A Noncoding Melanophilin Gene (MLPH) SNP at the Splice Donor of Exon 1 Represents a Candidate Causal Mutation for Coat Color Dilution in Dogs

Coat color dilution in several breeds of dog is characterized by a specific pigmentation 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 coding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5′-region 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 confirmed 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 dog

Spongiform Encephalopathy in a Miniature Zebu

The first case of spongiform encephalopathy in a zebu (Bos indicus) was identified in a zoo in Switzerland. Although histopathologic and immunohistochemical analyses of the central nervous system indicated a diagnosis of bovine spongiform encephalopathy (BSE), molecular typing showed some features different from those of BSE in cattle (B. taurus)

A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy

Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (P-CHISQ = 3.425e(-14), n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet-Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal andPeer reviewe

A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene

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

Coat color dilution in several breeds of dog is characterized by a specific pigmentation 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 coding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5'-region 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 confirmed 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

Strong Selection for Behavioural Resilience in Australian Stock Working Dogs Identified by Selective Sweep Analysis

Background: Working dog handlers and breeders have strong opinions on characteristics that are desirable in the breeds that they use to handle stock. Most of these characteristics are related to conformation or behaviour. This study explored whether the genetics underlying desirable working behaviour traits might be identified by selective sweep analysis; a method that identifies long regions of strong homozygosity combined with allelic divergence from a comparison group. For this analysis, we compared genomic haplotype architecture in two breeds derived from common founder stock but subjected to divergent selective pressures. The breeds studied were the Australian Kelpie, which is registered with the Australian National Kennel Council, and the Australian Working Kelpie, which is registered with the Working Kelpie Council. Results: A selective sweep spanning 3 megabases on chromosome 3 was identified in the Australian Working Kelpie. This region is the location of genes related to fear-memory formation and pain perception. Selective sweep loci of similar magnitude were observed in the Australian Kelpie. On chromosome 8 is a locus which may be related to behavioural excitability and on chromosome 30 is a smaller locus which most likely is related to morphology. Conclusions: Active working stock dogs of the Australian Working Kelpie breed have been bred primarily for gene loci influencing pain perception and fear memory formation. By contrast Australian Kelpies are commonly maintained in urban environments where these characteristics are not required and have been affected by selection for conformation and coat colour. The identified loci may aid in the identification of superior working dogs

Simulation-based roadmap for the integration of poly-silicon on oxide contacts into screen-printed crystalline silicon solar cells

We present a simulation-based study for identifying promising cell structures, which integrate poly-Si on oxide junctions into industrial crystalline silicon solar cells. The simulations use best-case measured input parameters to determine efficiency potentials. We also discuss the main challenges of industrially processing these structures. We find that structures based on p-type wafers in which the phosphorus diffusion is replaced by an n-type poly-Si on oxide junction (POLO) in combination with the conventional screen-printed and fired Al contacts show a high efficiency potential. The efficiency gains in comparsion to the 23.7% efficiency simulated for the PERC reference case are 1.0% for the POLO BJ (back junction) structure and 1.8% for the POLO IBC (interdigitated back contact) structure. The POLO BJ and the POLO IBC cells can be processed with lean process flows, which are built on major steps of the PERC process such as the screen-printed Al contacts and the Al2O3/SiN passivation. Cell concepts with contacts using poly-Si for both polarities (POLO 2-concepts) show an even higher efficiency gain potential of 1.3% for a POLO 2 BJ cell and 2.2% for a POLO 2 IBC cell in comparison to PERC. For these structures further research on poly-Si structuring and screen-printing on p-type poly-Si is necessary. © 2021, The Author(s)

PRNP promoter polymorphisms are associated with BSE susceptibility in Swiss and German cattle

