A nucleotide substitution in exon 8 of the glucosylceramidase beta gene is associated with Gaucher disease in sheep

Abstract

Gaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucosylceramidase beta (GBA; EC 3.2.1.45). Human Gaucher disease is caused by mutations in the GBA gene, and nearly 300 mutations have been identified. Gaucher disease has also been described in sheep, dogs and possibly pigs. A study of affected Southdown sheep from Australia described variation in GBA. Two SNPs (c.1142G>A in exon 8 and c.1400T>C in exon 10) were described and were both found to be homozygous in affected sheep. This raises the question of whether the disease is caused by both SNPs, as for human Gaucher the presence of multiple mutations in the same gene is not uncommon. We investigated variations in exons 8 and 10 in both Gaucher affected and asymptomatic Southdown sheep from Australia. In five affected Southdown sheep and 42 asymptomatic relatives (including the sires, dams and siblings of some of the affected sheep), polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis of exon 10 revealed two variants, and sequencing indicated the previously described SNP (c.1400T>C). The five affected sheep had genotype TT, but this genotype was also detected in the asymptomatic sheep. This suggests that this variation is not responsible for Gaucher disease.