title: Identification of a bovine beta-mannosidosis mutation and detection of two beta-mannosidase pseudogenes.
abstract: Beta-mannosidase deficiency results in beta-mannosidosis, a severe neurodegenerative lysosomal storage disease identified in cattle, goats, and humans. To more fully understand the molecular pathology of this disease, the mutation associated with bovine beta-mannosidosis was identified by sequence analysis of cDNA from an affected calf. A transition mutation of G to A at position 2574 of the cDNA coding sequence creates a premature stop codon near the 3' end of the protein coding region. To aid commercial breeders of Salers cattle, a PCR-based test was developed to detect the mutation for beta-mannosidosis carrier screening. Application of this test also revealed the presence of two beta-mannosidase pseudogenes. Portions of the pseudogenes were amplified with allele-specific primers and then sequenced. One pseudogene was highly homologous (>99% sequence identity) to the expressed cDNA sequence over the 1292 bp that were sequenced, while the other showed more divergence (83% sequence identity) in the 477 bp that were sequenced. Both are processed pseudogenes that are not expressed. The severity of the bovine beta-mannosidosis phenotype suggests that the 22 C-terminal amino acids of beta-mannosidase play an important role in the function of this enzyme.
authors.affiliation: Department of Pathology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Leipprandt
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: J E
authors.initials: JE
authors.lastname: Horvath
authors.forename: X T
authors.initials: XT
authors.lastname: Qiao
authors.forename: M Z
authors.initials: MZ
authors.lastname: Jones
authors.forename: K H
authors.initials: KH
authors.lastname: Friderici
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008361:Mannosidases / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011544:Pseudogenes / Q000235:genetics*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D008363:alpha-Mannosidosis / Q000201:enzymology / Q000235:genetics* / Q000662:veterinary*; D044902:beta-Mannosidase
chemical_list: D018388:Codon, Terminator; D018076:DNA, Complementary; D008361:Mannosidases; D044902:beta-Mannosidase