Topic 9 - Nutrigenomics

Question 1

What is the new approach to medication? (as opposed to the one-size-fits-all approach)

Answer 1

• rather than screening for chemicals with broad action against a disease, researchers are now using genomic info to design drugs that target a SPECIFIC pathway involved in the disease
• hopefully this new generation of drugs will work better AND cause fewer side effects than current treatments
• Such efforts are already starting to pay off, as seen by the success of gene-based drugs in the treatment of
  leukemia and other cancers

Question 2

Sometimes, averages don’t give us the full story. Give an example.

Answer 2

• weight loss nutritional intervention
• 3 months active weight loss, 3 months maintenance
• alternating low energy vs very low energy for 5 vs 2 days
• three 30 minute sessions of light-moderate physical activity per week
• Overall, participants lost 4.8% body weight during the
  intervention period

Question 3

What is the goal of personal nutrition & health?

Answer 3

The overall goal is to increase health using genetic, phenotypic, medical, nutritional, and other relevant information about
individuals to deliver more specific healthy eating guidance

Question 4

What can personalization be based on?

Answer 4

• biological evidence of differential responses to foods/nutrients depending on GENOTYPIC or PHENOTYPIC characteristics
• analysis of CURRENT BEHAVIOUR, PREFERENCES, BARRIERS, & OBJECTIVES and subsequent delivery of interventions, which motivate and enable each person to make appropriate changes to his or her eating pattern
• INTEGRATION of data on genetic, metabolic, behavioural, and sociocultural factors

Question 5

Genetics explain a significant portion of individual variability within a species. Explain.

Answer 5

• Any two humans differ for about 0.1 % of genetic material. This means that about one base pair out of every 1,000 will be different between any two individuals
• This 0.1% is responsible for the differences b/w individuals
• Including metabolic rate and predisposition to diseases

Question 6

What is a single nucleotide polymorphism (SNP)?

Answer 6

a gene variant in which only one nucleotide is different from the prevalent gene sequence

It was calculated that in the human genome at least 3 millions of SNPs are present.

Question 7

What is a genome?

Answer 7

an organism’s complete DNA info; it contains all of the instructions needed to built and maintain that organism

Question 8

What was the Human Genome Project?

Answer 8

• an international research effort to sequence the entire human genome and identify the genes that it contains
• Began in 1990, first draft published in 2001, and complete in 2003
• The final telomer to telomer sequence with no gaps was published in 2022

Question 9

Define nutrigenetics

Answer 9

• The study of how individual genetic differences can affect the way we respond to food and its components.
• The study of how individual genetic background affect the risk of developing chronic diseases
• The use of genetic characterisation in the interpretation of clinical trial data.

Question 10

Define nutrigenomics

Answer 10

• the study of the effects of foods and food constituents on gene expression on a global scale
• nutrigenomics is research focusing on identifying and understanding molecular-level interaction b/w nutrients and other dietary bioactives with the genome
• by measuring modulation of all transcribed RNA (transcriptomics), proteins (proteomics), or metabolites (metabolomics)

Question 11

Nutritional genomics is aimed at. . .

Answer 11

developing an understanding of how the body responds to food and its components via SYSTEMS BIOLOGY approaches

Question 12

What is systems biology?

Answer 12

an approach in biomedical research to understanding the larger picture—be it at the level of the organism, tissue, or cell—by putting its pieces together.

Question 13

What is bioinformatics?

Answer 13

• the use of computation to analyze, interpret, process, or report experimental data, associated with biological research

Question 14

What is Phenylketonuria?

Answer 14

• PKU is caused by mutations on chromosome 12 in the gene that codes for the liver enzyme PAH (phenylalanine hydroxylase)
• the mutated version of the enzyme is unable to properly break down phenylalanine (there is a BLOCK in biochemical pathway)
• PKU needs to be treated very shortly after birth with a dietary intervention to avoid severe neuronal development defects

Question 15

Consequences of phenylketonuria

Answer 15

1) build-up of PHE
2) phenylpyruvic acid build-up
3) toxic byproducts
4) tissue damage

Question 16

Examples of high phenylalanine foods

Answer 16

• high protein foods
• eggs
• meat
• dairy
• fish
• nuts / legumes

SHOULD be avoided in someone with phenylketonuria

Question 17

Examples of low phenylalanine foods

Answer 17

• low protein foods
• most veg
• most fruit
• sugars
• cookies, crackers

Question 18

PKU is caused by. . .

Answer 18

rare mutations (approximately 1 in 10,000 among Caucasians)

Question 19

What is colonic adaptation?

Answer 19

Lactose digestion doesn’t depend only from intestinal Lactase, carriers of the
persistent allele can still safely consume some lactose containing milk.
This is most likely due to the contribution of the intestinal microbiome.

While coming milk doesn’t affect the expression of lactase, in lactase-deficient
individuals, consuming lactose containing dairy products supports the growth of specific strains of bacteria that are able to digest lactase.

This process is referred to as colonic adaptation.

Question 20

Lactase persistence (e.g. in pops)

Answer 20

17% of Greeks

14% of Sardinians

80% of Finns and Hungarians

100% of Irish

11 to 32% of Central Asia

<5% of Native Americas, East Asians, most China, South Africans

Question 21

What might cause obesity?

Answer 21

• life style (diet, physical activity)
• genetic susceptibility (low)

monogenic syndromes are rare whereas polygenic disorders are more frequent

Question 22

The use of nutrigenetic testing to provide dietary advice is. . .

Answer 22

not ready for routine dietetics practice

Question 23

Why is Vitamin D important?

Answer 23

• intestine: increases absorption of Ca2+ and Pi
• bone: increases bone mineralization
• immune cells: induces differentiation
• tumour microenvironment: inhibits proliferation; induces differentiation; inhibits angiogenesis

activity mediated by Vitamin D receptor VDR

Question 24

Vitamin D: mechanism of action on the intestinal absorption of calcium

Answer 24

GENOMIC: activation of nuclear receptor and transcriptional regulation of downstream genes

NON-GENOMIC: too fast to be compatible with gene expression regulation;
Transcaltachia: the process by which Vitamin D rapidly initiates calcium absorption. It does this by stimulating endocytosis of Ca across brush border membrane, lysosome-mediated release of Ca within cytosol, and release of Ca across basal lateral membrane by exocytosis

Question 25

Vitamin D regulates gene expression in skin - Transcriptomic analysis

Answer 25

Out of the whole transcriptome investigated, the authors uncovered 86 differentially expressed (67 upregulated and 19 down-regulated) candidates that were functionally clustered into 5 annotation categories:

response to wounding, protease inhibition, secondary metabolite biosynthesis, cellular migration, and amine biosynthetic processes

Question 26

What is a common approach to interpreting gene expression data?

Answer 26

gene set enrichment analysis based on the functional annotation of the differentially expressed genes

Answer 27

• colours represent the GO group
• each node is a GO biological process and the edges shows the connectivity b/w each node based on the connection of the genes that it contains
• The size
  of the nodes depends on the
  amount of genes that are grouped.
• Nodes with no connections are colored in gray.
• Pathway analysis to group
  genes modulated in the study in meaningful group

GO = gene ontology analysis of common 1,25(OH)2D-regulated bioenergetics genes in THP-1 cells, CDs, and monocytes