The SHUMI SPAID Project

Risk of developing SPAID is associated with increased expression of Hyaluronan Synthase 2 (HAS2) on chromosome 13, the driver of long chain hyaluronan (HA) synthesis, which results in the thickened and wrinkled skin of the breed.

It is hypothesized that the recurrent inflammation experienced by some Shar-Pei dogs is related to the resultant over production and degradation of high molecular weight hyaluronic acid (HA), via natural homeostasis and numerous other environmental factors. The resultant low molecular weight HA acts as a danger associated molecular pattern and triggers inflammation in SPAID.

A CNV is a piece of DNA that exists multiple times in the dog’s genome, and in the case of Shar-Pei, there can be 2, 6, or 10 copies. Research has shown that there is a link between having a high CNV count, producing high amounts of hyaluronan and having SPAID. There are two breed specific CNVs associated with increased expression of HAS2, which are the “traditional” variant (14.3 kilobase) and the “meatmouth” variant (16.1 kilobase), both located on an overlapping region of chromosome 13.

References:

• “Absolute quantification reveals the stable transmission of a high copy number variant linked to autoinflammatory disease.” Olsson, M. et al. (2016)
• “A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs.” Olsson, M. et al. (2011)

Unlike CNV_16.1, mutant MTBP (Murine double minute 2 Binding Protein) is not related to hyaluronic acid accumulation but to alternate proinflammatory pathways related to MDM2 (Mouse Double Minute 2). The MTBP variant is predicted to affect the MDN2-binding protein domain, consequently promoting proinflammatory reactions in dogs carrying the mutation. The MTBP variant is located near CNV_16.1, which is suggested to increase the risk of SPAID in Shar-Pei dogs over their lifetime if there is a copy number variation in that region.

This test measures a single nucleotide polymorphism (SNP) in the gene MTBP. The genome can be read like a book, but using only four letters, A, G, C, T. These letters represent nucleotides in the genome. A SNP is a position where one of these letters’ changes, for example from a G to an A. The SNP in MTBP has been suggested to affect the way another part of the genome works, and through this disruption, generates an inflammatory response that results in SPAID

References:

• “Whole genome sequencing identifies missense mutation in MTBP in Shar-Pei affected with Autoinflammatory Disease (SPAID).” Metzger, J. et al. (2017)
• “Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis.” Olsson, M. et al. (2013)

Primary Lens Luxation (PLL) and Primary Open-angle Glaucoma (POAG) are two diseases thought to be caused by the same mutation in the ADAMTS17-gene and therefore are indistinguishable from a genetic standpoint5. The mutation is displayed as a 6 base pair deletion in exon 22 on the ADAMTS17 gene. Loss of vision can result in animals that have two copies of the defective, or mutant type (MT), gene (autosomal recessive inheritance).

References:

• “Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both.” Oliver, J. A. C. et al. (2018)

Each of the above tests can be preformed from a submission of a cheek swab sample. For more information please visit our sampling page.