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Nutrigenomics
Chapter 11
© 2007 Thomson - Wadsworth
Human Genome
• Human Genome Sequencing
Consortium
Finished human genome – 2003
• Entire set of genes
Blueprint 30,000 different proteins
© 2007 Thomson - Wadsworth
© 2007 Thomson - Wadsworth
Nutrigenomics
• Interaction between nutrients and
genotype
Variants can determine individual
response to dietary
factors…propensity to develop disease
• Pharmacogenomics
© 2007 Thomson - Wadsworth
© 2007 Thomson - Wadsworth
Overview of Genetics
• DNA – how to build an organism
Code varies from person to person
• Genome lies within nucleus of cell
Comprised of 22 pairs of
chromosomes
During mitosis all pairs are copied
During meiosis only one member of
each pair are copied
Karyotype
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Karyotype for Down syndrome
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Overview of Genetics
• Chromosomes
22 pairs are autosomes
1 pair determines sex
Alleles
• Nucleotides
Purine or pyrimidine base
• Adenine (A), guanine (G), thymine (T),
cytosine (C)
Ribose
Phosphate group
© 2007 Thomson - Wadsworth
© 2007 Thomson - Wadsworth
Overview of Genetics
• Complementary
strands
As always with
Ts
Gs always with
Cs
Doublestranded helical
formation
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DNA to protein
• Genetic Code
Codons - encode specific amino acid
chain
Promoter regions – noncoding
regulatory sequences
Intervening sequences
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© 2007 Thomson - Wadsworth
DNA to protein
• Transcription
 DNA unwinds encoding gene of interest
• Translation
 Copied by means of base pairing into
messenger RNA (mRNA)
 Partly dependent on dietary factors
• Posttranscriptional processing
• Protein assembly in ribosomes of RER
© 2007 Thomson - Wadsworth
© 2007 Thomson - Wadsworth
DNA to protein
• Transfer RNA (tRNA) serve as
anticodons
• Amino acids positioned in
sequence until stop codon is
reached
• Posttranslational modification
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Genetic Variation
• Polymorphisms – variations within
genes
May have profound effects
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Genetic Variation
• Inheritance
Autosomal dominant
• Familial hypercholesterolemia
Autosomal recessive
• PKU
• Cystic fibrosis
X-linked recessive
• Hemophilia
Y-linked
• Very rare – only in males
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Genetic Variation
• Inheritance
Phenotype – physical properties
Heterozygous – 2 different alleles
Homozygous – 2 identical alleles
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Genetic Variation
• Polygenic diseases
Obesity
Diabetes
Cancer
CVD
Single nucleotide polymorphisms
• SNPs
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© 2007 Thomson - Wadsworth
Genetic Variation
• SNPs
Single nucleotide exchanged for
another
Range from no alteration of function
to deleterious effects
Identification now focus of research
• Haplotypes – group of variants that occur
together
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Genetic Variation
• Other polymorphisms
Insertion or deletion
• Down syndrome
• Angelman syndrome
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Epigenetic Regulation
• Pattern of gene expression
DNA methylation
• See Fig. 11.8
• B12, folate, choline, methionine
• Impaired fetal development and cancer
Histone methylation
Acctylation
Phosphorylation
© 2007 Thomson - Wadsworth
© 2007 Thomson - Wadsworth
Diet and Gene
Expression
• PUFAs as ligands for PPARs
• Soy isoflavones
• Sulforaphane (broccoli)
• Measured using microarray
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© 2007 Thomson - Wadsworth
Nutrigenomics and
Disease
• Cancer
 Use of omega-3 & EPA for rare types
 Predicting benefit difficult in other types
• Responders and non-responders
 Colon cancer
• Folate intake and alcohol
• Fruits and vegetables
 Breast cancer
• Antioxidants
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Nutrigenomics and
Disease
• Obesity
Susceptibility with conducive
environment
Polygenic trait
Promising research
• Perilipin
• Serotonin receptor gene promoter
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Nutrigenomics and
Disease
• Thrifty Gene hypothesis
Metabolic status and fetal adaptation
predict disease in adulthood
Proneness to metabolic syndrome,
obesity, diabetes, CVD
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Nutrigenomics and
Disease
• Diabetes
Focus on type 2
Metabolic syndrome, insulin
resistance
GLUT 2
PPARy
APOE
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Nutrigenomics and
Disease
• Cardiovascular Disease
Dyslipidemias
Familial hypercholesterolemia
PUFAs on HDL
Omega-3s and TG
Omega-6s and inflammation
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Dietetics and
Genetics
• Understanding nutrient interactions and
genes
• Future of diet counseling
• Beware of home testing kits
 “DNA diet”
 Sciona
 Costly
• EGAPP Project
 To establish a coordinated process
© 2007 Thomson - Wadsworth