EPI * Exocrine Pancreatic Insufficiency
managing EPI
Current Research - updated September 4, 2009
We are very grateful to have two excellent U.S. universities supporting the cause of EPI. When Dr. Keith Murphy went to Clemson University of SC, as Professor and Chair of Genetics and Biochemistry, Clemson stepped forward as a major contributor to the EPI Genetic Research along with Dr. Leigh Anne Clark who was still at Texas A&M University, as Research Assistant Professor in the Dept of Pathobiology conducting the EPI Genetic Research study. May 2009, Dr. Leigh Anne Clark left Texas A&M University (TAMU) and accepted an Assistant Professor position at Clemson University in Clemson, South Carolina in the Genetics and Biochemistry Department. She now heads up her own Laboratory. Dr. Kate Tsai, also previously from Texas A&M, accepted a position in July 2009 at Clemson University as Research Assistant Professor and will be working on EPI Research along with Dr. Leigh Anne Clark.The Genetic EPI Research will now be conducted at Clemson University. Dr. Jorg Steiner, et al at Texas A&M University will continue to assist with Cobalamin & Folate testing and TLI testing for EPI.
Dr. Clark's Contact Information
To contact Dr. Clark, her office telephone number is: 1-864-656-4696; her email address is: lclark4@clemson.edu
Leigh Anne Clark, PhD.
Assistant Professor
Department of Genetics and Biochemistry
100 Jordan Hall
Clemson University
Clemson, South Carolina 29634
RESEARCH UPDATES
January 2010: Dr. Leigh Anne Clark has had the EPI Genetic SNP arrays ready to go to NIH for over a month, however, it has been difficult to secure a scheduled time to process this with NIH. Because of this delay, Dr. Keith E. Murphy, Professor and Chair of Genetics and Biochemistry at Clemson University has procured a SNP array platform for Clemson University (THANK YOU Dr. Keith Murphy !!!!) The platform has just arrived this week at Clemson allowing for the SNP array process to be performed in-house at Clemson. This is great news for our EPI Genetic Research effort and for all future genetic testing at Clemson University. Keep posted for genetic research updates soon.
July 24, 2009: Dr. Kate Tsai, also previously from Texas A&M, has accepted a position as Research Assistant Professor at Clemson University and will be working on EPI Research with Dr. Leigh Anne Clark.July 16, 2009: Clemson University is on schedule to order the SNP arrays this month. It should take approximately 4-6 weeks.
June 3, 2009: Dr. Clark has concluded the collection of EPI and non-EPI GSDs samples. And she has already isolated the DNA from all the blood samples submitted. The next step is that the researchers need to prepare the DNA for use on the SNP array. In July 2009 they plan on starting the next phase which is to order the arrays and start running them.
February 2009: Previously EPI was suspected to be caused by autosomal recessive genes, but that is no longer thought to be the case. The following is a summary by lead researcher, Keith E. Murphy, PhD on the results of the November 2008 study:
“To date, blood and serum samples have been collected from 31 unrelated German Shepherd Dogs (GSDs) having exocrine pancreatic insufficiency (EPI) and 45 unrelated GSDs that do not have EPI. In 2008, preliminary data were collected for 18 EPI-affected and 25 unaffected GSDs using the canine SNP array. This array is a newly-available technology that uses a comprehensive set of genetic markers, called single nucleotide polymorphisms (SNPs), to identify linkage with a trait. We were unable to identify a single region of interest but found that markers on multiple chromosomes were loosely linked with EPI. These data suggest that pancreatic insufficiency in the GSD is not inherited in an autosomal recessive fashion; but rather that it is likely a complex disorder, potentially having multiple genetic and environmental factors. To reduce the background (e.g., reduce false positives), it is necessary to collect SNP array data for additional EPI-affected and normal GSDs. To this end, we are presently collecting samples from additional dogs that will be used to probe the SNP array as part of a larger study.”
RESEARCHER COMMENTS (Dr. Leigh Anne Clark's Corner)
June 2009: "EPI does have a genetic/heritable component, but it is likely more complex than autosomal recessive. In fact, a test breeding in Europe between
2 affected dogs resulted in a litter with NO affected puppies. Most likely there are environmental factors (stress, virus, etc.) or multiple genes contributing.
Unfortunately, this means that there is no accurate way to identify carriers. Definitely do not breed affected dogs, and do not repeat matings that produced
EPI. It may also be safest to not line breed dogs that are "carriers."
If you would like to make a donation to help support EPI Research please feel free to donate via PayPal below or send a check to
Leigh Anne Clark,PhD. Ass't Prof of Dept of Genetics and Biochemistry, 100 Jordan Hall, CLEMSON UNIVERSITY, Clemson SC 29634-0318
THANK YOU!
