| http://purl.uniprot.org/citations/29162626 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29162626 | http://www.w3.org/2000/01/rdf-schema#comment | "Orofacial clefts are one of the most common birth defects, affecting 1-2 per 1000 births, and have a complex etiology. High-resolution array-based comparative genomic hybridization has increased the ability to detect copy number variants (CNVs) that can be causative for complex diseases such as cleft lip and/or palate. Utilizing this technique on 97 nonsyndromic cleft lip and palate cases and 43 cases with cleft palate only, we identified a heterozygous deletion of Isthmin 1 in one affected case, as well as a deletion in a second case that removes putative 3' regulatory information. Isthmin 1 is a strong candidate for clefting, as it is expressed in orofacial structures derived from the first branchial arch and is also in the same "synexpression group" as fibroblast growth factor 8 and sprouty RTK signaling antagonist 1a and 2, all of which have been associated with clefting. CNVs affecting Isthmin 1 are exceedingly rare in control populations, and Isthmin 1 scores as a likely haploinsufficiency locus. Confirming its role in craniofacial development, knockdown or clustered randomly interspaced short palindromic repeats/Cas9-generated mutation of isthmin 1 in Xenopus laevis resulted in mild to severe craniofacial dysmorphologies, with several individuals presenting with median clefts. Moreover, knockdown of isthmin 1 produced decreased expression of LIM homeobox 8, itself a gene associated with clefting, in regions of the face that pattern the maxilla. Our study demonstrates a successful pipeline from CNV identification of a candidate gene to functional validation in a vertebrate model system, and reveals Isthmin 1 as both a new human clefting locus as well as a key craniofacial patterning gene."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.org/dc/terms/identifier | "doi:10.1534/genetics.117.300535"xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Long A."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Houston D.W."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Murray J.C."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Manak J.R."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Mansilla M.A."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Petrin A.L."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Cornell R.A."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Standley J.M."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Lansdon L.A."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Darbro B.W."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Hulstrand A.M."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/author | "Brouillette R.B."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/name | "Genetics"xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/pages | "283-296"xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/title | "Identification of Isthmin 1 as a Novel Clefting and Craniofacial Patterning Gene in Humans."xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://purl.uniprot.org/core/volume | "208"xsd:string |
| http://purl.uniprot.org/citations/29162626 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29162626 |
| http://purl.uniprot.org/citations/29162626 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29162626 |
| http://purl.uniprot.org/uniprot/#_B1AKI9-mappedCitation-29162626 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29162626 |
| http://purl.uniprot.org/uniprot/B1AKI9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/29162626 |