Multiple ocular malformations in two sheepdogs homozygous for the merle mutation. Mutation analysis of the SILV gene and association study using MITF-associated markers.

摘要

Objective: Multiple ocular defects are common findings in homozygous merle dogs. Although a SINE-insertion causative for the merle phenotype has already been identified in the SILV gene on the canine chromosome 10, an association of this mutation with eye malformations has not been established yet. Material and methods: Four Old German Sheepdogs and four Australian Shepherds with the different types of the merle coat colours were genotyped for the SILV mutation to confirm the MM, Mm and mm genotypes. A sequence and haplotype analysis of SILV was performed. MITF that regulates SILV expression during embryogenesis was chosen as candidate being involved in the development of the ocular malformations. Flanking and intragenic markers were genotyped, and association analysis was performed. Results: All MM-dogs showed multiple ocular defects such as colobomata, microphthalmia, dyscoria and persistent pupillary membrane. No length difference in the SINE or polymorphisms in the exonic sequences between dogs with and without ophthalmological defects were detected. The SILV flanking markers showed complete co-segregation with the merle genotypes. We detected a significant association between MITF markers and ocular defects of the double merle-phenotypes. Conclusions: We could not detect mutations in the SILV gene to explain the double merle phenotype-associated eye malformations. The significant association of the MITF-linked markers may suggest that MITF could be involved in the development of the ocular defects in MM-dogs. These results have to be scrutinized because only three MM-dogs were available and these results have to be confirmed using a larger data set. Clinical relevance: Our results indicate that mutations in the SILV gene may not be responsible for the development of the ocular defects often seen in double merle dogs but a possible involvement of the MITF gene has to be discussed. If the role of MITF for these eye anomalies can be clarified in a study comprising much more dogs the associated mutations in MITF may be identified. Thus it would be possible to prevent these ocular malformations through selective breeding.