | doi = 10.4161/epi.25798 }}</ref> Indeed, methylation loss at H19 imprinted gene has been observed associated with [[methylenetetrahydrofolate reductase|MTHFR]] gene promoter [[DNA methylation|hypermethylation]] in semen samples from [[infertility|infertile]] males. <ref name="H19" />

===Prader-Willi/Angelman===
The first imprinted [[genetic disorder]]s to be described in humans were the reciprocally inherited [[Prader-Willi syndrome]] and [[Angelman syndrome]]. Both syndromes are associated with loss of the chromosomal region 15q11-13 (band 11 of the long arm of chromosome 15). This region contains the paternally expressed genes [[SNRPN]] and [[NDN (gene)|NDN]] and the maternally expressed gene [[UBE3A]].
*Paternal inheritance of a deletion of this region is associated with [[Prader-Willi syndrome]] (characterised by [[hypotonia]], [[obesity]], and [[hypogonadism]]).
*Maternal inheritance of the same deletion is associated with [[Angelman syndrome]] (characterised by [[epilepsy]], [[tremor]]s, and a perpetually smiling facial expression).

===Potential involvement in autism and schizophrenia===
{{Excerpt|Imprinted brain hypothesis}}

===DIRAS3 (NOEY2 or ARH1) ===
[[NOEY2|DIRAS3]] is a paternally expressed and maternally imprinted gene located on chromosome 1 in humans. Reduced DIRAS3 expression is linked to an increased risk of ovarian and breast cancers; in 41% of breast and ovarian cancers the protein encoded by DIRAS3 is not expressed, suggesting that it functions as a [[tumor suppressor gene]].<ref name="NOEY2">{{cite journal | vauthors = Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC | display-authors = 6 | title = NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 1 | pages = 214–219 | date = January 1999 | pmid = 9874798 | pmc = 15119 | doi = 10.1073/pnas.96.1.214 | bibcode = 1999PNAS...96..214Y | doi-access = free }}</ref> Therefore, if uniparental disomy occurs and a person inherits both chromosomes from the mother, the gene will not be expressed and the individual is put at a greater risk for breast and ovarian cancer.

===Other===
Other conditions involving imprinting include [[Beckwith-Wiedemann syndrome]], [[Silver-Russell syndrome]], and [[pseudohypoparathyroidism]].<ref name="AllisJenuwein2007">{{Cite book |url=https://books.google.com/books?id=_aqrvxbSiTcC&pg=PA440 |title=Epigenetics |vauthors=Allis CD, Jenuwein T, Reinberg D |publisher=CSHL Press |year=2007 |isbn=978-0-87969-724-2 |pages=440 |access-date=10 November 2010}}</ref>

[[Transient neonatal diabetes mellitus]] can also involve imprinting.<ref name="Scharfmann2007">{{Cite book |url=https://books.google.com/books?id=AzvFFxY-3CMC&pg=PA113 |title=Development of the Pancreas and Neonatal Diabetes |vauthors=Scharfmann R |publisher=Karger Publishers |year=2007 |isbn=978-3-8055-8385-5 |pages=113– |access-date=10 November 2010}}</ref>

The "[[imprinted brain hypothesis]]" argues that unbalanced imprinting may be a cause of [[autism]] and [[psychosis]].