@article{gookin_holmes_clarke_stauffer_meredith_vandewege_torres-machado_friedenberg_seiler_mathews_et al._2024, title={Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder}, volume={327}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00145.2024}, abstractNote={Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.}, number={4}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, Jody L. and Holmes, Jenny and Clarke, Lane L. and Stauffer, Stephen H. and Meredith, Bryanna and Vandewege, Michael W. and Torres-Machado, Nicole and Friedenberg, Steven G. and Seiler, Gabriela S. and Mathews, Kyle G. and et al.}, year={2024}, month={Oct}, pages={G513–G530} }
 @article{meurs_montgomery_friedenberg_williams_gilger_2021, title={A defect in the NOG gene increases susceptibility to spontaneous superficial chronic corneal epithelial defects (SCCED) in boxer dogs}, volume={17}, ISSN={1746-6148}, url={http://dx.doi.org/10.1186/s12917-021-02955-1}, DOI={10.1186/s12917-021-02955-1}, abstractNote={Abstract
                Background
                Superficial chronic corneal epithelial defects (SCCEDs) are spontaneous corneal defects in dogs that share many clinical and pathologic characteristics to recurrent corneal erosions (RCE) in humans. Boxer dogs are predisposed to SCCEDs, therefore a search for a genetic defect was performed to explain this susceptibility. DNA was extracted from blood collected from Boxer dogs with and without SCCEDs followed by whole genome sequencing (WGS). RNA sequencing of corneal tissue and immunostaining of corneal sections from affected SCCED Boxer dogs with a deletion in the NOG gene and affected non-Boxer dogs without the deletion were performed.
              
                Results
                A 30 base pair deletion at a splice site in Noggin (NOG) (Chr 9:31453999) was identified by WGS and was significantly associated (P < 0.0001) with Boxer SCCEDs compared to unaffected non-Boxer dogs. NOG, BMP4, MMP13, and NCAM1 all had significant fold reductions in expression and SHH was significantly increased in Boxers with the NOG deletion as identified by RNA-Seq. Corneal IHC from NOG deletion dogs with SCCEDs had lower NOG and significantly higher scores of BMP2.
              
                Conclusions
                Many Boxer dogs with SCCED have a genetic defect in NOG. NOG is a constitutive protein in the cornea which is a potent inhibitor of BMP, which likely regulate limbal epithelial progenitor cells (LEPC). Dysregulation of LEPC may play a role in the pathogenesis of RCE.
              }, number={1}, journal={BMC Veterinary Research}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Montgomery, Keith and Friedenberg, Steven G. and Williams, Brian and Gilger, Brian C.}, year={2021}, month={Jul} }
 @article{meurs_williams_deprospero_friedenberg_malarkey_ezzell_keene_adin_defrancesco_tou_2021, title={A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat}, volume={16}, ISSN={["1750-1172"]}, DOI={10.1186/s13023-021-01740-5}, abstractNote={Abstract
                Background
                Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation.

              
                Results
                A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001).

              
                Conclusion
                This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy.
              }, number={1}, journal={ORPHANET JOURNAL OF RARE DISEASES}, author={Meurs, Kathryn M. and Williams, Brian G. and DeProspero, Dylan and Friedenberg, Steven G. and Malarkey, David E. and Ezzell, J. Ashley and Keene, Bruce W. and Adin, Darcy B. and DeFrancesco, Teresa C. and Tou, Sandra}, year={2021}, month={Feb} }
 @article{hedgespeth_birkenheuer_friedenberg_olby_meurs_2021, title={A novel missense mutation of the NAT10 gene in a juvenile Schnauzer dog with chronic respiratory tract infections}, volume={35}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16100}, DOI={10.1111/jvim.16100}, abstractNote={AbstractAn 18‐month‐old intact male Schnauzer dog was evaluated for chronic, lifelong respiratory tract infections that were unresponsive to administration of a variety of antibiotics and corticosteroids. The dog developed persistent vomiting and diarrhea around 1 year of age that was minimally responsive to diet change, antibiotics, and corticosteroids. Despite supportive care, the dog was ultimately euthanized at 20 months of age due to persistent respiratory and gastrointestinal disease. Whole genome sequencing discovered a deleterious missense A/C mutation within the NAT10 gene, a gene essential for microtubule acetylation, appropriate ciliary development, and cytokinesis. Pipeline analysis of the genomes of 579 dogs from 55 breeds did not detect this mutation. Though never described in veterinary medicine, NAT10 mutation occurs in humans with ciliary aplasia, suggesting a pathophysiological mechanism for this dog and highlighting an associated mutation or possible novel genetic cause of chronic respiratory infections in dogs.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hedgespeth, Barry A. and Birkenheuer, Adam J. and Friedenberg, Steven G. and Olby, Natasha J. and Meurs, Kathryn M.}, year={2021}, month={May}, pages={1542–1546} }
