@article{carlson_wcisel_ackerman_romanet_christiansen_niemuth_williams_breen_stoskopf_dornburg_et al._2022, title={Transcriptome annotation reveals minimal immunogenetic diversity among Wyoming toads, Anaxyrus baxteri}, volume={4}, ISSN={["1572-9737"]}, url={https://doi.org/10.1007/s10592-022-01444-8}, DOI={10.1007/s10592-022-01444-8}, abstractNote={Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes.}, journal={CONSERVATION GENETICS}, author={Carlson, Kara B. and Wcisel, Dustin J. and Ackerman, Hayley D. and Romanet, Jessica and Christiansen, Emily F. and Niemuth, Jennifer N. and Williams, Christina and Breen, Matthew and Stoskopf, Michael K. and Dornburg, Alex and et al.}, year={2022}, month={Apr} }
 @article{peart_williams_pophaly_neely_gulland_adams_ng_cheng_goebel_fedrigo_et al._2021, title={Hi-C scaffolded short- and long-read genome assemblies of the California sea lion are broadly consistent for syntenic inference across 45 million years of evolution}, volume={6}, ISSN={["1755-0998"]}, DOI={10.1111/1755-0998.13443}, abstractNote={AbstractWith the advent of chromatin‐interaction maps, chromosome‐level genome assemblies have become a reality for a wide range of organisms. Scaffolding quality is, however, difficult to judge. To explore this gap, we generated multiple chromosome‐scale genome assemblies of an emerging wild animal model for carcinogenesis, the California sea lion (Zalophus californianus). Short‐read assemblies were scaffolded with two independent chromatin interaction mapping data sets (Hi‐C and Chicago), and long‐read assemblies with three data types (Hi‐C, optical maps and 10X linked reads) following the “Vertebrate Genomes Project (VGP)” pipeline. In both approaches, 18 major scaffolds recovered the karyotype (2n = 36), with scaffold N50s of 138 and 147 Mb, respectively. Synteny relationships at the chromosome level with other pinniped genomes (2n = 32–36), ferret (2n = 34), red panda (2n = 36) and domestic dog (2n = 78) were consistent across approaches and recovered known fissions and fusions. Comparative chromosome painting and multicolour chromosome tiling with a panel of 264 genome‐integrated single‐locus canine bacterial artificial chromosome probes provided independent evaluation of genome organization. Broad‐scale discrepancies between the approaches were observed within chromosomes, most commonly in translocations centred around centromeres and telomeres, which were better resolved in the VGP assembly. Genomic and cytological approaches agreed on near‐perfect synteny of the X chromosome, and in combination allowed detailed investigation of autosomal rearrangements between dog and sea lion. This study presents high‐quality genomes of an emerging cancer model and highlights that even highly fragmented short‐read assemblies scaffolded with Hi‐C can yield reliable chromosome‐level scaffolds suitable for comparative genomic analyses.}, journal={MOLECULAR ECOLOGY RESOURCES}, author={Peart, Claire R. and Williams, Christina and Pophaly, Saurabh D. and Neely, Benjamin A. and Gulland, Frances M. D. and Adams, David J. and Ng, Bee Ling and Cheng, William and Goebel, Michael E. and Fedrigo, Olivier and et al.}, year={2021}, month={Jun} }
 @article{hensley_tang_woodruff_defrancesco_tou_williams_breen_meurs_keene_cheng_et al._2017, title={Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy}, volume={21}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.13077}, DOI={10.1111/jcmm.13077}, abstractNote={AbstractCardiosphere‐derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non‐ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c‐kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, Michael Taylor and Tang, Junnan and Woodruff, Kathleen and Defrancesco, Teresa and Tou, Sandra and Williams, Christina M. and Breen, Mathew and Meurs, Kathryn and Keene, Bruce and Cheng, Ke and et al.}, year={2017}, month={Mar}, pages={1503–1512} }
 @article{santos_dias-pereira_williams_lopes_breen_2017, title={Malignant canine mammary tumours: Preliminary genomic insights using oligonucleotide array comparative genomic hybridisation analysis}, volume={222}, ISSN={["1532-2971"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85017123607&partnerID=MN8TOARS}, DOI={10.1016/j.tvjl.2017.03.005}, abstractNote={Neoplastic mammary disease in female dogs represents a major health concern for dog owners and veterinarians, but the genomic basis of the disease is poorly understood. In this study, we performed high resolution oligonucleotide array comparative genomic hybridisation (oaCGH) to assess genome wide DNA copy number changes in 10 malignant canine mammary tumours from seven female dogs, including multiple tumours collected at one time from each of three female dogs. In all but two tumours, genomic imbalances were detected, with losses being more common than gains. Canine chromosomes 9, 22, 26, 27, 34 and X were most frequently affected. Dissimilar oaCGH ratio profiles were observed in multiple tumours from the same dogs, providing preliminary evidence for probable independent pathogenesis. Analysis of adjacent samples of one tumour revealed regional differences in the number of genomic imbalances, suggesting heterogeneity within tumours.}, journal={VETERINARY JOURNAL}, author={Santos, Marta and Dias-Pereira, Patricia and Williams, Christina and Lopes, Carlos and Breen, Matthew}, year={2017}, month={Apr}, pages={68–71} }
 @article{simmons_dirksen_hildreth_dorr_williams_thomas_breen_toribio_rosol_2014, title={Canine Prostate Cancer Cell Line (Probasco) Produces Osteoblastic Metastases In Vivo}, volume={74}, ISSN={["1097-0045"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84905925151&partnerID=MN8TOARS}, DOI={10.1002/pros.22838}, abstractNote={AbstractBACKGROUNDIn 2012, over 240,000 men were diagnosed with prostate cancer and over 28,000 died from the disease. Animal models of prostate cancer are vital to understanding its pathogenesis and developing therapeutics. Canine models in particular are useful due to their similarities to late‐stage, castration‐resistant human disease with osteoblastic bone metastases. This study established and characterized a novel canine prostate cancer cell line that will contribute to the understanding of prostate cancer pathogenesis.METHODSA novel cell line (Probasco) was derived from a mixed breed dog that had spontaneous prostate cancer. Cell proliferation and motility were analyzed in vitro. Tumor growth in vivo was studied by subcutaneous, intratibial, and intracardiac injection of Probasco cells into nude mice. Tumors were evaluated by bioluminescent imaging, Faxitron radiography, µCT, and histology. RT‐PCR and genome‐wide DNA copy number profiling were used to characterize the cell line.RESULTSThe Probasco cells grew in vitro (over 75 passages) and were tumorigenic in nude mice. Probasco cells expressed high levels of BMP2, CDH1, MYOF, FOLH1, RUNX2, and SMAD5 modest CXCL12, SLUG, and BMP, and no PTHrP mRNA. Following intracardiac injection, Probasco cells metastasized primarily to the appendicular skeleton, and both intratibial and intracardiac injections produced osteoblastic tumors in bone. Comparative genomic hybridization demonstrated numerous DNA copy number aberrations throughout the genome, including large losses and gains in multiple chromosomes.CONCLUSIONSThe Probasco prostate cancer cell line will be a valuable model to investigate the mechanisms of prostate cancer pathogenesis and osteoblastic bone metastases. Prostate 74: 1251–1265, 2014. © 2014 Wiley Periodicals, Inc.}, number={13}, journal={PROSTATE}, author={Simmons, Jessica K. and Dirksen, Wessel P. and Hildreth, Blake E., III and Dorr, Carlee and Williams, Christina and Thomas, Rachael and Breen, Matthew and Toribio, Ramiro E. and Rosol, Thomas J.}, year={2014}, month={Sep}, pages={1251–1265} }
 @article{sanderson_norman_guethlein_ellis_williams_breen_park_magee_babrzadeh_warry_et al._2014, title={Definition of the Cattle Killer Cell Ig-like Receptor Gene Family: Comparison with Aurochs and Human Counterparts}, volume={193}, ISSN={["1550-6606"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84916894960&partnerID=MN8TOARS}, DOI={10.4049/jimmunol.1401980}, abstractNote={Abstract
               Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle.}, number={12}, journal={JOURNAL OF IMMUNOLOGY}, author={Sanderson, Nicholas D. and Norman, Paul J. and Guethlein, Lisbeth A. and Ellis, Shirley A. and Williams, Christina and Breen, Matthew and Park, Steven D. E. and Magee, David A. and Babrzadeh, Farbod and Warry, Andrew and et al.}, year={2014}, month={Dec}, pages={6016–6030} }
 @article{ito_frantz_williams_thomas_burnett_avery_breen_mason_timothy d. o'brien_modiano_2012, title={CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies}, volume={53}, ISSN={["1042-8194"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84862743178&partnerID=MN8TOARS}, DOI={10.3109/10428194.2011.654337}, abstractNote={Abstract Established cell lines are utilized extensively to study tumor biology and preclinical therapeutic development. However, they may not accurately recapitulate the heterogeneity of their corresponding primary disease. B-cell tumor cells are especially difficult to maintain under conventional culture conditions, limiting access to samples that faithfully represent this disease for preclinical studies. Here, we used primary canine diffuse large B-cell lymphoma to establish a culture system that reliably supports the growth of these cells. CD40 ligand, either expressed by feeder cells or provided as a soluble two-trimeric form, was sufficient to support primary lymphoma cells in vitro. The tumor cells retained their original phenotype, clonality and known karyotypic abnormalities after extended expansion in culture. Finally, we illustrate the utility of the feeder cell-free culture system for comparable assessment of cytotoxicity using dog and human B-cell malignancies. We conclude that this system has broad applications for in vitro preclinical development for B-cell malignancies.}, number={7}, journal={LEUKEMIA & LYMPHOMA}, author={Ito, Daisuke and Frantz, Aric M. and Williams, Christina and Thomas, Rachael and Burnett, Robert C. and Avery, Anne C. and Breen, Matthew and Mason, Nicola J. and Timothy D. O'Brien and Modiano, Jaime F.}, year={2012}, month={Jul}, pages={1390–1398} }
 @article{dhakal_maltecca_cassady_baloche_williams_washburn_2013, title={Calf birth weight, gestation length, calving ease, and neonatal calf mortality in Holstein, Jersey, and crossbred cows in a pasture system}, volume={96}, ISSN={["0022-0302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84871620780&partnerID=MN8TOARS}, DOI={10.3168/jds.2012-5817}, abstractNote={Holstein (HH), Jersey (JJ), and crosses of these breeds were mated to HH or JJ bulls to form purebreds, reciprocal crosses, backcrosses, and other crosses in a rotational mating system. The herd was located at the Center for Environmental Farming Systems in Goldsboro, North Carolina. Data for calf birth weight (CBW), calving ease (0 for unassisted, n=1,135, and 1 for assisted, n=96), and neonatal calf mortality (0 for alive, n=1,150, and 1 for abortions recorded after mid-gestation, stillborn, and dead within 48 h, n=81) of calves (n=1,231) were recorded over 9 calving seasons from 2003 through 2011. Gestation length (GL) was calculated as the number of days from last insemination to calving. Linear mixed models for CBW and GL included fixed effects of sex, parity (first vs. later parities), twin status, and 6 genetic groups: HH, JJ, reciprocal F(1) crosses (HJ, JH), crosses >50% Holsteins (HX) and crosses >50% Jerseys (JX), where sire breed is listed first. The CBW model also included GL as a covariate. Logistic regression for calving ease and neonatal calf mortality included fixed effects of sex, parity, and genetic group. Genetic groups were replaced by linear regression using percentage of HH genes as coefficients on the above models and included as covariates to determine various genetic effects. Year and dam were included as random effects in all models. Female calves (27.57±0.54 kg), twins (26.39±1.0 kg), and calves born to first-parity cows (27.67±0.56 kg) had lower CBW than respective male calves (29.53±0.53 kg), single births (30.71±0.19 kg), or calves born to multiparous cows (29.43±0.52 kg). Differences in genetic groups were observed for CBW and GL. Increased HH percentage in the calf increased CBW (+9.3±0.57 kg for HH vs. JJ calves), and increased HH percentage in the dams increased CBW (+1.71±0.53 kg for calves from HH dams vs. JJ dams); JH calves weighed 1.33 kg more than reciprocal HJ calves. Shorter GL was observed for twin births (272.6±1.1 d), female calves (273.9±0.6 d), and for first-parity dams (273.8±0.6 d). Direct genetic effects of HH alleles shortened GL (-3.5±0.7 d), whereas maternal HH alleles increased GL (2.7±0.6 d). Female calves had lower odds ratio (0.32, confidence interval=0.10-0.99) for neonatal calf mortality in second and later parities than did male calves. Maternal heterosis in crossbred primiparous dams was associated with reduced calf mortality.}, number={1}, journal={JOURNAL OF DAIRY SCIENCE}, author={Dhakal, K. and Maltecca, C. and Cassady, J. P. and Baloche, G. and Williams, C. M. and Washburn, S. P.}, year={2013}, month={Jan}, pages={690–698} }
 @article{thudi_shu_martin_lanigan_nadella_van bokhoven_werbeck_simmons_murahari_kisseberth_et al._2011, title={Development of a Brain Metastatic Canine Prostate Cancer Cell Line}, volume={71}, ISSN={["1097-0045"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79960740604&partnerID=MN8TOARS}, DOI={10.1002/pros.21341}, abstractNote={AbstractBACKGROUNDProstate cancer in men has a high mortality and morbidity due to metastatic disease. The pathobiology of prostate cancer metastasis is not well understood and cell lines and animal models that recapitulate the complex nature of the disease are needed. Therefore, the goal of the study was to establish and characterize a new prostate cancer line derived from a dog with spontaneous prostate cancer.METHODSA new cell line (Leo) was derived from a dog with spontaneous prostate cancer. Immunohistochemistry and PCR were used to characterize the primary prostate cancer and xenografts in nude mice. Subcutaneous tumor growth and metastases in nude mice were evaluated by bioluminescent imaging, radiography and histopathology. In vitro chemosensitivity of Leo cells to therapeutic agents was measured.RESULTSLeo cells expressed the secretory epithelial cytokeratins (CK)8, 18, and ductal cell marker, CK7. The cell line grew in vitro (over 75 passages) and was tumorigenic in the subcutis of nude mice. Following intracardiac injection, Leo cells metastasized to the brain, spinal cord, bone, and adrenal gland. The incidence of metastases was greatest to the central nervous system (80%) with a lower incidence to bone (20%) and the adrenal glands (16%). In vitro chemosensitivity assays demonstrated that Leo cells were sensitive to Velcade and an HDAC‐42 inhibitor with IC50 concentrations of 1.9 nm and 0.95 µm, respectively.CONCLUSIONThe new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases. Prostate 71:1251–1263, 2011. © 2011 Wiley‐Liss, Inc.}, number={12}, journal={PROSTATE}, author={Thudi, Nanda K. and Shu, Sherry T. and Martin, Chelsea K. and Lanigan, Lisa G. and Nadella, Murali V. P. and Van Bokhoven, Adrie and Werbeck, Jillian L. and Simmons, Jessica K. and Murahari, Sridhar and Kisseberth, William C. and et al.}, year={2011}, month={Sep}, pages={1251–1263} }
