Nutritional Genomics

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NUTRITIONAL GENOMICS BY: - NEERAJ KUMAR Animal Biotechnology Lab Kurukshetra University Kurukshetra

Contents : 

Contents INTRODUCTION NUTRIGENOMICS NUTRIGENETICS NUTRITIONAL GENOMICS RELATIONSHIPS EXPERIMENTAL MODEL SYSTEMS APPLICATION CHALLANGES ETHICS BUSINESS GLOBAL NETWORK CURRENT PROJECTS FUTURE CONCLUSION REFERENCES

Introductions : 

Introductions Science that utilize high throughput techniques for studying relationships between Human Genome, Nutrition and Health. Nutrigenomics Nutrigenetics

Nutrigenomics : 

Nutrigenomics Study the molecular relationships between nutrients and response of Genes. Mainly focus on effects of nutrient on expression of Genes.

Interaction of Nutrients and gene expression : 

Interaction of Nutrients and gene expression Direct - Nutrients act as ligand for transcription factor receptors. Indirect -Nutrients metabolise by primary or secondary pathways, altering concentrations of substrates/intermediates Indirect- Nutrients alter the signal transduction pathways and signaling.

PPARs are ligand activated transcription factors : 

PPAR Unsaturated fatty acids DNA transcription PPAR AGGTCAAGGTCA Gene Response element β oxidation PPARs are ligand activated transcription factors

Lipids and PPARs : 

Nutrient metabolism (lipid, glucose, AAs) - Inflammation - Lipid and glucose metabolism - Inflammation - Lipid metabolism - Inflammation PPARa PPARg PPARb Lipids and PPARs

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Why are PUFAs healthy? b-Oxidation FA synthesisTriglyceride synthesis PPAR Fatty acid oxidation genes + SREBP1 Lipogenic genes - VLDL PPAR-Peroxisome proliferator-activated receptors SREBP1-sterol response element binding protein1

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P P P P P PP2A PP2A Cho RE LIPOGENESIS AND GLYCOLYSIS NUCLEUS CYTOSOL GK G6P Xu5P INACTIVE ChREBP PLASMA MEMBRANE GLUCOSE mRNA PROTEIN P Carbohydrates and ChREBP

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Nutrients and Transcription factors

Nutrigenetics : 

Nutrigenetics Study the effect of genetic variations on interaction between nutrients and genes Analyses how genetic make up of individual affect their response to diet Ultimate goal is to provide nutritional recommdations for individuals according to their genetic make up

Genetic variations : 

Genetic variations All humans are 99.9% identical at gene sequence level(Kaput & Rodriguez 2004). 0.1% variations in sequence produce differences in phenotype. Most common type of genetic variation Is single nucleotide polymorphism(SNP).

Single Nucleotide Polymorphism (SNP) : 

Single Nucleotide Polymorphism (SNP) Change occur at single base SNPs makes 90% of all variations 3 Million SNPs are identified in humans Because of these SNPs individuals response differently to same diet

Folic acid and MTHFR : 

THF 5,10-methyene THF 5 methyl THF B12 MTHFR Homocysteine methionine SAM SAH DNA methylation METHIONIE SYNTHASE EFFECTS:- Homocyctein Methylation Folic acid and MTHFR

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The MTHFR gene, located on chromosome 1 consists of 11 exons & spans a region of about 20 kilobases Genetic variants : Two common SNPs 677C>T in exon 4 (alanine to valine) 1298A>C in exon 7 (glutamate to alanine) Heterozygosity and homozygosity for the genetic variant are associated with about a 35% & 70% reduction in enzyme activity,respectively

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Individuals NORMAL Wild type MTHFR Individuals Mutant MTHFR low Folate low Folate CANCERS AND C.V.D Individuals Mutant MTHFR High Folate NORMAL

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Nutrigenomics Nutrigenetics Personalized nutrition Nutritional genomics = Nutrigenomics + Nutrigenetics

Nutritional genomics relationships : 

Transcriptomics Proteomics Metabolomics Bioinformatics DNA Microarray 2D PAGE Mass Spectrometry GC/MS MIAMI/Nut Nutritional genomics relationships Nutritional genomics

Experimental model systems : 

Animals Cell lines eg:-Human caco-2 & HT-29 representing Gut, Human HepG2 cells for Liver Human eg:- Blood sample, cheek swab eg:- mouse,pig Experimental model systems

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Nutrients Colon, Gastric, Breasts cancer N-Acetyltransferase N-Acetyltransfer- Gene ase enzyme NAT catalyse the Acetylation of Hetrocyclic aromatic amines (HAA) found in cooked Red meat HAA Reactive DNA Cancer Metabolites NAT Application Study of relationship between diet and onset of diseases eg :- cancer

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Cancer (cont…) NAT-1 Slow Acetylator NAT-2 Fast Acetylator NAT-1 Genotype Red Meat NORMAL Individuals NAT-2 Genotype Red Meat COLON CANCER Individuals Hence NAT-2 Genotype Individuals can prevent onset of cancer by avoiding RED MEAT + +

Challenges : 

Complex nature of food Food= Macro+ Micro Nutrients Polygenic diseases Diseases involve many Genes eg:- Diabetes, Cancer etc, Cost Challenges

Ethics : 

Ethics What happened to Genetic Data Lack of Genomic education on the part of consumer Reliabilty Are the tests available to all without discrimination

Business : 

Salugen HAVEOS - Suppliment of Nutrients for Narcotics tolerance GenoTrim - Suppliment of nutrients for weight control SpaGen - Suppliment of nutrients for Mental wellnes Business Suracell Core nutrition- Nutrient formula that interact with body’s Repair system

Business (conti….) : 

Business (conti….) Sciona Others Genewize WellGen Mycellf DNA nutrition program

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Harvard University U C Davis U A B Aberdeen U I Chicago NuGO Tufts University = Centres INH Canada Korea Global Networks

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NuGO is a European funded network of excellence linking Human genome ,Nutrition & Health research NuGO funded by EU-vi FP (2004-2009) Primary aims of NuGO Trained European scientists to use post Genomic technologies in Nutritional research Develop & integrate Genome technologies for benefit of European Nutritional science Facilitate the application of these technologies in Nutritional research Create the world leading virtual centre of excellence in Nutrigenomics

Current projects : 

Coordinated by Dr. Helen Roche & Prof. Michael Gibney- Institute of Medicine & Deptt. Of clinic medicine Trinity college, Dublin (Ireland) Investigating relationship between dietary fats composition, Genotype & metabolic syndromes LIPGENE – DIET,GENOME & METABOLIC SYNDROMES DIOGENES - DIET,OBESITY & GENES Coordinated by University of Maasstricht , Netherland Contributing to better understandings of obesity & its alleviation by dietary means Current projects

Conti…. : 

NUCSYS – SYSTEM BIOLOGY OF NUCLEAR RECEPTORS Coordinated by Dept. of Biochemistry , University of Kuopio Contributing to better understanding of age related diseases & delay of ageing by dietary interventions FUNCTIONAL FOOD PROJECT Coordinated by Dr. Aidan Moloney & Dr. Frank Monaghan, University college ,Dublin (Ireland) Determining health benefits of CLA enriched beef within the context of Insulin resistance & Atherosclerosis Conti….

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NUTRITIONAL SYSTEM BIOLOGY PROJECT Coordinated by Dr. Bankje De Ross, Rowette Research institute , Aberdeen , U.K. Determining inter organ & cell specific transcriptomics & proteomics profiles in disease models. Relevant to Insulin Resistant & Atherosclerosis Conti….

Future : 

Future PERSONALISED NUTRITION – Diet according to person’s Genetic make up Novel Functional Foods NEW BIOMARKERS Gene expression profile during disease progres will be available for early detection of disease

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Individuals response differently to diet due to their Genetic make up. Nutritional Genomics is a science that help us to tailored our diet according to our Genes. This field is still in its infancy but the time is not far away when we can take the foods which our DNA likes Conclusion

DIET AND LIFE STYLE : 

DIET AND LIFE STYLE Dynamic interaction Genes Disease Optimal functioning

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wellness Illness Genes choices Precautions

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wellness Illness Genes Choices Precautions

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Muller M & Kersten S (2003) Nutrigenomics : goals and stratgies. Nature review genetics 4, 315-322 W.A.Walker & G.Blackburn (2004), Nutrition and Gene regulation. America Society for Nutrition Science 134,115-118 M.M.Bergmann,M.Bodzioch,M.L.Bonet,C.Defoort,Glietz,J.C.Mathers(2006), Bioethics in Human Nutrigenomics research: European Nutrigeniomics Organisation Workshop Report. British journal of Nutrition 95,1024-1027 Kaput J. Rodriguez RL (2004) Nutritional Genomics : the frontier in post Genomics Era. Physiol Genomics 16,166-167 Luan J. Browne PO, Harding A-H et.al.(2001) Evidences for gene-nutrient interactions at PPAR gamma locus.Diabetes 50,2023-2031 Kaput J. Ordovas JM, Ferguson L, et.al.(2205) The case for strategic international alliance to harness Nutritional Genomics for public and personal health. British journal Nutrition 94,623-632 References

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Mathers JC(2004) Chairman’s introduction : What we can expect to learn from Genomics ? Proc Nutr Soc 63,1-4 Fuchs D,Winkelmann I, Johnson IT, Mariman E, Wenzel U. & Daniel H.(2005) Proteomics in nutrition research : principles, technologies and applications. British Journal of Nutrition 94,302-314 German J.B. , Roberts M.A. & Watkins S.A.(2003) Personal metabolomics as a next generation nutritional assessment. Journal Nutrition 133,4260-4266 Mutch D.M. et.al(2005) Nutrigenomics and nutrigenetics : The emerging face of nutrition. FASABJ 19, 1602-1616

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“First it was smart drugs. Now it's smart diets “Eat right for your genotype”

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QUERIES