LINKAGE OF THE GENE FOR EQUINE COMBINED IMMUNODEFICIENCY DISEASE TO MICROSATELLITE MARKERS HTG8 AND HTG4 - SYNTENY AND FISH MAPPING TO ECA9

Equine combined immunodeficiency disease (CII)) is caused by homozygos ity for an autosomal recessive gene. To identify linked markers for th e disease, we studied a family segregating for the equine CID gene. A stallion and 19 of his CID-affected offspring were tested for marker s egregation at 23 microsatellite DNA loci. His CID-affected offspring i nherited only one of his two alleles at the HTG8 and HTG4 loci, namely HTG8-186 and HTG4-124, respectively. Lod scores for linkage to the CI D gene using a - of 0.01 were 5.34 for HTG8 and 2.37 for HTG4. The app arent genotypes also suggested linkage disequilibrium between the HTG8 -186 allele and the gene for CID. The gene for the DNA protein kinase catalytic subunit (DNA-PK) was recently suggested as a candidate gene for equine CID. A defect of this gene causes a disease in mice that is similar to equine CID. Therefore, we investigated whether this gene m ight be associated with the microsatellite markers. Analysis of a soma tic cell hybrid panel demonstrated synteny of DNA-PK with HTG4 and HTG 8 (Kentucky Synteny Group 3). Fluorescence in situ hybridization (FISH ) studies demonstrated that DNA-PK is located on horse chromosome ECA9 p12. This work supports the hypothesis of DNA-PK as the probable cause of equine CID.