Life Sciences Commons^™

Identifying Glioblastoma Gene Networks Based On Hypergeometric Test Analysis, Vasileios Stathias, Chiara Pastori, Tess Z. Griffin, Ricardo Komotar, Jennifer L. Clarke, Ming Zhang, Nagi G. Ayad

Department of Statistics: Faculty Publications

Patient specific therapy is emerging as an important possibility for many cancer patients. However, to identify such therapies it is essential to determine the genomic and transcriptional alterations present in one tumor relative to control samples. This presents a challenge since use of a single sample precludes many standard statistical analysis techniques. We reasoned that one means of addressing this issue is by comparing transcriptional changes in one tumor with those observed in a large cohort of patients analyzed by The Cancer Genome Atlas (TCGA). To test this directly, we devised a bioinformatics pipeline to identify differentially expressed genes in …

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we …

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of …

Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong

Katherine A. Fitzgerald

Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1beta, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1beta. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, …

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli

Katherine A. Fitzgerald

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …

Draft Genome Sequence Of New Bacillus Cereus Strain Tsu1, Hui Li, Suping Zhou, Terrance Johnson, Koen Vercruysse, Alexander J. Ropelewski, Theodore W. Thannhauser

Agricultural and Environmental Sciences Faculty Research

This paper reports the draft genome sequence of new Bacillus cereus strain tsu1, isolated on an agar-cellulose plate. The draft genome sequence is 5.81 Mb, revealing 5,673 coding sequences. It contains genes for cellulose-degradation and biosynthesis pathways of polyhydroxybutyrate (PHB) and 8 rRNA genes (5S, 16S, and 23S).

Comparative Population Genetics And Evolutionary History Of Two Commonly Misidentified Billfishes Of Management And Conservation Concern, Andrea M. Bernard, Mahmood S. Shivji, Eric Prince, Fabio H.V. Hazin, Freddy Arocha, Andres Domingo, Kevin A. Feldheim

Marine & Environmental Sciences Faculty Articles

Background: Misidentifications between exploited species may lead to inaccuracies in population assessments, with potentially irreversible conservation ramifications if overexploitation of either species is occurring. A notable showcase is provided by the realization that the roundscale spearfish (Tetrapturus georgii), a recently validated species, has been historically misidentified as the morphologically very similar and severely overfished white marlin (Kajikia albida) (IUCN listing: Vulnerable). In effect, no information exists on the population status and evolutionary history of the enigmatic roundscale spearfish, a large, highly vagile and broadly distributed pelagic species. We provide the first population genetic evaluation of the …

Profile Of The Unfolded Protein Response In C. Elegans Depleted Of The Translational Chaperone, Nac., Caylin S. Murray

Masters Theses, 2010-2019

The function of a protein is a direct consequence of its final structure, which is achieved by protein-folding processes that generate a tertiary state through the juxtaposition of locally formed secondary structures. Because all cells need functional proteins to survive, each contains robust and redundant mechanisms that regulate the folding of newly forming proteins, and the refolding of misfolded proteins that are often generated during stress. Essential to these mechanisms, chaperones are proteins that aid in protein folding of nascent and misfolding protein without being incorporated in the final structure. One chaperone complex, the nascent polypeptide-associated complex (NAC), aids in …

Inheritance Of Virulence In The Root Rot Pathogen Phytophthora Sojae, Sirjana Devi Shrestha

Electronic Thesis and Dissertation Repository

The oomycete Phytophthora sojae causes stem and root rot of soybean plants. The interaction of pathogen avirulence (Avr) and host resistance (R)-genes determine the disease outcome. The Avr3a mRNA transcript level is variable among P. sojae strains and determines virulence towards the R-gene Rps3a. To study the inheritance of virulence, genetic crosses and self-fertilizations were performed. A cross between P. sojae strains ACR10 and P7076 causes transgenerational gene silencing of Avr3a allele, and this effect is meiotically stable up to the F₅ generation. However, test-crosses of F₁ (Avr3a^ACR10/Avr3a …

