Radiation Hybrid Map, Physical Map and Low-Pass Genomic Sequence of the Canine prcd Region on CFA9, and Comparative Mapping with the Syntenic Region on Human Chromosome 17

Abstract

Abstract: : Purpose: Progressive rod cone degeneration (prcd) is a canine retinal disease that maps to the centromeric end of CFA9 in a region of synteny with the distal part of HSA17q. As such, prcd has been postulated as the only animal model of RP17, a human retinitis pigmentosa locus that maps to 17q22. Methods: In an effort to establish more detailed regions of synteny between dog CFA9 and the HSA17q-ter region, we created a robust gene-enriched CFA9-RH083000 map with 34 gene-based and 12 microsatellites, with the highest resolution and number of markers for the centromeric end of CFA9. Furthermore, we built approximately a 1.5 Mb physical map containing both GRB2 and GALK1, genes so far identified by meiotic linkage analysis as being closest to the prcd locus, and generated about 1.2 Mb low-pass (3.2x) canine sequence. Results: Canine to human comparative sequence analysis identified 49 transcripts that had been previously mapped to the HSA17q25 region. The generated low-pass canine sequence was annotated with a working draft of human sequence from HSA17q25, and we used this scaffold to order and orient the canine sequence against human. Conclusion: Despite established synteny between the prcd region of CFA9 and HSA17q25, we cannot conclusively exclude the RP17 locus in human as the locus homolog of prcd. It is still possible that prcd may be a true locus homolog of RP17, and the mapping differences now observed represent ancestral chromosomal micro-rearrangements between prcd and RP17 critical regions in dog and human. Alternatively, it is possible that prcd and RP17 both map in regions of synteny between CFA9 and HSA17q-ter where diseases in both dog and human show clinically similar phenotype, yet may be caused by mutations in two different genes critical for normal function and viability of retinal photoreceptors.

Keywords: retinal degenerations: hereditary • genetics • retina