The Genetic Revolution: Challenge for the Dietetics Profession The Human Genome Project will change

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The Genetic Revolution Challenge for the
Dietetics Profession The Human Genome
Project will change the practice of
dietetics forever. (White, J. JADA 100 (9)996)

• Dr. Betty J. Larson
• Concordia College
• Moorhead, MN 56562

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We are not all alike

• It will be possible to identify the genes that
  influence susceptibility to a disease.
• Once the gene is detected, MNT can be matched to
  the individual to prevent or effectively treat
  the disease.

When it comes to
diet,
one size does not fit all!

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The Challenge Are you ready for this client?

• A clients laboratory results show that he is
  heterozygous for ABC1 and has a null genotype for
  XYZ2. He has been referred to you for counseling
  on a diet appropriate for his genotype.

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The correct response for the client

• The client has an inherited susceptibility to
  cancer.
• The recommended diet would include large amounts
  of certain vegetables, special techniques for
  meat preparation

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American Dietetic Association recommends that to
be ready for the future we should

• 1. Require courses on diet-gene interactions
• 2. Include human genetics as a topic area on the
  RD
• exam
• 3. Develop internet-based communication and
• information hub for dietetics professionals
• 4. Sponsor training at ADA meetings
• 5. Begin dialogue regarding a new practice
  specialty
• in diet and genetic counseling
• 6. Encourage a health care system where personal
  counseling on diet-gene interactions is valued
  and reimbursed.

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Purpose of this presentation is to help us to be
ready for the future

• Explain the Human Genome Project
• Define genetic terms
• Show relationship between genetics and nutrition
• Recognize ethical issues
• Demonstrate how these genetic principles utilized
  in genetic engineering of foods

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The Cell
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Polypeptides

An
example of the amino acid sequence that

makes up the protein vasopressin
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Human Genome Project

• Started in 1990
• An international research program that will
  complete the mapping and sequencing of all DNA in
  the human body

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DNA (deoxyribonucleic acid)

• The chemical inside the nucleus of a cell that
  carries the genetic instructions for making
  living organisms.
• DNA exists as 2 paired or complementary strands
  forming a double helix.
• Each strand of DNA is made up of millions of
  chemical building blocks called bases
• (A) Adenine
• (T) Thymine
• (C )Cytosine
• (G) Guanine

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• The 4 bases are strung along a repetitive sugar
  (doxyribose phosphate backbone)
• The 2 strands of DNA are held together by pairing
  of the chemical bases.
• Adenine forms hydrogen bonds with thymine and
  cytosine forms hydrogen bonds with guanine.
• Bases are connected to each other by hydrogen
  bonds, abnormalities in these bonds cause some
  genetic diseases. Folic acid in prevention of
  neural tube defect may help overcome a defect in
  bonding and arrangement of bases at the cellular
  level in certain women.
• DNA holds the codes for making the body proteins

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Replication

• When the genetic code is switched on to make a
  protein, the information is copied, base by base,
  from DNA into a single new strand of
  complementary RNA.
• RNA is single stranded, its backbone is ribose
  and it contains uracil instead of thymine.
• Transcription is the process of events by which
  sequence of bases on DNA is copied to RNA.
• Translation is the sequence of events that
  converts the mRNA into a specific protein.

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Nutrition plays a role at the level of gene
expression.

• Process of transcription and translation can be
  controlled at several levels. There is a
  promoter region on DNA, initiator sequence,
  activators.
• Multiple iron-sulfur clusters are in the cell
  cytoplasm and they respond to the bodys iron
  status by impacting the half-life/stability of
  transferrin mRNA to control the production of the
  transferrin protein.
• In low iron the transferrin receptor mRNA has a
  longer, half-life thereby producing more
  transferrin mRNA to be translated into
  transferrin receptor proteins. Once made these
  transferrin receptor proteins increase uptake of
  iron.

