title: Variants in the UBR1 gene are not associated with chronic pancreatitis in Japan.
abstract: OBJECTIVE
  The UBR1 gene encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1. Loss-of-function mutations in the UBR1 gene cause Johanson-Blizzard syndrome, which involves pancreatic exocrine insufficiency. No previous studies have examined an association of UBR1 variants with pancreatitis, in part due to the large size of the gene. This study aimed to clarify whether UBR1 variants are associated with chronic pancreatitis (CP) by the application of targeted next generation sequencing.
  
  
  METHODS
  Exon sequences of the UBR1 gene from 389 Japanese patients with CP (188 idiopathic, 172 alcoholic, 20 hereditary, 9 familial) were captured by the HaloPlex target enrichment technology and subjected to next generation sequencing.
  
  
  RESULTS
  Ninety nine point two % of the coding regions of the UBR1 gene could be sequenced by ≥ 20 reads with a mean read depth of 595 and a median depth of 399. Fifteen non-synonymous variants including three novel ones [c.4514T > C (p.I1505T), c.4828C > G (p.H1610D) and c.4856A > T (p.D1619V)] and two synonymous variants were identified in the exonic regions. The frequency of any non-synonymous or synonymous variants was not different between the patients with CP and controls.
  
  
  CONCLUSIONS
  Variants in the UBR1 gene were not associated with CP in Japan.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: amasamune@med.tohoku.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Nakano
authors.affiliation: Division of Medical Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hamada
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nagasaki
authors.affiliation: Division of Medical Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D004247:DNA / Q000235:genetics; D005091:Exons; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007564:Japan / Q000453:epidemiology; D050500:Pancreatitis, Chronic / Q000453:epidemiology* / Q000235:genetics*; D011237:Predictive Value of Tests; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004247:DNA; C113474:UBR1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: HaloPlex; Johanson-Blizzard syndrome; Next generation sequencing; Trypsin; Ubiquitin-protein ligase E3 component n-recognin 1