{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:14:36Z","timestamp":1768565676103,"version":"3.49.0"},"reference-count":59,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U01DD000490"],"award-info":[{"award-number":["U01DD000490"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Gastroschisis remains an etiologic dilemma. We posit that an underlying genetic susceptibility either separately or coupled with a periconceptional environmental exposure stimulates an inflammatory response resulting in gastroschisis. To investigate the genetic link, we applied shared genomic segment (SGS) analysis, a novel approach to discover chromosomal segments that inherit in high\u2010risk multigenerational pedigrees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied pedigrees containing distantly related children with gastroschisis originating from a common ancestor. We used the Illumina OmniExpress genotyping array with &gt;700,000 SNPs. Samples from 40 affected children in 13 pedigrees (\u22653 affected children) were genotyped to generate the high\u2010density SNP data necessary to perform SGS analysis. Assessment of significance in SGS was determined empirically using simulations based on precise pedigree structure and modeling linkage disequilibrium (LD) for SNPs in the general population to properly account for genetic architecture. The LD model was estimated from the 1000 Genome Project using the same set of SNPs. Genome\u2010wide significance thresholds were determined for each pedigree.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified six pedigrees that contained genome\u2010wide statistically significant SGS regions inherited from a common founder. These regions were different in each pedigree, all contained immune pathway genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The genome\u2010wide significant regions support a genetic susceptibility for gastroschisis. The regions are compelling candidates for regionally focused genome sequencing, enabling the discovery of coding or noncoding (e.g., regulatory) risk variants, the latter of which are unlikely to be found using conventional exomic\/gene\u2010focused approaches. This technique provides a comprehensive and focused genomic interrogation that will help to advance our understanding of gastroschisis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1567","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T06:15:05Z","timestamp":1565072105000},"page":"1655-1664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Shared genomic segments in high\u2010risk multigenerational pedigrees with gastroschisis"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9171-7848","authenticated-orcid":false,"given":"Marcia L.","family":"Feldkamp","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Krikov","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myke J.","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Darlington","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Oregon  Eugene Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Sargent","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola J.","family":"Camp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine  Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1147"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.11.021"},{"issue":"9","key":"e_1_2_8_5_1","first-page":"2378","article-title":"Familiality of cancer in Utah","volume":"54","author":"Cannon\u2010Albright L.","year":"1994","journal-title":"Cancer Research"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.12.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30181"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2007.02.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0282-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181e17c75"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30183"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37437"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23041"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.22844"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076641"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcu.1870170312"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340208"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900913"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(96)00109-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"issue":"1","key":"e_1_2_8_22_1","first-page":"212","article-title":"Developmental anomalies in mice resulting from action of the gene, disorganization, a semidominant lethal","volume":"23","author":"Hummel K. 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