Retinal degeneration (RD) in the miniature long-haired Dachshund (MLHD) is a cone rod dystrophy, where the cone and rod receptors of the eye become depleted resulting in loss of visual acuity and eventual blindness. In a previous study of an early-onset RD (EORD), which segregated within a closed breeding colony of MLHD, a 44-nucleotide insertion (ins44) was identified in exon 2 of the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene.¹ Subsequent identification of EORD and late-onset RD (LORD) cases, all of which were homozygous for the ins44 insertion, allowed a second GWAS to be performed, which identified an age of onset modifying locus.² In this study we used a massively parallel sequencing dataset targeted to the modifying locus to identify an apparent deletion in exon 9 of MAP9 for EORD cases but not controls (LORD cases). Further investigation of this variant identified an unassembled scaffold, that would need to be incorporated into the genome to determine the exact nature of the variant identified. Use of BAC clone and long PCR product sequencing, with de novo assembly techniques, allowed the scaffold to be fully incorporated into the current genome build. The new assembly revealed evidence of a historic partial duplication of the MAP9 gene and a subsequent deletion, both through hypothesised homologous recombination events. Correction to the genome assembly and the consequences of the potential modifying mutation will be discussed.

References

1.  Mellersh CS, Boursnell ME, Pettitt L, Ryder EJ, Holmes NG, Grafham D, Forman OP, Sampson J, Barnett KC, Blanton S, Binns MM, Vaudin M. Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics. 2006;88:293–301.

2.  Miyadera K, Kato K, Boursnell M, Mellersh CS, Sargan DR. Genome-wide association study in RPGRIP1(-/-) dogs identifies a modifier locus that determines the onset of retinal degeneration. Mammalian Genome. 2012;23:212–223.