High density canine 170,000 SNPs array for recessive trait mapping in a canine pure breed

The present study aims to evaluate the basis of a motor-sensory neuropathy, recently reported in Rhodesian Ridgeback (RR) dogs and clinically similar to a group of human diseases known as Charcot-Marie-Tooth (CMT). In literature about 40 clinical subtypes are reported, all of them are inherited with variable transmission. In RR hereditary defects of development of Peripheral Nervous System were reported making this breed a possible animal model for comparative study of CMT. A family group of RR was reported to show tremors and fasciculations, limb muscle degeneration, atrophy, demyelination and myelin outfolding. The pathological cases showed clinically and histological characters very similar to three subtypes of human CMT: CMT4B-1, CMT4B-2 and CMT4H (autosomal recessive inheritance). Causative genes for these form of the disease are identified as MTMR2, MTMR13 and FGD4 respectively. Biological samples of three healthy dogs and three affected ones, all belonging to the same family group, were collected. Genomic DNA was extracted and parentage was verified comparing the genetic profiles using a panel of STRs internationally recognized. The human genes MTMR2, MTMR13 and FGD4 on dog genome nucleotide sequence assembly were identified and the homology and conservation were evaluated. Genome-wide Association (GWA) approach by 170.000 high-density SNPs DNA microarray (Illumina) to map potential candidate genes for CMT disease were used. Seventeen candidate regions were found using Homozigosity Mapping. The described method has been useful to identify the common regions in affected RR, anyway the results could be further on improved increasing sample size with subjects new blood lines.