Possibly relevant human trait(s) and/or gene(s) (MIM number): 612775

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Species-specific symbol: crd3

Mapping: By conducting an autozygosity-mapping analysis on 12 affected and 12 matched control Glen of Imaal Terriers, each genotyped with the Affymetrix Canine Genome 2.0 Array “Platinum Panel” (comprising "∼50.000 SNPs"), Kropatsch et al. (2010) highlighted a region on "CFA16 from 24.7 to 29.9 Mb".

In an independent study published just a week after Kropatsch et al. (2010) Goldstein et al (2010) undertook a GWAS on 21 affected and 22 matched control Glen of Imaal Terriers, each genotyped with the Affymetrix Version 2 Canine SNP chip (yielding 60,245 informative SNPs for analysis), Goldstein et al. (2010), highlighting a region on chromosome CFA16 "shared by six SNPs comprising an interval of approximately 4.4 Mb".

Molecular basis: Fine mapping and subsequent sequencing enabled Kropatsch et al. (2010) to identify the causal mutation as "a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon" in the ADAM9 gene.

A week later came a report of an independent exhaustive evaluation of candidate genes (both comparative positional and positional) that eventually enabled Goldstein et al. (2010) to identify the same causal mutation, namely "a large genomic deletion (over 20 kb) that removed exons 15 and 16 from the ADAM9 transcript, introduced a premature stop, and would remove critical domains from the encoded protein".

Breed: Glen of Imaal.

Associated gene: