APPLICATIONS OF NUTRIGENOMICS IN ANIMAL SCIENCE
INTRODUCTION
Nutrigenomics applies genomic technologies to study how nutrients affect expression of genes. With
the advent of the post genomic era and with the use of functional genomic tools, the new strategies for
evaluating the effects of nutrition on production efficiency and nutrient utilization are becoming available.
Nutrigenomics plays an efficient role in various fields of animal health like nutrition, production, reproduction,
disease process etc. Nutrigenomic approaches will enhance researchers‟ abilities to maintain animal health,
optimize animal performance and improve milk and meat quality.
In recent years, nutritional research has moved from classical epidemiology and physiology to
molecular biology and genetics. Following this trend, nutrigenomics has emerged as a novel and
multidisciplinary research field in nutritional science that aims to elucidate how diet can influence animal
health (Canas et al, 2009)5. Genomics is the study of the functions and interactions of all genes in the genome;
“nutrigenomics” applies genomic technologies to study how nutrients affect expression of genes. The study of
how genes and gene products interact with dietary chemicals to alter phenotype and, conversely, how genes
and their products metabolize nutrients is called nutritional genomics or “Nutrigenomics” (Kaput et al,
2005). Nutrigenomic studies will be very useful for elucidating the roles of food components in obesity
(Chadwick, 2004) in coronary heart diseases (Talmud, 2004) and cancer prevention (Davis and Hord, 2004).
Over the last decade, advances in the biochemical technologies available for examining functional
genomics have provided a number of new molecular tools for evaluating responses to nutritional strategies.
These tools are largely based on an understanding of the expression and control of specific genes and gene
products and have led to the development of the sciences associated with Nutrigenomics (Swanson et al.,
2003). From the research perspective, to explore the effect of dietary components on the genome, the crucial
stages of nutrigenomics are transcriptomics, proteomics and metabolomics. Application of these modern
research tools, known as “omics” technologies, should yield new knowledge on the course of molecular
processes in animal organisms and a more precise evaluation of the biological properties of feeds.
A number of molecular tools are used to evaluate the effects of dietary strategies on gene expression and
the flow of information from the genetic code (DNA) to biological functions and structure. These include
1) Transcriptomic tools that quantitatively evaluate the formation of m-RNA (gene expression),
2) Proteomic tools which measure the formation of specific proteins (protein expression)
3) Metabolomic tools it can measure the products from the resulting metabolic activities (metabolic
profiling).
The most powerful molecular tools for examining nutrient effects at the most basic level comes from high-
throughput microarrays (gene chips), that allow for the examination of the expression of thousand genes at a
time. These arrays have allowed investigators to directly examine the effects of nutrient supplies in great detail
and at the most rudimentary level of gene transcription (gene expression). These techniques not only allow for
an understanding of the effects of nutrition on individual genes, but also for the examination and comparison of
gene expression profiles (gene interactions).
How does diet affects our gene expression?
Virtually every day, researchers identify new genes that contribute to health and disease. Conditions
like breast cancer (109 genes) and asthma (27 genes) and diabetes (114 genes) highlight how broad these
genetic factors will become. At the same time, the new biotechnology methods are pinpointing how molecular
nutrients shape genomic activity. For examples, Vitamin A changes activity in over 500 genes; calcium in over
145, zinc over 60. Cholesterol, which is made by the body, influences over 30 genes, which shows that
molecular nutrients which might regulate cholesterol production are likely, in turn, to have important second
order effects. ( Daniel et al ,2005).
The four basic tenets of Nutrigenomics are:
i. Improper diets are risk factors for disease.
ii. Dietary chemicals alter gene expression and/or change genome structure
iii. The degree to which diet influences the balance between healthy and disease states may depend on an
individual’s genetic makeup.
iv. Some diet-regulated genes (and their normal, common variants) are likely to play a role in the onset,
incidence, progression, and/or severity of chronic diseases. Genes express themselves through proteins.
Enzymes are special proteins designed to get things started. Our genome instructs ribosomes to produce
many enzymes that destroy toxins. Some foods such as cauliflower, broccoli and brussels sprout contain
chemicals that actually tell our genes to direct biosynthesis of these enzymes. In some individuals, genes give
unclear instructions for making an enzyme that metabolizes the amino acid, phenylalanine. As a result, this
amino acid builds up, thereby causing brain damage. A diet restricting this amino acid will stop the damage if
detected in early infancy. Transfer of nutrients from gut to cells requires carrier and receptor proteins. Some
individuals have genes that direct overproduction of iron carrying proteins. The resulting iron overload is
extremely toxic and may lead to death. One gene that have received considerable attention and around which
there has been a great deal of research is the gene for the enzyme methylenetetrahydrofolate reductase
(MTHFR). Its relation to cardiovascular disease is confirmed. Currently, several nutrition related issues benefit
from genetic research. A number of conditions like phenylketonuria, caffeine intake and bone loss in
postmenopausal women, folic acid and heart disease, obesity, anorexia nervosa, vitamin C supplementation to
reduce cancer risk and low fat diet for high blood cholesterol levels, show the influence of genetic variation on
nutrition advice. The majority of practical applications of Nutrigenomics are just beginning to emerge. The
trend appears to be that certain individuals with particular variations in their genes will have increased need of
specific nutrients in their diet which will result in changes in translation of information in their genes.