To see other canine genetic research projects such as Megaesophagus that Dr. Clark is working on please visit:
http://www.caninemegaesophagus.org/Research_Genetics.html
The following are the researchers involved in the EPI Research Study:
Keith Murphy, Ph.D.
Professor and Chair, Dept of Genetics and Biochemistry, Clemson University
Grant for PAA from the CHF:
Murphy, K.E. and L.A. Clark (Co-Is). Analysis of a candidate gene for pancreatic acinar atrophy in the German Shepherd Dog. Canine Health Foundation. $22,680. 2004-2005.
Leigh Ann Clark, PhD in EPI
Ass't Professor, Dept of Genetics and Biochemistry, Clemson University
Dr. Clark studied under Dr. Murphy for her PhD and continues to work with him. She received the Texas A&M University College of Veterinary Medicine Fisher Institute Medical Research Award, 2004, for her dissertation, titled: Transmission genetics of pancreatic acinar atrophy in the German Shep Dog.
Kate Tsai, Ph.D., 
Research Ass't Professor, Dept of Genetics and Biochemistry, Clemson University (previously from Dept of Pathobiology Texas A&M University, College of Veterinary Medicine and Biomedical Sciences)
Jörg M. Steiner, med.vet., Dr.med.vet., PhD, DACVIM, DECVIM-CA
Associate Professor with the Department of Small Animal Medicine and Surgery
Texas A&M University, College of Veterinary Medicine and Biomedical Sciences
in special collaboration with:
David A. Williams MA VetMB PhD
Diplomate ACVIM, ECVIM-CA
Developer of the TLI test
SNP Technology
http://www.ncbi.nlm.nih.gov/About/primer/snps.html
What Are SNPs and How Are They Found?
A Single Nucleotide Polymorphism, or SNP (pronounced "snip"), is a small genetic change, or variation, that can occur within a person's DNA sequence. The genetic code is specified by the four nucleotide "letters" A (adenine), C (cytosine), T (thymine), and G (guanine). SNP variation occurs when a single nucleotide, such as an A, replaces one of the other three nucleotide letters—C, G, or T. An example of a SNP is the alteration of the DNA segment AAGGTTA to ATGGTTA, where the second "A" in the first snippet is replaced with a "T". On average, SNPs occur in the human population more than 1 percent of the time. Because only about 3 to 5 percent of a person's DNA sequence codes for the production of proteins, most SNPs are found outside of "coding sequences". SNPs found within a coding sequence are of particular interest to researchers because they are more likely to alter the biological function of a protein. Because of the recent advances in technology, coupled with the unique ability of these genetic variations to facilitate gene identification, there has been a recent flurry of SNP discovery and detection. | ||
Needles in a Haystack
Finding single nucleotide changes in the human genome seems like a daunting prospect, but over the last 20 years, biomedical researchers have developed a number of techniques that make it possible to do just that. Each technique uses a different method to compare selected regions of a DNA sequence obtained from multiple individuals who share a common trait. In each test, the result shows a physical difference in the DNA samples only when a SNP is detected in one individual and not in the other. Many common diseases in humans are not caused by a genetic variation within a single gene but are influenced by complex interactions among multiple genes as well as environmental and lifestyle factors. Although both environmental and lifestyle factors add tremendously to the uncertainty of developing a disease, it is currently difficult to measure and evaluate their overall effect on a disease process. Therefore, we refer here mainly to a person's genetic predisposition, or the potential of an individual to develop a disease based on genes and hereditary factors. Genetic factors may also confer susceptibility or resistance to a disease and determine the severity or progression of disease. Because we do not yet know all of the factors involved in these intricate pathways, researchers have found it difficult to develop screening tests for most diseases and disorders. By studying stretches of DNA that have been found to harbor a SNP associated with a disease trait, researchers may begin to reveal relevant genes associated with a disease. Defining and understanding the role of genetic factors in disease will also allow researchers to better evaluate the role non-genetic factors—such as behavior, diet, lifestyle, and physical activity—have on disease. Because genetic factors also affect a person's response to drug therapy, DNA polymorphisms such as SNPs will be useful in helping researchers determine and understand why individuals differ in their abilities to absorb or clear certain drugs, as well as to determine why an individual may experience an adverse side effect to a particular drug. Therefore, the recent discovery of SNPs promises to revolutionize not only the process of disease detection but the practice of preventative and curative medicine. | ||
SNPs and Disease Diagnosis