Transcriptomic And Proteomic Dynamics In The Metabolism Of A Diazotrophic Cyanobacterium, Cyanothece Sp. Pcc 7822 During A Diurnal Light-Dark Cycle, Louis Sherman

Louis A Sherman

Background: Cyanothece sp. PCC 7822 is an excellent cyanobacterial model organism with great potential to be applied as a biocatalyst for the production of high value compounds. Like other unicellular diazotrophic cyanobacterial species, it has a tightly regulated metabolism synchronized to the light-dark cycle. Utilizing transcriptomic and proteomic methods, we were able to quantify the relationships between transcription and translation underlying central and secondary metabolism in response to nitrogen free, 12 hour light and 12 hour dark conditions.

Results: By combining mass-spectrometry based proteomics and RNA-sequencing transcriptomics, we quantitatively measured a total of 6766 mRNAs and 1322 proteins at four …

The Birds Of Genome10k, Stephen J. O'Brien, David Haussler, Oliver A. Ryder

Biology Faculty Articles

Everyone loves the birds of the world. From their haunting songs and majesty of flight to dazzling plumage and mating rituals, bird watchers – both amateurs and professionals - have marveled for centuries at their considerable adaptations. Now, we are offered a special treat with the publication of a series of papers in dedicated issues of Science, Genome Biology and GigaScience (which also included pre-publication data release). These present the successful beginnings of an international interdisciplinary venture, the Avian Phylogenomics Project that lets us view, through a genomics lens, modern bird species and the evolutionary events that produced them.

Comparative Genome Analyses Reveal Distinct Structure In The Saltwater Crocodile Mhc., Weerachai Jaratlerdsiri, Janine Deakin, Ricardo M. Godinez, Xueyan Shan, Daniel G. Peterson, Sylvain Marthey, Eric Lyons, Fiona M. Mccarthy, Sally R. Isberg, Damien P. Higgins, Amanda Y. Chong, John St. John, Travis C. Glenn, David A. Ray, Jaime Gongora

College of Agriculture & Life Sciences Publications and Scholarship

The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters …

Regulation Of Three Nitrogenase Gene Clusters In The Cyanobacterium Anabaena Variabilis Atcc 29413, Teresa Thiel, Brenda Pratte

Biology Department Faculty Works

The filamentous cyanobacterium Anabaena variabilis ATCC 29413 fixes nitrogen under aerobic conditions in specialized cells called heterocysts that form in response to an environmental deficiency in combined nitrogen. Nitrogen fixation is mediated by the enzyme nitrogenase, which is very sensitive to oxygen. Heterocysts are microxic cells that allow nitrogenase to function in a filament comprised primarily of vegetative cells that produce oxygen by photosynthesis. A. variabilis is unique among well-characterized cyanobacteria in that it has three nitrogenase gene clusters that encode different nitrogenases, which function under different environmental conditions. The nif1 genes encode a Mo-nitrogenase that functions only in heterocysts, …

Regulation Of Three Nitrogenase Gene Clusters In The Cyanobacterium Anabaena Variabilis Atcc 29413, Teresa Thiel, Brenda S. Pratte

Teresa Thiel

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Dprp: A Database Of Phenotype-Specific Regulatory Programs Derived From Transcription Factor Binding Data, David T. W. Tzeng, Yu-Ting Tseng, Matthew Ung, I-En Liao, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Gene expression profiling has been extensively used in the past decades, resulting in an enormous amount of expression data available in public databases. These data sets are informative in elucidating transcriptional regulation of genes underlying various biological and clinical conditions. However, it is usually difficult to identify transcription factors (TFs) responsible for gene expression changes directly from their own expression, as TF activity is often regulated at the posttranscriptional level. In recent years, technical advances have made it possible to systematically determine the target genes of TFs by ChIP-seq experiments. To identify the regulatory programs underlying gene expression profiles, we …

Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li

Electronic Thesis and Dissertation Repository

BRAHMA (BRM) is a SWI/SNF-type chromatin remodeling ATPase that plays an important role in regulation of gene expression. Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a histone modification that is associated with transcriptionally repressed genes and catalyzed by Polycomb Group (PcG) proteins. BRM has been proposed to antagonize the function of PcG proteins but the underlying molecular mechanism is unclear. To understand how BRM regulates the function of PcG proteins during plant development, a genome-wide analysis of H3K27me3 in brm mutant was performed using chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Loss of BRM leads to increased …