The impact of this dietary change on an individual’s gene expression may be animprovement in their
projection disease trajectory over a life time.3 (Muller, M., Kersten, S.2003)
1. NUTRIGENOMICS: MEASURING NUTRITION RESPONSIVE GENOME ACTIVITY
A way to obtain insight in the methodological approaches of nutrigenomics is to see how an experiment
is actually set up and performed. The typical nutrigenomics experiment demands a clear plan based on several
a priori choices: 1. the actual approach, 2. the model system, 3. The type of nutrition or diet, 4. the appropriate
technological methods. The influence of nutrition on genome activity is studied almost always in a
comparative manner either by a direct or an indirect approach. The direct approach involves changes in the
nutrients presented to a model system followed by monitoring the changes in gene expression. This includes
for instance most of the human intervention studies. The indirect approach involves the study of nutrition-
related traits and disorders such as obesity, type 2 diabetes and cardiovascular disorders. In those studies gene
expression is compared Nutrigenomics, nutrigenetics, functional foods, personalized diet, networking between
subjects with and without the disorder and from the differences scientists hope to deduce the relevant
molecular pathways leading from health to disease under the influence of diet and lifestyle. The results of those
studies should lead to new targets for pharmacological or dietary intervention and to novel functional foods. In
nutrigenomics many different model systems are used ranging from in vitro cultured cells to animals and
humans. Many of our genes are active in a tissue- or organspecific manner requiring the analysis of gene
expression in the relevant biological material. Although methods for safely taking biopsies from humans are
rapidly extending and improving, there will always be at least some medical or ethical restrictions. Therefore,
scientists often rely on animal models like mouse, rat or pig, although also other models such as the nematode
C. elegans are increasingly used. The technology of generating transgenic, knock-out and knock-in mice has
considerably increased the attractiveness of using animal models (Santo et al ,2004).
The result is, that the ApoE3L mouse has a more human-like lipid profile and is therefore a preferred
model system for gene-diet interaction in the context of the metabolic syndrome. In addition, there is a growing
number of inbred mutant mouse strains with a monogenic nutrition-related trait which are excellent models for
studying the influence of diet on a particular genetic background. In part of the nutrigenomics studies, human
or animal tissue-specific cell lines or primary cells are used. An advantage is that the external influences, i.e.
the culture conditions, can be easily controlled or manipulated by changing specific nutrients followed by
monitoring of the effect on genome activity. In addition, cell lines are clonal in origin avoiding the
complication of genetic variation.
UNDERSTANDING DIET EFFECTS ON SPECIFIC GENES
Gene expression studies have become increasing valuable as a tool for examining specific effects of
nutrients and diseases on gene expression further expression studies have allowed for an improved
understanding of the physiological basis on the beneficial global effects of caloric restriction on aging (Lee et
al., 2002) and the effects of minerals such as selenium on intestinal function (Rao et al., 2001).
In poultry, gene expression studies are better understanding of disease resistance (Liu et al., 2003) and
of growth and tissue differentiation. These tools have also been used to differentiate effects of specific nutrient
forms. Afrakhte and Schultheiss, 2004 compared two forms of selenium, the inorganic selenite salt and an
organic form in selenium yeast, have suggested both functional differences and similarities with these dietary
forms. These were easily seen in the expression of some key genes associated with antioxidant systems In
addition, it has been possible to show tissue-specific effects of different forms of selenium with selenium yeast
inducing greater changes in gene expression in the intestinal tract (991 of 14,000 transcripts examined) and
sodium selenite inducing the greater changes in ovarian tissue (4135 of 14,000 transcripts examined).
INDIVIDUAL VARIATION WITHIN POPULATIONS
Variation of the individual response to diet can be explained by the underlying differences in genetics
across a population. Animals and humans have shown that individual genotypic variations can alter nutrient
metabolism, from relatively mild conditions like lactase gene polymorphisms that result in lactose intolerance
to potentially severe pathological conditions like phenylketonuria (Harvey et al 1998). Obesity and lipid
metabolism are currently the most studied examples of genetic influence on the development of a condition
resulting from nutrition (Debusk et al., 2005).
The quantity and quality of the diet modulates the expression of numerous genes in various tissues.
Each individual will respond to a specific diet in a unique manner that corresponds with their genetic profile.
One of the goals of nutrigenomics research is the development of consensus responses to specific dietary
stimuli so that anomalies can be identified and studied further. It is these anomalies that will provide the basis
for understanding how genetic differences are associated with specific response to nutrients, how genetic
differences in combination with diet result in maladies like obesity or improved animal performance.
