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Philipp U, Quignon P, Scott A, Rak S, Andre C, Breen M, Leeb T. Assignment of the canine myosin Va gene (MYO5A) to chromosome 30q14 by fluorescence in situ hybridization and radi-ation hybrid mapping. Cytogenet Genome Res. 2003; 101: 92C.

Idee und Versuchsplanung: Philipp, Leeb

Durchführung: Philipp, Quignon, Scott, Rak

Auswertung: Philipp, André, Breen, Leeb, Quignon, Scott Manuskript: Philipp, Leeb

Philipp U, Scott A, Quignon P, Andre C, Breen M, Leeb T. Assignment of the RAB27A gene to canine chromosome 30q15.1 by fluorescence in situ hybridization and radiation hybrid mapping.

Cytogenet Genome Res. 2003; 101: 92E.

Idee und Versuchsplanung: Philipp, Leeb

Durchführung: Philipp, Quignon, Scott

Auswertung: Philipp, André, Breen, Leeb, Quignon, Scott Manuskript: Philipp, Leeb

Philipp U, Quignon P, Scott A, Andre C, Breen M, Leeb T. Chromosomal assignment of the ca-nine melanophilin gene (MLPH): A candidate gene for coat color dilution in Pinschers. J Hered.

2005; 96: 774-776.

Idee und Versuchsplanung: Philipp, Leeb

Durchführung: Philipp, Quignon, Scott

Auswertung: Philipp, André, Breen, Leeb, Quignon, Scott Manuskript: Philipp, Leeb

Philipp U, Hamann H, Mecklenburg L, Nishino S, Mignot E, Günzel-Apel AR, Schmutz SM, Leeb T. Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs. BMC Genet. 2005; 6: 34.

Idee und Versuchsplanung: Philipp, Leeb, Mecklenburg

Durchführung: Philipp

Auswertung: Philipp, Hamann, Leeb

Manuskript: Philipp, Leeb

Externe kooperierende Autoren: Günzel-Apel, Mignot, Nishino, Schmutz

Drögemüller C, Philipp U, Haase B, Günzel-Apel AR, Leeb T. A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. J Hered. 2007; 98: 468-473.

Idee und Versuchsplanung: Philipp, Drögemöller, Leeb Durchführung: Philipp, Drögemöller, Haase Auswertung: Philipp, Drögemöller, Leeb

Manuskript: Drögemöller, Leeb

Kooperierende Autorin: Günzel-Apel

Philipp U, Broschk C, Vollmar A, Distl O. Evaluation of tafazzin as candidate for dilated car-diomyopathy in Irish wolfhounds. J Hered. 2007; 98: 506-509.

Idee und Versuchsplanung: Philipp, Distl Durchführung: Philipp

Auswertung: Philipp, Distl, Vollmar Manuskript: Philipp, Distl

Philipp U, Vollmar A, Distl O. Evaluation of six candidate genes for dilated cardiomyopathy (DCM) in Irish wolfhounds. Anim Genet. 2008; 39: 88-89.

Idee und Versuchsplanung: Philipp, Distl Durchführung: Philipp

Auswertung: Philipp, Distl, Vollmar Manuskript: Philipp, Distl

Philipp U, Vollmar A, Distl O. Evaluation of the Titin-cap Gene (TCAP) as candidate for dilated cardiomyopathy in Irish wolfhounds. Animal Biotechnol. 2008; 19: 231-236.

Idee und Versuchsplanung: Philipp, Distl Durchführung: Philipp

Auswertung: Philipp, Distl, Vollmar Manuskript: Philipp, Distl

Philipp U, Fecht S, Wöhlke A, Distl O. A sex-dependent functional polymorphism in the canine multidrug-resistance (MDR1) gene. submitted

Idee und Versuchsplanung: Philipp, Distl

Durchführung: Philipp, Fecht, Wöhlke Auswertung: Philipp, Distl, Fecht Manuskript: Philipp, Distl, Fecht

11 Anhang

Publikationen, die Bestandteil der Habilitationsschrift sind:

Cytogenet Genome Res. 2003; 101: 92C.

Assignment of the canine myosin Va gene (MYO5A) to chromosome 30q14 by fluorescence in situ hybridization and radiation hybrid mapping.

Philipp U, Quignon P, Scott A, Rak S, André C, Breen M, Leeb T.

Institute of Animal Breeding and Genetics, School of Veterinary Medicine Hannover, Hannover, Germany.

No abstract available.

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=CGR2003101001092C

Cytogenet Genome Res. 2003; 101: 92E.

Assignment of the RAB27A gene to canine chromosome 30q15.1 by fluorescence in situ hybridization and radiation hybrid mapping.

Philipp U, Scott A, Quignon P, André C, Breen M, Leeb T.

Institute of Animal Breeding and Genetics, School of Veterinary Medicine Hannover, Hannover, Germany.

No abstract available.

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=CGR2003101001092E

J Hered. 2005; 96: 774 - 776.

Chromosomal assignment of the canine melanophilin gene (MLPH): a candidate gene for coat color dilution in Pinschers.

Philipp U, Quignon P, Scott A, André C, Breen M, Leeb T.

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünt-eweg 17p, 30559 Hannover, Germany.

