Animals with mutations in COL4a4 present with autosomal recessive Alport
Syndrome (ARAS). Through sequencing of COL4a4, the mutation causative for
ARAS in the English Cocker Spaniel (ECS) has been identified. The
resulting protein is severely truncated due to a premature stop codon in
exon 3. This nonsense mutation occurs in the 7S domain and also causes
the loss of the entire collagenous and NC1 domains of the protein.
Methods for the identification of animals that harbor a mutation in the
COL4a4 gene are described. Mutations in the COL4a4 gene can be identified
from any biological sample such as a cell or tissue that contains genomic
DNA. Methods for identifying single nucleotide polymorphisms (SNPs) that
are inherited with the disease are also described. A microsatellite
marker that segregates with ARAS is also described that was identified
using linkage disequilibrium mapping.