A majority of this research has been fueled by the human and subsequent animal genome projects
including that for chicken and turkey, which will ultimately enable scientists to understand the functions of
genes and how they are regulated. This knowledge will provide information on how genes and nutrients
interact and the effect of individual genetic differences on diet and nutrition. Developing within this genome
era were technologies that were increasingly broad in scope that included automation, high throughput, and
data intensive. Many of these technologies also involved miniaturization of standard techniques to suit the new
high throughput experimental designs. These technologies have significant implications on nutrition research
and include aspects of genomics (polymorphism), functional genomics (gene expression), proteomics (protein
expression), and a recent addition to the field epigenetics (heritable factors overlaying the genome sequence).
APPLICATIONS OF NUTRIGENOMICS IN ANIMAL SCIENCE
The interface between the nutritional environment and cellular/genetic processes is being referred to as
“nutrigenomics.” Nutrigenomics seeks to provide a molecular genetic understanding for how common dietary
chemicals (i.e., nutrition) affect health by altering the expression and/or structure of an individual’s genetic
makeup. The fundamental concepts of the field are that the progression from a healthy phenotype to a chronic
disease phenotype must occur by changes in gene expression or by differences in activities of proteins and
enzymes and that dietary chemicals directly or indirectly regulate the expression of genomic information. We
present a conceptual basis and specific examples for this new branch of genomic research that focuses on the
tenets of nutritional genomics:
Common dietary chemicals act on the genome, either directly or indirectly, to alter gene expression or
structure.
Under certain circumstances and in some individuals, diet can be a serious risk factor for a number of
diseases.
Some diet-regulated genes (and their normal, common variants) are likely to play a role in the onset,
incidence, progression, and/or severity of chronic diseases.
The degree to which diet influences the balance between healthy and disease states may depend on an
individual’s genetic makeup; and
dietary intervention based on knowledge of nutritional requirement, nutritional status, and genotype
(i.e., “individualized nutrition”) can be used to prevent, mitigate, or cure chronic disease.( Kaput, et al.,
2004).
1. To develop animal feed/food matching to its genotype.
The goal of nutrigenomics or nutritional genomics is to develop foods and feeds that can be matched to
genotypes of animals to benefit health and enhance normal physiological processes. Using gene chips that
contain the genetic code of animal, researchers can measure the effects of certain nutritional supplements, and
how they alter the gene interactions of the body.
2.To select nutrients fine-tuned with genes of animal.
Nutrigenomics is not altering the genetics of an animal nor to genetically modify the animal rather we
are altering the activity of genes switching on good genes and keeping bad ones switched down. Through
nutrigenomics we are carefully selecting nutrients for fine-tuning genes and DNA present in every cell and
every tissue of an animal. For example, keeping stress response genes switched down with proper nutrition so
that the animal is healthier, more productive.
3. To understand role of nutritional management in performance (production/disease) of animal.
Gene expression studies will allow for the identification of pathways and candidate genes responsible
for economically important traits. Dietary manipulations and nutritional strategies are key tools for influencing
ruminant production. There is a usual belief that nutrition and genetic makeup both strongly influence the
reproductive performance of milking animals. This is particularly important during the transition period and
early lactation, when the animal is particularly sensitive to nutritional imbalances.
Nutrigenomics and nutritional genomics are providing new tools that can be used to more clearly
understand how nutritional management can be applied to address disease, performance and productivity in
animals. In the changing scenario of ruminant‟s nutrition the objective of nutrigenomics is to study the effects
of diet on changes in gene expression or regulatory processes that may be associated with various biological
processes related with animal health and production. In studies of steers under nutritional restriction due to
intake of poor quality feeds, expression of specific genes associated with protein turnover, cytoskeletal
remodeling, and metabolic homeostasis was clearly influenced by diet(Byrne et al ,2005).
Application of nutrigenomics to resolve the molecular markers important in nutrition research. There is
vary scares information about effect of diet on expression of genes related to productive or reproductive traits
of livestock, it may be possible to begin to understand the importance of the relationship between individual
nutrients and the regulation of gene expression. To understand this concept of nutrigenomics a study of diet
induced gene expression is discovered in which selenium deficiency shown to alter protein synthesis at
transcriptional level (Rao et al, 2001) It leads to adverse effect like enhancement of stress through up-
regulation of specific gene expression and signaling pathway. On the other hand genes responsible for
detoxification mechanism and protection from oxidative damage were hampered, these consequences
ultimately leads to alteration of phenotypic expression of related symptoms of selenium deficiency. From the
above example it is apparent that possibly nutrigenomics can be used to identify the specific markers to
manipulate gene expression through use of nutrients or their combinations so as to improve productive as well
as overall animal performance. Nutrigenomics will be a path-breaking tool through identification of pathways
and candidate genes responsible for dietary induced diseases and ultimately reduction in production losses due
to these diseases in animals. The discoveries of gene markers related to economically important traits like milk,
meat, wool production etc whose expression can be improved by dietary regimens is a need of today’s
nutrigenomic research, which will help for sustainable livestock production.
