Multiple congenital ocular anomalies in Icelandic horses

<p>Abstract</p> <p>Background</p> <p>Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (<it>PMEL17</it>, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.</p> <p>Results</p> <p>We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the <it>PMEL17 </it>mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the <it>PMEL17 </it>mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as <it>PMEL17 </it>heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies.</p> <p>One eye of a severely vision-impaired 18 month-old stallion, homozygous for the <it>PMEL17 </it>mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.</p> <p>Conclusions</p> <p>The MCOA syndrome is segregating with the <it>PMEL17 </it>mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.</p

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity

Genetic diversity in the modern horse illustrated from genome-wide SNP data

Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection

Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

Horses were domesticated from the Eurasian steppes 5,000–6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection

Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

Peer reviewe

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

Peer reviewe

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

(Re)framing the Arctic : A qualitative content analysis on Swedish media and state discourses during 2017-2019

This thesis seeks to study how the Arctic is framed in Swedish media and state discourse during 2017-2019. The nexus of security studies and the Arctic are increasingly important due to the perceived opportunities and challenges rising as consequences of human-induced climate change. Despite the increasingly difficult geopolitical situation, the international cooperation of the region has been relatively uncomplicated. This paradox has created a diverged research field and a split in how the media and state discourses frame the Arctic. Previous research lacks a holistic approach of comparing two discourses in one study and a focus on Sweden. This thesis utilizes an analytical framework based on securitization and frame theory to identify frames by using the security concepts: traditional security, environmental security, and desecuritization. The study identifies a similar use of securitizing frames by the media and desecuritizing frames by the state, as defined by previous research. However, the Swedish case is distinguished by a division within the state discourse, a trend previously not identified, and the dominant use of environmental security frames. The results suggest the need for continued research on origins for media and state discourses in the growing field of Arctic security studies

Differentiation of Brain and Reproductive Organs in Birds : Effects of Environmental Contaminants

The first objective of this thesis was to investigate effects of endocrine disruptors on the developing brain and gonads of bird embryos. The substances studied were the insecticide methoxychlor, and nine UV-filters (3-benzylidene camphor (3BC), 4 methyl benzylidene camphor (4MBC), benzophenone (BP) 1,2 and 3, 4 hydroxy benzophenone (4 HB), 4 dihydroxy benzophenone (4DHB), benzyl salicylate (BS), and ethyl-4-aminobenzoate Et-PABA)), commonly used in cosmetic products. Some of these substances have no estrogenic effect in vitro, but have been shown to be estrogenic in vivo. The PCB-mixture Clophen A50 is a well-known inducer of biotransformation enzymes and was co-administered with methoxychlor and the UV-filters 3BC and 4MBC. Exposure to 3BC or 4MBC caused ovotestis formation and malformations of the Müllerian ducts in Japanese quail embryos. Co-exposure to one of these compounds and Clophen A50 enhanced the effects, indicating that Clophen A50 potentiates the effects of the UV-filters. Embryonic co-exposure to Clophen A50 and methoxychlor caused a disturbed male sexual behaviour. The metabolites of methoxychlor are estrogen receptor (ER)α-selective, which indicates that the effects on behaviour following embryonic treatment were mediated by ERα. Another objective in this thesis was to localize estrogen receptors (ERs) in the brain of adult and embryonic Japanese quail. The ER localization provides a basis for mechanistic studies on effects of endocrine disruptors, by the identification of estrogen-responsive areas in the brain. We found that ERβ, not previously implicated in sex-differentiation of the brain, was the only ER-subtype present in a sexually dimorphic brain area during differentiation. In conclusion, the estrogenic effects of 3BC, 4MBC and methoxychlor were increased by co-exposure to PCB. These results raise concern since many wildlife species, as well as humans, carry large body burdens of persistent organic pollutants like PCBs, which potentially can interact and enhance the effects of other endocrine disruptors