The host specificity and climatic suitability of the gall flyCecidochares connexa(Diptera: Tephritidae), a potential biological control agent for Chromolaena odorata(Asteraceae) in Australia

The gall fly Cecidochares connexa (Diptera: Tephritidae) is a potential biological control agent for Chromolaena odorata in Australia. Its host specificity was determined against 18 species in the tribe Eupatorieae (Family Asteraceae) in which C. odorata belongs, in quarantine in Brisbane, Australia. Oviposition occurred and flies developed on only C. odorata and Praxelis clematidea, both of which are in the subtribe Praxelinae. P. clematidea is considered a weed outside tropical America. In both multiple-species-minus-C. odorata choice tests and single-species no-choice tests, the mean number of galls/plant was significantly greater on C. odorata (48 and 41, respectively) than on P. clematidea (2 and 9, respectively). There were also significantly more adults emerging from C. odorata (mean 129 and 169, respectively) in the two types of tests than from P. clematidea (1 and 8, respectively). Paired choice, multiple generation (continuation) and time dependent tests further clarified the extent that C. connexa could develop on P. clematidea. In these tests, the mean number of galls formed and the mean number of emerging adults were consistently less for P. clematidea than C. odorata and populations of C. connexa could not be maintained on P. clematidea. Galls were not seen on any other plant species tested. This study supports the results of host specificity testing conducted in seven other countries and confirms that C. connexa poses little risk to other plant species in Australia. C. connexa has been released in 10 countries and an application seeking approval to release in Australia has been submitted to the Australian Government.

The first genome sequence of a metatherian herpesvirus: Macropodid herpesvirus 1

While many placental herpesvirus genomes have been fully sequenced, the complete genome of a marsupial herpesvirus has not been described. Here we present the first genome sequence of a metatherian herpesvirus, Macropodid herpesvirus 1 (MaHV-1).

Temporal Variation in Physiological Biomarkers in Black Flying-Foxes (Pteropus alecto), Australia

Bats of the genus Pteropus (Pteropodidae) are recognised as the natural host of multiple emerging pathogenic viruses of animal and human health significance, including henipaviruses, lyssaviruses and ebolaviruses. Some studies have suggested that physiological and ecological factors may be associated with Hendra virus infection in flying-foxes in Australia; however, it is essential to understand the normal range and seasonal variability of physiological biomarkers before seeking physiological associations with infection status. We aimed to measure a suite of physiological biomarkers in P. alecto over time to identify any seasonal fluctuations and to examine possible associations with life-cycle and environmental stressors. We sampled 839 adult P. alecto in the Australian state of Queensland over a 12-month period. The adjusted population means of every assessed hematologic and biochemical parameter were within the reported reference range on every sampling occasion. However, within this range, we identified significant temporal variation in these parameters, in urinary parameters and body condition, which primarily reflected the normal annual life cycle. We found no evident effect of remarkable physiological demands or nutritional stress, and no indication of clinical disease driving any parameter values outside the normal species reference range. Our findings identify underlying temporal physiological changes at the population level that inform epidemiological studies and assessment of putative physiological risk factors driving Hendra virus infection in P. alecto. More broadly, the findings add to the knowledge of Pteropus populations in terms of their relative resistance and resilience to emerging infectious disease.

Coronavirus Infection and Diversity in Bats in the Australasian Region

Following the SARS outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. This study sought to identify the diversity and prevalence of coronaviruses in bats in the Australasian region. We identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. We did not detect any SARS-like betacoronaviruses, despite targeting rhinolophid bats, the putative natural host taxa. Our findings support the virus-host co-evolution hypothesis, with the detection of Miniopterus bat coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel betacoronavirus genotype from Pteropus alecto which is most closely related to Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the Philippines. We also detected possible cross-species transmission of bat coronaviruses, and the apparent enteric tropism of these viruses. Thus, our findings are consistent with a scenario wherein the current diversity and host specificity of coronaviruses reflects co-evolution with the occasional host shift.

Area-wide releases and evaluation of the parasitoid Eretmocerus hayati(Hymenoptera:Aphelinidae) for silverleaf whitefly control

Silverleaf whitefly (SLW), Bemisia tabaci biotype B, is a major horticultural pest that costs Queensland vegetable growers millions of dollars in lost production and control measures each year. In the Bowen and Burdekin districts of North Queensland, the major cultivated SLW host crops are tomatoes, melons, green beans, pumpkins, eggplants, and cucumbers, which cover a total production area of approximately 6500 ha. Eretmocerus hayati, an effective SLW parasitoid, was imported into Australia by CSIRO in 2002 and released from quarantine in 2004. In 2006, DAFF established a mass-rearing unit for E. hayati at Bowen Research Station to provide E. hayati for release on vegetable farms within its SLW integrated pest management research program. A total of 1.3 million E. hayati were released over three seasons on 34 vegetable farms in the Bowen and Burdekin districts (October 2006 to December 2008). Post-release samplings were conducted across the release area over this time period with parasitism levels recorded in tomatoes, melons, beans, eggplants, pumpkins, and various SLW weed hosts. Sample data show that E. hayati established at most release sites as well as some non-release sites, indicating natural spread. Overall results from these three years of evaluation clearly demonstrated that E hayati releases played a significant role in SLW control. In most crops sampled, E hayati exerted between 30 and 80% parasitism. Even in regularly sprayed crops, such as tomato and eggplant, E. hayati was able to achieve an overall average parasitism of 45%.

Evaluation of tomato production systems at Bowen in mitigating the risk of fruit fly infestation: a systems approach for market access

Queensland fruit flies Bactrocera tryoni and B. neohumeralis are considered major quarantine pests of tomato, a major crop in the horticultural production district around Bowen, North Queensland, Australia. Preharvest and/or postharvest treatments are required to meet the market access requirements of both domestic and international trading partners. The suspension from use of dimethoate and fenthion, the two insecticides used for fruit fly control, has resulted in the loss of both pre and postharvest uses in fresh tomato. Research undertaken quantitatively at Bowen evaluated the effectiveness of pre-harvest production systems without specific fruit fly controls and postharvest mitigation measures in reducing the risk of fruit fly infestation in tomato. A district-wide trapping using cue-lure baited traps was undertaken to determine fruit fly seasonal patterns in relation to the cropping seasons. A total of 17,626 field-harvested and 11,755 pack-house tomatoes were sampled from ten farms over three cropping seasons (2006-2009). The fruit were incubated and examined for fruit fly infestation. No fruit fly infested fruit were recorded over the three seasons in either the field or the pack-house samples. Statistical analyses showed that upper infestation levels were extremely low (between 0.025 and 0.062%) at the 95% confidence level. The trap catches showed a seasonal pattern in fruit fly activity, with low numbers during the autumn and winter months, rising slightly in spring and peaking in summer. This seasonal pattern was similar over the four seasons. The main two species of fruit fly caught were B. tryoni and B. neohumeralis. Based on the results, it is clear that the risk of fruit fly infestation is extremely low under the current production systems in the Bowen region.

Towards web-based semantic enrichment of 3D insects

Natural history collections are an invaluable resource housing a wealth of knowledge with a long tradition of contributing to a wide range of fields such as taxonomy, quarantine, conservation and climate change. It is recognized however [Smith and Blagoderov 2012] that such physical collections are often heavily underutilized as a result of the practical issues of accessibility. The digitization of these collections is a step towards removing these access issues, but other hurdles must be addressed before we truly unlock the potential of this knowledge.

Natural variation and Biogeography of the melon fruit fly, Zeugodacus cucurbitae (Diptera : Tephritidae), in Southeast-Asia and the west-pacific

This thesis used multidisciplinary approaches which greatly enhance our understanding of population structure and can be particularly powerful tools for resolving variation of melon fly over geographic and temporal scales, and for determining invasive pathways. The results from this thesis reinforce the value of integrating multiple data sets to better understand and resolve natural variation within an important pest to determine whether there are cryptic species, discrete lineages or host races, and to identify dispersal pathways in an invasive pest. These results are instructive for regional biosecurity, trade and quarantine, and provide important background for future area-wide management programmes. The integrative methodology adopted in this thesis is applicable to a variety of other insect pests.

Applications of coralline hydroxyapatite with bioabsorbable containment and reinforcement as bone graft substitute : An experimental study

The aim of the present experimental study was to find out if the applications of coralline hydroxyapatite (HA) can be improved by using bioabsorbable containment or binding substance with particulate HA in mandibular contour augmentation and by using bioabsorbable fibre-reinforced HA blocks in filling bone defects and in anterior lumbar interbody fusion. The use of a separate curved polyglycolide (PGA) containment alone or together with a fast resorbing polyglycolide/polylactide (PGA/PLA) binding substance were compared to the conventional non-contained method in ridge augmentation in sheep. The contained methods decreased HA migration, but the augmentations did not differ significantly. The use of the containment caused a risk for wound dehiscence and infection. Histologically there was a rapid connective tissue ingrowth into the HA graft and it was more abundant with the PGA containment compared to the non-contained augmentation and even additionally rich when the HA particles were bound with PGA/PLA copolymer. However, the bone ingrowth was best in the non-contained augmentation exceeding 10-12 % of the total graft area at 24 weeks. Negligible or no bone ingrowth was seen in the cases where the polymer composite was added to the HA particles and, related to that, foreign-body type cells were seen at the interface between the HA and host bone. The PGA and poly-dl/l-lactide (PDLLA) fibre-reinforced coralline HA blocks were studied in the metaphyseal and in the diaphyseal defects in rabbits. A rapid bone ingrowth was seen inside the both types of implants. Both PGA and PDLLA fibres induced an inflammatory fibrous reaction around themselves but it did not hinder the bone ingrowth. The bone ingrowth pattern was directed according to the loading conditions so that the load-carrying cortical ends of the implants as well as the implants sited in the diaphyseal defects were the most ossified. The fibre-reinforced coralline HA implants were further studied as stand-alone grafts in the lumbar anterior interbody implantation in pigs. The strength of the HA implants proved not to be adequate, the implants fractured in six weeks and the disc space was gradually lost similarly to that of the discectomized spaces. Histologically, small quantities of bone ingrowth was seen in some of the PGA and PDLLA reinforced coralline implants while no bone formation was identified in any of the PDLLA reinforced synthetic porous HA implants. While fragmented, the inner structure of the implants was lost, the bone ingrowth was minimal, and the disc was replaced by the fibrous connective tissue. When evaluated radiologically the grade of ossification was assessed as better than histologically, and, when related to the histologic findings, CT was more dependable than the plain films to show ossification of the implanted disc space. Local kyphosis was a frequent finding along with anterior bone bridging and ligament ossification as a consequence of instability of the implanted segment.

lac Repressor Is an Antivirulence Factor of Salmonella enterica: Its Role in the Evolution of Virulence in Salmonella

The genus Salmonella includes many pathogens of great medical and veterinary importance. Bacteria belonging to this genus are very closely related to those belonging to the genus Escherichia. lacZYA operon and lacI are present in Escherichia coli, but not in Salmonella enterica. It has been proposed that Salmonella has lost lacZYA operon and lacI during evolution. In this study, we have investigated the physiological and evolutionary significance of the absence of lacI in Salmonella enterica. Using murine model of typhoid fever, we show that the expression of Lacl causes a remarkable reduction in the virulence of Salmonella enterica. Lacl also suppresses the ability of Salmonella enterica to proliferate inside murine macrophages. Microarray analysis revealed that Lacl interferes with the expression of virulence genes of Salmonella pathogenicity island 2. This effect was confirmed by RT-PCR and Western blot analysis. Interestingly, we found that SBG0326 of Salmonella bongori is homologous to lacI of Escherichia coli. Salmonella bongori is the only other species of the genus Salmonella and it lacks the virulence genes of Salmonella pathogenicity island 2. Overall, our results demonstrate that Lacl is an antivirulence factor of Salmonella enterica and suggest that absence of lacI has facilitated the acquisition of virulence genes of Salmonella pathogenicity island 2 in Salmonella enterica making it a successful systemic pathogen.

Evaluation of the Biocompatibility of Poly (ortho ester), Copolymer of ε-caprolactone/D,L-lactide and the Composite of Copolymer of ε-caprolactone/D,L-lactide and Tricalciumphosphate as Bone Filling Material

The purpose of this series of studies was to evaluate the biocompatibility of poly (ortho) ester (POE), copolymer of ε-caprolactone and D,L-lactide [P (ε-CL/DL-LA)] and the composite of P(ε-CL/DL-LA) and tricalciumphosphate (TCP) as bone filling material in bone defects. Tissue reactions and resorption times of two solid POE-implants (POE 140 and POE 46) with different methods of sterilization (gamma- and ethylene oxide sterilization), P(ε-CL/DL-LA)(40/60 w/w) in paste form and 50/50 w/w composite of 40/60 w/w P(ε-CL/DL-LA) and TCP and 27/73 w/w composite of 60/40 w/w P(ε-CL/DL-LA) and TCP were examined in experimental animals. The follow-up times were from one week to 52 weeks. The bone samples were evaluated histologically and the soft tissue samples histologically, immunohistochemically and electronmicroscopically. The results showed that the resorption time of gamma sterilized POE 140 was eight weeks and ethylene oxide sterilized POE 140 13 weeks in bone. The resorption time of POE 46 was more than 24 weeks. The gamma sterilized rods started to erode from the surface faster than ethylene oxide sterilized rods for both POEs. Inflammation in bone was from slight to moderate with POE 140 and moderate with POE 46. No highly fluorescent layer of tenascin or fibronectin was found in the soft tissue. Bone healing at the sites of implantation was slower than at control sites with the copolymer in small bone defects. The resorption time for the copolymer was over one year. Inflammation in bone was mostly moderate. Bone healing at the sites of implantation was also slower than at the control sites with the composite in small and large mandibular bone defects. Bone formation had ceased at both sites by the end of follow-up in large mandibular bone defects. The ultrastructure of the connective tissue was normal during the period of observation. It can be concluded that the method of sterilization influenced the resorption time of both POEs. Gamma sterilized POE 140 could have been suitable material for filling small bone defects, whereas the degradation times of solid EO-sterilized POE 140 and POE 46 were too slow to be considered as bone filling material. Solid material is difficult to contour, which can be considered as a disadvantage. The composites were excellent to handle, but the degradation time of the polymer and the composites were too slow. Therefore, the copolymer and the composite can not be recommended as bone filling material.

Basement membrane and provisional matrix components (collagen type IV, laminins and von Willebrand factor) in rheumatoid arthritis and Sjögren s syndrome

The aim of this study was twofold- Firstly, to determine the composition of the type IV collagen which are the major components of the basement membrane (BM), in the synovial lining of the rheumatoid arthritis (RA) patient and in the BM in the labial salivary gland of the Sjögrens syndrome (SS) patient. Secondly, this thesis aimed to investigate the role of the BM component laminin α4 and laminin α5 in the migration of neutrophils from the blood vessels thorough the synovial lining layer into synovial fluid and the presence of vWF in the microvasculature of labial salivary gland in SS. Our studies showed that certain α chains type IV collagen are low in RA compared to control synovial linings, while laminin α5 exhibited a pattern of low expression regions at the synovial lining interface towards the joint cavity and fluid. Also, high numbers of macrophage-like lining cells containing MMP-9 were found in the lining. MMP-9 was also found in the synovial fluid. Collagen α1/2 (IV) mRNA was found to be present in high amount compared to the other α(IV) chains and also showed intense labelling in immunohistochemical staining in normal and SS patients. In healthy glands α5(IV) and α6(IV) chains were found to be continuous around ducts but discontinuous around acini. The α5(IV) and α6(IV) mRNAs were present in LSG explants and HSG cell line, while in SS these chains seemed to be absent or appear only in patches around the ductal BM and tended to be absent around acini in immunohistochemical staining, indicating that their synthesis and/or degradation seemed to be locally regulated around acinar cells. The provisional matrix component vWF serves as a marker of vascular damage. Microvasculature in SS showed signs of focal damage which in turn might impair arteriolar feeding, capillary transudation and venular drainage of blood. However, capillary density was not decreased but rather increased, perhaps as a result of angiogenesis compensatory to microvascular damage. Microvascular involvement of LSG may contribute to the pathogenesis of this syndrome. This twofold approach allows us to understand the intricate relation between the ECM components and the immunopathological changes that occur during the pathogenesis of these inflammatory rheumatic disease processes. Also notably this study highlights the importance of maintaining a healthy ECM to prevent the progression or possibly allow reversal of the disease to a considerable level. Furthermore, it can be speculated that a healthy BM could quarantine the inflamed region or in case of cancer cells barricade the movement of malignant cells thereby preventing further spread to the surrounding areas. This understanding can be further applied to design appropriate drugs which act specifically to maintain a proper BM/BM like intercellular matrix composition.

