Genome-wide association and linkage analyses localize a progressive retinal atrophy locus in Persian cats.

Hereditary eye diseases of animals serve as excellent models of human ocular disorders and assist in the development of gene and drug therapies for inherited forms of blindness. Several primary hereditary eye conditions affecting various ocular tissues and having different rates of progression have been documented in domestic cats. Gene therapy for canine retinopathies has been successful, thus the cat could be a gene therapy candidate for other forms of retinal degenerations. The current study investigates a hereditary, autosomal recessive, retinal degeneration specific to Persian cats. A multi-generational pedigree segregating for this progressive retinal atrophy was genotyped using a 63 K SNP array and analyzed via genome-wide linkage and association methods. A multi-point parametric linkage analysis localized the blindness phenotype to a ~1.75 Mb region with significant LOD scores (Z ≈ 14, θ = 0.00) on cat chromosome E1. Genome-wide TDT, sib-TDT, and case-control analyses also consistently supported significant association within the same region on chromosome E1, which is homologous to human chromosome 17. Using haplotype analysis, a ~1.3 Mb region was identified as highly associated for progressive retinal atrophy in Persian cats. Several candidate genes within the region are reasonable candidates as a potential causative gene and should be considered for molecular analyses.

Author Correction: Applications and efficiencies of the first cat 63 K DNA array.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Applications and efficiencies of the first cat 63K DNA array.

The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.

Author Correction: Applications and efficiencies of the first cat 63K DNA array.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Japanese Bobtail: vertebral morphology and genetic characterization of an established cat breed.

Several cat breeds are defined by morphological variation of the tail. The Japanese Bobtail is a breed that has been accepted for registration only within the past 50 years; however, the congenital kinked tail variants defining this breed were documented in the Far East centuries ago and the cats are considered 'good luck' in several Asian cultures. The recent discovery of the mutation for the tailless Manx phenotype has demonstrated that the Japanese Bobtail does not have a causative mutation in the same gene (T-Box). Here, a simple segregation analysis of cats bred from a pedigreed Japanese Bobtail demonstrated a simple autosomal dominant mode of inheritance with variable expression of the tail length and kink placement. Unexpectedly, radiological examinations of the entire vertebral column of kink-tailed cats indicated variation from the normal vertebral feline formula (C7, T13, L7, S3, Cd20-24), including cats with mostly one reduction of thoracic vertebrae (C7, T12, L7, S3), and an average of 15.8 caudal vertebrae. A few cats had variation in the number of cervical vertebrae. Several transitional vertebrae and anomalous ribs were noted. One cat had a bifid vertebra in the tail. Most cats had hemivertebrae that were usually included in the tail kink, one of which was demonstrated by gross pathology and histopathology. The abnormal vertebral formula or the placement of the kink in the tail did not coincide with morbidity or mortality.