{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T02:03:28Z","timestamp":1777687408264,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2010,9,9]],"date-time":"2010-09-09T00:00:00Z","timestamp":1283990400000},"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":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The body of most animals display left\u2013right asymmetry of internal organs. Alteration of such asymmetry results in severe congenital defects particularly affecting the cardiovascular system. The earliest known genes involved in asymmetry, the Nodal signalling cascade, are expressed asymmetrically during embryonic development. <jats:italic>Nodal<\/jats:italic> was discovered in the mouse, but orthologs (also involved in left\u2010right specification) were reported in ascidians, sea\u2010urchins, and snails. Mutations in Nodal\u2010pathway genes cause alteration of several aspects of chirality, but not entirely mirror phenotypes of the body. Other factors upstream of <jats:italic>nodal<\/jats:italic> must be involved in the generation of left\u2013right asymmetry. In snails, breeding experiments have demonstrated that chirality is controlled by a nuclear gene with maternal effect. Given the available evidence, we propose that an evolutionarily conserved genetic basis of chirality (the same that controls left\u2013right asymmetry in snails) is a major synapomorphy of the Bilateria. This hypothesis fits with the observation that: (a) the proportion of patients with heterotaxy and a detected mutation in a gene of the Nodal cascade is actually low, and (b) horizontal recurrence of laterality defects is remarkably more frequent than vertical recurrence, and includes a notable number of affected sibs and\/or repeated abortions from unaffected mothers. Identification of the maternal gene(s) involved will allow for the identification of homozygous females at risk of having affected children and spontaneous abortions, and would provide a general medical framework for understanding the genetics of most alterations of chirality. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33655","type":"journal-article","created":{"date-parts":[[2010,9,9]],"date-time":"2010-09-09T20:59:57Z","timestamp":1284065997000},"page":"2419-2425","source":"Crossref","is-referenced-by-count":28,"title":["Shells and heart: Are human laterality and chirality of snails controlled by the same maternal genes?"],"prefix":"10.1002","volume":"152A","author":[{"given":"Marco","family":"Oliverio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Versacci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,9,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084576"},{"key":"e_1_2_6_3_1","first-page":"263","article-title":"Genetic variation and evolution of coiling chirality in snails","volume":"8","author":"Asami T","year":"1993","journal-title":"Forma"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esn032"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000202800.85341.6e"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/81695"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1180"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-142X.2002.02021.x"},{"key":"e_1_2_6_9_1","first-page":"895","volume-title":"Invertebrates","author":"Brusca RC","year":"2003"},{"key":"e_1_2_6_10_1","first-page":"214","volume-title":"From DNA to diversity: Molecular genetics and the evolution of animal design","author":"Carroll SB","year":"2001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.10.008"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2006.04.004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1242\/dev.111.4.969","article-title":"A novel retrovirally induced embryonic lethal mutation in the mouse: Assessment of the developmental fate of embryonic stem cells homozygous for the 413.d proviral insertion","volume":"111","author":"Conlon FL","year":"1991","journal-title":"Development"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.7.1919"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2009.181685"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01954484"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4701.099786"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.21121"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.05.008"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.34.3.503"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/514857"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00848443"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/339079"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.48.2.406"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07603"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg732"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/mollus\/eyi023"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04625"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1982.tb01402.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/302289"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990101)82:1<70::AID-AJMG14>3.0.CO;2-Y"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08597"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2004.08.006"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90477-8"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200005000-00002"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/381158a0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(03)00797-9"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10376"},{"key":"e_1_2_6_39_1","first-page":"154","article-title":"Transposition of great arteries. Understanding its pathogenesis","volume":"3","author":"Marino B","year":"2002","journal-title":"Ital Heart J Suppl"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn411"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-002-0242-3"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.08.002"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320160108"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(87)90956-8"},{"key":"e_1_2_6_45_1","volume-title":"Cardiovascular diseases. Genetics, epidemiology, and prevention","author":"Nora JJ","year":"1991"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80197-5"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21788"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.857987"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103707"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2005.12.003"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.8041"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.05.012"},{"key":"e_1_2_6_53_1","volume-title":"Invertebrate zoology: A functional evolutionary approach","author":"Ruppert EE","year":"2004"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.041603.094522"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.08.018"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00114-05-0045-2"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.58.1501.269"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esp058"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1086\/380998"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.13.1.53"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199802)250:2<210::AID-AR11>3.0.CO;2-R"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-008-0230-3"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(99)80064-1"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/361543a0"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.18.4.301"}],"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.33655","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T05:57:26Z","timestamp":1697003846000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,9]]},"references-count":64,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1002\/ajmg.a.33655"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33655","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,9]]}}}