In 1998 the NEAA Board voted to participate in the AKC/CHF Donor Advised Fund program. Since that time, donations to that fund have been authorized for use toward several research projects. Below is a list of completed, closed and active grants as well as an abstract describing each project.
Grant 01894-A Documentation of disease-causing ticks
Final Report to Grant Sponsor from Investigator:
Many species of Ehrlichia exist, but the most detrimental of these affect canines. Unfortunately, Ehrlichia incidence is increasing in the southeastern United States. The primary approach to Ehrlichiosis prevention is through tick control, which includes application of acaricides to hosts and the habitat. We identified three Ehrlichia species in two species of ticks (A. americanum and I. scapularis) and two Anaplasma species in two tick species (A. americanum and I. scapularis). The most frequently collected ticks on canines, D. variabilis (American dog tick), did not have any Ehrlichia. We then screened all of the collected ticks for Rickettsia and did not identify any pathogenic Rickettsia within those ticks. There was no spatial clustering of Ehrlichia or Rickettsia positive ticks. The identification of pathogenic Ehrlichia and non-pathogenic Rickettsia within two different tick species warrants further investigations to understand the etiological agents and interactions of the vectors responsible for the high incidence of Ehrlichiosis and Rickettsiosis in the region. Such research will improve surveillance and diagnostic protocols, provide insights into improving management practices, and inform the public on how to protect their dogs from ticks and their associated pathogens.
Grant: 01670-A: Pinpointing the causal mutation(s) underlying a genome-wide association signal for hereditary cataract in Northern breeds
Principal Investigator: Dr. Sally L Ricketts, PhD
Research Institution: Animal Health Trust
Report to Grant Sponsor from Investigator:
We have conducted a study to resequence a region of the genome on canine chromosome 18 that we previously found to be statistically associated with hereditary cataract (HC) in Northern, or Arctic, breeds in a genome-wide association study, in order to identify causative mutation(s) for HC in these breeds. We defined HC in these breeds as dogs with cataracts in both eyes located within the posterior polar subcapsular region of the lens. We have used molecular targeted sequencing technology to obtain data for approximately 3.8 million letters of DNA spanning the HC-associated region of the genome in ten Siberian Huskies (five HC cases and five control dogs with clear eyes over the age of 6 years). In this dataset we found over 35,000 variants among the ten dogs and the Boxer reference genome sequence. We devised a computer program to examine the segregation of each variant with HC using both a dominant and recessive genetic model and we found 200 variants that showed perfect segregation with HC in our ten dogs. We excluded variants where the potential 'risk' allele was the same as the Boxer reference genome sequence, as it is unlikely that these would represent causal mutations. This left us with 78 variants that we checked manually against online databases to assess which were within, or very close to, gene coding regions. This confirmed that ten variants were located in gene coding regions. Two of these coding variants were predicted to cause a change in the protein sequence of the gene and were found to be potentially damaging to protein function by analysis of online databases. Furthermore, the non-risk allele was highly conserved among many different animal species, which is additional evidence to suggest that it is important for normal function of the protein. We assessed these two variants in 200 Siberian Huskies, 200 Alaskan Malamutes and 130 Samoyeds and found that one of the variants showed strong statistical association with HC in two of the breeds. However, this variant is very common in both dogs with HC and in older dogs with clear eyes, and doesn't completely account for HC in our samples. It may be that this is a susceptibility variant and there is an environmental component to HC that affects how the genetic susceptibility is expressed, however, before we explore this possibility we are continuing with our analysis of the resequencing data to ensure we have completed a fully comprehensive investigation of the region.
1658: Urinary Protein and Gene Expression Characterization and Comparison with Renal Biopsy Findings and Clinical Data in Dogs with Proteinuric Renal Diseases
Grant Status: Open
Grant Amount: $80,000
Dr. Mary B Nabity, DVM, PhD, Texas A&M University
January 1, 2012 - December 31, 2014
Sponsor(s): Papillon Club of America, Soft Coated Wheaten Terrier Club of America, Inc.
Disease(s): Protein-Losing Nephropathy
Donate to Support this Grant
Primary glomerular diseases are very common causes of chronic kidney disease (CKD), which is a significant source of illness and death in dogs, affecting up to 15% of elderly individuals. Early treatment generally prolongs the lives of dogs with CKD, but timely detection can be difficult and the outcome for each patient based on current, early non-invasive testing is unpredictable. While glomeruli are often the initiating site of kidney disease in dogs, collateral damage to the tubulointerstitium (TI) is important in determining disease severity and progression because of the extensive interplay between these 2 kidney compartments. Evaluations of urinary proteins have enhanced the early identification of TI and glomerular damage and demonstrated prognostic utility in people with CKD. In addition, particular urinary cells (called podocytes) that wash down from damaged glomeruli have been evaluated, with increased podocyte detection indicating greater severity of glomerular damage and thus poorer prognosis for glomerular disease in people. The purpose of this study is to evaluate promising indicators of kidney injury that might improve detection and/or assessment of progression or prognosis in dogs with CKD. We plan to use urine samples from dogs with various kidney diseases to measure: 1) urinary proteins indicating tubular and glomerular damage, and 2) gene expression profiles indicating podocyte loss. Results will be correlated with conventional measures of tubular and glomerular function, kidney biopsy findings, and information regarding disease outcome to determine the utility of the novel tests to non-invasively detect and accurately assess kidney damage in dogs.
Grant 01480: Leptospirosis an emerging concern
Final Report to Grant Sponsor from Investigator:
Leptospirosis is a re-emerging infectious disease of dogs, people, and wildlife. Infected dogs may develop acute renal failure but also multiple-organ failure and even death. This is one of the most commonly diagnosed infectious diseases in dogs at UC Davis. We now have vital information about hot spots for risk of canine leptospirosis as well as epidemiological information including breed and vaccination status for affected dogs, exposure routes, and serovars. Importantly, we demonstrate that small dog breeds are indeed vulnerable to leptospirosis and thus vaccine protocols need to include them. We have ongoing surveillance in these hot spots to detect cases in order to obtain bacterial isolates and critical data on patterns of leptospiral infection in blood and urine. One promising aspect of ongoing research is the interaction of canine and wildlife leptospirosis, and whether some wild animals that may enter yards and suburban landscape could be a source of infection to dogs. Our data to date implicate squirrels and skunks, although other wildlife species or domestic farm animal species may be important sources to dogs even in their home yards. Further molecular characterization of infection will help us understand this linkage. The most important jobs in our to-do for Leptospira research at present are to use molecular techniques to understand dog-wildlife risk and to continue surveillance and use molecular approaches to determine the pathophysiology of infection by west-coast strains of Leptospira in dogs.
Grant no: 386
Report rec'd 10/3/2008 (due 6/30/08)
Title of Grant: Elucidation of the Genetic Defect in Familial Renal Disease in the Norwegian Elkhound
Principal Investigator: Peter Leegwater
Research Institution: University of Utrecht
Start Date : 7/1/2005
Association mapping identified 10 MB genomic region containing 153 genes. The PI has not been able to fine map this region down. Until they can be get more samples and narrow this region down, a mutation is not able to be detected in such a large region.
Only one of the objectives was able to be completed because the other two relied on the success of the first.
The PI plans to continue the research when more samples and employee resources are available.
Completed Grant No: 1663 — Identifying the Genetic Casue of Canine Progressive Rod-cone Dysplasia (PRCD Type of PRA)
Researcher: George J. Brewer, MD – University of Michigan (University)
Researcher: George J. Brewer, MD – University of Michigan (University) Abstract: Using both cloning and DNA sequencing, researchers ruled out five genes (of an identified 31 candidate genes) as the causative gene for Progressive Rod-Cone Disease (PRCD), a form of Progressive Retinal Atrophy, an inherited disease that leads to blindness. With continued research, the cloning and sequencing of the other 26 candidate genes can be completed. Once the genetic cause and mutation are found, direct DNA tests, which are more accurate than linkage tests, can be developed to help breeders make breeding decisions in order to reduce or eliminate this disease. All 31 candidate genes were known to be in the region of the chromosome linked to PRCD by researchers at Cornell.
