What is nutritional genomics, and what dilemmas does it raise?

What is nutritional genomics, and what dilemmas does it raise? Dr Siân Astley NuGO Communications Manager

Food Health maintenance Disease development Health maintenance Disease development Nutritional Genomics It’s about food, who we are, and our health

DNA deoxyribonucleic acid

nucleus cell How much and where is it? • Every cell contains your DNA • Approximately 2 metres stored in the nucleus • 22 pairs chromosomes plus XX or XY

A C T G Recipe of life • Four unique chemicals called bases • guanine, cytosine, thymine or adenine • Sugar • Phosphate group

T G T C G A A A C A C T G

A Genomics and Genotyping DNA base-pair • This the genome • Study of the genome is genomics • Structural • Functional T With the kind permission of Dr Ruan Elliott The genome and genomics • Each chromosome contains 50,000-250,000 base-pairs • Total number of base-pairs is 3,000,000,000

Regions with the DNA sequence Code for protein Code for regulation of that protein 30,000-40,000 in the human genome Basic unit of heredity 1-2% of the sequence 1-2% controls when, how much and frequency with which a gene is read 96% has no known function Gene GCTAGCTAGCCAGTAGCTGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTACCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTCTATGACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGT

Genotyping • We inherit genes from each parent but the result is unique • Inheritance of some characteristics is simple, e.g. eye colour • Others interact to give a result that it a mixture, e.g. hair colour • The genes that you inherit make up your genotype • The resulting product is your phenotype • Genotyping determines the genes you inherited but not the result • Predictable phenotypes include those associated with disease, e.g. cystic fibrosis • Age-related diseases are controlled by many genes

Gene machinery GCTAGCTAGCCAGTAGCTGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTACCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTCTATGACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTTGACTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGAAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACG

Coding sequence for protein GCTAGCTAGCCAGTAGCTGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCTTAGGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTACCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTCTATGACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTTGACTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGAAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAGCTAGTACGTATCTGGGGATTTTAGCTAGCCAGTAGCCTAGCCAGTAGCTAGTACGTATCTAGTACGTATCGATGTTTGGGGATTTTAGCTAGCCAGTAGCTAGTACGTATCGATGTTTGGGGATTCTAGCCAGTAGCTAGTACG

U U U T U T T T T G G T T T C C C C C C C C G G G G G A A A A A A A A A A A RNA

U U G C G A A • DNA → RNA is transcription • Study of all the RNA sequences from a cell is transcriptomics Transcriptomics With the kind permission of Dr Ruan Elliott RNA – Ribonucleic acid • Identical to DNA • Thymine replaced with uracil • Able to leave the nucleus

M U U U T Y T U M M P Y T T M G C C C G A A A A DNA → RNA → Protein

DNA → RNA → Protein • RNA → protein is called translation • 20 distinct amino acids make up all proteins • Interaction between AA and other molecules creates protein structures • All proteins are 3-dimensional • Some proteins are made up from bundles of smaller proteins • Addition of other molecules post-translation • e.g. iron in haemoglobin

acid to alkaline large small Proteomics With the kind permission of Abigael Polley Protein • The collection of proteins, which a genome codes, is called the proteome • The study of the proteome is called proteomics • The 1º-4ºstructure of proteins determines their unique characteristics • Very difficult to retain shape and function in isolated proteins • Proteomics is more difficult that genomics, genotyping & transcriptomics

Metabolomics • Study of these processes and their metabolites is called metabolomics With the kind permission of Drs Ian Colquhoun and Marianne Defernez Metabolites and metabolism • Proteins are responsible for cell: • Structure • Growth • Reproduction • Coordination of these activities throughout the body

Tiny differences • Effects on health are different from one person to the next • What determines these differences?

lysine threonine → K T The nature of individuality • Differences from the published sequence between individuals • These are known as polymorphisms • Single nucleotide polymorphism (SNP) = a swap of a single letter in the code ATGACGTATCCAGTAGCTAGTAAGTATCGATGTTCTAGCCAGTAG ATGACGTATCCAGTAGCTAGTACGTATCGATGTTCTAGCCAGTAG • May make the protein product work more or less well • More than 1.5 million SNPs known in the genome • Estimated 200,000 in the gene sequences

DNA - genes Health Maintenance Disease Development RNA Genomics and Genotyping Metabolites Protein Proteomics Metabolomics Transcriptomics Food With the kind permission of Dr Ruan Elliott

Should our food match our genes? • How food interacts with our genes, RNA, proteins and metabolites • How this affects the health & disease • Offer specific information • Targeted, if not at individuals, then at least groups within the population at large • Early developments most likely in those with recognised food-related disease

Social, ethical, legal & economic Scientific What dilemmas does nutrigenomics raise? • Allowing choice • What to tell and when • Ownership • Profit • Methods are relatively untried and untested, and not panacea • How reliable is the information? • Are we able to interpret and understand it? People-centred research

The European Nutrigenomics Organisation (NuGO) • Network of Excellence • Nutrigenomics is too big to work alone! • Bringing together expertise and facilities • 22 partner organisation in 10 European Countries • UK, France, Germany, Netherlands, Norway, Sweden, Ireland, Italy, Poland & Spain • €17.3M for 6 years • Self funding and in the position to answer real questions about how our food interacts with our genes, and affects our health

Exploring our dilemmas • Dr Oonagh Corrigan (Faculty of Social and Political Sciences, University of Cambridge, and Cambridge Genetics Knowledge Park) will talk about the bioethics debate surrounding human genome research in 'They're my genes!’ • Dr Marcus Cooke (Senior Lecturer, Department of Cancer Studies, University of Leicester and Leicester Royal Infirmary NHS Trust) will ask the question whether there more to diet than meets the eye • Dr Keith Grimaldi (Chief Scientist - Sciona Ltd) will expand on the application of nutrigenomics in the real world away from the laboratory in benefits and challenges of commercial gene tests

What is nutritional genomics, and what dilemmas does it raise?