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions …

Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood

Doctoral Dissertations

Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …

Suppression Of Neurodegenerative Symptoms Via Suppressor Of Levy Mutation In Drosophila Melanogaster, William Kaputa

Forensic Science Theses

Mutation of the levy gene on chromosome 2 of Drosophila melanogaster has previously been shown to cause temperature-induced paralysis and neurodegeneration. The Suppressor of levy mutation, Su(levy), also on chromosome 2, modulates the effects of the levy mutation and partly rescues the wild-type phenotype. The goal of this research was to determine if Su(levy) mutation alleviates the effects of neurodegeneration caused by mutations associated with Alzheimer’s and Parkinson’s diseases in humans. The mutant genes used were hLRRK2, α-Synuclein, DJ1-α, Pink, Parkin, and Aβ-42. To determine this, flies carrying the above-mentioned mutant genes were …

Genetic Structure Of Yellow Perch Populations In Coastal Areas Of Eastern Lake Michigan, Jessica N. Wesolek

Masters Theses

Genetic population substructure is often overlooked because of discontinuities between management and actual population structure as in the case of yellow perch, an ecologically and economically important indigenous fish species in the Laurentian Great Lakes. A knowledge gaps pertaining to the natural history of yellow perch relates to the biological connectivity between nearshore Lake Michigan and drowned river mouth (DRM) lakes, where it remains unclear whether resident yellow perch from Lake Michigan use DRM lakes for spawning or whether DRM lakes contribute to nearshore yellow perch populations in Lake Michigan. I used DNA fingerprinting (genotyping) to explore biological connectivity between …

Comparative Genomics Reveals Insights Into Avian Genome Evolution And Adaptation, Guojie Zhang, Cai Li, Qiye Li, Bo Li, Dennis M. Larkin, Chul Lee, Jay F. Storz, Agostinho Antunes, Matthew J. Greenwold, Robert W. Meredith, Anders Ödeen, Jie Cui, Qi Zhou, Luohao Xu, Hailin Pan, Zongji Wang, Lijun Jin, Pei Zhang, Haofu Hu, Wei Yang, Jiang Hu, Jin Xiao, Zhikai Yang, Yang Liu, Qiaolin Xie, Hao Yu, Jinmin Lian, Ping Wen, Fang Zhang, Hui Li, Yongli Zeng, Zijun Xiong, Shiping Liu, Long Zhou, Zhiyong Huang, Na An, Jie Wang, Quimei Zheng, Yingqi Xiong, Guangbiao Wang, Bo Wang, Jingjing Wang, Yu Fan, Rute R. Da Fonseca, Alonzo Alfaro-Núñez, Mikkel Schubert, Ludovic Orlando, Tobias Mourier, Jason T. Howard, Ganeshkumar Ganapathy, Andreas Pfenning, Osceola Whitney, Miriam V. Rivas, Erina Hara, Julia Smith, Marta Farré, Jitendra Narayan, Gancho Slavov, Michael N. Romanov, Rui Borges, João Paulo Machado, Imran Khan, Mark S. Springer, John Gatesy, Federico G. Hoffmann, Juan C. Opazo, Olle Håstad, Roger H. Sawyer, Heebal Kim, Kyu-Won Kim, Hyeon Jeong Kim, Seoae Cho, Ning Li, Yinhua Huang, Michael W. Bruford, Xiangjiang Zhan, Andrew Dixon, Mads F. Bertelsen, Elizabeth Derryberry, Wesley Warren, Richard K. Wilson, Shengbin Li, David A. Ray, Richard E. Green, Stephen J. O'Brien, Darren Griffin, Warren E. Johnson, David Haussler, Oliver A. Ryder, Eske Willerslev, Gary R. Graves, Per Alström, Jon Fjeldså, David P. Mindell, Scott V. Edwards, Edward L. Braun, Carsten Rahbek, David W. Burt, Peter Houde, Yong Zhang, Huanming Yang, Jian Wang, Avian Genome Consortium, Erich D. Jarvis, M. Thomas P. Gilbert, Jun Wang

