Molekulargenetische Untersuchungen beim Hund

Die genealogische Abstammung von Zuchtpopulationen wurde bei deutschen Weimaraner Jagdhunden im Vergleich zu weiteren Rassen und dem Wolf für Y-chromosomale und mitochondriale DNA-Sequenzen analysiert. Nur vier Weimaraner-Urväter und drei Urmütter wurden nachgewiesen. Wegen kleiner Stichproben konnte trotz immenser Vielfalt nicht belegt werden, dass maternale und paternale Haplotypen-Variabilitäten bei anderen Rassen und beim Wolf weniger eingeschränkt sind. Um die genetische Ursache für generalisierte Progressive Retina Atrophie (PRA) für fünf Hunderassen zu kartieren, wurden Kopplungsanalysen anhand von Kandidatengenen sowie genomweit angestellt. Da keine Marker/PRA-Kopplung nachweisbar war, wurden Homozygotie-Kartierungen mittels SNP-$\it microarrays$ durchgeführt. Für Irish Glen of Imaal Terrier (GIT) wurde die PRA-Region auf Chromosom 16 lokalisiert, die das Gen $\textit {a disintegrin and metalloprotease domain 9}$ umfasst. Hierin wurde eine 24kb-Deletion als PRA-Ursache bei GITs identifiziert

Molecular Genetics of Sex Identification, Breed Ancestry and Polydactyly in the Norwegian Lundehund Breed

The Norwegian Lundehund breed of dog has undergone a severe loss of genetic diversity as a result of inbreeding and epizootics of canine distemper. As a consequence, the breed is extremely homogeneous and accurate sex identification is not always possible by standard screening of X-chromosomal loci. To improve our genetic understanding of the breed we genotyped 17 individuals using a genome-wide array of 170 000 single nucleotide polymorphisms (SNPs). Standard analyses based on expected homozygosity of X-chromosomal loci failed in assigning individuals to the correct sex, as determined initially by physical examination and confirmed with the Y-chromosomal marker, amelogenin. This demonstrates that identification of sex using standard SNP assays can be erroneous in highly inbred individuals

Data from: Molecular genetics of sex identification, breed ancestry and polydactyly in the Norwegian Lundehund breed

The Norwegian Lundehund breed of dog has undergone a severe loss of genetic diversity as a result of inbreeding and epizootics of canine distemper. As a consequence, the breed is extremely homogeneous and accurate sex identification is not always possible by standard screening of X-chromosomal loci. To improve our genetic understanding of the breed we genotyped 17 individuals using a genome-wide array of 170 000 single nucleotide polymorphisms (SNPs). Standard analyses based on expected homozygosity of X-chromosomal loci failed in assigning individuals to the correct sex, as determined initially by physical examination and confirmed with the Y-chromosomal marker, amelogenin. This demonstrates that identification of sex using standard SNP assays can be erroneous in highly inbred individuals

Data from: Molecular genetics of sex identification, breed ancestry and polydactyly in the Norwegian Lundehund breed

The Norwegian Lundehund breed of dog has undergone a severe loss of genetic diversity as a result of inbreeding and epizootics of canine distemper. As a consequence, the breed is extremely homogeneous and accurate sex identification is not always possible by standard screening of X-chromosomal loci. To improve our genetic understanding of the breed we genotyped 17 individuals using a genome-wide array of 170 000 single nucleotide polymorphisms (SNPs). Standard analyses based on expected homozygosity of X-chromosomal loci failed in assigning individuals to the correct sex, as determined initially by physical examination and confirmed with the Y-chromosomal marker, amelogenin. This demonstrates that identification of sex using standard SNP assays can be erroneous in highly inbred individuals

Lundehund1.ped

Single nucleotide polymorphism (SNP) raw data files for 17 Lundehund dogs for use with the software PLINK: PED file

Lundehund1_information

Text file with sample number (FID), individual identification (IID) and sex for 17 Lundehund dogs

Lundehund1.map

Single nucleotide polymorphism (SNP) raw data files for 17 Lundehund dogs for use with the software PLINK: MAP file

Kropatsch et al 2015 Norwegian Lundehund Y mtDNA genetic data

Excel file containing genotypes of three variable mitochondrial DNA (mtDNA) sites in the ATP synthase subunit 6 gene, a 3’portion of ATP synthase subunit 8 gene and a portion of D-loop sequence as well as of nine Y-chromosomal markers (five single nucleotide polymorphisms (SNPs) and four microsatellites) in 57 Norwegian Lundehund individuals sorted by gender (m: male, f: female). The genotypes of the mtDNA sites and the Y-chromosomal SNPs show the nucleotide identified at the respective position. The genotypes of Y-chromosomal microsatellites are given as fragment lengths. For mtDNA and Y-chromosomal SNPs exchange positions are indicated according to the mtDNA reference sequence or Embl accession numbers, respectively. For Y-chromosomal microsatellites, simple repeat motifs are shown. Missing genetic data is indicated as “-“

A large deletion in RPGR\it RPGR causes XLPRA in Weimaraner dogs

$\textbf {Background:}$ Progressive retinal atrophy (PRA) belongs to a group of inherited retinal disorders associated with gradual vision impairment due to degeneration of retinal photoreceptors in various dog breeds. PRA is highly heterogeneous, with autosomal dominant, recessive or X-linked modes of inheritance. In this study we used exome sequencing to investigate the molecular genetic basis of a new type of PRA, which occurred spontaneously in a litter of German short-hair Weimaraner dogs. $\textbf {Results:}$ Whole exome sequencing in two PRA-affected Weimaraner dogs identified a large deletion comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator $\textit {(RPGR)}$ gene known to be involved in human retinitis pigmentosa and canine PRA. Screening of 16 individuals in the corresponding pedigree of short-hair Weimaraners by qPCR, verified the deletion in hemizygous or heterozygous state in one male and six female dogs, respectively. The mutation was absent in 88 additional unrelated Weimaraners. The deletion was not detectable in the parents of one older female which transmitted the mutation to her offspring, indicating that the $\it RPGR$ deletion represents a $\textit {de novo}$ mutation concerning only recent generations of the Weimaraner breed in Germany. $\textbf {Conclusion:}$ Our results demonstrate the value of an existing DNA biobank combined with exome sequencing to identify the underlying genetic cause of a spontaneously occurring inherited disease. Identification of the genetic cause has allowed the development of a diagnostic test, which should help to eradicate the PRA causing mutation from the respective canine line. Thus, planning of future pairings is facilitated and manifestation of this type of PRA can be prevented