OMIA:002621-9940 : Gaucher disease, type II in Ovis aries (sheep)
Categories: Lysosomal storage disease
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2011
Molecular basis: Karageorgos et al. (2011) reported this disorder in Southdown sheep in Australia being due to two "missense mutations c.1142G>A (p.C381Y) and c.1400C>T (p.P467L)" in the gene for β-glucocerebrosidase (GBA).
After analysis in additional animals and use of variant prediction algorithms, Zhou et al. (2017) concluded that their results "suggest that [the] c.1142G>A [variant] in exon 8 of GBA is the causative mutation of Gaucher disease in the Southdown sheep studied." In contrast, the c.1400C>T (p.P467L) variant exists in homozygous form in asymptomatic animals.
Pathology: Winner et al. (2023) "characterised pathological changes in GD [Gaucher disease] lamb brain and compared the histological findings to those in GD patient post-mortem tissue, to determine the validity of the sheep as a model of this disease. ... Our findings suggest that the ovine model of GD exhibits similar pathological changes to human, mouse, and drosophila type II GD brain ... ."
South Down (Sheep) (VBO_0001611).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|GBA||glucosidase, beta, acid||Ovis aries||-||no genomic information (-..-)||GBA||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|231||South Down (Sheep)||Gaucher disease, type||GBA||missense||Naturally occurring variant||Oar_rambouillet_v1.0||1||g.111561271C>T||c.1142G>A||p.(C381Y)||Oar_v3.1 position is g.103978212C>T||rs429928390||2017||29023809||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Cabasso, O., Kuppuramalingam, A., Lelieveld, L., Van der Lienden, M., Boot, R., Aerts, J.M., Horowitz, M. :|
|Animal models for the study of Gaucher disease. Int J Mol Sci 24:, 2023. Pubmed reference: 38003227 . DOI: 10.3390/ijms242216035.|
|Winner, L.K., Beard, H., Karageorgos, L., Smith, N.J., Hopwood, J.J., Hemsley, K.M. :|
|The ovine Type II Gaucher disease model recapitulates aspects of human brain disease. Biochim Biophys Acta Mol Basis Dis 1869:166658, 2023. Pubmed reference: 36720445 . DOI: 10.1016/j.bbadis.2023.166658.|
|2022||Murray, S.J., Mitchell, N.L. :|
|The translational benefits of sheep as large animal models of human neurological disorders. Front Vet Sci 9:831838, 2022. Pubmed reference: 35242840 . DOI: 10.3389/fvets.2022.831838.|
|2017||Hein, L.K., Rozaklis, T., Adams, M.K., Hopwood, J.J., Karageorgos, L. :|
|Lipid composition of microdomains is altered in neuronopathic Gaucher disease sheep brain and spleen. Mol Genet Metab 121:259-270, 2017. Pubmed reference: 28532689 . DOI: 10.1016/j.ymgme.2017.05.010.|
|Zhou, H., Zhang, Y., Suter, R., Gong, H., Fang, Q., Zhou, P., Hickford, J.G.H. :|
|A nucleotide substitution in exon 8 of the glucosylceramidase beta gene is associated with Gaucher disease in sheep. Anim Genet 48:733-734, 2017. Pubmed reference: 29023809 . DOI: 10.1111/age.12613.|
|2016||Karageorgos, L., Hein, L., Rozaklis, T., Adams, M., Duplock, S., Snel, M., Hemsley, K., Kuchel, T., Smith, N., Hopwood, J.J. :|
|Glycosphingolipid analysis in a naturally occurring ovine model of acute neuronopathic Gaucher disease. Neurobiol Dis 91:143-54, 2016. Pubmed reference: 26976737 . DOI: 10.1016/j.nbd.2016.03.011.|
|2011||Karageorgos, L., Lancaster, MJ., Nimmo, JS., Hopwood, JJ. :|
|Gaucher disease in sheep. J Inherit Metab Dis 34:209-15, 2011. Pubmed reference: 20978939 . DOI: 10.1007/s10545-010-9230-3.|
- Created by Imke Tammen2 on 09 Feb 2023
- Changed by Imke Tammen2 on 09 Feb 2023
- Changed by Imke Tammen2 on 27 Nov 2023