Lecture 2 - The Role of Genes as a Determinant of Lifetime Health Flashcards
1
Q
Define Nutrigenomics and Nutrigenetics
A
- Nutrigenomics = the effect of diet on genes. Some genes are more sensitive to nutrition
- Nutrigenetics = the study of how genetic differences arising from polymorphisms modify dietary effects (genes —–> metabolism)
- So, they are the opposite of one another as nutrigenomics have food influencing genes and then nutrigenetics are genes influencing our diet
- We are all different when it comes to these
2
Q
Explain how chromosomes - DNA - and genes are related
A
- Chromosomes exist within a cell nucleus
- Chromosomes are made of DNA strands that contain bases: adenine, guanine, cytosine, and tyrosine
- Genes make up DNA
- People have different alleles which have variations in bases
3
Q
What is the central dogma of biology?
A
- DNA is transcribed to RNA
- RNA is translated into proteins
4
Q
Explain genotype and phenotype via Mendel’s peas
A
- A yellow plump pea is AABB and thus dominant form. It is bred with the recessive wrinkly green form aabb.
- The green wrinkly: It’s genotype is aabb and its phenotype is green, wrinkled
- When bred with the dominant AABB form its genotype is AaBb (dominant genotype) and its phenotype is yellow, plump
4
Q
What is nutrigenetics the study of?
A
- Study of how genetic differences arising from polymorphisms modifies dietary effects
- Genes —-> Metabolism
5
Q
What are polymorphisms? What is a SNP?
A
- Polymorphisms are substitutions of a base pair
- SNP: single nucleotide polymorphism
6
Q
Explain single nucleotide polymorphism and how it can have varying impacts
A
- a single nucleotide is substituted for something else and it can cause changes
- With a normal protein (Person 1) you will have a DNA sequence. One nucleotide base may be substituted
- Person 2: Substitution but the protein is normal despite DNA variation and you will have no negative effects
- Person 3: Substitution can cause low or non-functioning protein. Can lead to disease (e.g. sickle cell) or increased susceptibility to disease (e.g. lung cancer)
7
Q
What is sickle cell disease?
A
- An example of a single nucleotide polymorphism that impacts genotype and phenotype
- Causes red blood cells to not have proper formation/function, originates at the level of DNA
- Base pairs are switched around so it forms Valine instead of Glutamic acid and leads to different formation
8
Q
Explain the HemoglobinS Allele and how they can impact RBCs
A
- Sickle cell is caused from autosomal recessive HbS + HbS
- AA - homozygous for the ‘normal’ Hb allele (disc-shaped RBCs)
- AT - heterozygous for the Hb/HbS alleles (some disc-shaped and some with potential to sickle - no clinical symptoms)
- TT - homozygous for HbS allele (RBCs can sickle causing sickle cell disease)
9
Q
What is SREBP-1c?
A
- Sterol response element binding protein
- An example of a SNP in response to diet
- Gene that regulates lipid metabolism
- SNP + high fat diet = overexpression
- Overexpression associated with dyslipidemia, impaired glucose metabolism, Type-2 diabetes
- Need a lower fat diet in order to counteract the overregulation of lipid metabolism
10
Q
What is Apolipoprotein E4?
A
- An example of a SNP in response to diet
- Regulates lipoprotein-cholesterol clearance from plasma (rather than E1,E2,E3)
- ApoE4 allele + high fat diet results in higher LDL levels
- Higher risk of CV outcomes, and Alzheimers disease
11
Q
Define myostatin
A
Myostatin is a hormone that inhibits muscle protein synthesis
12
Q
Explain how whippets are impacted by SNPs
A
- Whippets = racing dogs
- MTSN gene variant mh (deletion)
- if myostatin inhibits muscle synthesis then it is a deletion of the myostatin so there would be increased muscle
- +/+ normal muscle and speed
- +/mh more muscle and faster speed = heterozygous
- mh/mh bulky muscle and slower. Mutant of both. Muscles are dysfunctional so they are slower
13
Q
Explain Prader-Willi Syndrome (PWS)
A
- An example of a snp related to genes and obesity
- chromosomal deletion with multiple genes affected
- hypothalamic dysfunction: growth hormone, hunger-satiety hormones, other endocrine
- short stature, lower lean mass, hyperphagia (lack of satiety leading to insatiable hunger), developmental delays
- Failure-to-thrive in infancy –> food seeking in early childhood (insatiable hunger)
14
Q
How does nutrigenetics impact metabolism and how can this be modified?
A
- Genetic differences arising from polymorphisms can alter metabolism
- Genetic polymorphisms can not be changed. They can go from generation to generation.
- Dietary modification can be made to amount of energy and nutrients and types of diet depending on the Snp
15
Q
Define nutrigenomics
A
- the application of nutrition to the entirety of gene expression: the interaction between diet and genes
- study of how nutrition influences gene expression (on/off)
- Food —-> Gene expression
- Change in phenotype (physical looks) without a change in genotype
16
Q
Explain the concept of epigenetics
A
- changes in gene expression (phenotype) caused by mechanisms other than changes in the underlying DNA
- Non-genetic factors cause the organism’s genes to be expressed differently
- Allows for adaptations to environment
- Changes remain through cell divisions
22
Q
What does DNA methylation mean?
A
- Methyl groups can be added at any place along DNA sequence
- Done via DNA methyltransferases
- Note: DNA methylation changes how things are folded together
23
Q
What can DNA methylation and histone modification do?
A
- DNA methylation and histone modification can cause genes to turn off for active DNA
- Which means that although they have the same DNA, a liver cell is a liver cell and a brain cell is a brain cell because they have different epigenetic codes
- Cells know what to become via DNA methylation and histones. DNA needs to be in a certain structure to be functional, if not then turned off.
24
Q
Can we have changes in phenotypes over our lifetime? Explain.
A
- Environmental factors such as diet, stress, exercise, smoking, alcohol drugs, pathogens, and weather can impact our DNA
- DNA methylation, histone modification, and chromatin remodeling will be impacted
- This then changed our phenotype in regards to physical shape, disease susceptibility, stress response, behavior, longevity
27
Q
Explain the life-course model
A
- As we age the risk of non-communicable diseases increases
- 4 life stages including fetal life, infancy and childhood, adolescence, and adult life
- By adult life there is an accumulated risk of non-communicable disease
- Demonstrates how lifetime exposures can increase risk
34
Q
What does the dutch famine demonstrate?
A
- Times of rationing where there was an extreme decrease in caloric intake
- Changes in DNA methylation in genes related to growth (bc malnourished)
- Women were pregnant at this time and their offspring showed higher glucose levels, higher LDL/HDL ratios, CHD %, and microalbuminuria (impacts kidneys)
- Depended on time frame of when they were pregnant
- Before and after pregnancies the adults had normal results
40
Q
Explain the Thrifty Phenotype Model
A
- Fetus has been able to adapt in utero to pull more nutrients in from the blood because it is being malnourished
- nutrient restriction leaders to slow growth and a small baby and thrifty adaptation
- In a nutrient poor postnatal environment, thrift is a survival advantage
- In a postnatal environment that is nutrient rich, obesity and metabolic syndrome can result
