YTCAF GRANTS SUPPORT --- 2009

Morris Animal Foundation Grant Funding

MAF GRANT DO8CA-001  ---   $3,000

Cornell University 2009

Genetic of Portosystemic Vascular Anolmalies
and
 Microvascular Dysplsia in Small Breed Dogs

Sharon A. Center, DVM, DiplACVIM

Morris Animal Foundation Grant DO8CA-001

Genetics of Portosystemic Vascular Anomalies and Microvascular Dysplasia in Small Breed Dogs

Sharon A. Center, DVM – Principal Investigator

Cornell University

Since data from physical and behavioral characteristics (phenotype) of families (pedigrees) do not support a single gene mutation this grant is screening multiple families in multiple breeds to look for other genes which may Modify the R1 region in affected small breed dogs.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

UPDATE:  OCTOBER 27, 2009

Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders that cause abnormal liver circulation in small terrier breeds of dogs.  The prevalence ranges from 30 to 80 percent.  Many dogs with PSVA are overtly ill because the liver cannot remove toxins from food.  Dogs with MVD, on the other hand, may only demonstrate intolerance to standard drug dosages.  In the first phase of the study, researchers from Cornell University prepared DNA from 44 Carin Terriers and six additional breeds --- Yorkshire Terriers, Tibetan Spaniels, Maltese, Norfolk Terriers, Miniature Schnauzers and Havanese --- for genotyping analysis.  Researchers hope to identify genetic markers for these disorders and then use the markers to develop an affordable genetic test that identifies carriers.  This test would be a tool to reduce and eventually eliminate the occurrence of these liver disorders.  The study is also providing a research associate and an assistant professor, both of  whom are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

 MAF GRANT DO7CA-152  ---  $3,000

University of Georgia 2009

Real Time Polymerase Chain Reaction for Viral
and
 Bacterial Acid Detection in Dogs with Meningoencephalitis

Scott Shatzberg, DVM, Ph.D.

  CHF Grant Funding

CHF GRANT 963 --- $7,000

Cornell University 2008-09

Genotyping Small Breed Dogs with Portosytemic Vascular Anomalies
and
Microvascular Dysplasia

Sharon A. Center, DVM, DiplACV

  AKC CHF Grant 963

Genotyping small breed dogs with Portosystemic Vascular Anomalies and Microvascular Dysplasia

