| http://purl.uniprot.org/citations/33568816 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33568816 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33568816 | http://www.w3.org/2000/01/rdf-schema#comment | "Long non-coding RNAs (lncRNAs) can be important components in gene-regulatory networks1, but the exact nature and extent of their involvement in human Mendelian disease is largely unknown. Here we show that genetic ablation of a lncRNA locus on human chromosome 2 causes a severe congenital limb malformation. We identified homozygous 27-63-kilobase deletions located 300 kilobases upstream of the engrailed-1 gene (EN1) in patients with a complex limb malformation featuring mesomelic shortening, syndactyly and ventral nails (dorsal dimelia). Re-engineering of the human deletions in mice resulted in a complete loss of En1 expression in the limb and a double dorsal-limb phenotype that recapitulates the human disease phenotype. Genome-wide transcriptome analysis in the developing mouse limb revealed a four-exon-long non-coding transcript within the deleted region, which we named Maenli. Functional dissection of the Maenli locus showed that its transcriptional activity is required for limb-specific En1 activation in cis, thereby fine-tuning the gene-regulatory networks controlling dorso-ventral polarity in the developing limb bud. Its loss results in the En1-related dorsal ventral limb phenotype, a subset of the full En1-associated phenotype. Our findings demonstrate that mutations involving lncRNA loci can result in human Mendelian disease."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41586-021-03208-9"xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41586-021-03208-9"xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Rivolta C."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Rivolta C."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Timmermann B."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Timmermann B."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Farage L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Farage L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Mundlos S."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Mundlos S."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Rajagopal S."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Rajagopal S."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Superti-Furga A."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Superti-Furga A."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Chan W.L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Chan W.L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Bonafe L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Bonafe L."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Grote P."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Grote P."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Carvalho D.R."xsd:string |
| http://purl.uniprot.org/citations/33568816 | http://purl.uniprot.org/core/author | "Carvalho D.R."xsd:string |