{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:06:07Z","timestamp":1790769967949,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked at loss-of-function of a subset of Caenorhabditis elegans orthologs of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done. We turned to zebrafish as a developmental model and, using a number of surrogate phenotypes, we screened Hsa21 genes for effects on early embyrogenesis. We prepared a library of 164 cDNAs of conserved protein coding genes, injected mRNA into early embryos and evaluated up to 5 days post-fertilization (dpf). Twenty-four genes produced a gross morphological phenotype, 11 of which could be reproduced reliably. Seven of these gave a phenotype consistent with down regulation of the sonic hedgehog (Shh) pathway; two showed defects indicative of defective neural crest migration; one resulted consistently in pericardial edema; and one was embryonic lethal. Combinatorial injections of multiple Hsa21 genes revealed both additive and compensatory effects, supporting the notion that complex genetic relationships underlie end phenotypes of trisomy that produce DS. Together, our data suggest that this system is useful in the genetic dissection of dosage-sensitive gene effects on early development and can inform the contribution of both individual loci and their combinatorial effects to phenotypes relevant to the etiopathology of DS.<\/jats:p>","DOI":"10.1534\/g3.118.200144","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T17:15:22Z","timestamp":1526318122000},"page":"2215-2223","source":"Crossref","is-referenced-by-count":54,"title":["Survey of Human Chromosome 21 Gene Expression Effects on Early Development in\n                    <i>Danio rerio<\/i>"],"prefix":"10.1093","volume":"8","author":[{"given":"Sarah","family":"Edie","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, Institute of Genetic Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norann A","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen C","family":"Leitch","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna K","family":"Klinedinst","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Physiology, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette","family":"Lebron","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Physiology, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey F","family":"Thole","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Institute of Genetic Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"McCallion","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Institute of Genetic Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Katsanis","sequence":"additional","affiliation":[{"name":"Center for Human Disease Modeling, Duke University, Durham, NC 27701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger H","family":"Reeves","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Institute of Genetic Medicine, Baltimore, MD 21205"},{"name":"Johns Hopkins University School of Medicine, Department of Physiology, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,1]]},"reference":[{"key":"2021042013310804200_bib1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1086\/520000","article-title":"Classification of human chromosome 21 gene-expression variations in down syndrome: impact on disease phenotypes.","volume":"81","author":"A\u00eft Yahya-Graison","year":"2007","journal-title":"Am. 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