4. Nutrient-Gene interaction.
The diet has long been regarded as a complex mixture of natural substances that supplies both the
energy and building blocks to develop and sustain the organism. However, nutrients have a variety of
biological activities. Some nutrients have been found to act, as radical scavengers known as antioxidants and as
such are involved in protection against diseases. Other nutrients have shown to be potent signaling molecules
and act as nutritional hormones (Muller and Kersten, 2003). Some of the plant secondary metabolites also
known as photochemical act as a modulator of animal health and production.
1) To understanding the aging process in animals.
A nutrigenomic approach can be applied to understanding the aging process in companion animals.
Healthy adult animals given the same foods can be studied to identify the gene expression and biochemical
differences characteristic of the aging process. Foods for senior animals can then be rationally designed and
evaluated for their ability to modify gene expression profiles in animals to more closely reflect those found in
healthy adult animals, which has the potential to improve health and quality of life. In addition, canine and
feline nutrigenomic studies may provide evidence that nutrigenomics can improve health and quality of life for
humans.
6.Nutrigenomics and immune system.
The concept underlying nutrigenomics is that nutrition is the key element of health maintenance,
particularly for the immune system, so that an optimum level of nutrition will ensure optimum animal health.
A deficiency of an essential nutrient will eventually affect the body’s performance. The immune system is
particularly sensitive to deficiencies, and once the immune system is compromised, negative consequences
follows. There is a defined relationship between production and immune status of animals. Higher the
production, more sensitive is the immune system of animal. Two decades ago, the main aim of animal
nutritionists was to design ration so to avoid deficiencies. Deficiency is now rare in modern livestock
production systems. So we can now move to the next stage rather than merely preventing deficiency, we can
strive to actually meet the animal’s exact requirements from its diet, in order that it can meet its genetic
potential.
8) Nutrigenomics and diseases.
Essential nutrients and other bioactive food components can serve as important regulators of gene
expression patterns. Macronutrients, vitamins, minerals, and various phytochemicals can modify gene
transcription and translation, which can alter biological responses such as metabolism, cell growth, and
differentiation, all of which are important in the disease process. Genome wide monitoring of gene expression
using DNA microarrays allows the simultaneous assessment of the transcription of thousands of genes and of
their relative expression between normal cells and diseased cells or before and after exposure to different
dietary components. This information should assist in the discovery of new biomarkers for disease diagnosis
and prognosis prediction and of new therapeutic tools. Many diseases and disorders are related to suboptimal
nutrition in terms of essential nutrients, imbalance of macronutrients, or event toxic concentrations of certain
food compounds. There are multietioetiological diseases which are due to interaction of different nutrients
along with several genes (Mariman, 2006).
Remarkable diversity in all living beings differences in food digestion, nutrient absorption, metabolism,
and excretion have been observed and genetic diseases in these processes have been reported. The functional
integrity of gene is mainly depends on metabolic signals that the nucleus receives from internal factors, e.g.
hormones, and external factors, e.g. nutrients, which are among the most influential of environmental stimuli.
Genomes evolve in response to many types of environmental stimuli, including nutrition. Therefore, the
expression of genetic information can be highly regulated by, nutrients, micronutrients, and photochemicals
found in food (Van Ommen, 2004).
In eye diseases
Recent finding on the implication of nutritional and genetic factors in age-related eye diseases: age-
related macular degeneration (AMD; a degenerative disease of the retina) and cataract (opacification of the
lens). Because of direct exposure to light, the eye is particularly sensitive to oxidative stress. Antioxidants,
such as vitamin E, C or zinc, clearly have a protective effect in AMD and probably in cataract. In addition, two
carotenoids, lutein and zeaxanthin, may play a more specific role in the eye: they accumulate in the retina,
where they form the macular pigment, and in the lens. Finally, docosahexaenoic acid (an omega-3
polyunsaturated fatty acid) is particularly important for the retina, where it exerts structural, functional and
protective actions. Besides, these diseases are strongly influenced by genetics, as demonstrated by familial and
twin studies. The apolipoprotein E4 allele is associated with a reduced risk of AMD, while an association of
AMD with complement factor H polymorphism has recently been demonstrated. (Stintzing et al ,2002)
In diabetes
Type-2 diabetes is a metabolic disorder associated with impaired carbohydrate, protein, and lipid
metabolism. This is further linked to inactive lifestyle and consumption of 'wrong' foods. We know that certain
foods that are high in sugar and white starches can make the symptoms of diabetes worse. However, people
with diabetes will have different responses to particular foods because of their different genes. For example, a
study found that physicians recommend changes to diet and an increase in physical activity for type 2 diabetes
patients, but only 20% of patients can actually control symptoms through these interventions. This is where
nutrigenomics can help manage type-2 diabetes.
