SummaryIn domestic goats, the polled intersex syndrome (PIS) refers to XX female‐to‐male sex reversal associated with the absence of horn growth (polled). The causal variant was previously reported as a 11.7 kb deletion at approximately 129 Mb on chromosome 1 that affects the transcription of both FOXL2 and several long non‐coding RNAs. In the meantime the presence of different versions of the PIS deletion was postulated and trials to establish genetic testing with the existing molecular genetic information failed. Therefore, we revisited this variant by long‐read whole‐genome sequencing of two genetically female (XX) goats, a PIS‐affected and a horned control. This revealed the presence of a more complex structural variant consisting of a deletion with a total length of 10 159 bp and an inversely inserted approximately 480 kb‐sized duplicated segment of a region located approximately 21 Mb further downstream on chromosome 1 containing two genes, KCNJ15 and ERG. Publicly available short‐read whole‐genome sequencing data, Sanger sequencing of the breakpoints and FISH using BAC clones corresponding to both involved genome regions confirmed this structural variant. A diagnostic PCR was developed for simultaneous genotyping of carriers for this variant and determination of their genetic sex. We showed that the variant allele was present in all 334 genotyped polled goats of diverse breeds and that all analyzed 15 PIS‐affected XX goats were homozygous. Our findings enable for the first time a precise genetic diagnosis for polledness and PIS in goats and add a further genomic feature to the complexity of the PIS phenomenon.

Horns are the most obvious common feature of Bovidae. The naturally occurring absence of horns in these species, also known as polledness, is of surprisingly heterogeneous nature, although they are Mendelian traits. This review compares in detail the molecular differences among the causes of inherited polledness in the domestic ruminant species of cattle, yak, sheep, and goat based on the causal gene variants that have been discovered in recent years. The genetic causes for the lack of horns in small ruminants seem not only to be more complex, e.g., in sheep, breed-specific characteristics are still unexplained, but in goats, there is also the associated disorder of intersexuality—polled intersex syndrome (PIS). In connection with animal welfare and the associated discussion about a legal ban on the dehorning of all farm animals, naturally hornless animals and the causal genetic variants are of increasing research interest in the age of genome editing. However, the low acceptance of genetic engineering in livestock, especially in European societies, limits its use in food-producing animals. Therefore, genotype-based targeted selection of naturally occurring variants is still a widely used method for spreading this desired trait within and across populations, at least in cattle and sheep.

We investigated four European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome (EDS), a connective tissue disorder. The kittens were sired by the same tomcat, but were born by three different mothers. The kittens had easily torn skin resulting in non-healing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All four affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect co-segregation with the autosomal recessive EDS phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of EDS in humans, mice, dogs, cattle and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allow to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed EDS.

There is a growing concern about the loss of animal genetic resources. The aim of this study was to analyze the genetic diversity and potential peculiarity of the endangered Kosovar sheep breed Balusha. For this purpose, a dataset consisting of medium-density SNP chip genotypes (39,879 SNPs) from 45 Balusha sheep was generated and compared with SNP chip genotypes from 29 individuals of a second Kosovar breed, Bardhoka. Publicly available SNP genotypes from 39 individuals of the relatively closely located sheep breeds Istrian Pramenka and Ruda were additionally included in the analyses. Analysis of heterozygosity, allelic richness and effective population size was used to assess the genetic diversity. Inbreeding was evaluated using two different methods (FIS, FROH). The standardized FST (di) and cross-population extended haplotype homozygosity (XPEHH) methods were used to detect signatures of selection. We observed the lowest heterozygosity (HO = 0.351) and effective population size (Ne5 = 25, Ne50 = 228) for the Balusha breed. The mean allelic richness levels (1.780–1.876) across all analyzed breeds were similar and also comparable with those in worldwide breeds. FROH estimates (0.023–0.077) were highest for the Balusha population, although evidence of decreased inbreeding was observed in FIS results for the Balusha breed. Two Gene Ontology (GO) TERMs were strongly enriched for Balusha, and involved genes belonging to the melanogenesis and T cell receptor signaling pathways, respectively. This could result from selection for the special coat color pattern of Balusha (black head) and resistance to certain infectious diseases. The analyzed diversity parameters highlight the urgency to preserve the local Kosovar Balusha sheep as it is clearly distinguished from other sheep of Southeastern Europe, has the lowest diversity level and may harbor valuable genetic variants, e.g., for resistance to infectious diseases.