Species-specific and Indication-based Use of Antimicrobials in Dogs, Cats, Cattle and Horses in Finland : Data collected using three different methods

Increasing antimicrobial resistance in bacteria has led to the need for better understanding of antimicrobial usage patterns. In 1999, the World Organisation for Animal Health (OIE) recommended that an international ad hoc group should be established to address human and animal health risks related to antimicrobial resistance and the contribution of antimicrobial usage in veterinary medicine. In European countries the need for continuous recording of the usage of veterinary antimicrobials as well as for animal species-specific and indication-based data on usage has been acknowledged. Finland has been among the first countries to develop prudent use guidelines in veterinary medicine, as the Ministry of Agriculture and Forestry issued the first animal species-specific indication-based recommendations for antimicrobial use in animals in 1996. These guidelines have been revised in 2003 and 2009. However, surveillance on the species-specific use of antimicrobials in animals has not been performed in Finland. This thesis provides animal species-specific information on indication-based antimicrobial usage. Different methods for data collection have been utilized. Information on antimicrobial usage in animals has been gathered in four studies (studies A-D). Material from studies A, B and C have been used in an overlapping manner in the original publications I-IV. Study A (original publications I & IV) presents a retrospective cross-sectional survey on prescriptions for small animals at the Veterinary Teaching Hospital of the University of Helsinki. Prescriptions for antimicrobial agents (n = 2281) were collected and usage patterns, such as the indication and length of treatment, were reviewed. Most of the prescriptions were for dogs (78%), and primarily for the treatment of skin and ear infections most of which were treated with cephalexin for a median period of 14 days. Prescriptions for cats (18%) were most often for the treatment of urinary tract infections with amoxicillin for a median length of 10 days. Study B (original publication II) was a retrospective cross-sectional survey where prescriptions for animals were collected from 17 University Pharmacies nationwide. Antimicrobial prescriptions (n = 1038) for mainly dogs (65%) and cats (19%) were investigated. In this study, cephalexin and amoxicillin were also the most frequently used drugs for dogs and cats, respectively. In study C (original publications III & IV), the indication-based usage of antimicrobials of practicing veterinarians was analyzed by using a prospective questionnaire. Randomly selected practicing veterinarians in Finland (n = 262) recorded all their antimicrobial usage during a 7-day study period. Cattle (46%) with mastitis were the most common patients receiving antimicrobial treatment, generally intramuscular penicillin G or intramammary treatment with ampicillin and cloxacillin. The median length of treatment was four days, regardless of the route of administration. Antimicrobial use in horses was evaluated in study D, the results of which are previously unpublished. Firstly, data collected with the prospective questionnaire from the practicing veterinarians showed that horses (n = 89) were frequently treated for skin or wound infections by using penicillin G or trimethoprim-sulfadiazine. The mean duration of treatment was five to seven days. Secondly, according to retrospective data collected from patient records, horses (n = 74) that underwent colic surgery at the Veterinary Teaching Hospital of the University of Helsinki were generally treated according to national and hospital recommendations; penicillin G and gentamicin was administered preoperatively and treatment was continued for a median of three days postoperatively. In conclusion, Finnish veterinarians followed well the national prudent use guidelines. Narrow-spectrum antimicrobials were preferred and, for instance, fluoroquinolones were used sparingly. Prescription studies seemed to give good information on antimicrobials usage, especially when combined with complementary information from patient records. A prospective questionnaire study provided a fair amount of valuable data on several animal species. Electronic surveys are worthwhile exploiting in the future.

Leuconostoc spoilage of refrigerated, packaged foods

Leuconostoc spp. are lactic acid bacteria (LAB) implicated in food spoilage, especially on refrigerated, modified atmosphere packaged (MAP) meats. The overall aim of this thesis was to learn more about Leuconostoc spp. as food spoilage organisms with a focus on commercial products where LAB spoilage is considered a problem and the main factor limiting shelf-life. Therefore, we aimed to identify Leuconostoc spp. involved in food spoilage, as well as to characterise the spoilage reactions they caused and their contamination sources during poultry meat processing. In addition, we examined the distribution of strains of Leuconostoc gasicomitatum in different food commodities. Finally, we analysed the genome content of L. gasicomitatum LMG 18811 with a special focus on metabolic pathways related to food spoilage. The findings show that Leuconostoc gelidum and L.gasicomitatum were responsible for the discoloration and off-odours developed in beef steaks. Together with Leuconostoc mesenteroides, these Leuconostoc spp., also cause spoilage of vegetable sausages. In contrast, we showed that Leuconostoc spp. are not important for the shelf-life or quality of non-marinated broiler products although, in marinated broiler fillet products, Leuconostoc spp., L.gasicomitatum in particular, are considered spoilage organisms. Furthermore, the findings of the contamination survey we carried out in a poultry processing plant indicated that spoilage Leuconostoc spp. are derived from the processing environment rather than from the broilers, and that air movement distributes psychrotrophic spoilage LAB, including leuconostocs, and has an important role in meat contamination during poultry processing. Pulsed-field gel electrophoresis (PFGE) based genotyping of L. gasicomitatum strains demonstrated that certain genotypes are common in various meat products. In contrast, genotypes associated with meat were not recovered in vegetable-based sources. This suggests that these two food categories either become contaminated with, or favour the growth of different genotypes. Furthermore, the results indicated that the meat processing environment contributes to L. gasicomitatum contamination as certain genotypes were repeatedly identified from products of the same processing plant. Finally, the sequenced and annotated genome of L.gasicomitatum LMG 18811 allowed us to identify the metabolic pathways and reactions resulting in food spoilage.

Identifying Genetic Risk Factors in Canine Autoimmune Disorders

Autoimmune diseases are more common in dogs than in humans and are already threatening the future of some highly predisposed dog breeds. Susceptibility to autoimmune diseases is controlled by environmental and genetic factors, especially the major histocompatibility complex (MHC) gene region. Dogs show a similar physiology, disease presentation and clinical response as humans, making them an excellent disease model for autoimmune diseases common to both species. The genetic background of canine autoimmune disorders is largely unknown, but recent annotation of the dog genome and subsequent development of new genomic tools offer a unique opportunity to map novel autoimmune genes in various breeds. Many autoimmune disorders show breed-specific enrichment, supporting a strong genetic background. Furthermore, the presence of hundreds of breeds as genetic isolates facilitates gene mapping in complex autoimmune disorders. Identification of novel predisposing genes establishes breeds as models and may reveal novel candidate genes for the corresponding human disorders. Genetic studies will eventually shed light on common biological functions and interactions between genes and the environment. This study aimed to identify genetic risk factors in various autoimmune disorders, including systemic lupus erythematosus (SLE)-related diseases, comprising immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis arteritis (SMRA) as well as Addison s disease (AD) in Nova Scotia Duck Tolling Retrievers (NSDTRs) and chronic superficial keratitis (CSK) in German Shepherd dogs (GSDs). We used two different approaches to identify genetic risk factors. Firstly, a candidate gene approach was applied to test the potential association of MHC class II, also known as a dog leukocyte antigen (DLA) in canine species. Secondly, a genome-wide association study (GWAS) was performed to identify novel risk loci for SLE-related disease and AD in NSDTRs. We identified DLA risk haplotypes for an IMRD subphenotype of SLE-related disease, AD and CSK, but not in SMRA, and show that the MHC class II gene region is a major genetic risk factor in canine autoimmune diseases. An elevated risk was found for IMRD in dogs that carried the DLA-DRB1*00601/DQA1*005011/DQB1*02001 haplotype (OR = 2.0, 99% CI = 1.03-3.95, p = 0.01) and for ANA-positive IMRD dogs (OR = 2.3, 99% CI = 1.07-5.04, p-value 0.007). We also found that DLA-DRB1*01502/DQA*00601/DQB1*02301 haplotype was significantly associated with AD in NSDTRs (OR = 2.1, CI = 1.0-4.4, P = 0.044) and the DLA-DRB1*01501/DQA1*00601/DQB1*00301 haplotype with the CSK in GSDs (OR=2.67, CI=1.17-6.44, p= 0.02). In addition, we found that homozygosity for the risk haplotype increases the risk for each disease phenotype and that an overall homozygosity for the DLA region predisposes to CSK and AD. Our results have enabled the development of genetic tests to improve breeding practices by avoiding the production of puppies homozygous for risk haplotypes. We also performed the first successful GWAS for a complex disease in dogs. With less than 100 cases and 100 controls, we identified five risk loci for SLE-related disease and AD and found strong candidate genes involved in a novel T-cell activation pathway. We show that an inbred dog population has fewer risk factors, but each of them has a stronger genetic risk. Ongoing studies aim to identify the causative mutations and bring new knowledge to help diagnostics, treatment and understanding of the aetiology of SLE-related diseases.