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OMIA:002621-9940 : Gaucher disease, type II in Ovis aries (sheep)

Categories: Lysosomal storage disease

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 230900 (trait) , 606463 (gene)

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.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

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 ... ."

Breed: 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

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GBA glucosidase, beta, acid Ovis aries 1 NC_056054.1 (105408943..105400242) GBA Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.
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Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002621-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

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.

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  • Created by Imke Tammen2 on 09 Feb 2023
  • Changed by Imke Tammen2 on 09 Feb 2023
  • Changed by Imke Tammen2 on 27 Nov 2023