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Using cat breeds to find genetic diseases

Aug 19, 2013
Alhaddad H, Khan R, Grahn RA, et al. Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds. PLoS ONE. 2013; 8: e53537. Free, full text article

Genome-wide association studies (GWAS) of hereditary and infectious diseases have been a major focus of recent cat health studies. Information regarding linkage disequilibrium (LD) is crucial for effective association studies. Linkage disequilibrium (LD) is defined as the non-random association of alleles at different loci on chromosomes in a gamete. This study’s objective was to look at the extent of LD in domestic cats, especially within the cat breeds. A custom DNA array was developed and genotyped across 18 globally recognized breeds and two distinct random bred populations. 

Development of cat breeds has followed four major strategies:
1) The most common strategy has been the manipulation of a subset of cats from a natural population (e.g., Norwegian Forest Cat, Persians)
2) The selection of a novel mutation that produces a unique trait that arose in a single cat, generally also from a random bred population, while using selective mating to fix these traits to define the breed (e.g., Selkirk Rex)
3) Mixing lineages to create cross-breed hybrids (e.g., Ocicat)
4) Developing breeds that are interspecies crosses (e.g., Bengal).

In population analysis, there is a clear separation between eastern and western populations, while the Abyssinian and Ocicat breeds appear equidistant between both populations. LD was found to be shortest in the Siberian and most extended in Burmese. In evaluating what the results mean to GWA studies, eastern breeds are likely to generate successful studies, especially the domestic Burmese, where GWAS are more likely to achieve results even with few cases and controls. Western breeds such as Turkish Angora, Cornish Rex, Japanese Bobtail, Manx, Russian Blue, Siberian, and random bred cats may require larger number of cases and controls or an array with higher density of single nucleotide polymorphisms (SNPs). The linkage disequilibrium estimates found with this study can improve the design of GWA studies and the search for candidate genes. [VT]

Funding: this project was partially funded by Winn Feline Foundation grant W09-009.

See also:
Kurushima JD, Lipinski MJ, Gandolfi B, et al. Variation of cats under domestication: genetic assignment of domestic cats to breeds and worldwide random-bred populations. Animal genetics. 2013; 44: 311-24. 

genetics feline genome breeds

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