Untersuchungen zu familiären und rassespezifischen ...

Augenmissbildungen bei homozygoter Merle-Mutation 75
mutation in the SILV gene or mutations in other genes could be responsible for these
ocular anomalies.
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 was chosen as candidate being
involved in the development of the ocular malformations. MITF regulates SILV
expression during embryogenesis and thus, should be an appropriate candidate
gene. Flanking and intragenic markers were genotyped, and association analysis
was performed.
Results: All three dogs homozygous for the SINE insertion mutation in SILV 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 of SILV 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: DNA polymorphisms in the SILV gene did not show an association
with the double merle phenotype-associated eye malformations. The significant
association of the MITF-linked markers suggests that MITF could be involved in the
development of the ocular defects in dogs homozygous for merle.
Clinical relevance: Our results indicate a possible involvement of the MITF-gene in
the development of the ocular defects often seen in double merle dogs. When the
role of MITF can be clarified for these eye anomalies and associated mutations in
MITF are identified, then it would be possible to prevent these ocular malformations
through selective breeding.
Key words: dog, SILV, MITF, coloboma, microphthalmia, mutation