title: A deletion in the intergenic region upstream of Ednrb causes head spot in the rat strain KFRS4/Kyo.
abstract: Head spot is one of the phenotypes identified in the KFRS4/Kyo rat strain. Although previous linkage analysis suggested that Ednrb, which is frequently involved in coat color variations in various animals, could be the gene responsible for this phenotype, no mutations have been identified in its coding region.
  
  
  
  To identify mutations causative of this phenotype in KFRS4/Kyo, we analyzed target capture sequencing data that we recently generated. Our target capture method has a unique feature, i.e., it covers not only exonic regions but also conserved non-coding sequences (CNSs) among vertebrates; therefore, it has the potential to detect regulatory mutations. We identified a deletion of approximately 50 kb in length approximately 50 kb upstream of Ednrb. A comparative analysis with the epigenomic data in the corresponding region in humans and mice showed that one of the CNSs might be an enhancer. Further comparison with Hi-C data, which provide information about chromosome conformation, indicated that the putative enhancer is spatially close to the promoter of Ednrb, suggesting that it acts as an enhancer of Ednrb.
  
  
  
  These in silico data analyses strongly suggest that the identified deletion in the intergenic region upstream of Ednrb, which might contain a melanocyte-specific enhancer, is the mutation causative of the head spot phenotype in the KFRS4/Kyo rat strain.
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, 812-8582, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, 812-8582, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, 812-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saito
authors.affiliation: Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Chiba, 292-0818, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan. mikita@bioreg.kyushu-u.ac.jp.|AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, 812-8582, Japan. mikita@bioreg.kyushu-u.ac.jp.
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D021901:DNA, Intergenic; D057890:Epigenomics; D006801:Humans; D051379:Mice; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D044023:Receptor, Endothelin B / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D021901:DNA, Intergenic; D044023:Receptor, Endothelin B; C000622698:ednrb protein, rat
keywords: Comparative genomics; Conserved non-coding sequence; Exome; Head spot; Rat; Regulatory mutation; Target capture sequencing