MMCB EXAM WITH VERIFIED SOLUTION
Types of mononucleotide substitutions (2) - ANSWER - Transition (same type of base)
- Transversion (purine to pyrimidine or viceversa)
Possible consequences of a point mutation leading to an exonic nucleotide substitution
(4) - ANSWER Silent or synonymous
Missense
Nonsense or stop gain
Elongation or stop loss
The introduction of a premature termination codon (PTC) in a nonsense mutation can
lead to: (2) - ANSWER - Truncated protein
- activation of the Nonsense-Mediated mRNA Decay (NMD) pathway
Mutations that affect the structure of a gene can occur in three different portions of a
gene: - ANSWER 1. Exons
2. Splicing sites (insertion of introns or truncated exons, exclusion of exons)
3. Regulatory sequences (abnormal expression)
What are dominant negative mutations? - ANSWER Dominant-negative mutations are
characterized by a gene product that adversely affects the wild-type one, usually by
dimerizing (combining) with it.
Possible functional mutations in a gene (4): - ANSWER 1. LoF
2. GoF
3. Dominant negative
4. Lethal
How many SNPs on average do we find in the human genome? - ANSWER 683 million
Are SNPs always neutral? - ANSWER No, they can have functional consequences
What is a microsatellite? - ANSWER A common polymorphism constituted by tandem
repeats flanked by unique simple copies sequences
examples of AD diseases (6) - ANSWER 1. Polydactyly
2. Brachydactyly
,3. Achondroplasia
4. Huntington
5. Marfan
6. Neurofibromatosis
Examples of AR diseases (3) - ANSWER 1. Phenylketonuria
2. Sickle cell anemia
3. Cystic fibrosis
Five basic patterns of inheritance: - ANSWER 1. Autosomal dominant
2. Autosomal recessive
3. X-linked dominant
4. X-linked recessive
5. Y-linked
X-linked dominant diseases (2): - ANSWER Fragile X syndrome
Al port syndrome (kidney disease)
X-linked recessive diseases (2): - ANSWER 1. Haemophilia
2. Colour blindness
Y-linked conditions (3): - ANSWER Hypertrichosis
Hairy ears
Infertility
What is the penetrance of a character? - ANSWER The penetrance of a character, for a
given genotype, is defined as the probability that a person who has the genotype will
manifest the character.
Define expressivity - ANSWER Variable expression is characterized by the presence in
people of the same genotype, which however is associated with different degrees of the
disease.
Expressivity and penetrance are influenced by (2): - ANSWER Environmental factors
Modifier genes
How many genes in the mitochondrial genome? What do they encode? - ANSWER 37
genes, 13 encode proteins of oxidative phosphorylation, 24 encode functional RNAs
,What is heteroplasmy? - ANSWER Presence of more than one type of mtDNA in the cell
What is the consequence of heteroplasmy? - ANSWER Different degrees of severity of
mitochondrial disease
Mechanism of heteroplasmy - ANSWER During oocyte maturation and meiosis healthy
and diseased mitochondria are distributed differentially in oocytes, leading to some
oocytes carrying more defective genes than others within the same mother
Definition of phenocopies - ANSWER Phenotypes induced by the environment that
resemble a genetic disease
Most important example of phenocopies - ANSWER Thalidomide-induced phocomelia
Definition of complementation: - ANSWER Two diseased alleles compensate each other
and the phenotype is wild-type
Micro satellites are... (question in the slides) - ANSWER Characterised by 2-4 bases that
repeat 15-100 times
Are there more SNPs or microsatellites in the human genome? - ANSWER SNPs
How many genes in humans code for proteins? How many for RNAs? - ANSWER 20k
proteins, 50k RNA
What is the principle behind Linkage Analysis? - ANSWER We follow the segregation
pattern of the suspected gene and polymorphisms with known position scattered in the
genome, if they co-segregate they are probably in the same locus
Multiplex families (useful in the context of LA) are characterized by: (3) - ANSWER 1.