 @article{herrmann_linder_meurs_friedenberg_cullen_olby_bizikova_2021, title={Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12972}, DOI={10.1111/vde.12972}, abstractNote={BackgroundJunctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone.ObjectivesTo characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant.AnimalsFive of eight puppies in an Australian cattle dog cross‐bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing.Methods and materialsPost‐mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.ResultsClinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post‐mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3‐chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance.Conclusions and clinical relevanceA novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Linder, Keith E. and Meurs, Kathryn M. and Friedenberg, Steven G. and Cullen, Jonah and Olby, Natasha and Bizikova, Petra}, year={2021}, month={Aug}, pages={379-+} }
 @article{williams_friedenberg_keene_tou_defrancesco_meurs_2021, title={Use of whole genome analysis to identify shared genomic variants across breeds in canine mitral valve disease}, volume={6}, ISSN={["1432-1203"]}, DOI={10.1007/s00439-021-02297-w}, abstractNote={Familial mitral valve prolapse in human beings has been associated with several genetic variants; however, in most cases, a known variant has not been identified. Dogs also have a naturally occurring form of familial mitral valve disease (MMVD) with similarities to the human disease. A shared genetic background and clinical phenotype of this disease in some dog breeds has indicated that the disease may share a common genetic cause. We evaluated DNA from 50 affected dogs from five different dog breeds in a whole genome sequencing approach to identify shared variants across and within breeds that could be associated with MMVD. No single causative genetic mutation was found from the 50 dogs with MMVD. Ten variants were identified in 37/50 dogs around and within the MED13L gene. These variants were no longer associated with MMVD when evaluated with a larger cohort including both affected and unaffected dogs. No high/moderate impact variants were identified in 10/10 miniature poodles, one was identified in 10/10 Yorkshire Terriers and 10/10 dachshunds, respectively, 14 were identified in 10/10 Miniature schnauzers, and 19 in 10/10 CKCS. Only one of these could be associated with the cardiac valve (Chr12:36801705, COL12A1; CKCS) but when evaluated in an additional 100 affected CKCS the variant was only identified in 84/100 affected dogs, perhaps indicating genetic heterogeneity in this disease. Our findings indicate that development of MMVD in the dog may be related to a combination of genetic and environmental factors that impact specific molecular pathways rather than a single shared genetic variant across or within breeds.}, journal={HUMAN GENETICS}, author={Williams, Brian and Friedenberg, Steven G. and Keene, Bruce W. and Tou, Sandy P. and DeFrancesco, Teresa C. and Meurs, Kathryn M.}, year={2021}, month={Jun} }
 @article{olby_friedenberg_meurs_deprospero_guevar_lau_yost_guo_shelton_2020, title={A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels}, volume={30}, ISSN={0960-8966}, url={http://dx.doi.org/10.1016/j.nmd.2020.02.021}, DOI={10.1016/j.nmd.2020.02.021}, abstractNote={The purpose of this study was to report the findings of clinical and genetic evaluation of a 3-month old male Boykin spaniel (the proband) that presented with progressive weakness. The puppy underwent a physical and neurological examination, serum biochemistry and complete blood cell count, electrophysiological testing, muscle biopsy and whole genome sequencing. Clinical evaluation revealed generalized neuromuscular weakness with tetraparesis and difficulty holding the head up and a dropped jaw. There was diffuse spontaneous activity on electromyography, most severe in the cervical musculature. Nerve conduction studies were normal, the findings were interpreted as consistent with a myopathy. Skeletal muscle was grossly abnormal on biopsy and there were necklace fibers and abnormal triad structure localization on histopathology, consistent with myotubular myopathy. Whole genome sequencing revealed a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). The puppy was humanely euthanized at 5 months of age. The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant. This naturally occurring mutation in Boykin spaniels causes a severe form of X-linked myotubular myopathy, comparable to the human counterpart.}, number={5}, journal={Neuromuscular Disorders}, publisher={Elsevier BV}, author={Olby, Natasha J. and Friedenberg, Steven and Meurs, Kathryn and DeProspero, Dylan and Guevar, Julien and Lau, Jeanie and Yost, Oriana and Guo, Ling T. and Shelton, G. Diane}, year={2020}, month={Mar}, pages={353–359} }