BACKGROUND: Non-synonymous polymorphisms within the prion protein gene (PRNP) influence the susceptibility and incubation time for transmissible spongiform encephalopathies (TSE) in some species such as sheep and humans. In cattle, none of the known polymorphisms within the PRNP coding region has a major influence on susceptibility to bovine spongiform encephalopathy (BSE). Recently, however, we demonstrated an association between susceptibility to BSE and a 23 bp insertion/deletion (indel) polymorphism and a 12 bp indel polymorphism within the putative PRNP promoter region using 43 German BSE cases and 48 German control cattle. The objective of this study was to extend this work by including a larger number of BSE cases and control cattle of German and Swiss origin. RESULTS: Allele, genotype and haplotype frequencies of the two indel polymorphisms were determined in 449 BSE cattle and 431 unaffected cattle from Switzerland and Germany including all 43 German BSE and 16 German control animals from the original study. When breeds with similar allele and genotype distributions were compared, the 23 bp indel polymorphism again showed a significant association with susceptibility to BSE. However, some additional breed-specific allele and genotype distributions were identified, mainly related to the Brown breeds. CONCLUSION: Our study corroborated earlier findings that polymorphisms in the PRNP promoter region have an influence on susceptibility to BSE. However, breed-specific differences exist that need to be accounted for when analyzing such data

For none, one, or two polarities—How do POLO junctions fit best into industrial Si solar cells?

We present a systematic study on the benefit of the implementation of poly-Si on oxide (POLO) or related junctions into p-type industrial Si solar cells as compared with the benchmark of Passivated Emitter and Rear Cell (PERC). We assess three aspects: (a) the simulated efficiency potential of representative structures with POLO junctions for none (=PERC+), one, and for two polarities; (b) possible lean process flows for their fabrication; and (c) experimental results on major building blocks. Synergistic efficiency gain analysis reveals that the exclusive suppression of the contact recombination for one polarity by POLO only yields moderate efficiency improvements between 0.23%abs and 0.41%abs as compared with PERC+ because of the remaining recombination paths. This problem is solved in a structure that includes POLO junctions for both polarities (POLO2), for whose realization we propose a lean process flow, and for which we experimentally demonstrate the most important building blocks. However, two experimental challenges—alignment tolerances and screen-print metallization of p+ poly-Si—are unsolved so far and reduced the efficiency of the “real” POLO2 cell as compared with an idealized scenario. As an intermediate step, we therefore work on a POLO IBC cell with POLO junctions for one polarity. It avoids the abovementioned challenges of the POLO2 structure, can be realized within a lean process flow, and has an efficiency benefit of 1.59%abs as compared with PERC—because not only contact recombination is suppressed but also the entire phosphorus emitter is replaced by an n+ POLO junction

Allelic Heterogeneity at the Equine KIT Locus in Dominant White (W) Horses

White coat color has been a highly valued trait in horses for at least 2,000 years. Dominant white (W) is one of several known depigmentation phenotypes in horses. It shows considerable phenotypic variation, ranging from ∼50% depigmented areas up to a completely white coat. In the horse, the four depigmentation phenotypes roan, sabino, tobiano, and dominant white were independently mapped to a chromosomal region on ECA 3 harboring the KIT gene. KIT plays an important role in melanoblast survival during embryonic development. We determined the sequence and genomic organization of the ∼82 kb equine KIT gene. A mutation analysis of all 21 KIT exons in white Franches-Montagnes Horses revealed a nonsense mutation in exon 15 (c.2151C>G, p.Y717X). We analyzed the KIT exons in horses characterized as dominant white from other populations and found three additional candidate causative mutations. Three almost completely white Arabians carried a different nonsense mutation in exon 4 (c.706A>T, p.K236X). Six Camarillo White Horses had a missense mutation in exon 12 (c.1805C>T, p.A602V), and five white Thoroughbreds had yet another missense mutation in exon 13 (c.1960G>A, p.G654R). Our results indicate that the dominant white color in Franches-Montagnes Horses is caused by a nonsense mutation in the KIT gene and that multiple independent mutations within this gene appear to be responsible for dominant white in several other modern horse populations