Many affected individuals
2. Multiple generations available
3. Clear-cut phenotype (no phenocopies, fully penetrant...)
Haplotype definition: - ANSWER A group of alleles along a chromosome
What is the recombination fraction (θ)? - ANSWER Number of recombinant gametes/
number of informative meioses
Relationship between the recombination fraction (θ) and the distance between two
alleles on a chromosome: - ANSWER The smaller θ, the closer the two loci (θ=50% loci
are independent, <50% means linkage)
When is a meiosis not informative in the context of Linkage analysis? - ANSWER When
information is lacking from parents
When is an individual called a compound heterozygous? - ANSWER When he has two
recessive alleles that are different from each other (e.g. different mutations)
, Lod-score definition: - ANSWER a statistical estimate of whether two "loci" (the marker
locus and the disease locus) are likely to lie near each other on a chromosome.
LOD (logarithm of the odds) score is equal to: - ANSWER Log10(probability that loci are
in linkage/ probability that they are not)
For what values of LOD score is the linkage considered proven? - ANSWER When the
maximum lod-score Z(q) >= 3, linkage is considered proven (1 in 1000)
Gene responsible for Cystic fibrosis - ANSWER CFTR (CF transmembrane conductance
regulator), located on chromosome 7
4 systems that are the most affected by cystic fibrosis: - ANSWER Respiratory
Gastrointestinal
Pancreas
Reproductive (males infertile)
Function of normal CFTR: - ANSWER Chloride out of the cell, inhibits ENaC (sodium
stays out)
How many people are affected by CF among Caucasians? - ANSWER 1 in 2500
How many different mutations of CFTR can cause CF? What is the most common? -
ANSWER More than 2000, ΔF508
Symptoms of CF in newborn (3): - ANSWER Meconium ileus
Delayed meconium
Salty skin
What is the most effective method to detect mutations (even the rarest ones) in the
CFTR gene? - ANSWER Next generation sequencing
Effect of defective CFTR channel in the airways and in sweat glands: - ANSWER In the
airways: CFTR normally lets Cl out and inhibits ENaC (Na in), defects cause thick mucus
because water is absorbed by the cell
Types of mononucleotide substitutions (2) - ANSWER - Transition (same type of base)
- Transversion (purine to pyrimidine or viceversa)
Possible consequences of a point mutation leading to an exonic nucleotide substitution
(4) - ANSWER Silent or synonymous
Missense
Nonsense or stop gain
Elongation or stop loss
The introduction of a premature termination codon (PTC) in a nonsense mutation can
lead to: (2) - ANSWER - Truncated protein
- activation of the Nonsense-Mediated mRNA Decay (NMD) pathway
Mutations that affect the structure of a gene can occur in three different portions of a
gene: - ANSWER 1. Exons
2. Splicing sites (insertion of introns or truncated exons, exclusion of exons)
3. Regulatory sequences (abnormal expression)
What are dominant negative mutations? - ANSWER Dominant-negative mutations are
characterized by a gene product that adversely affects the wild-type one, usually by
dimerizing (combining) with it.
Possible functional mutations in a gene (4): - ANSWER 1. LoF
2. GoF
3. Dominant negative
4. Lethal
How many SNPs on average do we find in the human genome? - ANSWER 683 million
Are SNPs always neutral? - ANSWER No, they can have functional consequences
What is a microsatellite? - ANSWER A common polymorphism constituted by tandem
repeats flanked by unique simple copies sequences
examples of AD diseases (6) - ANSWER 1. Polydactyly
2. Brachydactyly
,3. Achondroplasia
4. Huntington
5. Marfan
6. Neurofibromatosis
Examples of AR diseases (3) - ANSWER 1. Phenylketonuria
2. Sickle cell anemia
3. Cystic fibrosis
Five basic patterns of inheritance: - ANSWER 1. Autosomal dominant
2. Autosomal recessive
3. X-linked dominant
4. X-linked recessive
5. Y-linked
X-linked dominant diseases (2): - ANSWER Fragile X syndrome
Al port syndrome (kidney disease)
X-linked recessive diseases (2): - ANSWER 1. Haemophilia
2. Colour blindness
Y-linked conditions (3): - ANSWER Hypertrichosis
Hairy ears
Infertility
What is the penetrance of a character? - ANSWER The penetrance of a character, for a
given genotype, is defined as the probability that a person who has the genotype will
manifest the character.
Define expressivity - ANSWER Variable expression is characterized by the presence in
people of the same genotype, which however is associated with different degrees of the
disease.
Expressivity and penetrance are influenced by (2): - ANSWER Environmental factors
Modifier genes
How many genes in the mitochondrial genome? What do they encode? - ANSWER 37
genes, 13 encode proteins of oxidative phosphorylation, 24 encode functional RNAs
,What is heteroplasmy? - ANSWER Presence of more than one type of mtDNA in the cell
What is the consequence of heteroplasmy? - ANSWER Different degrees of severity of
mitochondrial disease
Mechanism of heteroplasmy - ANSWER During oocyte maturation and meiosis healthy
and diseased mitochondria are distributed differentially in oocytes, leading to some
oocytes carrying more defective genes than others within the same mother
Definition of phenocopies - ANSWER Phenotypes induced by the environment that
resemble a genetic disease
Most important example of phenocopies - ANSWER Thalidomide-induced phocomelia
Definition of complementation: - ANSWER Two diseased alleles compensate each other
and the phenotype is wild-type
Micro satellites are... (question in the slides) - ANSWER Characterised by 2-4 bases that
repeat 15-100 times
Are there more SNPs or microsatellites in the human genome? - ANSWER SNPs
How many genes in humans code for proteins? How many for RNAs? - ANSWER 20k
proteins, 50k RNA
What is the principle behind Linkage Analysis? - ANSWER We follow the segregation
pattern of the suspected gene and polymorphisms with known position scattered in the
genome, if they co-segregate they are probably in the same locus
Multiplex families (useful in the context of LA) are characterized by: (3) - ANSWER 1.
Many affected individuals
2. Multiple generations available
3. Clear-cut phenotype (no phenocopies, fully penetrant...)
Haplotype definition: - ANSWER A group of alleles along a chromosome
What is the recombination fraction (θ)? - ANSWER Number of recombinant gametes/
number of informative meioses
Relationship between the recombination fraction (θ) and the distance between two
alleles on a chromosome: - ANSWER The smaller θ, the closer the two loci (θ=50% loci
are independent, <50% means linkage)
When is a meiosis not informative in the context of Linkage analysis? - ANSWER When
information is lacking from parents
When is an individual called a compound heterozygous? - ANSWER When he has two
recessive alleles that are different from each other (e.g. different mutations)
, Lod-score definition: - ANSWER a statistical estimate of whether two "loci" (the marker
locus and the disease locus) are likely to lie near each other on a chromosome.
LOD (logarithm of the odds) score is equal to: - ANSWER Log10(probability that loci are
in linkage/ probability that they are not)
For what values of LOD score is the linkage considered proven? - ANSWER When the
maximum lod-score Z(q) >= 3, linkage is considered proven (1 in 1000)
Gene responsible for Cystic fibrosis - ANSWER CFTR (CF transmembrane conductance
regulator), located on chromosome 7
4 systems that are the most affected by cystic fibrosis: - ANSWER Respiratory
Gastrointestinal
Pancreas
Reproductive (males infertile)
Function of normal CFTR: - ANSWER Chloride out of the cell, inhibits ENaC (sodium
stays out)
How many people are affected by CF among Caucasians? - ANSWER 1 in 2500
How many different mutations of CFTR can cause CF? What is the most common? -
ANSWER More than 2000, ΔF508
Symptoms of CF in newborn (3): - ANSWER Meconium ileus
Delayed meconium
Salty skin
What is the most effective method to detect mutations (even the rarest ones) in the
CFTR gene? - ANSWER Next generation sequencing
Effect of defective CFTR channel in the airways and in sweat glands: - ANSWER In the
airways: CFTR normally lets Cl out and inhibits ENaC (Na in), defects cause thick mucus
because water is absorbed by the cell
