Whole genome sequencing reveals a 7 base-pair deletion in DMD exon 42 in a dog with muscular dystrophy

• DOI: 10.1007/s00335-016-9675-2
• Publication Date: 2016-12-27T06:58:17Z
• Authors: Peter P. Nghiem; Luca Bello; Cindy Balog-Alvarez; Sara Mata López; Amanda Bettis; Heather Barnett; Briana Hernandez; Scott J. Schatzberg; Richard J. Piercy; Joe N. Kornegay
• Keywords: Human genetics

Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on X-chromosome. Truncating mutations in DMD cause loss of dystrophin and classical clinical syndrome. Spontaneous associated phenotypes occur several other species. The mdx mouse model golden retriever (GRMD) canine have been used extensively to study disease pathogenesis show efficacy side effects putative treatments. Certain high-risk, so-called hot spot areas can be particularly helpful modeling molecular therapies. Identification specific has greatly enhanced new genomic methods. Whole genome, next generation sequencing (WGS) recently define patient mutations, but not dystrophic dogs. A dystrophin-deficient Cavalier King Charles Spaniel (CKCS) dog was evaluated at functional, histopathological, biochemical, level. affected dog's phenotype compared previously reported dystrophinopathies. WGS then detect 7 base pair deletion exon 42 (c.6051-6057delTCTCAAT mRNA), predicting frameshift transcription truncation translation. confirmed with conventional PCR Sanger sequencing. This mutation secondary hotspot area distinct from one identified earlier 5′ donor splice site intron 50 CKCS breed.