Nutrigenomics can come to aid through clinical diagnostics for phenotypes such as insulin level and
glucose tolerance, as well as through metabolomics diagnostics in which diabetes biomarkers (biochemical
substances viz. glucose, cholesterol, creatine, and fatty acids that indicate the susceptibility and progress of the
disease) are assessed. Researches have shown that 'over expression' of SREBP -1a and SREBP -1c (t-RNAs
that activate genes involved in the synthesis and uptake of cholesterol, fatty acids, and triglycerides) play an
important role in the development of diabetes. Another research has suggested that presence of certain gut
microbes increased fat reserves and insulin resistance, and thus may have an influence on the development of
type-2 diabetes. Similarly, certain fibers modulated cholesterol absorption in the gastrointestinal tract, thus
playing an important role in defining nutrient bioavailability. This would help experts understand the complex
relationship of diet-gene interaction of the diabetic person and provide more efficacious dietary
recommendations. In the same way, nutrigenomics can also help in developing treatments for type-2 diabetes
through personalized diet. And they have proven to be more effective than certain drugs. For example, the
drug, rosiglitazone, commonly used by type-2 diabetics, is known to alter lipid metabolism in liver tissues and
adipose tissues leading to liver toxicity with prolonged use. On the other hand, nutrients found in certain diets
have the same metabolic pathway as the said drug, but without its side effects. Typical nutritional studies
analyzing the response of an intervention group to controls provided the same diet lacking a specific nutrients
or nutrients. Simple examples analyzed serum lipid changes in response to a high fat vs control diet or
determined differences in nutrient intakes between groups of individuals who have a disease (cases) versus
those that do not (i.e., controls). Results of such studies are averages of all members of the control and all
members of the intervention group. While population attributable risk yields useful guidelines, it does not
provide information for individual members of the group nor can it be confidently applied to individuals not in
the study. Low intakes of vitamin D have also been associated with an incidence and pathogenicity of Type 2
diabetes mellitus. (Kaput et al.,2008)
9.Nutrigenomics And Cancer prevention
Cancer incidence is projected to increase in the future and an effectual. Preventive strategy is required
to face this challenge. Alteration of dietary habits is potentially an effective approach for reducing cancer risk.
Assessment of biological effects of a specific food or bioactive component that is linked to cancer and
prediction of individual susceptibility as a function of nutrient nutrient- interactions and genetics is an essential
element to evaluate the beneficiaries of dietary interventions. In general, the use of biomarkers to evaluate
individuals susceptibilities to cancer must be easily accessible and reliable. However, the response of
individuals to bioactive food components depends not only on the effective concentration of the bioactive food
components, but also on the target tissues. This fact makes the response of individuals to food components
vary from one individual to another.
Nutrigenomics focuses on the understanding of interactions between genes and diet in an individual and
how the response to bioactive food components is influenced by an individual’s genes. Nutrients have shown
to affect gene expression and to induce changes in DNA and protein molecules. Nutrigenomic approaches
provide an opportunity to study how gene expression is regulated by nutrients and how nutrition affects gene
variations and epigenetic events. Finding the components involved in interactions between genes and diet in an
individual can potentially help identify target molecules important in preventing and/or reducing the symptoms
of cancer (Ali M. Ardekani and Sepideh Jabbari, 2009).
10.) Nutrigenomics and reproduction.
The science of nutrigenomics has begun to use information obtained from basic studies of the genome
to evaluate the effects of diet and nutrient management schemes on gene expression. Preliminary studies have
shown the value of such techniques and suggest that it will be possible to use specific gene expression patterns
to evaluate the effects of nutrition on key metabolic processes relating to reproductive performance. While the
effects of nutrition on fertility are only partially understood, modern nutrigenomics will undoubtedly play a
key role in developing strategies for addressing some of the limitations in reproductive performance. Currently,
oligo based and cDNA microarray techniques make it possible to understand many of the factors controlling
the regulation of gene transcription and globally evaluate gene expression profiles by looking at the relative
abundance of gene-specific mRNA in tissues. These techniques provide an unprecedented amount of
information and are only now being used to examine key reproductive, developmental, and performance
characteristics in cattle. They also promise to provide a tremendous amount of new information that can be
used to understand and diagnose key issues that limit reproductive performance (Dawson ,2006).
NUTRIGENOMICS AND THE OMIC TECHNOLOGIES
The sequencing of the genomes has led to the development of a whole new scientific methodology.
These new areas of scientific study usually include the 'omics' suffix. The technical developments have given
us novel tools enabling high throughput genome wide approaches. These tools form the basis of the biomics
era; genomics (covering DNA), transcriptomics (RNA), proteomics (protein), metabolomics (metabolites) and
systems biology (integrating all of these), with bioinformatics enabling the storage, integration and analysis of
the overwhelmingly complex data set produced. Nutrigenomics aims to determine the influence of common
dietary ingredients on the genome, and attempts to relate the resulting different phenotypes to differences in the
cellular and/or genetic response of the biological system (Mutch et al, 2008). More practically, nutrigenomics
describes the use of functional genomic tools to probe a biological system following a nutritional stimulus that
will permit an increased understanding of how nutritional molecules affect metabolic pathways and
homeostatic control. Nutrigenetics, on the other hand, aims to understand how the genetic makeup of an
individual coordinates their response to diet, and thus considers underlying genetic polymorphisms. It
embodies the science of identifying and characterizing gene variants associated with differential responses to
nutrients, and relating this variation to disease states. Therefore, both disciplines aim to unravel diet/genome
interactions; however, their approaches and immediate goals are distinct. Nutrigenomics will unravel the
optimal diet from within a series of nutritional alternatives, whereas, nutrigenetics will yield critically
important information that will assist clinicians in identifying the optimal diet for a given individual, i.e.
personalized nutrition.
