| http://purl.uniprot.org/citations/24281155 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24281155 | http://www.w3.org/2000/01/rdf-schema#comment | "The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS(C96Y) background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.org/dc/terms/identifier | "doi:10.1534/genetics.113.157800"xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Jiang P."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Park S.Y."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Bell G.I."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Kreitman M."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Selleck S.B."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Wittkopp P.J."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Ludwig M.Z."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Arun B."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Tamarina N.A."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Vilhjalmsson B.J."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Barse L."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "Dickerson D.A."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/author | "He B.Z."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/name | "Genetics"xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/pages | "557-567"xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/title | "Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin."xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://purl.uniprot.org/core/volume | "196"xsd:string |
| http://purl.uniprot.org/citations/24281155 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24281155 |
| http://purl.uniprot.org/citations/24281155 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24281155 |
| http://purl.uniprot.org/uniprot/#_A0A0B4KER9-mappedCitation-24281155 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24281155 |
| http://purl.uniprot.org/uniprot/#_D5SHU8-mappedCitation-24281155 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24281155 |