Untersuchungen zu familiären und rassespezifischen ...

MITF as candidate for deafness in Dalmatian dogs 116
sensorineural deafness (CCSD) than dogs from any other breed (Juraschko et al.
2003a; Muhle et al. 2002; Rak and Distl 2005). About 80 breeds are reported to be at
risk to develop CCSD (Strain 2004). Most of them possess the allele s w (extreme
white) or s p (piebald spotting) at the S locus. Dalmatian dogs with blue eye color are
more frequently affected by CCSD, whereas Dalmatians with patches develop CCSD
more rarely (Famula et al. 2000; Strain 2004; Juraschko et al. 2003a). The
association between CCSD in white dogs and iris color has been also identified for
other dog breeds (Strain 2004).
An association between an intragenic SNP in MITF and white spotting was reported
for Newfoundland dogs, boxers and beagle crosses (Rothschild et al. 2006). In a
genome-wide association study, DNA polymorphisms in the M promoter of MITF
were found to be associated with the extreme white coat color and flash (partial white
coloring) phenotype in boxers and bull terriers (Karlsson et al. 2007). Two mutations,
a short interspersed element (SINE), located about 3000 bp upstream of the M
promoter of MITF, and a length polymorphism in the M promoter (LP-MITF-M),
located 60-95 bp upstream of the TATA box of the M promoter, co-segregated with
the pigmentation status of the examined dogs including extreme white (s w ), piebald
(s p ), irish spotted (s i ) and solid (S) animals in the analysis. Specific genotypes for any
of these pigmentation variants could be identified: solid dogs do not harbor the SINE
and show a short LP-MITF-M (29-32 bp), whereas extreme white and piebald dogs
show the SINE and a longer LP-MITF-M (35-36 bp). Irish spotted dogs lack the SINE,
but also possess a long LP-MITF-M. The SINE is present in Dalmatian dogs, and a
unique LP-MITF-M (32 bp) could be identified for this breed.
MITF is also an appropriate candidate for congenital deafness. Mitf mi-bw mice show
white coat color and hearing loss (Tietz 1963). MITF is also responsible for the
human Waardenburg syndrome II, which is characterized by sensorineural deafness
and lack of pigmentation in hair, skin and iris (Bondurand et al. 2000). Therefore,
MITF is a suitable candidate for congenital sensorineural deafness related to
pigmentation status. In this study, the association of MITF-associated markers with
hearing status and iris color was investigated in Dalmatian dogs employing a case-
control study.