Jay F. Storz Publications

Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses …

Cloning And Expression Analysis Of Drosophila Extracellular Cu Zn Superoxide Dismutase, Michael J. Blackney, Rebecca Cox, David Shepherd, Joel D. Parker

Joel D Parker

In the present study, we cloned and sequenced the mRNAs of the Sod3 [extracellular Cu Zn SOD (superoxide dismutase)] gene in Drosophila and identified two mRNA products formed by alternative splicing. These products code for a long and short protein derived from the four transcripts found in global expression studies (Flybase numbers Dmel\CG9027, FBgn0033631). Both mRNA process variants contain an extracellular signalling sequence, a region of high homology to the Sod1 (cytoplasmic Cu Zn SOD) including a conserved AUG start, with the longer form also containing a hydrophobic tail. The two fully processed transcripts are homologous to Caenorhabditis elegans Sod3 …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations & Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Novel Protein Secretion And Chitin Utilization Machinery Of Flavobacterium Johnsoniae, Sampada Suresh Kharade

Theses and Dissertations

Flavobacterium johnsoniae, a member of phylum Bacteroidetes, is a gliding bacterium that digests insoluble chitin. A novel protein secretion system, the Type IX secretion system (T9SS), secretes the motility adhesins SprB and RemA and is also required for chitin utilization. In order to understand F. johnsoniae chitin utilization and the role of the T9SS, Fjoh_4555 (chiA) was targeted for analysis. Disruption of chiA resulted in cells that failed to digest chitin and complementation restored this ability. Antisera raised against ChiA were used to characterize its secretion. ChiA was secreted in soluble form by wild-type cells but remained cell-associated in T9SS …

Gene Electro Transfer Of Plasmid Encoding Vascular Endothelial Growth Factor For Enhanced Expression And Perfusion In The Ischemic Swine Heart, Barbara Y. Hargrave, Robert Strange Jr., Sagar Navare, Michael Stratton, Niculina Burcus, Len Murray, Cathryn Lundberg, Anna A. Bulysheva, Fanying Li, Richard Heller

Bioelectrics Publications

Myocardial ischemia can damage heart muscle and reduce the heart's pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone. Higher gene expression was also seen in ischemic versus non-ischemic groups with parameters 20 Volts (p

Review Of "The Pku Paradox: A Short History Of A Genetic Disease" By D. B. Paul And J. P. Brosco, John B. Jenkins

Biology Faculty Works

No abstract provided.

The Conservation Genetics Of Two Emydid Turtles: Emydoidea Blandingii And Malaclemys Terrapin, Charlotte Lizana Petre

Master's Theses

Conservation of turtles is complicated by their sensitivity to habitat degradation and overexploitation. I used microsatellites and standard population genetic analyses to explore genetic diversity, population structure, paternity and demographic history in two emydid turtles that are currently experiencing threats to their survival. The Blanding’s turtle, Emydoidea blandingii, has experienced habitat fragmentation throughout its range, and this study focuses on a population in Massachusetts where hatchlings from one population are being translocated to establish a new population. I found evidence of multiple paternity within clutches and found no significant reduction in genetic diversity when comparing the source population and …

Genetic Dissection Of Neuromuscular Diseases Affecting Domestic Dogs, Caitlin Rinz

All Dissertations

The domestic dog, Canis familiaris, has a unique population structure that lends itself to the study of hereditary diseases. Purebred dogs populations are genetically isolated and as a result are affected by more than 400 naturally occurring diseases, many of which have human counterparts. In the last 15 years, dogs have emerged as a model for the study of human hereditary diseases, fueling the development of resources including a 7.6X coverage reference genome and single nucleotide polymorphism (SNP) genotyping arrays.

Congenital myasthenic syndrome (CMS) is a neuromuscular disorder of both humans and dogs in which transmission across the neuromuscular …