GENOMICS AND INSULTS SET STAGE FOR PROCESS THAT ARE MODIFIED
Credentialing is defined as “omic” changes that bring about a phenotypic changeROLE OF TRANSCRIPTOMICS IN NUTRIGENOMICS
Ttranscriptome is the complete set of RNA that can be produced from the genome. Transcriptomics is
the study of the transcriptome, i.e. gene expression at the level of the mRNA. Using either cDNA or
oligonucleotide microarray technology, it describes the approach in which gene expression (mRNA) is
analyzed in a biological sample at a given time under specific conditions. It is the most widely used “omics”
technologies. Regulation of the rate of transcription of genes by food components represents an intriguing site
for regulation of an individual’s phenotype (Trujillo et al, 2006). The host of essential nutrients and other
bioactive food components can serve as important regulators of gene expression patterns. Macronutrients,
vitamins, minerals, and various phytochemicals can modify gene transcription and translation, which can alter
biological responses such as metabolism, cell growth, and differentiation.
The aim of transcriptomics is to determine the level of all or a selected subset of genes based on the
amount of RNA present in tissue samples. Transcriptomics is concerned with the expression of genes in
animals. In dairy industry, an effective utilization of microarray technology was beneficial to study mammary
gland tissues (milk production and udder health), muscle growth and development and myogenesis process
(beef production) and the role of gut microflora on nutritional diet intake in ruminants (health and food safety).
ROLE OF PROTEOMICS IN NUTRIGENOMICS
Proteomics is the study of all the proteins in a particular cell, tissue or compartment (Banks et
al.2000).The major tools of proteomics are two dimensional (2D) gel electrophoresis and mass spectrometry
(MS). Proteomic analysis was quite effective and useful to evaluate the effect of dietary methionine on breast-
meat accretion and protein expression in skeletal muscle of broiler chickens (Corzo et al.,2006) Via a tandem
mass spectrometer, a total of 190 individual proteins were identified from Pectorali major muscle tissue; three
of them were recognized which differed distinctly between the treatment proteome and could be considered as
potential biomarkers regulated by a methionine deficiency in broiler chickens.
ROLE OF METABOLOMICS IN NUTRIGENOMICS
Metabolomics represents the final step in understanding the function of genes and their proteins. The
aim of metabolomics is to determine the sum of all metabolites (other substances than DNA, RNA or protein)
in a biological system: organism, organ, tissue or cell (Müller and Kersten, 2003). Techniques employed to
investigate the metabolome include nuclear magnetic resonance (NMR) spectroscopy, high performance liquid
chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). These methods are capable of
resolving and quantifying a wide range of compounds in a single sample. The main characteristics of these new
technologies were miniaturization, automation, high throughput and computerization (Corthesy-Theulaz et
al .,2005). In experiments performed by (Bertram et al., 2006) metabolomic analysis was implemented to
detect the changes in the biochemical profiles of plasma and urine from pigs fed with high-fibre rye bread
((Bertram et al., 2006)). Two diets with similar levels of dietary fibre and macronutrients, but with contrasting
levels of wholegrain ingredients, were prepared from whole rye and fed to pigs. Using an explorative approach,
the studies disclosed the biochemical effects of a wholegrain diet on plasma betaine content and excretion of
betaine and creatinine. ARKERS
Biomarkers
Biomarkers are the genetic variants that predict the risk of disease and improve diagnosis and risk
assessment. Genetic polymorphism may be partially responsible for variation in individual’s response to
bioactive food component. Single nucleotide polymorphisms (SNP) are becoming increasingly recognized to
have an important influence on disease risk, for example, inherited polymorphism in BRCA1 is the gene
responsible for breast cancer susceptibility. If someone consume less fruits and vegetables were reported to be
at the greatest risk of developing breast cancer because of a polymorphism that causes a valine to alanine
change in the ninth position in the signal sequence for the enzyme manganese dependent superoxide dismutase.
correlations between mildly elevated homocysteine levels and cardiovascular disease risk. Methylene tetra
hydrofolate reductase helps to convert homocysteine to methionine. Due to SNPs (C677T and A1298C) which
reduce MTHFR activity it leads to increase in plasma concentrations of homocysteine and thereby to venous
thromboembolic disease, ischemic arterial disease and neural tube defects. Treatment with folic acid
supplementation helps to overcome the effects of these polymorphisms in MTHFR gene. Similarly a number of
polymorphic genes have been implicated to cancer development e.g. MCIR (melanocortin 1 receptor gene)
have been associated with several types of skin and prostrate cancers. There are claims of dietary supplements
that protects against diseases like cancer. New foods are developed as functional foods. Obesity has become a
major public health problem. Mutations in genes like leptin and leptin receptor genes have emerged as leading
candidates towards predicting obesity. Once the mutations are detected in the family, the physician might be in
a position to offer diet restriction/intervention at an early stage of life.( Subbiah Ravi et al 2006)
SCHEMATIC OVERVIEW OF INTEGRATION OF OMICS TECHNOLOGY IN ANIMAL
FEEDING AND NUTRITIONAL RESEARCH
SCHEMATIC REPRESENTATION OF NUTRIGENOMIC ACT ON MOLECULAR LEVEL
Microarray Technology: A Promising Tool in Nutrigenomics
Microarray technology is a powerful tool for the global evaluation of gene expression profiles in tissues
and for understanding many of the factors controlling the regulation of gene transcription. This technique not
only provides a considerable amount of information on markers and predictive factors that may potentially
characterize a specific clinical picture, but also promises new applications for therapy. One of the most recent
applications of microarrays concerns nutritional genomics. Nutritional genomics, known as nutrigenomics,
aims to identify and understand mechanisms of molecular interaction between nutrients and/or other dietary
bioactive compounds and the genome. Actually, many nutrigenomic studies utilize new approaches such as
microarrays, genomics, and bioinformatics to understand how nutrients influence gene expression. The
coupling of these new technologies with nutrigenomics promises to lead to improvements in diet and health. In
fact, it may provide new information which can be used to ameliorate dietary regimens and to discover novel
natural agents for the treatment of important diseases such as diabetes and cancer. This critical review gives an
overview of the clinical relevance of a nutritional approach to several important diseases, and proposes the use
of microarray for nutrigenomic studies. (Andrea Masotti., et al 2010).
CONCLUSION
Nutrigenomic approaches will enhance researchers‟ abilities to maintain animal health, optimize
animal performance and improve milk and meat quality. Nutrigenomics is a rapidly emerging science still in its
beginning stages. It is uncertain whether the tools to study protein expression and metabolite production have
been developed to the point as to enable efficient and reliable measurements. Also once such research has been
achieved, it will need to be integrated together in order to produce results and dietary recommendations. All of
these technologies are still in the process of development.
REFERENCES
Andrea Masotti., Letizia Da Sacco., Gian Franco Bottazzo,And Anna Alisi. 2010. Microarray Technology: A
Promising Tool In Nutrigenomics .Critical Reviews In Food Science And Nutrition,50:693–698 .
Jim Kaput and Raymond L., Rodriguez. 2004.Nutritional genomics: the next frontier in the postgenomic era.
Physiol Genomics., 16: 166–177.
Ali M. Ardekani and Sepideh Jabbari. 2009. Nutrigenomics and Cancer. Avicenna J Med Biotech 1(1): 9-17
Canas, V.G., Simo, C., Leon, C. 2009. Advances in Nutrigenomics research: novel and future analytical
approaches to investigate the biological activity of natural compounds and food functions. J Pharm Biomed
Anal., 51(2):290-304.
Kaput, J., Ordovas, J. M., Ferguson, L. 2005. The case for strategic international alliances to harness
nutritional genomics for public and personal health. Brit J Nutr., 94:623-32.
Trayhurn, P. 2005. Nutritional genomics-"Nutrigenomics". British Journal Nutrition ;89: 1-2.
Chadwick, R. 2004. Nutrigenomics, individualism and public health. Proc Nutr So., 63:161-166.
Talmud, PJ.2004. How to identify gene-environment interactions in a multifactorial disease: CHD as an
example. Proc Nutr Soc., 63: 5-10.
Davis, CD,, Hord, NG.2005. Nutritional “omics” technologies for elucidating the role(s) of bioactive food
components in colon cancer prevention. J Nutr., 135: 2694-2697.
Muller, M., Kersten, S. 2003. Nutrigenomics: Goals and Strategies. Nat Rev Genet., 4:315-322.
Lundeen T. Nutrigenomics speeds (Nutrition & Health: Dairy). Feedstuffs, 10.
Dawson, KA., Harrison, GA. 2007. Using Nutrigenomic Approaches for Understanding Forage Quality and
Nutrient Restriction. In: 22nd Annual Southwest Nutrition & Management Conference;22-23.
Byrne, KA., Wang, YH., Lehnert, SA.2005. Gene expression profiling of muscle tissue in Brahman steers
during nutritional restriction. J Anim Sci., 83:1-12.
Rao, L., Puschner, B., Prolla, TA. 2001. Gene expression profiling of low selenium status in the mouse
intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J
Nutr.,131:3175-3181.
Mariman, C. M.2006. Nutrigenomics and nutrigenetics: the „omics‟ revolution in nutritional science.
