{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:48Z","timestamp":1790278848476,"version":"4.1.0"},"reference-count":54,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES026819"],"award-info":[{"award-number":["R01ES026819"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Developmental biologists rely on genetics-based approaches to understand the origins of congenital abnormalities. Recent advancements in genomics have made it easier than ever to investigate the relationship between genes and disease. However, nonsyndromic birth defects often exhibit non-Mendelian inheritance, incomplete penetrance or variable expressivity. The discordance between genotype and phenotype indicates that extrinsic factors frequently impact the severity of genetic disorders and vice versa. Overlooking gene-environment interactions in birth defect etiology limits our ability to identify and eliminate avoidable risks. We present mouse models of sonic hedgehog signaling and craniofacial malformations to illustrate both the importance of and current challenges in resolving gene-environment interactions in birth defects. We then prescribe approaches for overcoming these challenges, including use of genetically tractable and environmentally responsive in vitro systems. Combining emerging technologies with molecular genetics and traditional animal models promises to advance our understanding of birth defect etiology and improve the identification and protection of vulnerable populations.<\/jats:p>","DOI":"10.1242\/dev.191064","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T17:29:44Z","timestamp":1595006984000},"source":"Crossref","is-referenced-by-count":49,"title":["Gene-environment interactions: aligning birth defects research with complex etiology"],"prefix":"10.1242","volume":"147","author":[{"given":"Tyler G.","family":"Beames","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-4090","authenticated-orcid":false,"given":"Robert J.","family":"Lipinski","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"2021042700584000300_DEV191064C1","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1242\/dev.142919","article-title":"A process engineering approach to increase organoid yield","volume":"144","author":"Arora","year":"2017","journal-title":"Development"},{"key":"2021042700584000300_DEV191064C2","doi-asserted-by":"publisher","first-page":"067010","DOI":"10.1289\/EHP2662","article-title":"Elucidating gene-by-environment interactions associated with differential susceptibility to chemical exposure","volume":"126","author":"Balik-Meisner","year":"2018","journal-title":"Environ. 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