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 (CID) is caused by homozygosity for an autosomal recessive gene. To identify linked markers for the disease, we studied a family segregating for the equine CID gene. A stallion and 19 of his CID-affected offspring were tested for marker segregation at 23 microsatellite DNA loci. His CID-affected offspring inherited 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 CID gene using a theta of 0.01 were 5.34 for HTG8 and 2.37 for HTG4. The apparent 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 might be associated with the microsatellite markers. Analysis of a somatic cell hybrid panel demonstrated synteny of DNA-PK with HTG4 and HTG8 (Kentucky Synteny Group 3). Fluorescence in situ hybridization (FISH) studies demonstrated that DNA-PK is located on horse chromosome ECA9p12. This work supports the hypothesis of DNA-PK as the probable cause of equine CID.
Bailey
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E
M H Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington 40546-0099, USA.
Reid
R C
RC
Skow
L C
LC
Mathiason
K
K
Lear
T L
TL
McGuire
T C
TC
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses / Q000235:genetics*; D006822:Hybrid Cells; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000662:veterinary*; D017404:In Situ Hybridization, Fluorescence; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats