(Editorial) Special Issue: "Canine Genetics 2".

Wolves were the first animal species to become domesticated by humans, approximately 30,000-50,000 years ago. Human-directed dog breeding over thousands of generations has generated more than 350 recognized breeds displaying surprisingly different phenotypes with respect to morphology, behavior and disease predispositions. The domestication of wolves and the subsequent breeding of dogs can be viewed as one of humankind's oldest and largest genetic experiments and provides us with unique opportunities for research. Dogs have not only become human's best friend but were also described as geneticists' best friend in a past issue of Science. In recognition of the importance of canine genetics, this Special Issue, entitled "Canine Genetics 2", was compiled. It represents a sequel to the former Special Issue "Canine Genetics", which was published in 2019. During the last 15 years, the canine community has heavily relied on a reference genome derived from the female Boxer Tasha. "Canine Genetics 2" includes an article describing a greatly improved version of this important community resource. This Special Issue further contains several reports related to monogenic or complex inherited diseases in dogs. Finally, important aspects of wild canid research, genetic diversity in different populations and canine morphology were investigated

cDNA cloning and sequencing of the human ryanodine receptor type 3 (RYR3) reveals a novel alternative splice site in the RYR3 gene

AbstractThe human ryanodine receptor type 3 (RYR3) was cloned from a fetal brain cDNA library and its complete sequence was determined (EMBL accession number AJ001515). The sequenced cDNA spanned 15 564 bp and contained an open reading frame of 14 613 bp. The corresponding protein consisted of 4870 amino acids with a calculated molecular mass of 552 kDa. Amino acid sequence identities to the RYR3 proteins from rabbit, mink, and chicken were 96%, 95%, and 83% respectively. A previously unidentified alternative splice site was detected generating a transcript that lacked bases 11 569–11 650 and encoded a truncated protein

Genetisches Rätsel gelöst: So entstehen die Farbmuster im Hundefell

An international team of researchers including scientists from the Institute of Genetics of the University of Bern has unraveled the enigma of inheritance of coat color patterns in dogs. The researchers discovered that a genetic variant responsible for a very light coat in dogs and wolves originated more than two million years ago in a now extinct relative of the modern wolf.Ein internationales Konsortium von Forschenden mit Beteiligung des Instituts für Genetik der Universität Bern konnte zeigen, wie Fellfarben bei Hunden vererbt werden. Zudem konnten sie nachweisen, dass eine Genvariante für helles Fell bei Hunden und Wölfen von einem inzwischen ausgestorbenen Verwandten des Wolfs stammt und mehr als zwei Millionen Jahre alt ist

X-linked anhidrotic ectodermal dysplasia (ED1) in men, mice, and cattle

Ectodermal dysplasias are a large group of rare genetic disorders characterized by impaired development of hair, teeth, and eccrine glands in humans, mice, and cattle. Here, we review the cloning, mutation analyses, and functional studies of the known causative genes for the X-chromosomal anhidrotic ectodermal dysplasia (ED1) in these species. Mutations in the ectodysplasin 1 (ED1) gene are responsible for X-linked anhidrotic ectodermal dysplasia. The ED1 gene encodes a signaling molecule of the tumor necrosis factor family that is involved in development of ectodermal appendages. The bovine disorder may serve as an animal model for human ED1

Genetics of inherited skin disorders in dogs

Canine genodermatoses represent a broad spectrum of diseases with diverse phenotypes. Modern genetic technology including whole genome sequencing has expedited the identification of novel genes and greatly simplified the establishment of genetic diagnoses in such heterogeneous disorders. The precise genetic diagnosis of a heritable skin disorder is essential for the appropriate counselling of owners regarding the course of the disease, prognosis and implications for breeding. Understanding the underlying pathophysiology is a prerequisite to developing specific, targeted or individualized therapeutic approaches. This review aims to create a comprehensive overview of canine genodermatoses and their respective genetic aetiology known to date. Raising awareness of genodermatoses in dogs is important and this review may help clinicians to apply modern genetics in daily clinical practice, so that a precise diagnoses can be established in suspected genodermatoses

A single base deletion in the SLC45A2 gene in a Bullmastiff with oculocutaneous albinism.

Oculocutaneous albinism type 4 (OCA4) in humans and similar phenotypes in many animal species are caused by variants in the SLC45A2 gene, encoding a putative sugar transporter. In dog, two independent SLC45A2 variants are known that cause oculocutaneous albinism in Doberman Pinschers and several small dog breeds respectively. For the present study, we investigated a Bullmastiff with oculocutaneous albinism. The affected dog was highly inbred and resulted from the mating of a sire to its own grandmother. We obtained whole genome sequence data from the affected dog and searched specifically for variants in candidate genes known to cause albinism. We detected a single base deletion in exon 6 of the SLC45A2 gene (NM_001037947.1:c.1287delC) that has not been reported thus far. This deletion is predicted to result in an early premature stop codon. It was confirmed by Sanger sequencing and perfectly co-segregated with the phenotype in the available family members. We genotyped 174 unrelated dogs from diverse breeds, all of which were homozygous wildtype. We therefore suggest that SLC45A2:c.1287delC causes the observed oculocutaneous albinism in the affected Bullmastiff

A 4 Mb High Resolution BAC Contig on Bovine Chromosome 1q12 and Comparative Analysis With Human Chromosome 21q22

The bovine RPCI-42 BAC library was screened to construct a sequence-ready ~4 Mb single contig of 92 BAC clones on BTA 1q12. The contig covers the region between the genes KRTAP8P1 and CLIC6. This genomic segment in cattle is of special interest as it contains the dominant gene responsible for the hornless or polled phenotype in cattle. The construction of the BAC contig was initiated by screening the bovine BAC library with heterologous cDNA probes derived from 12 human genes of the syntenic region on HSA 21q22. Contig building was facilitated by BAC end sequencing and chromosome walking. During the construction of the contig, 165 BAC end sequences and 109 single-copy STS markers were generated. For comparative mapping of 25 HSA 21q22 genes, genomic PCR primers were designed from bovine EST sequences and the gene-associated STSs mapped on the contig. Furthermore, bovine BAC end sequence comparisons against the human genome sequence revealed significant matches to HSA 21q22 and allowed the in silico mapping of two new genes in cattle. In total, 31 orthologues of human genes located on HSA 21q22 were directly mapped within the bovine BAC contig, of which 16 genes have been cloned and mapped for the first time in cattle. In contrast to the existing comparative bovine–human RH maps of this region, these results provide a better alignment and reveal a completely conserved gene order in this 4 Mb segment between cattle, human and mouse. The mapping of known polled linked BTA 1q12 microsatellite markers allowed the integration of the physical contig map with existing linkage maps of this region and also determined the exact order of these markers for the first time. Our physical map and transcript map may be useful for positional cloning of the putative polled gene in cattle. The nucleotide sequence data reported in this paper have been submitted to EMBL and have been assigned Accession Numbers AJ698510–AJ698674

Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?

Equine insect bite hypersensitivity (IBH) is the most common skin disease affecting horses. It is described as an IgE-mediated, Type I hypersensitivity reaction to salivary gland proteins of Culicoides insects. Together with Th2 cells, epithelial barrier cells play an important role in development of Type I hypersensitivities. In order to elucidate the role of equine keratinocytes in development of IBH, we stimulated keratinocytes derived from IBH-affected (IBH-KER) (n = 9) and healthy horses (H-KER) (n = 9) with Culicoides recombinant allergens and extract, allergic cytokine milieu (ACM) and a Toll like receptor ligand 1/2 (TLR-1/2-L) and investigated their transcriptomes. Stimulation of keratinocytes with Culicoides allergens did not induce transcriptional changes. However, when stimulated with allergic cytokine milieu, their gene expression significantly changed. We found upregulation of genes encoding for CCL5, -11, -20, -27 and interleukins such as IL31. We also found a strong downregulation of genes such as SCEL and KRT16 involved in the formation of epithelial barrier. Following stimulation with TLR-1/2-L, keratinocytes significantly upregulated expression of genes affecting Toll like receptor and NOD-receptor signaling pathway as well as NF-kappa B signaling pathway, among others. The transcriptomes of IBH-KER and H-KER were very similar: without stimulations they only differed in one gene (CTSL); following stimulation with allergic cytokine milieu we found only 23 differentially expressed genes (e.g. CXCL10 and 11) and following stimulation with TLR-1/2-L they only differed by expression of seven genes. Our data suggests that keratinocytes contribute to the innate immune response and are able to elicit responses to different stimuli, possibly playing a role in the pathogenesis of IBH

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

Lists of DEGs between LPS stimulated and unstimulated PBMCs. For every effect studied (LPS, and interaction effects: LPS:Fam1, LPS:Fam2) the list of genes differentially expressed at false discovery rate < 0.001 with log 2 fold changes is given. (XLSX 198 kb