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Investigation of parallel and simultaneous selection for collie eye anomaly and ivermectin toxicosis
  1. K. Mizukami, DVM, PhD1,
  2. A. Yabuki, DVM, PhD1,
  3. D. Endoh, DVM, PhD2,
  4. H. S. Chang, DVM, PhD1,
  5. K. W. Lee, DVM, PhD3,
  6. M. Nakayama, DVM, PhD4,
  7. K. Kushida, DVM1,
  8. M. Kohyama, DVM1,
  9. J. I. Lee, DVM, PhD5 and
  10. O. Yamato, DVM, PhD1
  1. 1Laboratory of Clinical Pathology, Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Kohrimoto, Kagoshima 890-0065, Japan
  2. 2Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University, 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan
  3. 3Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 702-701, Korea
  4. 4Nakayama Veterinary Hospital, 6-1 Minamifukuro, Nara, Nara 630-8342, Japan
  5. 5Laboratory of Veterinary Public Health I, College of Veterinary Medicine, Chonnam National University, 300 Yonbongdong, Bukgu, Gwangju 500-757, Korea
  1. E-mail for correspondence: osam{at}

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Collie eye anomaly (CEA) is an inherited canine ocular disorder causing regional choroidal hypoplasia and coloboma of the optic disk or adjacent areas, and is associated with a 7.8-kilo base pair (bp) deletion in the canine NHEJ1 gene (Parker and others 2007). A 4-bp deletion in the canine MDR1/ABCB1 gene (MDR1 gene defect) causes neurotoxicosis after administration of P-glycoprotein substrates such as ivermectin (Gramer and others 2011). These two mutations are common in collie-related and sighthound breeds, suggesting a possible parallel selection of the two defects, although these canine genes are located on different chromosomes: NHEJ1 on chromosome 37 and MDR1 on chromosome 14 (Parker and others 2007, Gramer and ­others 2011).

Recently, a very high frequency of the CEA mutation has been reported in the Hokkaido inu, a traditional Japanese breed; this is the first identification of a CEA-predisposed breed not classified as collies or sighthounds (Mizukami and others 2012a). A native Japanese breed, the shiba inu, has been previously localised near collies in multibreed cluster analyses (Parker and others 2007), suggesting that collies and such native Asian breeds share more genetic traits than one may realise. However, prevalence of the MDR1 gene defect in the Hokkaido inu is unknown. Furthermore, epidemiologic surveys targeting potential breeds likely to possess these two mutations have not been performed. This study investigated allele frequencies of these multiple dog breeds and checked whether a parallel and simultaneous selection for these two mutations has occurred.

In this study, 1331 DNA samples were collected from nine dog breeds including two collie-related breeds (collie and border collie), one sighthound (Saluki), two non-collie European …

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