{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T23:09:34Z","timestamp":1766617774172},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T00:00:00Z","timestamp":1376524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>A variety of hypotheses have been proposed to explain the association between trisomy and increasing maternal age in humans, virtually all of which assume that the underlying mechanisms involve meiotic errors. However, recently Hult\u00e9n and colleagues [Hulten et al., 2010b] proposed a provocative model\u2014the Oocyte Mosaicism Selection Model (OMSM)\u2014that links age\u2010dependent trisomy 21 to pre\u2010meiotic errors in the ovary. Specifically, they propose that nondisjunctional events occur in a proportion of germ cells as they mitotically proliferate, resulting in mosaicism for trisomy 21. Assuming that the presence of an additional chromosome 21 delays meiotic progression, these cells would be ovulated later in reproductive life, resulting in an age\u2010dependent increase in aneuploid eggs. Because this model has important clinical implications, we initiated studies to test it. We first analyzed oocytes from two trisomy 21 fetuses, combining immunostaining with FISH to determine the likelihood of detecting the additional chromosome 21 at different stages of meiosis. The detection of trisomy was enhanced during the earliest stage of prophase (leptotene), before homologs synapsed. Accordingly, in subsequent studies we examined the chromosome content of leptotene oocytes in seven second trimester female fetuses, analyzing three chromosomes commonly associated with human trisomies (i.e., 13, 16, and 21). In contrast to the prediction of the OMSM, we found no evidence of trisomy mosaicism for any chromosome. We conclude that errors in pre\u2010meiotic germ cells are not a major contributor to human aneuploidy and do not provide an explanation for the age\u2010related increase in trisomic conceptions. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36120","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T03:30:27Z","timestamp":1376623827000},"page":"2495-2503","source":"Crossref","is-referenced-by-count":14,"title":["Germline mosaicism does not explain the maternal age effect on trisomy"],"prefix":"10.1002","volume":"161","author":[{"given":"Ross","family":"Rowsey","sequence":"first","affiliation":[{"name":"Washington State University School of Molecular Biosciences and Center for Reproductive Biology Pullman Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kashevarova","sequence":"additional","affiliation":[{"name":"Washington State University School of Molecular Biosciences and Center for Reproductive Biology Pullman Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Murdoch","sequence":"additional","affiliation":[{"name":"Washington State University School of Molecular Biosciences and Center for Reproductive Biology Pullman Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"Dickenson","sequence":"additional","affiliation":[{"name":"Program on Reproductive Health and the Environment University of California San Francisco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Woodruff","sequence":"additional","affiliation":[{"name":"Program on Reproductive Health and the Environment University of California San Francisco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Washington Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Hunt","sequence":"additional","affiliation":[{"name":"Washington State University School of Molecular Biosciences and Center for Reproductive Biology Pullman Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"Hassold","sequence":"additional","affiliation":[{"name":"Washington State University School of Molecular Biosciences and Center for Reproductive Biology Pullman Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000063045"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20000904)94:1<35::AID-AJMG8>3.0.CO;2-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.4.661"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm148"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a137379"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000014956"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000661"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.06.069"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151851"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/280417a0"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(02)00163-8"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(92)90033-6"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31913"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31918"},{"key":"e_1_2_5_16_1","first-page":"125","article-title":"Parental trisomy 21 mosaicism","volume":"34","author":"Harris DJ","year":"1982","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00389450"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35066065"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2000.570201.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.3.159"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/218022a0"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1672"},{"key":"e_1_2_5_23_1","first-page":"1","article-title":"Issues pertaining to the impact and etiology of trisomy 21 and other aneuploidy in humans; a consideration of evolutionary implications, maternal age mechanisms, and other matters","volume":"311","author":"Hook EB","year":"1989","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-1-21"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920210793176056"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0088"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002251"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.54"},{"key":"e_1_2_5_29_1","first-page":"392","volume-title":"Essential reproduction","author":"Johnson MH","year":"2013"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1445"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1086\/427266"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.08.023"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60562-7"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.94"},{"key":"e_1_2_5_35_1","first-page":"1","article-title":"Births: Final data for 2010","volume":"61","author":"Martin JA","year":"2012","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.3885"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2011.03.003"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3245"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000033"},{"key":"e_1_2_5_40_1","first-page":"1015","article-title":"DNA polymorphism analysis in families with recurrence of free trisomy 21","volume":"51","author":"Pangalos CG","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018445520117"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00204931"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.032003"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-06-0243"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei079"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370737"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340578"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/7.1.49"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.605910"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02335088"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00273450"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2007.10.015"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200512077"},{"key":"e_1_2_5_54_1","first-page":"628","article-title":"Advanced maternal age and the risk of down syndrome characterized by the meiotic stage of chromosomal error: A population\u2010based study","volume":"58","author":"Yoon PW","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070594"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36120","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T22:59:17Z","timestamp":1696633157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,15]]},"references-count":54,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1002\/ajmg.a.36120"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36120","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,15]]}}}