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• Iron also controls ferritin synthesis at the
  level of translation.
• Zinc, Copper, Cadmium, Vitamin A and Vitamin D
  can all influence gene expression.
• Very clear that vitamins and minerals dont just
  regulate as co-enzymes or cofactors for enzymes,
  but control transcription of genes,
  post-transcription and translation.
• A better understanding of this process will
  clarify mutations in human disease.

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Genetic Code

• Every 3 bases (called a triplet or condon) along
  a strand of DNA specifies an amino acid to be
  incorporated into a protein, in what is called
  the genetic code.
• The triplet composed of the bases guanine,
  cytosine, and adenine is the genetic triplet code
  for the amino acid alanine.
• GAA, ATT, ATG are all examples of condons
• In the ctyoplasm, the mRNA attaches to ribosomal
  RNA and one codon at a time sequentially directs
  the assembly of amino acid molecules into
  proteins. It may be ready-to-go or new
  post-translation processing.

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Gene

• A gene is a segment of a DNA that encodes
  instructions that allow a cell to produce a
  specific protein such as an enzyme or a receptor
  or carrier protein.
• The functional and physical unit of heredity
  passed from parent to offspring. Genes are pieces
  of DNA, and most genes contain the information
  for making a specific protein.

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• Each gene is composed of long stretches of DNA
  that can be divided into 3 separate classes.
• Exons - parts of the gene that actually provide
  the specific instructions (the coding region) for
  making a protein
• Introns - noncoding stretches of DNA
• In addition to exons and introns each gene also
  contains a noncoding region at its beginning that
  serves to regulate when, and to what extent, the
  gene is expressed. It is the regulatory region
  of the gene (on-off switch). That responds to
  signals.

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Chromosome

• One of the threadlike "packages" of genes and
  other DNA in the nucleus of a cell.
• Each chromosome contains many genes.
• Bases are the letters, codons the words, genes
  the sentences and chromosomes the chapters on how
  to put together the human.

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Human Genome

• The genetic material within our cells contains
  the complete set of instructions for making an
  organism, called its genome.
• The human genome is the entire manual. Every
  cell contains the entire genome.
• The human genome is organized into 46
  chromosomes. Of these chromosomes, 44 are in 22
  pairs (autosomes) in which one chromosome is
  inherited from Mom and one from Dad. In
  addition, females inherit an X chromosome from
  each parent, whereas males inherit an X
  chromosome from Mom and a Y from Dad.

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Your genes are like

• a hand youve been dealt in a game of cards.
• Theres nothing you can do about the cards so you
  just have to do the best with what you have.

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Genetic Variation

• Although thousands of random changes occur every
  day in the DNA of a cell as a result of heat and
  metabolic accidents, only a few accumulate in a
  year.
• Remarkable repair mechanisms travel the strand of
  DNA

Aliens
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Microarray Analysis

• A computer applies tiny dots of DNA from
  different genes to a glass slide in a grid-like
  pattern.
• Then it uses ultraviolet light to detect abnormal
  genes.

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Genetics vs. Environment

• Genetics determines susceptibility to disease,
  but whether or not a predisposed individual
  develops the disease may depend on environmental
  factors such as nutrition.

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How are genes related to nutrition?

• Digestion
• Absorption
• Metabolism
• Excretion
• Taste

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Metabolic Differences

• Vitamin and mineral needs
• Sodium levels
• 30-60 of variance due to genetics
• Cholesterol
• 50 of variance due to genetics
• Fiber affecting cholesterol
• Phytochemical effectiveness
• Bone Density
• 75 of variance due to genetics

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Diseases Linked to Genetics

• Hypertension
• Obesity
• Diabetes Mellitus
• Cancer
• Osteoporosis
• Alzheimers Disease
• Cystic Fibrosis

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Obesity

• The Pima Indians in Arizona and in Sonora Mexico
  share the same genetic make-up but the Arizona
  population has the highest prevalence of Type II
  Diabetes Mellitus in the world, whereas their
  Mexican counterparts are lean and healthy.
  (Bennett, PH (1999) Nutrition Reviews 57S61-S64
  and Valencia, ME, et al (1999) Nutrition Reviews
  57 S55-58)
• Bouchard demonstrated with identical twins that
  although the genetic predisposition existed for
  obesity, development of obesity was not a forgone
  conclusion. (Bouchard, et al (1990) NEJM
  3221477-1482).

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Obesity Continued

• Therefore, while we might be genetically
  predisposed to obesity, our environment and diet
  allows it to occur.
• Furthermore, genetic make-up appears to determine
  which obese individuals benefit from particular
  diet therapies and even exercise. (Barsch et al
  (2000) Nature 404644-651, and Chagnon et al
  (2000) Obesity Research 889-117, and Martinez
  et al (2000), Eruopean J. Clin Nutrition 54
  S56-S60.

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Gluten-Sensitive Enteropathy

• Individuals with gluten-sensitive enteropathy
  have a genetic pre-disposition but do not
  manifest the disease if they do not eat gluten.
  They still have the genes but dietary intake
  prevents expression of the gene.

(Murray, Am J. Clin. Nutr (1999) 69 354-365)
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Homocysteine

• Individuals with a common genetic variation in
  the 5,10-methyl-enetetrahy-drofolate reductase
  gene are predis-posed to increased levels of
  homocysteine (a risk factor for CVD. You do not
  develop increased levels if you consume adequate
  folate. Nutrition fills the genetic gap.

Kang (1988) Am J. Hum Genet 43414-421. Jacques
(1996) Circulation 937-9. Verhoeff (1998)
Atherosclerosis 141161-166)
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Hypertension

• Genetic variability in components in the
  renin-angiotension-aldosterone system have
  correlated with hypertension and its response to
  a low-salt diet.

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Coronary Heart Disease

• Both genetics and environmental factors influence
  risk of CHD.
• Genes influence levels of total cholesterol,
  lipoproteins, hypertension and obesity

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• Which apolipoprotein E variants (apoE 2, 3, or 4)
  individuals have affects their risk of CVD and
  their response to dietary manipulation.
  (Simopoulos (1999) Nutr Rev 57S10-S19).
• For example, the common advice to increase PS
  ratio benefits men with genotype ApoE4/ApoE3 or
  (4/3) but not women with the ApoE 3/2 genotype.
  (Cobb et al (1992) Circulation 86849-857.)
• Oat Bran promotes a hypocholesterolemic response
  in those with the ApoE 3/3 genotype but not in
  those with 4/4 or 4/3. (Uusitupa, et al (1992) J
  Am Coll Nutr 11651-659.

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Lipoprotein Study

• General population is divided into two groups
  Phenotype A and B
• Phenotype A large, buoyant LDL
• Phenotype B small, dense LDL
• At higher risk for CHD
• Krauss, Dreon. Low density lipoprotein
  subclasses and response to a low-fat diet in men.
  Am. J. Clin. Nutr (supppl) 1995
• Identification of genetic polymorphisms that
  influence lipoproteins and CHD risk eventually
  will lead to genetic markers for this disease.
• The same genetic factors that determine an
  individuals blood lipid profile and CHD risk
  will also influence response to diet.

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Diet Response related to Genes

• 72 premenopausal women and 105 healthy adult men
  consumed low fat diets for 6-8 weeks
• Both men and women in the Phenotype B group were
  shown to have a decrease in the total number of
  LDL particles
• Although, 41 of Phenotype A showed an adverse
  affect with a change to more of the atherogenic
  Phenotype B patterned LDLs
• Dreon, Fernstom, Miller FASEB J. 8L121m 1994
• Dreon, DM, Krauss, RM Circulation 86 (suppl)
  1-405, 1992

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Cancer Risk

• Inherited or spontaneous occurrence?
• Only 5-10 is inherited, but those individuals
  have an 85 chance of getting breast cancer
• Also, they are at higher risk for reoccurrence
  and ovarian cancer
• It is now identifiable so these individuals can
  be monitored more closely

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Plant Phytonutrients

• The plant phytonutrients genistein and quercetin
  appear to work at the level of gene expression to
  decrease the risk of prostate and liver cancer,
  respectively.

