Module 1: Genetics of Obestiy

Question 1

What is a genome? (3 answers)

Answer 1

1. The genetic material of an organism
2. Contains an organism’s hereditary information
   3.Consists of both coding and non-coding information

Question 2

C-value paradox

Answer 2

Organismal complexity not correlated with genome size

Question 3

Why sequence genomes?
“PPPP”

Answer 3

Prediction, prevention, personalization, participation

Question 4

Enzyme that metabolizes caffeine

Answer 4

CYPIA2

Question 5

What does the SNP that alters CYPIA2 enzyme lead to?

Answer 5

-Slow metabolizers of caffeine
-Fast metabolizers of caffeine

Question 6

Gene-caffeine’s effect on performance is especially relevant for:

Answer 6

Longer durations of exercise or fatigue accumulation (aerobic/muscular endurance)

Question 7

What does the ADORA2A gene do?

Answer 7

Encode for adenosine A2A receptor
1. encourages vasodilation (increase coronary circulation
2. Regulates dopamine and glutamate release
3. Promotes sleep (adenosine through binding to rec.)

Question 8

How does caffeine affect ADORA2A

Answer 8

Blocks receptor, causes feelings of wakefulness

Question 9

How to read sanger method for sequencing (on the gel)

Answer 9

Bottom to top

Question 10

2 approaches to sequencing the human genome

Answer 10

Public Consortium (Human Genome Project)
-entire genome (introns & exons)
-sequence using BACS
Private Consortium (Celera Genomics)
-protein coding regions
-shotgun sequencing

Question 11

Public (BAC) sequencing steps

Answer 11

1. Fragment DNA (larger)
2. Amplify fragments (BAC holds 150kb fragments)
3. Align BACSs(sequence landmarks 200-500bp)
4. Fragmenting BACs
5. Sanger sequencing
6. Sequence alignment

Question 12

Private (Shotgun) sequencing steps

Answer 12

1. Fragment DNA (smaller)
2. Amplifying fragments
5. Sanger sequencing
6. Sequence alignment

Question 13

Advantages/disadvantages of BAC sequencing

Answer 13

Advantages:
1. Reduced chance to misassemble-location better known
2. Sequencing step is quick- dont need to assemble both ends of DNA
Disadvantages:
1. Bioinformatically heavy
2. Experimentally laborious and time consuming

Question 14

Advantages/Disadvantages of shotgun sequencing

Answer 14

Advantage:
1.Overall process is experimentally quicker
Disadvantages:
1. Bioinformatically heavy
2. Major problems dealing w repeat sequences in DNA

Question 15

Microscopic structural variants

Answer 15

-Aneuploidy
-Heteromorphism

Question 16

Small-scale variants

Answer 16

-Non-coding DNA (“junk DNA”)
-Copy Number Variant (CNV) and segmental duplications (SDs)
-Inversions (reverse orientation)
-Translocation (change position, same sequence)
-Single nucleotide polymorphisms (SNP)
(single base pair changes)

Question 17

CNV and SD location on genome

Answer 17

CNV:
-spread out over genome
-are not random
-approx 6% of human genome
SD:
-back to back on chromosome
-approx 12% of human genome

Question 18

Direct and indirect affects of SD and CNVs

Answer 18

Direct:
-influences gene expression (i.e, dosage sensitive genes) -common in genes involved in immune function/defence responses to bacteria
Indirect:
-causing structural rearrangements within chromosome

Question 19

What is CCL3L1 & relationship to SD

Answer 19

Protein that competes with HIV particle to bind CCR5 receptor
-more SD’s = less chance of HIV particle bind = less chance of HIV

Question 20

What is alpha amylase (AM1) and relationship to CNV

Answer 20

-breaks down dietary polysaccharides into disaccharides
-Amylase in saliva proportional to AMY1 copy number
-High starch diet = high copy number

Question 21

CNVs and obesity findings

Answer 21

Small amount of obese subjects heterogenous for deletions (lower copy number)
-very rare
Lean individuals have higher CNV on chromosome 16 (590kb reg)

Question 22

Genomic imprinting

Answer 22

Heritable, sex-specific DNA silencing
-1 expressed, 1 silenced through methylation

Question 23

What genes do genomic imprinting occur in

Answer 23

Genes involved in fetal growth and nutrient metabolism

Question 24

Health consequences of imprinting

Answer 24

-Protection offered by diploidy no longer exists
-Increases risk for disease

Question 25

Genetic conflict theory

Answer 25

Paternally expressed genes: maximize use of maternal resources so that offspring becomes stronger
Maternally expressed genes: minimizes use of maternal resources, ensuring both offspring and mother’s survival

Question 26

Imprinted gene through lifespan

Answer 26

-silenced through life, resets during egg/sperm formation

Question 27

Diseases associated with
genetic imprinting

Answer 27

Prader-Willi syndrome (PWS)(paternal silencing chromosome 15)
Angelman syndrome (AS)(maternal silencing chromosome 15)

Question 28

Symptoms/prevalance of PWS

Answer 28

Approx 1 in 15,000
-obesity
-excessive hunger
-hypergonadism
-sleep apnea
-behavioural problems
-mild/moderate intellectual disabilities
-MOST COMMON CAUSE FOR LIFE-THREATENING OBESITY IN KIDS

Question 29

Symptoms/prevalence of AS

Answer 29

Approx 1 in 12,000-20,000
-severe intellectual disabilities
-absence of speech
-uncontrolled laughter
-smaller sized heads
-NO OBESITY

Question 30

What does ‘allele” describe

Answer 30

Specific location in the genome where a common variant exists - “common” = >5% of people

Question 31

What SNPS have the strongest association w BMI and obesity

Answer 31

FTO and MC4R genes
*note: SNPs SIGNIFICANTLY associated w common obesity are rare

Question 32

What is known about FTO

Answer 32

Fat mass and obesity related gene
-highly expressed in hypothal.
-appetite suppressing
-demethylase
-adipocyte development
-complete loss of function FTO leads to death

Question 33

FTO alleles

Answer 33

AA allele = risk allele
-develop into white lipid-storing adipocytes
TT allele = protective
-develop into beige energy-dissipating adipocytes