Each person's genetic material contains a unique SNP pattern that is made up of many different genetic variations. Researchers have found that most SNPs are not responsible for a disease state. Instead, they serve as biological markers for pinpointing a disease on the human genome map, because they are usually located near a gene found to be associated with a certain disease. Occasionally, a SNP may actually cause a disease and, therefore, can be used to search for and isolate the disease-causing gene. To create a genetic test that will screen for a disease in which the disease-causing gene has already been identified, scientists collect blood samples from a group of individuals affected by the disease and analyze their DNA for SNP patterns. Next, researchers compare these patterns to patterns obtained by analyzing the DNA from a group of individuals unaffected by the disease. This type of comparison, called an "association study", can detect differences between the SNP patterns of the two groups, thereby indicating which pattern is most likely associated with the disease-causing gene. Eventually, SNP profiles that are characteristic of a variety of diseases will be established. Then, it will only be a matter of time before physicians can screen individuals for susceptibility to a disease just by analyzing their DNA samples for specific SNP patterns. | ||
SNPs and Drug Development
As mentioned earlier, SNPs may also be associated with the absorbance and clearance of therapeutic agents. Currently, there is no simple way to determine how a patient will respond to a particular medication. A treatment proven effective in one patient may be ineffective in others. Worse yet, some patients may experience an adverse immunologic reaction to a particular drug. Today, pharmaceutical companies are limited to developing agents to which the "average" patient will respond. As a result, many drugs that might benefit a small number of patients never make it to market. In the future, the most appropriate drug for an individual could be determined in advance of treatment by analyzing a patient's SNP profile. The ability to target a drug to those individuals most likely to benefit, referred to as "personalized medicine", would allow pharmaceutical companies to bring many more drugs to market and allow doctors to prescribe individualized therapies specific to a patient's needs. | ||
SNPs and NCBI
Because SNPs occur frequently throughout the genome and tend to be relatively stable genetically, they serve as excellent biological markers. Biological markers are segments of DNA with an identifiable physical location that can be easily tracked and used for constructing a chromosome map that shows the positions of known genes, or other markers, relative to each other. These maps allow researchers to study and pinpoint traits resulting from the interaction of more than one gene. NCBI plays a major role in facilitating the identification and cataloging of SNPs through its creation and maintenance of the public SNP database (dbSNP). This powerful genetic tool may be accessed by the biomedical community worldwide and is intended to stimulate many areas of biological research, including the identification of the genetic components of disease. | ||
NCBI's "Discovery Space" Facilitating SNP Research | ||
 | ||
| Figure 1. The NCBI Discovery Space. | ||
| Records in dbSNP are cross-annotated within other internal information resources such as PubMed, genome project sequences, GenBank records, the Entrez Gene database, and the dbSTS database of sequence tagged sites. Users may query dbSNP directly or start a search in any part of the NCBI discovery space to construct a set of dbSNP records that satisfy their search conditions. Records are also integrated with external information resources through hypertext URLs that dbSNP users can follow to explore the detailed information that is beyond the scope of dbSNP curation. Reproduced with permission from Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K."dbSNP: the NCBI database of genetic variation." Nucleic Acids Research. 2001; 29:308-311. | ||
Revised: September 20, 2007. |
Previous Research
2005 Linkage analysis and gene expression profile of pancreatic acinar atrophy in the German Shepherd Dog
2003 Pancreatic acinar atrophy in German shepherd dogs and rough-coated Collies Etiopathogenesis and response to long-term enzyme replacement treatment Department of Clinical Veterinary Sciences, Section of Medicine - Faculty of Veterinary Medicine-University of Helsinki, Finland https://oa.doria.fi/bitstream/handle/10024/749/pancreat.pdf?sequence=1
2002
Inheritance of pancreatic acinar atrophy in German Shepherd Dogs E. Michael Moeller , BS Jörg M. Steiner , Dr med vet, PhD http://avmajournals.avma.org/doi/abs/10.2460/ajvr.2002.63.1429
1999
Exocrine Pancreatic Atrophy in German Shepherd Dogs and Rough-coated Collies:
An End Result of Lymphocytic Pancreatitis
M. E. WIBERG, S. A. M. SAARI, AND E. WESTERMARCK
http://www.vetpathology.org/cgi/reprint/36/6/530.pdf
For next pahse of blood collections
INSTRUCTIONS (for next phase collections):
If in the future additional BLOOD SAMPLES are needed (Shiloh Shepherds and GSD-mixes) at a later date - - it will be announced.
The blood contribution instructions will remaind the same, but sent to Clemson Univ instead of Texas A&M.
1. Dog will need to fast 12 hours before the draw.
2. Draw approximately 10ml blood into syringe
3. Fill purple-top with 5-6mls
4. Invert the tube several times after filling
5. Fill red-top tube with remainder of blood
6. Spin blood to separate serum
7. After separation, transfer serum to second red-top tube
8. Please make sure tubes are clearly labeled
9. Return samples in a Styrofoam cooler with a freezer pack.
10. Do not ship on a Friday.
11. Ship standard overnight via Fed Ex: Ship to: Clemson University, 51 New Cherry Road, 319 BRC Bldg, Clemson SC 29634