Reference number : GC-2017-Q1-01614, amendment number : , agreement type : G, recipient legal name : Mallard, Bonnie (University of Guelph), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : This research
addresses genetic and epigenetic mechanisms that control bovine immunity to
better understand disease resistance of food-producing dairy species.
Diseases of livestock are a major problem for modern agriculture affecting
animal and human health. The immune system is composed of genetically
regulated cells and molecules with specialized ability to control response to
infectious disease. Understanding the biological, genetic and epigenetic
relationships within the immune system can facilitate identification of
individuals with superior immune response (IR) and enhanced disease resistance.
To that end, we devised the first patented system identifying cattle with
elevated inherent IR. With our unique ability to identify high (H), low (L) and
average (A) immune responders based on Estimated Breeding Values of their antibody (AMIR) and cell-mediated immune response (CMIR) to type 1 and 2 test antigens,
we have a novel tool to further examine the genes, molecules and pathways that
underpin these diverse phenotypes. In fact, H responders have about half of the disease of other phenotypes requiring less use of antibiotics. Since these IR traits are heritable (h2~25%) these genes can be passed on to their offspring to improve future generations. 
 
The immune system uniquely has the ability to vary and adapt host responses to control diverse pathogens. Identifying individuals with enhanced immuno-competence, is a method to naturally improve a range of innate and adaptive defense mechanisms, as well as to improve overall animal health. However, little is known about the genes, genetic pathways, or epigenetic influences that control H, L, or A immune responses and require further investigation. 
 
Therefore the goals for this
research are: 
 
 1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in the
nature (quality) and expression (quantity) of key IR
genes and molecules. Improved understanding of these differences will lead to
better comprehension of disease resistance in important food-producing species, as well
as development of new tools to improve animal health. 
 
 2- To improve knowledge of gene expression associated with these IR phenotypes and learn about the epigenetic marks on the DNA that regulate their expression.
Our recent data show epigenetic regulation of key bovine cytokines and we
hypothesize this will extend to other genes and account for some of the
variation between these IR phenotypes. 
 
 This combined genetic and biological research, utilizing individuals with known
IR phenotypes based on their breeding values, provides a unique
opportunity to study bovine immunity. This approach allows knowledge expansion
regarding the various factors which dictate variation in immune responsiveness
helping to ensure animal health and well-being in an important milk and meat producing
species. These results are expected to also relate to other biological systems., program purpose french : This research
addresses genetic and epigenetic mechanisms that control bovine immunity to
better understand disease resistance of food-producing dairy species.
Diseases of livestock are a major problem for modern agriculture affecting
animal and human health. The immune system is composed of genetically
regulated cells and molecules with specialized ability to control response to
infectious disease. Understanding the biological, genetic and epigenetic
relationships within the immune system can facilitate identification of
individuals with superior immune response (IR) and enhanced disease resistance.
To that end, we devised the first patented system identifying cattle with
elevated inherent IR. With our unique ability to identify high (H), low (L) and
average (A) immune responders based on Estimated Breeding Values of their antibody (AMIR) and cell-mediated immune response (CMIR) to type 1 and 2 test antigens,
we have a novel tool to further examine the genes, molecules and pathways that
underpin these diverse phenotypes. In fact, H responders have about half of the disease of other phenotypes requiring less use of antibiotics. Since these IR traits are heritable (h2~25%) these genes can be passed on to their offspring to improve future generations. 
 
The immune system uniquely has the ability to vary and adapt host responses to control diverse pathogens. Identifying individuals with enhanced immuno-competence, is a method to naturally improve a range of innate and adaptive defense mechanisms, as well as to improve overall animal health. However, little is known about the genes, genetic pathways, or epigenetic influences that control H, L, or A immune responses and require further investigation. 
 
Therefore the goals for this
research are: 
 
 1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in the
nature (quality) and expression (quantity) of key IR
genes and molecules. Improved understanding of these differences will lead to
better comprehension of disease resistance in important food-producing species, as well
as development of new tools to improve animal health. 
 
 2- To improve knowledge of gene expression associated with these IR phenotypes and learn about the epigenetic marks on the DNA that regulate their expression.
Our recent data show epigenetic regulation of key bovine cytokines and we
hypothesize this will extend to other genes and account for some of the
variation between these IR phenotypes. 
 
 This combined genetic and biological research, utilizing individuals with known
IR phenotypes based on their breeding values, provides a unique
opportunity to study bovine immunity. This approach allows knowledge expansion
regarding the various factors which dictate variation in immune responsiveness
helping to ensure animal health and well-being in an important milk and meat producing
species. These results are expected to also relate to other biological systems., agreement title english : Mechanisms and Genes that Shape Bovine Host Defence and Impact Disease Outcomes in High and Low Immune Responder Phenotypes, agreement title french : Mechanisms and Genes that Shape Bovine Host Defence and Impact Disease Outcomes in High and Low Immune Responder Phenotypes, agreement number : RGPIN, agreement value : 170000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada