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January 2007

Functional Genomics

T. A. Ferris
J. Pérez Laspiur
J.L. Burton
P.M. Coussens
Dept. of Animal Science

Functional genomics is a new tool used to study the link between genes and various functions of animals. The tool enables scientists to see what genes are turned on or off as a result of environmental influences, treatments, or physiological conditions. The knowledge gained about gene expression and functions using functional genomics will first help scientists better understand physiological functions and pathways. Already, researchers are using functional genomics to learn more about diseases such as coliform mastitis. In the future, it may be possible to regulate and select for sets of identified genes to improve animal performance, health, and well-being.

Performance traits, genetics, and environment

A dairy cow’s performance (P) is dependent upon genes (G) from her parents, plus the environment in which she resides (E), as depicted in the equation “P = G + E”. E is the sum of environmental and physiological factors that influence a trait, for example, the amount of milk a cow produces, and may include hormonal changes, nutrition, weather, health, age, season, and stress. Currently, producers and AI studs select superior animals as parents to improve G and management practices, environments, and “products” to improve E are being developed.

For many years, genetic ability of an animal has been estimated for the collective effects of G using Predicted Transmitting Abilities (PTA) for traits such as milk production and fat test. PTAs are computed without knowing what genes are actually involved, their function, when they are expressed, or their DNA sequence. This approach, along with research into environmental factors affecting production and physiological responses, has resulted in significant improvements for many economically important traits in dairy cattle. Now functional genomics allows scientists to take their studies of genetics farther than PTAs, because it is possible to examine thousands of genes in appropriate cells of animals in response to various treatments, physiological changes such as the process of calving, and environmental conditions such as diet, housing, or heat stress.

What is functional genomics?

Functional genomics provide the potential to link animal traits such as disease resistance or milk production with specific genes, yielding new knowledge about physiological functions such as milk secretion, immune response, digestion, and metabolism at the cellular level (1). This is done by determining which genes are turned on or off as a result of treatments, physiological changes, or environmental conditions. For example, differences in genes expressed can be determined in diseased tissue of animals and that of their healthy counterparts. From these gene expression profiles, the genes that trigger various pathways responsible for specific functions in the cow can be understood.

Using knowledge gained from functional genomics

Currently, identifying key genes in physiological pathways is the main goal of functional genomics (2,3). For example, scientists are using functional genomics to study why dairy cows are more susceptible to some diseases just prior to calving and how environmental and physiological factors affect gene expression. Once scientists identify genes that cause a beneficial response to a change in environment or treatment, they may be able to develop methods to regulate the appropriate genes. Such methods could involve simple management changes, or using new preventive vaccines, therapeutic drugs, nutritional supplements, or technologies to enhance or block gene expression.

How is functional genomics performed?

When genes are turned on, proteins are synthesized, and when they are turned off, proteins are not synthesized. In this manner, genes are like a set of hundreds of switches that turn on and off to regulate functions. To determine which genes are turned on or off by a condition or treatment, a laboratory tool called a microarray is used. A microarray is a glass slide holding thousands of genes from a dairy cow or other animal. Using a microarray allows scientists to compare the gene expression between a healthy and a diseased dairy cow, and possibly identify the pathways that certain genes enable when they are turned on. Knowing what pathways these genes control helps us understand what is going on when a cow is treated or influenced by a physiological condition. This knowledge may lead to development of new management tools to improve the cow’s health or production.

How is this technology being used today?

A large group of animal scientists belonging to the U.S. National Bovine Functional Genomics Consortium (NBFGC) is using functional genomics. The NBFGC developed a genetic library that contains DNA sequences for 18,263 genes in the bovine genome (4). Scientists in the NBFGC are using functional genomics to learn more about:

  • nutrient partitioning during the transition period
  • fertility
  • partition-induced suppression of the immune system
  • milk composition and yield
  • heat stress
  • transportation stress
  • pathogenesis of disease.

Summary

For years, genetic evaluations have been estimated using quantitative methods to compute PTAs for dairy sires and cows without being able to consider the many specific genes involved. Today functional genomics tools allow scientists to link genes with specific functions to further understand animal biology. This is done by addressing:

  • which genes are turned on or off as a result of a condition or treatment
  • which genes might be involved in a pathway
  • what conditions trigger a pathway

With a better understanding of biology, it may be possible to develop new management tools and methods to turn on or turn off the expression of appropriate genes and to select parents with sets of desired genes.

References

1. Burton, J. L., et al. 2004. From genes to dairy farms. Michigan Dairy Review 9(1): 12-15.
2. Burton, J. L., et al. 2005. Gene expression signatures in neutrophils exposed to glucocorticoids: A new paradigm to explain “neutrophil dysfunction” in parturient dairy cows. Vet. Immunol. Immunopathol., Special Functional Genomics Issue 105(3-4):197-219.
3. Coussens P. M., et al. 2003. Evidence for a novel gene expression program in peripheral blood mononuclear cells from Mycobacterium avium subsp. paratuberculosis-infected cattle. Infect. Immun. 71(11):6487-6498.
4. Suchyta, S. P., et al. 2003. Development and testing of a high-density cDNA microarray resource for cattle. Physiol. Genomics 15: 158-164.

 

 

 

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