 @article{meurs_friedenberg_kolb_saripalli_tonino_woodruff_olby_keene_adin_yost_et al._2019, title={A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death}, volume={138}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-019-01973-2}, DOI={10.1007/s00439-019-01973-2}, abstractNote={The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.}, number={5}, journal={Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Friedenberg, Steven G. and Kolb, Justin and Saripalli, Chandra and Tonino, Paola and Woodruff, Kathleen and Olby, Natasha J. and Keene, Bruce W. and Adin, Darcy B. and Yost, Oriana L. and et al.}, year={2019}, month={Feb}, pages={515–524} }
 @inproceedings{talley_zimmer_bolotnov_2016, title={Coalescence prevention algorithm for level set method}, DOI={10.1115/fedsm2016-7608}, abstractNote={The application of interface tracking methods to bubbly flow modeling has grown in recent years due to improvements in computing performance and development of more efficient solvers. However, the standard formulation of most interface tracking methods is not designed to physically handle the interface interactions at reasonable grid sizes. Regardless of the method used, a high grid resolution is required in the liquid film region in order to properly model drainage process during bubble interaction, which in certain conditions prevents the coalescence. This makes large scale (many bubbles) simulations unaffordable. One of the popular interface tracking approached is the level-set (LS) method. To simulate realistic bubble coalescence behavior in the LS method an algorithm with the capability of delaying or preventing the process of multiple simultaneous coalescence events has been developed.
               Bubble interaction plays a significant role in high void fraction flow behavior and affects the transition to other flow regimes (e.g. churn-turbulent or slug flows). The described algorithm allows to improve the accuracy of predicting coalescence events in these relevant cases and has been tested in a variety of conditions and computational meshes.
               This novel algorithm uses the LS method field to detect when bubbles are in close proximity, indicating a potential coalescence event, and applies a subgrid scale force to simulate the unresolved liquid drainage force. The subgrid-model is introduced by locally modifying the surface tension force near the liquid film drainage area. The algorithm can also simulate the liquid drainage time of the thin film by controlling the length of time the increased surface tension has been applied. Thus a new method of modeling bubble coalescence has been developed.
               Several test cases were designed to demonstrate the capabilities of the algorithm. The simulations, including a mesh study, confirmed the abilities to identify and prevent coalescence as well as implement the time tracking portion, with an additional 10–25% computational cost. Ongoing tests aim to verify the algorithm’s functionality for simulations with different flow conditions, a ranging number of bubbles, and both structured and unstructured computational mesh types. Specifically, a bubble rising towards a free surface provides a test of performance and demonstrates the ability to consistently prevent coalescence. In addition, a two bubble case and a seven bubble case provide a more complex demonstration of how the algorithm performs for larger simulations. These cases are compared to much more expensive simulations capable of resolving the liquid film drainage (through very high local mesh resolution), to investigate how the algorithm replicates the liquid film drainage process.}, booktitle={Proceedings of the asme fluids engineering division summer meeting, 2016, vol 1b}, author={Talley, M. L. and Zimmer, M. D. and Bolotnov, I. A.}, year={2016} }
 @article{friedenberg_strange_guillaumin_vangundy_crouser_papenfuss_2016, title={Effect of disrupted mitochondria as a source of damage-associated molecular patterns on the production of tumor necrosis factor alpha by splenocytes from dogs}, volume={77}, number={6}, journal={American Journal of Veterinary Research}, author={Friedenberg, S. G. and Strange, H. R. and Guillaumin, J. and VanGundy, Z. C. and Crouser, E. D. and Papenfuss, T. L.}, year={2016}, pages={604–612} }
 @article{friedenberg_meurs_2016, title={Genotype imputation in the domestic dog}, volume={27}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-016-9636-9}, abstractNote={Application of imputation methods to accurately predict a dense array of SNP genotypes in the dog could provide an important supplement to current analyses of array-based genotyping data. Here, we developed a reference panel of 4,885,283 SNPs in 83 dogs across 15 breeds using whole genome sequencing. We used this panel to predict the genotypes of 268 dogs across three breeds with 84,193 SNP array-derived genotypes as inputs. We then (1) performed breed clustering of the actual and imputed data; (2) evaluated several reference panel breed combinations to determine an optimal reference panel composition; and (3) compared the accuracy