Module 1: Genetics of Obestiy Flashcards
What is a genome? (3 answers)
- The genetic material of an organism
- Contains an organism’s hereditary information
3.Consists of both coding and non-coding information
C-value paradox
Organismal complexity not correlated with genome size
Why sequence genomes?
“PPPP”
Prediction, prevention, personalization, participation
Enzyme that metabolizes caffeine
CYPIA2
What does the SNP that alters CYPIA2 enzyme lead to?
-Slow metabolizers of caffeine
-Fast metabolizers of caffeine
Gene-caffeine’s effect on performance is especially relevant for:
Longer durations of exercise or fatigue accumulation (aerobic/muscular endurance)
What does the ADORA2A gene do?
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.)
How does caffeine affect ADORA2A
Blocks receptor, causes feelings of wakefulness
How to read sanger method for sequencing (on the gel)
Bottom to top
2 approaches to sequencing the human genome
Public Consortium (Human Genome Project)
-entire genome (introns & exons)
-sequence using BACS
Private Consortium (Celera Genomics)
-protein coding regions
-shotgun sequencing
Public (BAC) sequencing steps
- Fragment DNA (larger)
- Amplify fragments (BAC holds 150kb fragments)
- Align BACSs(sequence landmarks 200-500bp)
- Fragmenting BACs
- Sanger sequencing
- Sequence alignment
Private (Shotgun) sequencing steps
- Fragment DNA (smaller)
- Amplifying fragments
- Sanger sequencing
- Sequence alignment
Advantages/disadvantages of BAC sequencing
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
Advantages/Disadvantages of shotgun sequencing
Advantage:
1.Overall process is experimentally quicker
Disadvantages:
1. Bioinformatically heavy
2. Major problems dealing w repeat sequences in DNA
Microscopic structural variants
-Aneuploidy
-Heteromorphism
Small-scale variants
-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)
CNV and SD location on genome
CNV:
-spread out over genome
-are not random
-approx 6% of human genome
SD:
-back to back on chromosome
-approx 12% of human genome
Direct and indirect affects of SD and CNVs
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
What is CCL3L1 & relationship to SD
Protein that competes with HIV particle to bind CCR5 receptor
-more SD’s = less chance of HIV particle bind = less chance of HIV
What is alpha amylase (AM1) and relationship to CNV
-breaks down dietary polysaccharides into disaccharides
-Amylase in saliva proportional to AMY1 copy number
-High starch diet = high copy number
CNVs and obesity findings
Small amount of obese subjects heterogenous for deletions (lower copy number)
-very rare
Lean individuals have higher CNV on chromosome 16 (590kb reg)
Genomic imprinting
Heritable, sex-specific DNA silencing
-1 expressed, 1 silenced through methylation
What genes do genomic imprinting occur in
Genes involved in fetal growth and nutrient metabolism
Health consequences of imprinting
-Protection offered by diploidy no longer exists
-Increases risk for disease
Genetic conflict theory
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
Imprinted gene through lifespan
-silenced through life, resets during egg/sperm formation
Diseases associated with
genetic imprinting
Prader-Willi syndrome (PWS)(paternal silencing chromosome 15)
Angelman syndrome (AS)(maternal silencing chromosome 15)
Symptoms/prevalance of PWS
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
Symptoms/prevalence of AS
Approx 1 in 12,000-20,000
-severe intellectual disabilities
-absence of speech
-uncontrolled laughter
-smaller sized heads
-NO OBESITY
What does ‘allele” describe
Specific location in the genome where a common variant exists - “common” = >5% of people
What SNPS have the strongest association w BMI and obesity
FTO and MC4R genes
*note: SNPs SIGNIFICANTLY associated w common obesity are rare
What is known about FTO
Fat mass and obesity related gene
-highly expressed in hypothal.
-appetite suppressing
-demethylase
-adipocyte development
-complete loss of function FTO leads to death
FTO alleles
AA allele = risk allele
-develop into white lipid-storing adipocytes
TT allele = protective
-develop into beige energy-dissipating adipocytes