Pinschers affected by coat color dilution show a specific pigmentation phenotype. The dilute pigmentation phenotype leads to a silver-blue appearance of the eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in Pinschers is sometimes accompanied by hair loss and a recurrent infection of the hair follicles. In human and mice, several well-characterized genes are responsible for similar pigment variations. To investigate the genetic cause of the coat color dilution in Pinschers, we isolated BAC clones containing the canine ortholog of the known murine color dilution gene Mlph. RH mapping of the canine MLPH gene was performed using an STS marker derived from BAC sequences. Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the canine MLPH gene was assigned to CFA25q24.

http://jhered.oxfordjournals.org/cgi/content/full/96/7/774

BMC Genet. 2005; 6: 34.

Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs.

Philipp U, Hamann H, Mecklenburg L, Nishino S, Mignot E, Günzel-Apel AR, Schmutz SM, Leeb T.

Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünt-eweg 17p, 30559 Hannover, Germany.

BACKGROUND: Pinschers and other dogs with coat color dilution show a characteristic pig-mentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the me-lanophilin gene (MLPH). RESULTS: We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed cosegregation for at least one polymorphism in an MLPH exon and the dilute phenotype.

No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this muta-tion was present in homozygous state in four dogs of other breeds with wildtype pigmentamuta-tion, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pin-schers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phe-notype. CONCLUSION: This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymor-phisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183202/?tool=pubmed

J Hered. 2007; 98: 468 - 473.

A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs.

Drögemöller C, Philipp U, Haase B, Günzel-Apel AR, Leeb T.

Institute of Genetics, Vetsuisse Faculty, University of Berne, Bremgartenstrasse 109a, 3001 Ber-ne, Switzerland. Coat color dilution in several breeds of dog is characterized by a specific pig-mentation phenotype and sometimes accompanied by hair loss and recurrent skin inflammation, the so-called color dilution alopecia or black hair follicular dysplasia. Coat color dilution (d) is inherited as a Mendelian autosomal recessive trait. In a previous study, MLPH polymorphisms showed perfect cosegregation with the dilute phenotype within breeds. However, different dilute haplotypes were found in different breeds, and no single polymorphism was identified in the co-ding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5'-re-gion of the canine MLPH gene and identified a strong candidate single nucleotide polymorphism within the nontranslated exon 1, which showed perfect association to the dilute phenotype in 65 dilute dogs from 7 different breeds. The A/G polymorphism is located at the last nucleotide of exon 1 and the mutant A-allele is predicted to reduce splicing efficiency 8-fold. An MLPH mRNA expression study using quantitative reverse transcriptase-polymerase chain reaction con-firmed that dd animals had only about approximately 25% of the MLPH transcript compared with DD animals. These results provide preliminary evidence that the reported regulatory MLPH mutation might represent a causal mutation for coat color dilution in dogs.

http://jhered.oxfordjournals.org/cgi/content/full/98/5/468

J Hered. 2007; 98: 506 - 509.

Evaluation of tafazzin as candidate for dilated cardiomyopathy in Irish wolfhounds.

Philipp U, Broschk C, Vollmar A, Distl O.

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünt-eweg 17p, 30559

Hannover, Germany.

Dilated cardiomyopathy (DCM) is a common disease in humans and dogs. Large-breed dogs and especially Irish wolfhounds belong to the frequently affected breeds. Male Irish wolfhounds show a significantly higher prevalence of DCM than females. Therefore, we evaluated X chro-mosome markers for linkage with DCM as well as a human candidate gene on the X chromoso-me. A set of X chromosomal microsatellites was genotyped in Irish wolfhound families segrega-ting for DCM. In addition, exon and intron sequences of the tafazzin (TAZ) gene were assayed for polymorphisms segregating in these families. Statistical analysis of the microsatellite markers did not reveal linkage to DCM. Furthermore, all Irish wolfhounds included in this study were monomorphic for TAZ, and only 8 sequence differences to the Dog Genome Assembly 2.1 could be found. The results indicate that due to the lack of mutations, TAZ is unlikely to cause DCM in Irish wolfhounds.

http://jhered.oxfordjournals.org/cgi/content/full/98/5/506

Anim Genet. 2008; 39: 88 - 89.

Evaluation of six candidate genes for dilated cardiomyopathy in Irish wolfhounds.

Philipp U, Vollmar A, Distl O.

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünt-eweg 17p, 30559

Hannover, Germany.

No abstract available.

http://www3.interscience.wiley.com/journal/119401064/abstract

Anim Biotechnol. 2008; 19: 231 - 236.

Evaluation of the titin-cap gene (TCAP) as candidate for dilated cardiomyopathy in Irish wolfhounds.

Philipp U, Vollmar A, Distl O.

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.

Dilated cardiomyopathy (DCM) is a myocardial disorder characterized by left ventricular dilata-tion and impaired systolic contracdilata-tion. Irish wolfhounds (IW) and other large breed dogs are most commonly disposed to DCM. We analyzed the titin-cap (TCAP, telethonin) gene as candi-date for DCM. Genomic DNA was analyzed in eight DCM affected and five DCM-free IWs.

cDNA was sequenced in one DCM-affected IW and two unaffected dogs, one Tibetan terrier and one Dachshund. Compared to the Boxer reference sequence, one sequence difference was identi-fied in the 3'UTR and two in the intron sequence. In the IWs the sequences were monomorphic.

In order to rule out a breed-specific haplotype that predisposes to DCM, the polymorphisms we-re genotyped in 24 Elo dogs, a bwe-reed mix established from nine diffewe-rent bwe-reeds. The analysis showed that the mutations were not restricted to IW. Moreover, 80% of the Elos were homo-zygous for the IW haplotype. We conclude that TCAP can most likely be eliminated as cause for DCM in IWs.

http://www.informaworld.com/smpp/content~db=all?content=10.1080/10495390802281952

BIOLOGICAL SCIENCE