of two commonly used software algorithms (Beagle and IMPUTE2). Breed clustering was well preserved in the imputation process across eigenvalues representing 75 % of the variation in the imputed data. Using Beagle with a target panel from a single breed, genotype concordance was highest using a multi-breed reference panel (92.4 %) compared to a breed-specific reference panel (87.0 %) or a reference panel containing no breeds overlapping with the target panel (74.9 %). This finding was confirmed using target panels derived from two other breeds. Additionally, using the multi-breed reference panel, genotype concordance was slightly higher with IMPUTE2 (94.1 %) compared to Beagle; Pearson correlation coefficients were slightly higher for both software packages (0.946 for Beagle, 0.961 for IMPUTE2). Our findings demonstrate that genotype imputation from SNP array-derived data to whole genome-level genotypes is both feasible and accurate in the dog with appropriate breed overlap between the target and reference panels.}, number={9-10}, journal={MAMMALIAN GENOME}, author={Friedenberg, S. G. and Meurs, K. M.}, year={2016}, month={Oct}, pages={485–494} }
 @article{friedenberg_brown_meurs_law_2018, title={Lymphocyte Subsets in the Adrenal Glands of Dogs With Primary Hypoadrenocorticism}, volume={55}, ISSN={["1544-2217"]}, DOI={10.1177/0300985816684914}, abstractNote={ Primary hypoadrenocorticism, or Addison’s disease, is an autoimmune condition common in certain dog breeds that leads to the destruction of the adrenal cortex and a clinical syndrome involving anorexia, gastrointestinal upset, and electrolyte imbalances. Previous studies have demonstrated that this destruction is strongly associated with lymphocytic-plasmacytic inflammation and that the lymphocytes are primarily T cells. In this study, we used both immunohistochemistry and in situ hybridization to characterize the T-cell subtypes involved. We collected postmortem specimens of 5 dogs with primary hypoadrenocorticism and 2 control dogs and, using the aforementioned techniques, showed that the lymphocytes are primarily CD4+ rather than CD8+. These findings have important implications for improving our understanding of the pathogenesis and in searching for the underlying causative genetic polymorphisms. }, number={1}, journal={VETERINARY PATHOLOGY}, author={Friedenberg, S. G. and Brown, D. L. and Meurs, K. M. and Law, J. McHugh}, year={2018}, month={Jan}, pages={177–181} }
 @article{friedenberg_chdid_keene_sherry_motsinger-reif_meurs_2016, title={Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.7.693}, abstractNote={Abstract
OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM).
ANIMALS 8 dogs with and 5 dogs without DCM.
PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM.
RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Friedenberg, Steven G. and Chdid, Lhoucine and Keene, Bruce and Sherry, Barbara and Motsinger-Reif, Alison and Meurs, Kathryn M.}, year={2016}, month={Jul}, pages={693–699} }
 @article{meurs_weidman_rosenthal_lahmers_friedenberg_2016, title={Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns}, volume={248}, ISSN={["1943-569X"]}, DOI={10.2460/javma.248.10.1135}, abstractNote={Abstract
OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs.
DESIGN Prospective case series and pedigree investigation.
ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines.
PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed.
RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out.
CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged.}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Meurs, Kathryn M. and Weidman, Jess A. and Rosenthal, Steven L. and Lahmers, Kevin K. and Friedenberg, Steven G.}, year={2016}, month={May}, pages={1135–1138} }
 @article{friedenberg_buhrman_chdid_olby_olivry_guillaumin_o’toole_goggs_kennedy_rose_et al._2015, title={Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs}, volume={68}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-015-0894-6}, DOI={10.1007/s00251-015-0894-6}, abstractNote={Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.}, number={3}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Friedenberg, Steven G. and Buhrman, Greg and Chdid, Lhoucine and Olby, Natasha J. and Olivry, Thierry and Guillaumin, Julien and O’Toole, Theresa and Goggs, Robert and Kennedy, Lorna J. and Rose, Robert B. and et al.}, year={2015}, month={Dec}, pages={205–217} }
 @article{friedenberg_brooks_monnig_cooper_2013, title={Successful treatment of a dog with massive 5-fluorouracil toxicosis}, volume={23}, number={6}, journal={Journal of Veterinary Emergency and Critical Care (San Antonio, Tex. : 2001)}, author={Friedenberg, S. G. and Brooks, A. C. and Monnig, A. A. and Cooper, E. S.}, year={2013}, pages={643–647} }
 @article{friedenberg_meurs_mackay, title={Evaluation of artificial selection in Standard Poodles using whole-genome sequencing}, volume={27}, number={11-12}, journal={Mammalian Genome}, author={Friedenberg, S. G. and Meurs, K. M. and Mackay, T. F. C.}, pages={599–609} }