Canine beta -galactosidase gene and GM1-gangliosidosis

摘要

The acid beta -galactosidase cDNA of Portuguese Water (PW) dogs was isolated and sequenced. The entire encoding region of the gene consists of 2004 nucleotides coding a protein of 668 amino acids. Its encoding sequence indicates approximately 86.5% identity at the nucleotide level and about 81% identity at the amino acid level with the encoding region of the human acid beta -galactosidase gene. The deduced amino acid sequence contains a 24-amino acid putative signal sequence, 6 possible glycosylation sites, and 7 cysteine residues. A homozygous recessive mutation, causing GM1-gangliosidosis in PW dogs, was identified at nucleotide G200->A in exon 2 resulting in an Arg60->His (mutation R60H) amino acid substitution. The mutation creates a new restriction enzyme site for PmlI. Genotyping 115 dog samples for this acid beta -galactosidase gene alteration readily distinguished affected homozygous recessive (n=5), heterozygous carriers (n=50), and normal homozygotes (n=60). DNA mutation analysis provided a method more specific than enzyme assay of beta -galactosidase for determination of carriers.