Davis, et al (1999). Nutr Cancer
35167-174. Kang, et al (1999). Nutr Cancer
35175-179.
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Alzheimers Experiment

• Injected a gene into the brain that causes
  production of a nerve growth factor
• It is hoped this factor will be able to reproduce
  the missing factor and reverse the disease

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Ethical Issues

• Misinterpretation and misuse of information
• Personal rights
• Do we want to know?

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Dietitians perspective

• Not just genetics
• Genomics
• The study of genes and how they influence health
  and disease
• Its our responsibility to understand the
  connections between genes, nutrition, and disease
  

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Knowledge of genetics is not only important for
MNT but for an understanding of our food!

• The health professional must be able to explain
  the use of biotechnology in food development
  because consumers are confused.
• In Europe they refer to our new foods as
  Frankenfood!

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Biotechnology is the application of living
organisms to develop new products

• The terms genetic engineering, recombinant DNA
  (rDNA) technology, gene splicing and genetic
  modification often are used interchangeably.
• These phrases refer to specific processes used in
  biotechnology, describe the movement or transfer
  of genetic material from one source to another.

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Applications of Biotechnology

• Products of biotechnology were commonplace
  centuries before Watson and Crick defined the
  structure of DNA.

In 1800 BC with the use of fermentation, humans
first used microorganisms to produce wine,
beer and leavened bread.
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Biotechnology holds great promise

• Biotechnology has potential in the fields of
  medicine, environmental protection, food
  production and agriculture.

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Biotechnology provides opportunities for
protection of the environment

• Genetically modified bacteria may be used to
  convert organic wastes from municipalities into
  useful products, including sugar, alcohol and
  methane compounds that can be alternative fuels.

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Opportunities in food production

• Chymosin was first approved in the US in 1990 as
  a pure enzyme from genetic engineering that
  replaces rennet in the production of cheese.

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Opportunities in Agriculture

• In 1994, the first genetically engineered plant
  food product, a vine-ripened tomato, was
  available to consumers.

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Plant biotechnology is the addition of selected
traits to plants to develop new plant varieties.

• Allows for the transfer of a greater variety of
  genetic information in a more controlled manner
  than traditional plant breeding.

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Applications

• Disease protection, which provides intrinsic
  protection from a specific virus or fungal
  disease.
• Insect protection, which provides intrinsic
  protection from targeted pests.
• Tolerance to a specific environmentally
  compatible herbicide, allowing for more effective
  weed control.

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Improved nutritional value

• Golden rice with improved vitamin A content could
  reduce blindness in developing countries.
• Bananas which would convey resistance to cholera.

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Organizations recognize the safety of
biotechnology

• The American Dietetic Association
• American Medical Association
• National research Council
• World Health Organization

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Myths and Facts about Food Biotechnology

• Myth 1 The application of biotechnology to
  crops and food is very different from traditional
  agricultural methods.
• Myth 2 Foods produced using biotechnology have
  not been established as safe nor are they
  adequately regulated.
• Myth 3 The application of biotechnology to food
  only benefits food producers not consumers.

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Myths Continued

• Myth 4 Without special labeling, consumers face
  unknown risks from food biotechnology.
• Myth 5 Crops produced using biotechnology will
  negatively impact the environment.
• Myth 6 The production of crops resistant to
  certain pests and weeds will lead to Super Bugs
  and/or super Weeds immune to existing methods
  of pest and weed management.

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Myths Continued

• Myth 7 biotechnology cannot relieve world
  hunger.
• Myth 8 The long-term effects of foods developed
  using biotechnology are unknown.