Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 277600 (trait) , 608990 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Primary open angle glaucoma

Species-specific symbol: POAG

Inheritance: From a colony of Beagles with POAG, established in 1972 (Gelatt, 1972; Gelatt et al., 1977), Gelatt and Gum (1981) provided substantial evidence of autosomal recessive inheritance.

Mapping: By genotyping "19 affected and 10 carrier dogs from the POAG Beagle colony using version 2 of the Affymetrix Canine Genome SNP array", Kuchtey et al. (2011) conducted a GWAS that mapped the POAG locus to a 4Mb region on chromosome CFA20.

Molecular basis: By sequencing one affected, one carrier and one normal dog from the POAG Beagle colony, for the entire 4MB candidate region described in the Mapping section above, Kuchtey et al. (2011) identified the causal mutation as a "56097365 G->A variant [Gly661Arg] . . . within exon 17 of ADAMTS10, a member of the disintegrin and metalloproteinase with thrombospondin motifs family of secreted proteases involved in formation of the extracellular matrix". The authors noted that "glycine at position 661 is completely conserved in 38 vertebrate species". By genotyping Beagle dogs not belonging to the POAG Beagle colony, Kuchtey et al. (2013) provided strong supportive evidence for the 56097365 G->A variant [Gly661Arg] being a causal mutant of POAG in this breed. Kanemaki et al. (2013) provided evidence that variants in ADAMTS10 are not causal for this disorder in Shiba-Inus and Shih-Tzus, but that variants in SRBD1 (another comparative candidate gene) "play an important role in glaucoma pathology in both Shiba-Inus and Shih-Tzus". Ahonen et al. (2014) reported a different likely causal mutation in Norwegian Elkhound: "A fully segregating missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected NEs (pFisher = 3.5×10-27) with a high carrier frequency (25.3%). The mutation interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10, likely affecting its functional capacity".

Breeds: Beagle (Dog) (VBO_0200131), Norwegian Elkhound (Dog) (VBO_0200955).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: