MMCB TEST WITH COMPLETE
SOLUTION
silent/synonymous mutation - ANSWER •CTA (Leu) → CTG (Leu)
•no effect
missense mutation - ANSWER •CAG (Glu) → GTG (Val)
•ex. sickle cell anemia
nonsense/stop gain mutation - ANSWER •AAG (Lys) → TAG (STOP)
•ex. β thalassemia
β thalassemia - ANSWER •autosomal recessive nonsense mutation (*chr:11*)
•β-globin and α-globin are building blocks of hemoglobin
•insufficient β-globin chains are produced and there is an excess of α-globin
•results in the production of abnormal and insufficient hemoglobin → severe anemia
loss-of-function mutations - ANSWER •loss of a functional protein
•ex. oncosupressor genes
gain-of-function mutations - ANSWER •lead to a protein with altered function
•ex. oncogenes
dominant-negative mutations - ANSWER •produces an altered gene product that acts
antagonistically to the normal gene product
•shows a dominant pattern of inheritance
•ex. mutated p53 protein not only loses its normal function but also interferes with the
function of the wild-type p53 protein on the other allele
lethal mutation - ANSWER •causes death
•ex. sonic hedgehog (SHH) mutation (holoprosencephaly)
missense mutation consequences - ANSWER NOT easily predictable. However, you can
hypothesize the possible deleteriousness of mutations.
,•type of amino acid (non-polar amino acid into a polar one, small into big, acid into basic,
etc.)
•conservation observed amongst the species (ex. substituting the Aspartic acid —
conserved from humans to zebrafish — with a Cysteine residue)
•position in the 3D structure (ex. substitute a hydrophobic amino acid in the centre with
a hydrophilic one)
nonsense mutation consequences - ANSWER •production of a truncated protein (not
fully functional)
•activation of the Nonsense-Mediated mRNA Decay
Nonsense-Mediated mRNA Decay (NMD) - ANSWER •cellular quality control mechanism
in eukaryotic cells
•responsible for degrading mRNA that contain premature stop codons or other
abnormalities
•helps prevent the synthesis of truncated or nonfunctional proteins
thrombosis - ANSWER blood clot
embolism - ANSWER sudden blockage of a blood vessel by an embolus (moving blood
clot)
linkage disequilibrium - ANSWER •non-random association of alleles at different genes
→ inheritance is correlated (physical proximity, selection, genetic drift)
•LD = 1
linkage equilibrium - ANSWER •alleles of different genes are inherited independently of
each other → inheritance is not correlated
•LD = 0
Mandelian disease - ANSWER •genetic disorders caused by mutations in a single gene
•follows Mendelian inheritance patterns
•ex. haemophilia, colour blindness, sickle cell anemia, thalassemia, phenylketonuria,
cystic fibrosis
oncogenes - ANSWER •genes that, when mutated, have the potential to cause cancer
•ex: growth factors, growth factor receptors, signal transducers, transcription factors,
cell cycle components
Transcriptomics - ANSWER analyzes the complete set of genes expressed as
transcripts or mRNA
,isoforms - ANSWER •any of two or more functionally similar proteins that have a
*similar* but *not identical* amino acid sequence and are either encoded by different
genes or by RNA transcripts from the same gene which have had different exons
removed
arterial thrombosis - ANSWER •clot forms in an artery
•can block blood flow to vital organs and tissues (ex. heart attack, stroke)
•distal tissue becomes pale, perishingly cold, painful, pulseless, and ultimately will
undergo infarction
deep venous thrombosis - ANSWER •clot forms in a deep vein (typically legs)
•if a part of the clot breaks loose and travels to the lungs, it can cause pulmonary
embolism (PE)
•distal tissues become swallowed, reddened, and tender (congested)
cystic fibrosis - ANSWER •mutations in the CFTR gene on *chr:7*
•defective or nonfunctional CFTR protein (regulates Cl- ion and water flow in epithelial
cells) → thick and sticky mucus production
•obstructs air passages, leading to breathing difficulties and recurrent lung infections
•digestive issues arise due to blocked pancreatic ducts, causing malabsorption of
nutrients
•type 1: no synthesis
•type 2: block in processing
•type 3: block in channel regulation
•type 4: altered conductance
•type 5: reduced synthesis
ΔF508 - ANSWER •most common missense mutations
•CFTR protein misfolded and degraded before it reaches the cell surface
fitness - ANSWER •ability of an organism to survive and reproduce in its environment
deleterious mutations - ANSWER decrease the fitness of the organism
beneficial mutations - ANSWER increase the fitness of the organism
neutral mutations - ANSWER no deleterious or beneficial effect (Polymorphisms)
penetrance - ANSWER •% of people with a genetic variant who exhibit signs and
, symptoms of a genetic disorder
•if some people with the variant do not develop features of the disorder, the condition is
said to have reduced (or incomplete) penetrance
depurination - ANSWER •removal of purine bases (A + G) from DNA, creating apurinic
(abasic) sites in the strand → mutations
•5,000 purine depurinations per day per cell
deamination - ANSWER •removal of an amino group from nucleotide bases (primarily
affecting C), leading to base-pair mismatches
•100 C deaminations per day per cell
phosphodiester bonds "nick" - ANSWER •single-strand breaks in the DNA backbone
•can occur due to various factors
•if not repaired, contribute to genetic instability
alkylation - ANSWER addition of methyl/ethyl group to bases or backbone
oxidation - ANSWER •cellular metabolism and other factors create reactive oxygen
species (ex. O2-, OH-, and H2O2)
•damage base, sugar and backbone, crosslink DNA with proteins
intercalating agents - ANSWER •insertion of molecules between the planar bases
•hydrophobic heterocyclic ring molecules that resemble the ring structure of base pairs
•structural modifications inhibit transcription/replication/DNA repair
base analogues - ANSWER •molecules that can substitute for normal bases in nucleic
acids
•result in altered base pairings and structural changes that affect DNA replication/gene
transcription
UV - ANSWER •UVC (100-280 nm): shortest and most energetic portion of the spectrum;
absorbed by the atmospheric ozone
•UVB (280-315 nm): largest effect on the top layer of skin; could cause redness, burning,
and skin cancer
•UVA (315-400 nm): reaches deep into the layers of skin; associated with skin aging
ionizing radiation - ANSWER •Gamma Rays: particularly damaging because they can
create double-strand breaks (DSB), which are difficult to repair
SOLUTION
silent/synonymous mutation - ANSWER •CTA (Leu) → CTG (Leu)
•no effect
missense mutation - ANSWER •CAG (Glu) → GTG (Val)
•ex. sickle cell anemia
nonsense/stop gain mutation - ANSWER •AAG (Lys) → TAG (STOP)
•ex. β thalassemia
β thalassemia - ANSWER •autosomal recessive nonsense mutation (*chr:11*)
•β-globin and α-globin are building blocks of hemoglobin
•insufficient β-globin chains are produced and there is an excess of α-globin
•results in the production of abnormal and insufficient hemoglobin → severe anemia
loss-of-function mutations - ANSWER •loss of a functional protein
•ex. oncosupressor genes
gain-of-function mutations - ANSWER •lead to a protein with altered function
•ex. oncogenes
dominant-negative mutations - ANSWER •produces an altered gene product that acts
antagonistically to the normal gene product
•shows a dominant pattern of inheritance
•ex. mutated p53 protein not only loses its normal function but also interferes with the
function of the wild-type p53 protein on the other allele
lethal mutation - ANSWER •causes death
•ex. sonic hedgehog (SHH) mutation (holoprosencephaly)
missense mutation consequences - ANSWER NOT easily predictable. However, you can
hypothesize the possible deleteriousness of mutations.
,•type of amino acid (non-polar amino acid into a polar one, small into big, acid into basic,
etc.)
•conservation observed amongst the species (ex. substituting the Aspartic acid —
conserved from humans to zebrafish — with a Cysteine residue)
•position in the 3D structure (ex. substitute a hydrophobic amino acid in the centre with
a hydrophilic one)
nonsense mutation consequences - ANSWER •production of a truncated protein (not
fully functional)
•activation of the Nonsense-Mediated mRNA Decay
Nonsense-Mediated mRNA Decay (NMD) - ANSWER •cellular quality control mechanism
in eukaryotic cells
•responsible for degrading mRNA that contain premature stop codons or other
abnormalities
•helps prevent the synthesis of truncated or nonfunctional proteins
thrombosis - ANSWER blood clot
embolism - ANSWER sudden blockage of a blood vessel by an embolus (moving blood
clot)
linkage disequilibrium - ANSWER •non-random association of alleles at different genes
→ inheritance is correlated (physical proximity, selection, genetic drift)
•LD = 1
linkage equilibrium - ANSWER •alleles of different genes are inherited independently of
each other → inheritance is not correlated
•LD = 0
Mandelian disease - ANSWER •genetic disorders caused by mutations in a single gene
•follows Mendelian inheritance patterns
•ex. haemophilia, colour blindness, sickle cell anemia, thalassemia, phenylketonuria,
cystic fibrosis
oncogenes - ANSWER •genes that, when mutated, have the potential to cause cancer
•ex: growth factors, growth factor receptors, signal transducers, transcription factors,
cell cycle components
Transcriptomics - ANSWER analyzes the complete set of genes expressed as
transcripts or mRNA
,isoforms - ANSWER •any of two or more functionally similar proteins that have a
*similar* but *not identical* amino acid sequence and are either encoded by different
genes or by RNA transcripts from the same gene which have had different exons
removed
arterial thrombosis - ANSWER •clot forms in an artery
•can block blood flow to vital organs and tissues (ex. heart attack, stroke)
•distal tissue becomes pale, perishingly cold, painful, pulseless, and ultimately will
undergo infarction
deep venous thrombosis - ANSWER •clot forms in a deep vein (typically legs)
•if a part of the clot breaks loose and travels to the lungs, it can cause pulmonary
embolism (PE)
•distal tissues become swallowed, reddened, and tender (congested)
cystic fibrosis - ANSWER •mutations in the CFTR gene on *chr:7*
•defective or nonfunctional CFTR protein (regulates Cl- ion and water flow in epithelial
cells) → thick and sticky mucus production
•obstructs air passages, leading to breathing difficulties and recurrent lung infections
•digestive issues arise due to blocked pancreatic ducts, causing malabsorption of
nutrients
•type 1: no synthesis
•type 2: block in processing
•type 3: block in channel regulation
•type 4: altered conductance
•type 5: reduced synthesis
ΔF508 - ANSWER •most common missense mutations
•CFTR protein misfolded and degraded before it reaches the cell surface
fitness - ANSWER •ability of an organism to survive and reproduce in its environment
deleterious mutations - ANSWER decrease the fitness of the organism
beneficial mutations - ANSWER increase the fitness of the organism
neutral mutations - ANSWER no deleterious or beneficial effect (Polymorphisms)
penetrance - ANSWER •% of people with a genetic variant who exhibit signs and
, symptoms of a genetic disorder
•if some people with the variant do not develop features of the disorder, the condition is
said to have reduced (or incomplete) penetrance
depurination - ANSWER •removal of purine bases (A + G) from DNA, creating apurinic
(abasic) sites in the strand → mutations
•5,000 purine depurinations per day per cell
deamination - ANSWER •removal of an amino group from nucleotide bases (primarily
affecting C), leading to base-pair mismatches
•100 C deaminations per day per cell
phosphodiester bonds "nick" - ANSWER •single-strand breaks in the DNA backbone
•can occur due to various factors
•if not repaired, contribute to genetic instability
alkylation - ANSWER addition of methyl/ethyl group to bases or backbone
oxidation - ANSWER •cellular metabolism and other factors create reactive oxygen
species (ex. O2-, OH-, and H2O2)
•damage base, sugar and backbone, crosslink DNA with proteins
intercalating agents - ANSWER •insertion of molecules between the planar bases
•hydrophobic heterocyclic ring molecules that resemble the ring structure of base pairs
•structural modifications inhibit transcription/replication/DNA repair
base analogues - ANSWER •molecules that can substitute for normal bases in nucleic
acids
•result in altered base pairings and structural changes that affect DNA replication/gene
transcription
UV - ANSWER •UVC (100-280 nm): shortest and most energetic portion of the spectrum;
absorbed by the atmospheric ozone
•UVB (280-315 nm): largest effect on the top layer of skin; could cause redness, burning,
and skin cancer
•UVA (315-400 nm): reaches deep into the layers of skin; associated with skin aging
ionizing radiation - ANSWER •Gamma Rays: particularly damaging because they can
create double-strand breaks (DSB), which are difficult to repair
