@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={Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by the amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of cystic fibrosis transmembrane conductance regulatory protein (CFTR) in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR were compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR were quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish a significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared with control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for}, 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{vandewege_gutierrez_davis_forstner_mali_2024, title={Patterns of genetic divergence in the Rio Grande cooter (Pseudemys gorzugi), a riverine turtle inhabiting an arid and anthropogenically modified system}, ISSN={["1465-7333"]}, DOI={10.1093/jhered/esae011}, abstractNote={Abstract
               The lower Rio Grande and Pecos River of the southwest United States have been heavily modified by human activities, profoundly impacting the integrity of their aquatic wildlife. In this context, we focused our study on the population genomics of the Rio Grande Cooter (Pseudemys gorzugi), a freshwater turtle of increasing conservation concern, residing in these two rivers and their tributaries. The genetic data revealed two distinct populations: one in the Pecos and Black Rivers of New Mexico and another in the Rio Grande and Devils River of Texas, with admixed individuals identified at the confluence of the Rio Grande and Pecos River. In addition to having a smaller geographic range, we found lower observed heterozygosity, reduced nucleotide diversity, and a smaller effective population size (Ne) in New Mexico population. Our results depict a significant isolation-by-distance pattern across their distribution, with migration being notably infrequent at river confluences. These findings are pivotal for future conservation and restoration strategies, emphasizing the need to recognize the unique needs of each population.}, journal={JOURNAL OF HEREDITY}, author={Vandewege, Michael W. and Gutierrez, Javier and Davis, Drew R. and Forstner, Michael R. J. and Mali, Ivana}, year={2024}, month={Feb} }
 @article{rivas_vandewege_ueda_kaplan_reader_roberts_stern_2024, title={Transcriptomic and genetic profiling in a spontaneous non-human primate model of hypertrophic cardiomyopathy and sudden cardiac death}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-82770-4}, abstractNote={Hypertrophic cardiomyopathy (HCM) afflicts humans, cats, pigs, and rhesus macaques. Disease sequelae include congestive heart failure, thromboembolism, and sudden cardiac death (SCD). Sarcomeric mutations explain some human and cat cases, however, the molecular basis in rhesus macaques remains unknown. RNA-Seq of the LV tissues of five HCM-affected and seven healthy control rhesus macaques was employed for differential transcriptomic analyses. DNA from 15 severely HCM-affected and 21 healthy geriatric rhesus macaques were selected for whole-genome sequencing. A genome-wide association study (GWAS) of disease status and SCD outcome was performed. 614 down- and 1,065 upregulated differentially expressed genes (DEGs) were identified between groups. The top DEG (MAFF) was overexpressed in affected animals (log2FoldChange = 4.71; PAdjusted-value = 1.14E-133). Channelopathy-associated enriched terms were identified in ~ 57% of downregulated DEGs providing transcriptomic evidence of hypertrophic and arrhythmic disease processes. For GWAS, no putative variant withstood segregation. Polygenic modeling analysis resulted in poor prediction power and burden testing could not explain HCM by an association of multiple variants in any gene. Neither single nor compound genetic variant(s), or identified polygenic profile, suggest complex genotype–phenotype interactions in rhesus macaques. Brought forth is an established dataset of robustly phenotyped rhesus macaques as an open-access resource for future cardiovascular disease genetic studies.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rivas, Victor N. and Vandewege, Michael W. and Ueda, Yu and Kaplan, Joanna L. and Reader, Jrachel and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2024}, month={Dec} }
 @article{opazo_vandewege_hoffmann_zavala_melendez_luchsinger_cavieres_vargas-chacoff_morera_burgos_et al._2023, title={How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member}, volume={40}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msad014}, abstractNote={AbstractStudying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.}, number={2}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Opazo, Juan C. and Vandewege, Michael W. and Hoffmann, Federico G. and Zavala, Kattina and Melendez, Catalina and Luchsinger, Charlotte and Cavieres, Viviana A. and Vargas-Chacoff, Luis and Morera, Francisco J. and Burgos, Patricia V and et al.}, year={2023}, month={Feb} }