Sharon A. Center, DVM – Principal Investigator

Cornell University

This study is exploring PSVA and MVD with the goal to identify a genetic marker for PSVA/MVD that will allow development of a genetic test.  Extensive pedigree analyses support an autosomal dominant but incompletely penetrant mode of transmission, explaining the dismal success of attempted trait elimination based on SBA.  It is important to eliminate this trait because affected dogs cause owner dissatisfaction, financial burden, and negative breed publicity, in addition to patient suffering.  We have discovered significant linkage between the PSVA/MVD trait and genetic markers on one chromosome in a large kindred of Tibetan Spaniels.  Findings have been confirmed with flanking markers and demonstration of similar linkage in Cairn Terriers and Maltese, and a smaller pedigree of Havanese.  The project will pursue further genetic mapping (microsatellites, SNPs) of the PSVA/MVD trait in these and additional breeds, and undertake association mapping using DNA banked from unrelated pure breed dogs with PSVA (n = 100).  We have accumulated blood for SBA measurements and DNA extraction from 1,081 dogs in informative pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, Yorkshire Terrier, Havanese, and Miniature Schnauzer).  These dogs are kindred related (3-generations) and in most circumstances involved > 9 pedigrees.  We have additionally accumulated samples on > 2,000 dogs (SBA and DNA) in these and other breeds that will be used for assessment of identified PSVA/MVD gene loci (other breed  examples:  Papillon, Soft Coat Fox Terrier, Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker Spaniel, Lhasa Aspo, Boston Terrier, Norwich Terrier, Bischon, Border Terrier, Chihuahua). The project is currently mapping newly acquired pedigrees to the chromosomal region of interest to confirm linkage needed to justify SNP analysis in our region of interest.  A SNP array has been developed and the project will shortly proceed to fine gene SNP mapping.

~~~~~~~~~~~~~~~~~~~~~~~~~

UPDATE 5-31-09

Genotyping Small Breed Dogs with Portosystemic Vascular Anomalies (PSVA) and Microvascular Dysplasia (MVD) Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders causing malformation of the liver circulation.  Afflecting a large number of small pure breed dogs, this trait causes high serum bile acid (SBA) and has a prevalence ranging from 15% to 85%.  The severe PSVA phenotype causes animal suffering, owner dissatisfaction, financial burden, and negative breed publicity.  The less severe MVD phenotype allows silent trait perpetuation.  Our goal is to identify a genetic marker for PSVA/MVD that will allow development of an affordable genetic test to guide breeding practices.  Extensive pedigree analyses supports an autosomal dominant, incompletely penetrant made of transmission that is likely polygenic, consistent with the dismal success of attempted trait elimination based solely on SBA concentrations.  Significant linkage between the PSVA/MVD trait and a critical region on a single chromosome is confirmed in small purebred dog breeds under study.  Genotyping samples have been acquired from > 1,500 dogs from informative pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, York-shire Terrier, Havanese, Miniature Schnauzer).  Development of informative pedigrees (including parents and 2 or more siblings of a PSVA or MVD dog, including affected and unaffected dogs) are needed from Papillons, Miniature Schaunzers, Shih Tzus and Pugs.  Individual samples from > 2,000 dogs (SBA & DNA) in multiple breeds (also including Soft Coat Fox Terrier, Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker Spaniel, Lhasa Aspo, Boston Terrier, Norwich Terrier, Bischon Frishe, Border Terrier, and Chihuahua) are on hand for assessment of identified PSVA/MVD disease risk loci as the project progresses.  The study is currently fine mapping a critical region using a custom designed SNP array developed for the project

~~~~~~~~~~~~~~~~~~~~~~~~~~

UPDATE 12-21-09

Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders causing malformation of the liver circulation.  Afflicting a large number of small pure breed dogs, this trait causes high serum bile acid (SBA) and has a prevalence ranging from 15% to 85%.  The severe PSVA phenotype causes animal suffering, owner dissatisfaction, financial burden, and negative breed publicity.  The less severe MVD phenotype allows silent trait perpetuation.  Our goal is to identify a genetic marker for MSVA/MVD that will allow development of an affordable genetic test to guide breeding practices.  SNP mapping in a region with microsatellite linkage supports an autosomal dominant, incompletely penetrant or polygenic mode of trait inheritance.  Specific mathematical models for trait inheritance in different breeds are being developed.  The study is fine mapping critical regions using custom designed SNP and sequencing arrays exploring for risk haplotypes that may be useful for discriminating affected from carrier dogs (test development).  Genotyping samples have been acquired from >1,500 dogs from informative pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, Yorkshire Terrier, Havanese, Miniature Schnauzer).  Development of informative pedigrees (including parents and 2 or more siblings of a PSVA or MVD dog, including affected and unaffected dogs) are still needed from Papillons, Miniature Schnauzers, Shih Tzuz and Pugs.  Genotyping data is consistent with wide genetic saturation of the trait in breeds with high disease prevalence.  Individual samples from >2,000 dogs (SBA & DNA) in multiple breeds (also including Soft Coat Fox Terrier; Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker Spaniel, Lhasa Aspo, Boston Terrier, Norwich Terrier, Bischon Frishe, Border Terrier and Chihuahua) are on hand for assessment of identified PSVA/MVD disease risk loci as the project progresses.

Other Grant Funding

 RABIES CHALLENGE FUND --- $2,500

W. Jean Dodds, DVM with Hemopet

and

Ronald Schultz, DVM, wi the University of Wisconsin

This is a long term study that is ongoing and studying the long term effects of the rabies vaccine over a consecutive period of time.

There are two concurrent canine rabies vaccine challenge studies (one for 5 years and one for 7 years), a study of canine rabies vaccine adjuvants, and a rabies vaccine adverse reactions reporting system.  The primary purpose of the Fund is to improve the safety of canine rabies vaccines and to determine, by challenge, if they confer longer immunity than currently established.