Completed Grant No: 2012 — Development of PCR Multiplexed Canine Marker Panels for the Purposes of Genome Screening and Linkage Analysis
Researcher: Marcia Eggleston, PhD – University of California, Davis (University)
Abstract: A number of tests have been developed to screen for affected or carrier animals with genetic diseases. The development of many of these tests was possible due to the availability of information regarding similar disorders in humans. The majority of disorders affecting purebred dogs have no known counterpart in humans and therefore no candidate gene. However, an indirect test that screens for a strong association of a microsatellite DNA marker with a disease phenotype can be incorporated in a simple diagnostic test for carriers of that trait. The ultimate goal of the research is to design marker panels containing a minimum of 300 microsatellite markers covering all the linkage groups or chromosomes of the canine genome. The Veterinary Genetics Laboratory has completed panels containing 100 markers with known map locations. This project will incorporate at least 200 additional markers that will then represent the entire canine genome and allow effective screening for linkage or markers to disease gene(s).
Closed Grant No: 2434 — Recombinant Thyrotropin (TSH): Standard for the Next Generation of Canine TSH Immunoassays with Improved Sensitivity
Researcher: Duncan Ferguson, DVM, PhD – University of Georgia (University)
Abstract: Hypothyroidism, a failure of the thyroid gland, is the most common hormonal abnormality in dogs, causing a variety of medical problems in many breeds, including hair loss and skin infections. The measurement of serum levels of the pituitary hormone thyrotropin (TSH) has been used as a reliable and sensitive screening test for ghyroid glandular insufficiency in human medicine for many years, but the first generation assays for canine TSH (cTSH) are missing as many as one out of four cases by hypothyroidism, resulting in no improvement in diagnostic sensitivity compared to total T4 measurement. Furthermore, the available assays have not been sensitive enough to distinguish low values of cTSH from those in the normal range. Towards the goal of improving current and future immunoassay sensitivity based upon a pure recombinant canine TSH(cTSH) hormone standard, our laboratory has succeeded in cloning and sequencing the two peptide subunits of canine TSH and have expressed them in small quantities. Using techniques recently developed in our parallel work on equine TSH, we plan to express and purify recombinant canine TSH in high quantities and validate its use as a pure immunoassay standard to facilitate its worldwide use.
Completed Grant No: 2616 — Molecular Analysis of Contributory Factors of Osteoarthritis in Canine Hip Dysplasia
Researcher: Alpana Ray, PHD – University of Missouri, Columbia (University)
Abstract: Hip Dysplasia is a common disease of dogs that ultimately leads to osteoarthritis (OA), a serious debilitating condition, which at present, is treated by symptomatic management of pain. Accidental injuries also lead to the development of OA. Cartilage degeneration is fundamental to the pathogenesis of OA. We propose to study the transcriptional control of MMP-1, a major enzyme involved in the degradation of articular cartilage. Expression of MMP-1 gene and the corresponding protein is markedly increased under osteoarthritic condition. Because cytokines like IL-1 and TNF increase expression of MMP-1 and biomechanical factors also influence its expression in osteoarthritic, unstable joints, the objectives are to understand what components of the promoter region of canine MMP-1 gene are influenced by these factors. At present no data is available on canine MMP-1 gene regulation. This proposal is aimed towards understanding the regulation of canine MMP-1 gene expression in response to biomechanical stress and cytokines by isolating canine MMP-1 gene, identifying the regulatory elements in the promoter responsive to biomechanical stress and cytokines, and analyzing MMP-1 expression in chondrocytes of articular cartilage form normal and osteoarthritic dogs with the intent to develop novel therapeutic drugs to combat this disease.
The above was last updated April 2013