Biotechnol Appl Biochem., 44:119-128.
Van Ommen, B. 2004. Nutrigenomics: Exploiting systems biology in the nutrition and health arenas.
Nutrition;20:2-8.
Muller, M., Kersten, S.2003. NutriGenomics, Goals and Strategies, Nature Rev. Genet., 4: 315-322
Daniel, D., Wu1, Rosina Weber1, and Fredric, D.2005.AbramsonCase-Based Framework for Leveraging
NutriGenomics Knowledge and Personalized Nutrition Counselling, 26.
Dawson, KA. 2006. Nutrigenomics: Feeding the genes for improved fertility. Anim Reprod Sci., 96:312-222.
Mutch, D. M., Wahli, W. & Williamson, G., 2005. Nutrigenomics and Nutrigenetics: the emerging faces of
nutrition. FASEB J 2008;19: 1602–1616.
Trujillo, E., Davis,, C., Milner, J.2006. Nutrigenomics, proteomics, metabolomics, and the practice of dietetics.
J Am Diet Assoc., 106(3): 403-13.
Takamatsu, K., Tachibana, N., Matsumoto, I. 2004. Soy protein functionality and nutrition analysis.
Biofactors;21:49-53.
Tachibana, N., Matsumoto, I., Fukui K. 2005. Intake of soy protein isolate alters hepatic gene expression in
rats. J Agr Food Chem., 53: 4253-4257.
Endo, Y., Fu Z., Abe K.2002.Dietary protein quantity and quality effect rat hepatic gene expression. J Nut.,
132: 3632-3637.
Ron, M., Israeli, G., Seroussi, E. 2007.Combining mouse mammary gland gene expression and comparative
mapping for the identifi cation of candidate genes for QTL of milk production traits in cattle. BMC Genomics.,
8:183-193.
Te Pas MF., Hulsegge, I., Coster, A. 2007. Biochemical pathways analysis of microarray results: regulation of
myogenesis in pigs. BMC Develop Biol., 7: 66-80.
Ferraz A, Ferraz LZ, Ojeda, A. 2008. Transcriptome architecture across tissues in the pig. BMC Genomic.,
9:173-180.
Banks, RE., Dunn, MJ., Hochstrasser, DF.2000.Proteomics: New perspectives, new biomedical opportunities.
Lancet., 356: 1749-1756.
Corzo, A., Kidd MT., Dozier WA, 2006. Protein expression of pectoralis major muscle in chickens in
response to dietary methionine status. Brit J Nutr.,95:703-708.
Corthesy-Theulaz I., den Dunnen JT., Ferre P,2005. Nutrigenomics: The impact of biomics technology on
nutrition research. Ann Nutr Metab., 49: 355-365.
Bertram, H. C., Bach Knudsen, K. E. and Serena, A. 2006. NMR-based metabolomic studies reveal changes in
the biochemical profile of plasma and urine from pigs fed high-fibre rye bread. Brit J Nutr., 95: 955-962.
Swanson, K.S., L.B. Schook and G.C. Fahey. 2003. Nutritional genomics: Implications for companion
animals. J. Nutr., 133:3033-3040.
Lee, C.K., D.B. Allison, J. Brand, R. Weindruch and T.A. Prolla. 2002. Transcriptional profiles associated
with aging and middle age-onset caloric restriction in the mouse heart. PNAS. 99:14988-14993
(www.pnas.org/cgi/doi/10.1073/pnas.232308999)
Rao, L., B. Puschner and T.A. Prolla. 2001. Gene expression profiling of low selenium status in the mouse
intestine: Transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J.
Nutr. 131: 3175-3181.
Liu, H.C., H.H. Cheng., V. Tirunagaru., L. Sofer, and J. Burnside. 2001. A strategy to identify positional
candidate genes conferring Marek’s disease resistance by integrating DNS microarrays and genetic mapping.
Anim. Genet. 32:351-359.
Afrakhte, M., and T.M. Schultheiss. 2004. Construction and analysis of a subtracted library and microarray of
cDNAs expressed specifically in chicken heart progenitor cells. Dev. Dyn. 230:290-8.
Santo, S.M., Vlijmen, B.L., van Duyvenvoorde, W., Offermans, E.H., Havekes, L.M.,Arnault, I., Auger, J.,
Princen, H.M. (2004) Absence of an atheroprotective effect ofthe garlic powder printanor in APOE*3-Leiden
transgenic mice. Atherosclerosis:177:291-297.
Stintzing, FC., Stintzing, AS., Carle, R., Frei, B. 2002. Wrolstad R,Color and antioxidant properties of
cyanidin-based anthocyanin pigments, J Agric Food Chem, 50, , 6172-6181.
Kaput, J.2008. Nutrigenomics research for personalized nutrition and medicine, Curr Opin Biotechnol.,
19(2):110–120.
Subbiah Ravi MT. 2006.Nutrigenetics and nutracueticals: The next wave riding on personalised medicine,
Transl Res., 149, 55-61.