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26 Cards in this Set
- Front
- Back
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Nutrigenomics
(Definition) |
The study of how foods interacts with our genome:
- How dietary chemicals alter gene expression - How genetic differences (gene variants) affect the metabolic and physiologic response to food - How diet-regulated genes may play a role in the incidence, progression, or severity of chronic disease - How dietary interventions based on knowledge of genotype (i.e., "personalized nutrition") can be used to prevent, mitigate or cure chronic disease |
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The Age of Genomics
Phase 1 |
Sequencing
The map of the human genome is virtually complete More than 30,000 genes have been identified More than 1 million sequence variations have been identified |
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The Age of Genomics
Phase 2 |
Functional Genomics
What do all these variations do? What is their clinical impact? How can we use genomics in our clinical practice? |
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Single Nucleotide Polymorphisms
(SNPs) |
A variation in the genome sequence
Human genome contains >106 SNPs May be in coding/non-coding regions There functions may vary depending on its location |
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Depending on its location, a SNP may...
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Alter gene expression or response
Alter messenger RNA processing Alter protein structure and function Do nothing |
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Alleles
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A variant gene with a frequency of greater than 1% in a population
Created by SNPs or by nucleotide insertions, deletions, inversions Synonymous (no change AA sequence) Non-synonymous (alters sequence) Not all SNPs are alleles (freq < 0.01) Not all alleles are SNPs (insertions, deletions, inversions, translocations) |
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Gene Evolution
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Germ cell DNA mutations occur most often at time of meiosis (male>>female)
Sexual reproduction spreads mutations Mutations that are not lethal are neutral Natural selection acts on mutations that affect reproductive fitness, success, or likelihood of reaching reproductive age |
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Diet-Gene Interactions
The Impact of Variant Alleles |
Increase (decrease) macro and micro nutrient absorption or metabolism
In the setting of a modern-day diet, alleles that modulate nutrient absorption could: - Increase the salutary effects of specific nutrients - Induce nutrient toxicity - Induce nutrient deficiency - Increase the disease protective (or inducing) effects of specific nutrients in carriers |
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Diet and Gene Evolution
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Lactase and dietary calcium absorption
ApoA4-2 and dietary cholesterol absorption ApoA4-S and dietary DHA secretion in milk |
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Lactase
Diet and Gene Evolution |
A beta-disaccharidase located in the brush border of intestinal enterocytes
High levels appear shortly after birth mRNA and protein levels fall sharply at the time of weaning in all mammals In most human populations lactase levels fall throughout childhood and are low by the end of adolescence |
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Lactase Persistence
Diet and Gene Evolution |
In some populations there is a high frequency of adult lactase persistence
Autosomal dominant trait with north --> south, east --> west frequency gradient These populations have a historically high intake of milk and dairy products Mapped to a SNP (C/T-13910) upstream of the lactase gene on chromosome 2 |
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Apolipoprotein A-IV
Diet and Gene Evolution |
Member of a ancient family of proteins that control lipoprotein metabolism
Gene located on chromosome 11 Expressed only in the small intestine Synthesis increase by dietary lipid absorption Regulatory role in chylomicron assembly, secretion, and intravascular metabolism |
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ApoA-IV-2 Allele
Diet and Gene Evolution |
SNP encodes a Q360H substitution
H-allele frequency = 5-12% in the United States and northwestern Europe Very rare in Asian, African, Aboriginal, and Native American populations Alters protein structure and function: the H-isoprotein has higher lipid affinity Blunts the LDL response to a high cholesterol diet Reduces intestinal cholesterol absorption |
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The Mammalian Paradigm
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Internal Gestation
- Placental nutrient transfer Larger Brains - Ex-utero neural maturation - Requires effective transfer of (omega) 3 fatty acids (DHA) to the developing brain Post-Natal Delivery of Nutrients - Lactation - Altered lipid metabolism |
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ApoA-IV-S Allele
Diet and Gene Evolution |
SNP encodes a T347S substitution
S-allele frequency = 20-25% worldwide, suggesting that it is an ancient allele that predates the radiation out of Africa The S-isoprotein has lower lipid affinity Associated with rapid chylomicron clearance, increase BMI, and increase adiposity |
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The Molecular Evolution of the ApoA-IV-S Allele
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Apo A-IV-S accelerates post-prandial intravascular chylomicron clearance
More rapid chylomicron clearance may increase the flux of dietary fat into milk The apoA-IV-S allele may have evolved by conferring a neonatal nutritional advantage |
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The Thrifty Gene Hypothesis
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Proposed in 1962 by geneticist James Neel
Postulates that certain genes evolved to maximize metabolic efficiency and nutrient storage In ancient times, thrifty genes would have conferred a selective advantage during periods of famine. However, in abundant times, thrifty genes predispose carriers to diseases caused by dietary excess Ethnic groups with a history of food scarcity will have undergone greater evolutionary pressure, and may harbor more thrifty genes than other populations. |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: CONSERVE ENERGY?
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Ancient Function: Conserve energy
Nutrient Change: Caloric excess Modern Disease: Obesity, Diabetes |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: INCREASE TG ABSORPTION?
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Ancient Function: Increase TG absorption
Nutrient Change: High dietary fat Modern Disease: Obesity, ASCVD |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: INCREASE STEROL ABSORPTION?
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Ancient Function: Increase sterol absorption
Nutrient Change: High dietary lipids Modern Disease: Gallstones, ASCVD |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: INCREASE MILK LIPID TRANSFER?
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Ancient Function: Increase milk lipid transfer
Nutrient Change: Caloric plenty Modern Disease: Hyperlipidemia |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: LACTOSE ABSORPTION?
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Ancient Function: Lactose absorption
Nutrient Change: Milk widely used Modern Disease: "Intolerance" |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: CONSERVE SODIUM?
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Ancient Function: Conserve Sodium
Nutrient Change: Wide availability Modern Disease: Hypertension |
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What are the Nutrient Change and Modern diesease(s) associated with the Ancient Function: CONSERVE IRON?
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Ancient Function: Conserve iron
Nutrient Change: Wide availability Modern Disease: Hemochromatosis |
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Genomics and Dietary Rx
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Assess present macro and micro nutrient status and future requirements
Identify noxious foodstuffs and enable portioning for symptomatic relief Guide prescription of foods and diets for disease treatment and prevention Predict response to dietary intervention |
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Genomics Tools
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High capacity DNA Sequencers
Robotic SNP and Allele Analysis DNA Arrays NutraGene DietScan |
