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.

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