 @article{cardona_milner_alleman_williams_vernau_breen_tompkins_2011, title={BCR-ABL translocation in a dog with chronic monocytic leukemia}, volume={40}, ISSN={["0275-6382"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952244126&partnerID=MN8TOARS}, DOI={10.1111/j.1939-165x.2010.00277.x}, abstractNote={Abstract:A 9‐year‐old female spayed mixed breed dog was evaluated at the University of Florida Small Animal Hospital for marked leukocytosis with no associated clinical signs. CBC abnormalities included marked leukocytosis (106,000/μL), marked monocytosis (78,000/μL), and the presence of 13% blast cells (13,832/μL), supporting a diagnosis of leukemia. Cytopenias and dysplastic changes in other cell lines were not present. Microscopic examination of bone marrow showed hypercellular uniparticles with a marginal increase in frequency of unclassified blast cells (2%), but was otherwise unremarkable. Flow cytometric immunophenotyping of blood cells determined that leukemic cells were CD45+, CD14+, and CD34–, and based on side scatter and CD45 reactivity the marrow contained 19% monoblasts. By immunocytochemical staining, the leukemic cells in the bone marrow were CD11b+, CD11c+, CD11d+, MHC‐II+, MPO+, and CD34–. Fluorescence in situ hybridization (FISH) analysis of peripheral blood leukocytes documented a chromosomal translocation producing a BCR‐ABL gene hybrid, similar to the “Philadelphia” chromosome abnormality recognized in human chronic myelogenous leukemia, as well as a phosphatase and tensin homolog (PTEN) gene deletion. Hydroxyurea therapy was attempted, but was ineffective; the dog died 7 months after initial presentation. Clinical and laboratory findings and the protracted course supported a diagnosis of chronic monocytic leukemia (CMoL) and, to our knowledge, this is the first case of CMoL with a BCR‐ABL chromosomal abnormalitiy described in dogs. This may have clinical implications for treatment of dogs with chronic leukemias associated with particular genetic mutations. However, more case studies are needed to further characterize this disease.}, number={1}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Cardona, Janice A. Cruz and Milner, Rowan and Alleman, A. Rick and Williams, Christina and Vernau, William and Breen, Matthew and Tompkins, Mary}, year={2011}, month={Mar}, pages={40–47} }
 @article{palkopoulou_lipson_mallick_nielsen_rohland_baleka_karpinski_ivancevici_to_kortschak_et al., title={A comprehensive genomic history of extinct and living elephants}, volume={115}, number={11}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Palkopoulou, E. and Lipson, M. and Mallick, S. and Nielsen, S. and Rohland, N. and Baleka, S. and Karpinski, E. and Ivancevici, A. M. and To, T. H. and Kortschak, D. and et al.}, pages={E2566–2574} }
 @article{tonomura_elvers_thomas_megquier_turner-maier_howald_sarver_swofford_frantz_ito_et al., title={Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers}, volume={11}, number={2}, journal={PLoS Genetics}, author={Tonomura, N. and Elvers, I. and Thomas, R. and Megquier, K. and Turner-Maier, J. and Howald, C. and Sarver, A. L. and Swofford, R. and Frantz, A. M. and Ito, D. and et al.} }
 @article{alfoldi_di palma_grabherr_williams_kong_mauceli_russell_lowe_glor_jaffe_et al., title={The genome of the green anole lizard and a comparative analysis with birds and mammals}, volume={477}, number={7366}, journal={Nature}, author={Alfoldi, J. and Di Palma, F. and Grabherr, M. and Williams, C. and Kong, L. S. and Mauceli, E. and Russell, P. and Lowe, C. B. and Glor, R. E. and Jaffe, J. D. and et al.}, pages={587–591} }
 @article{green_braun_armstrong_earl_nguyen_hickey_vandewege_st john_capella-gutierrez_castoe_et al., title={Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs}, volume={346}, number={6215}, journal={Science}, author={Green, R. E. and Braun, E. L. and Armstrong, J. and Earl, D. and Nguyen, N. and Hickey, G. and Vandewege, M. W. and St John, J. A. and Capella-Gutierrez, S. and Castoe, T. A. and et al.}, pages={1335-} }