title: A molecular study of congenital erythropoietic porphyria in cattle.
abstract: Previous studies have shown that congenital erythropoietic porphyria (CEP) in cattle is caused by an inherited deficiency of the enzyme uroporphyrinogen III synthase (UROS) encoded by the UROS gene. In this study, we have established the pedigree of an extended Holstein family in which the disease is segregating in a manner consistent with autosomal recessive inheritance. Biochemical analyses demonstrated accumulation of uroporphyrin, thus confirming that it is indeed insufficient activity of UROS which is the cause of the disease. We have therefore sequenced all nine exons of UROS in affected and non-affected individuals without detecting any potential causative mutations. However, a single nucleotide polymorphism (SNP) located within the spliceosome attachment region in intron 8 of UROS is shown to segregate with the disease allele. Our study supports the hypothesis that CEP in cattle is caused by a mutation affecting UROS; however, additional functional studies are needed to identify the causative mutation.
authors.affiliation: Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Dyrlaegevej 68, Frederiksberg C, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Agerholm
authors.forename: P W
authors.initials: PW
authors.lastname: Thulstrup
authors.forename: M J
authors.initials: MJ
authors.lastname: Bjerrum
authors.forename: C
authors.initials: C
authors.lastname: Bendixen
authors.forename: C B
authors.initials: CB
authors.lastname: Jørgensen
authors.forename: M
authors.initials: M
authors.lastname: Fredholm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017092:Porphyria, Erythropoietic / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D016415:Sequence Alignment; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics*
chemical_list: D014576:Uroporphyrinogen III Synthetase