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N. M. Ellinwood, J. K. Jens, M. M. Rutz, M. P. Faylon, E. M. Snella, M. H. Kuehn, G. J. McLellan; Preliminary Characterization of the Genetics and Inheritance of Primary Congenital Glaucoma in a Spontaneous Feline Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):883.
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© ARVO (1962-2015); The Authors (2016-present)
To more fully characterize the inheritance and genetics of primary congenital glaucoma (PCG) in a recently identified feline model.
In parallel with ongoing structural and functional characterization of the model, breeding studies were conducted with the aim of producing affected cats and generating informative pedigrees to facilitate molecular genetic characterization. To date, 15 breedings have produced 57 offspring with informative genetics for mapping studies. Statistical analysis involved Chi-squared testing of assumptions of recessive inheritance. Molecular genetic evaluations were designed to more definitively exclude candidate genes. Using the March 2006 Felis catus draft assembly (Broad Release 3), 43 primer pairs were designed to amplify sequences from three candidate genes and their respective chromosomes (PitX2/chromosome B1, Myoc/chromosome F1, Cyp1B1/chromosome/A3). Previously, analysis of the coding regions of these genes showed no association with the condition. Sequences from the founders of this pedigree were generated by PCR, sequenced and analyzed to identify fully informative or partially informative single nucleotide polymorphisms (SNPs). Restriction Fragment Length Polymorphism (RFLP) analysis of informative SNPs was conducted in affected and unaffected offspring.
Results of further breeding studies within this pedigree have yielded 15 families segregating glaucoma. In these families the expected number of affected cats is 23 and the observed number is 21, yielding a significant statistical result (p=0.001) in support of autosomal recessive inheritance. The SNP discovery and genotyping yielded the following results. Of the PCRs, 38 (88%) were successful, and of these, 30 of primer set sequences yielded readable sequence. From these sequences we identified 87 SNPs (average of 1 SNP/80 bp, +/- 111 bp) of which 20 are informative in our pedigree. Of the three candidate genes/chromosomes targeted, an informative SNP was analyzed for PitX2, which yielded a MboII site. To date, initial genotyping of this SNP cannot discount an association between this gene and feline PCG segregating in this Siamese/Domestic Short Haired cat mixed pedigree.
Breeding studies indicate that feline PCG is inherited as an autosomal recessive condition. PitX2 has not been definitively excluded as a candidate gene
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