Mapping the gene for Trapped Neutrophil Syndrome, an autoimmune disease in Border collies
Trapped Neutrophil Syndrome (TNS) is an autosomal recessive disease which has spread through the Border collie population due to extensive breeding from champion dogs and subsequent inbreeding. To attempt to identify the mutation responsible for TNS the Functional Candidate Gene (FCG) approach was used in conjunction with autozygosity analysis to perform exclusion mapping of 7 candidate genes. The candidate genes were identified based on two diseases: myelokathexis and Warts, Hypogammaglobulinemia, Immunodeficiency and Myelokathexis (WHIM) in the model organism humans. Identification of the mutation responsible will allow for dogs to be used as a model organism for similar diseases in humans and elimination of the disease through DNA testing and selective breeding.
Sequencing of one candidate, CXCR4 involved in WHIM, revealed no differences between affected and control dogs To eliminate mutations from other regions of this gene as the cause of TNS, potentially polymorphic microsatellites, close to CXCR4 were developed for use in autozygosity analysis (homozygosity for a haplotype due to Identity By Descent), A lack of homozygosity allowed this gene to be excluded as the cause of TNS. Autozygosity analysis using known microsatellite markers for each of the remaining candidate genes suggest thay are not the cause of TNS. The next step in identifying the cause of TNS is a whole genome scan looking for regions of homozygosity in affected dogs and linkage analysis in large pedigrees using regularly spaced microsatellite markers which will reveal candidate regions of the genome for fine mapping.