Department of Population, Health, and Reproduction, School of Veterinary Medicine, University of California at Davis
Linkage analysis is a fundamental research tool for identifying candidate regions of chromosomes for disease traits. The value of linkage analysis is base on the power of the pedigree. Power is a statistical estimate based on structure and samples size of a population. For the feline inherited head defect, power was not obtained for linkage analysis until 50 DNA donations, 72% affected kittens, were received in the first quarter of 2005. These cats were related to 131 samples received over the previous 10 years. The project sample database has over 515 DNA samples, but the 215 DNA samples (181 of which were used in the linkage analysis) that form 3 pedigrees have been one major key to the successful identification of a region containing the feline head defect.
Linkage analysis of the Burmese, and Burmese/Bombay/American Shorthair pedigrees has limited the feline head defect to a 15Mb region of a feline chromosome. Within the region there are over 250 genes, of which, at least 6 have known function in developmental pathways. Research is continuing to narrow the region of interest, which will hopefully identify the causative gene. The continuing donation of affect DNAs and their parent's DNA will continue to increase the power of the analysis and should lead to identification of the causative gene. The gene will be analyzed for mutations affecting gene function. Once a mutation completely linked to the disease, is found, a DNA test will be developed suitable for commercial production.