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Nutrigenomics (Definitions (Epigenetics (Epigenetic modifications (natural…

- - - - inherited and determines a trait.
  - - - Genotype is the starting place, environment, actions of other genes and
        random events can influence the resulting phenotype
  - - - Nearly every human
        cell contains 23 pairs
        of chromosomes
        
        – 1 - 22 and XY or XX
        • XY = Male
        • XX = Female
        
        consist of DNA
        – molecular strings of A, C, G, &
        T
        – base pairs, A-T, C-G
        
        No two people possess the same DNA except identical twins
        
        still not identical as DNA will be expressed differently
        
        During development in the womb and after birth, our surroundings, exposures,
        and nutrition influence how our genes are expressed and how our bodies and
        minds develop.
  - - - determines what is expressed in the phenotype
  - - - the physical options for a trait inherited from a gene
  - - - like a box containing an assortment of options
  - - - natural occurrences and influenced by
        diet and lifestyle amongst other factors
        
        Modifications define how the
        information in genes is expressed and used by cells, including when or even if
        a given gene is expressed; whether the gene is switched ‘on’ or ‘off’.
        
        It is not an alteration in the genetic code itself, but a change in phenotype,
        rather than genotype.
  - - - A - Adenine
        T - Thymine
        C - Cytosine
        G - Guanine 3 binding sites
        2 binding sites
- - - - Methyl group substrates include:
        • DNA and RNA
        • Chemicals
        • Neurotransmitters and hormones
        • Immune cells
        • Nerves
    - - A methyl group is
        
        1 carbon bound to 3 hydrogen
  - - - will divert to reactive oxidative
        quinone pathways that damage neurons and vascular endothelial cells
  - - - 50% heterozygous
      - Many MTHFR polymorphisms > 40 identified
      - SNP’s associated with reduced enzymatic activity in
        activating or methylating folate
  - - - –Synthesis of nucleic acids (for DNA production/repair and tRNA)
      - Single carbon metabolism (methylation)
      - –Interconversion of amino acids (for neurotransmitter production and
        detoxification)
      - –Formation and maturation of RBC, WBC and platelet production
    - - Uncooked leafy greens
      - Functional enzymes
      - Available receptors
      - Vitamins, minerals and pH
        • B2
        • B6
        • B12
      - Acidic environment (for absorption)
  - - - Broccoli
      - mushrooms
      - cauliflower
      - bean sprouts
      - avocados
      - fish, eggs, dairy, beef
      - spinach
      - garlic, onion
    - - Spinach
      - turnip greens
      - beans
      - sunflower seeds
  - - - Heterozygous = 1 copy of the gene from either parent
      - Homozygous = 1 copy of the gene from each parent
      - MTHFR C677T Heterozygous = 40% loss of function
      - • MTHFR C677T Homozygous = 75% loss of function
      - MTHFR A1298C Heterozygous = 20% loss of function
      - • MTHFR A1298C Homozygous = 40% loss of function
    - - MTHFR 677C C>T
        
        A 56-year-old patient with severe CVD, after interventions including two angioplasties and a CABG (coronary artery bypass
        graft), suffered a stroke
        
        However, with further evaluation after his stroke, through the lens of functional assessment, he was
        found to have a marked elevation of homocysteine (22 mmoles/liter with normal 6-8 mmoles/liter). He was tested
        genetically and found to have a specific genetic uniqueness, homozygous 677C to T polymorphism of MTFHR
        (methylenetetrahydrofolate reductase). This SNP (single nucleotide polymorphism) produces a variant enzyme that
        requires extraordinarily high doses of folate to facilitate coenzyme binding and MTHFR enzyme activity. His treatment plan
        focused on his genetic, proteomic, and metabolomic uniqueness. With appropriate nutrient intervention, his serum
        homocysteine equilibrated into the normal range, and he had no further demonstrable progression
  - - - GSH regenerates (recycles directly and indirectly a variety of other
        antioxidants including vitamin C, alpha lipoic acid and vitamin E
      - More than 6% of the total energy (ATP) production of the whole
        body may be used to synthesize and regulate intracellular
        glutathione levels.
      - GSH is the only non-enzyme antioxidant that does not itself
        become a free radical after it has quenched a free radical. In fact,
        oxidized glutathione (GSSG) induces delta wave sleep.
      - an essential component of antioxidant
        enzymes including glutathione peroxidases and genetically
        determined family of glutathione transferases
      - Major chelator of heavy metals
      - Detoxifies organic pollutants via phase II hepatic
        detoxification
      - GSH levels decrease with age (1% per year)
      - a major protector of mitochondrial DNA (MtDNA)
      - Maintenance of normal MtDNA directly correlates with
        maximum life span
    - - Stress
      - Radiation
      - Drugs
      - Pollution
      - Poor diet
      - Build up of toxins
      - Oxidative stress
      - Build up of free radicals
      - Infection
      - Aging
      - Injury/trauma/burns
- - - - can have dramatic affects
        Consider a basic sentence made of 3 letter words
        the dog ate the cat
        What if an early deletion of a single letter took place ?
        ted oga tet hec
        
        Location is the primary concern. An insertion at the very end of a
        sentence makes little or no functional difference as it only affects
        one triplet (1 amino acid)
    - - Can occur anywhere in the gene code and affects are dependant
        upon the frequency of the substitution.
  - - - occur in coding regions, non coding regions or between genes
        (intergenic)
- - - - 56% of drugs that cause ADRs are metabolized by
        polymorphic phase I enzymes, of which 86% are CYP
        P45
    - - Biological
        
        gender
        
        age
        
        renal function
        
        liver function
      - Inherited
    - - smoking
      - alcohol
        consumption
      - diet,
      - drug-drug
        interaction
  - - - • Oxidation
        
        loss of electrons by atom or molecule
      - Reduction
        
        gain of electrons by atom or molecule
      - Hydrolysis
        
        chemical breakdown of a compound due to reaction with water
  - - - Glucoronidation
      - Sulfation
      - Acetylation
      - • Methylation
- - - - BRCA1
      - BRAC2
- - - - 'A SNP map promises to revolutionize both mapping diseases
        and tracing human history'
- - - - somehow a
        trait that existed in the first pairing
        was hidden but re-emerged in later
        generations when allowed to self
        fertilise
        
        Penetrance
        
        The probability that a dominant
        allele will exhibit the associated
        phenotype
        
        Incomplete Penetrance
        Link Title
        
        The degree by which an allele
        expresses its phenotype is
        variable