General Principles Week 3 REV

Question 1

Topic 1: The Genetic Code and Mutations
TLO 1.1: Explain the central dogma of genetics
The central dogma of genetics outlines the flow of genetic information in living organisms:

Answer 1

The central dogma is summarized as:

DNA → RNA → Protein.

Question 2

Topic 1: The Genetic Code and Mutations

Replication:

Answer 2

DNA is duplicated to ensure genetic material is inherited by daughter cells during cell division.

Question 3

Topic 1: The Genetic Code and Mutations

Transcription:

Answer 3

DNA is transcribed into RNA (specifically, mRNA) by RNA polymerase.

Question 4

Topic 1: The Genetic Code and Mutations

Transcription occurs in the nucleus and involves:
Promoters:
Exons:
Introns:

Answer 4

Promoters: Regions of DNA that signal RNA polymerase to start transcription.

Exons and introns: Exons are coding regions of mRNA; introns are spliced out.

Question 5

Topic 1: The Genetic Code and Mutations

Translation:

Answer 5

mRNA is translated into proteins at the ribosome.

Question 6

3. Translation: mRNA is translated into proteins at the ribosome. This process involves:

tRNA:
Ribosomes:
Codons:

Answer 6

tRNA: Delivers amino acids.

Ribosomes: Facilitate peptide bond formation between amino acids.

Codons: Groups of three nucleotides in mRNA that encode specific amino acids.

Question 7

TLO 1.2: Describe the genetic code and codons
Genetic Code:

Answer 7

A set of rules dictating how nucleotide sequences in mRNA are translated into proteins.

Question 8

TLO 1.2: Describe the genetic code and codons

Codons:

Answer 8

Triplet nucleotide sequences (e.g., AUG) that code for amino acids or regulatory signals.

Question 9

TLO 1.2: Describe the genetic code and codons

• Start codon:
• Stop codons:

Answer 9

• Start codon: AUG (methionine) initiates protein translation.
• Stop codons: UAA, UAG, UGA terminate translation.

Question 10

TLO 1.2: Describe the genetic code and codons

Universal:
Degenerate:
Non-overlapping: .

Answer 10

TLO 1.2: Describe the genetic code and codons
Key Features:
* Universal: Shared by almost all organisms.
* Degenerate: Multiple codons can encode the same amino acid (e.g., UUU and UUC both encode phenylalanine).
* Non-overlapping: Each nucleotide is part of only one codon.

The genetic code is universal because all species use the same four bases A,T,C and G, and each base sequence codes for the same amino acid in all species. despite the 64 possible codons (sequence of three bases), there are only 20 possible amino acids. This means that multiple codons code for one amino acid, meaning the code is degenerate. Overlapping refers to how the code is read. The first three bases are read as one codon, then the next three as the second etc, therefore each base is read only once and the bases do not overlap.

Question 11

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Mutation:

Answer 11

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Mutation: A permanent change in the DNA sequence that can affect protein function.

Question 12

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Point mutations:

Answer 12

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Point mutations: A single nucleotide substitution.

Question 13

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Silent mutation:

Answer 13

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Silent mutation: No change in the encoded amino acid (e.g., CUU → CUC, both encode leucine).

Question 14

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Missense mutation:

Answer 14

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Missense mutation: Changes the amino acid (e.g., Glu → Val in sickle cell anemia).

A missense mutation is a DNA change that results in different amino acids being encoded at a particular position in the resulting protein. Some missense mutations alter the function of the resulting protein.

Question 15

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Nonsense mutation:

Answer 15

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Nonsense mutation: Converts a codon into a stop codon (e.g., UGC → UGA).

Question 16

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Frameshift mutations:

Answer 16

TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations

Frameshift mutations: Caused by insertion or deletion of nucleotides not in multiples of three, disrupting the reading frame.

Example: Adding one nucleotide to AUG-CUU becomes AUC-UUC, altering all downstream amino acids.

Question 17

TLO 1.4: Describe trinucleotide repeat disorders

Examples:

Answer 17

TLO 1.4: Describe trinucleotide repeat disorders

Disorders caused by the abnormal expansion of three-nucleotide sequences within or near genes.

Normal individuals have stable numbers of repeats, but expanded repeats cause disease.

Examples:

Huntington’s disease: CAG repeats in the HTT gene cause toxic proteins.

Fragile X syndrome: CGG repeats in the FMR1 gene lead to gene silencing.

Myotonic dystrophy: CTG repeats in the DMPK gene interfere with protein interactions.

Question 18

TLO 1.5: Define anticipation with disease examples

Anticipation:

Answer 18

A phenomenon where a genetic disorder worsens or manifests earlier in subsequent generations due to repeat expansions.

Examples:
Huntington’s disease: Earlier onset with paternal inheritance.
Myotonic dystrophy: Severity increases with maternal transmission.

Question 19

Topic 2: Single Gene Disorders

Gene:

Answer 19

Topic 2: Single Gene Disorders

Gene: A DNA sequence encoding a protein or functional RNA.

Question 20

Topic 2: Single Gene Disorders

Locus:

Answer 20

Topic 2: Single Gene Disorders

Locus: A gene’s location on a chromosome.

Question 21

Topic 2: Single Gene Disorders

Allele:

Answer 21

Topic 2: Single Gene Disorders

Allele: Variant forms of a gene.

Question 22

Topic 2: Single Gene Disorders

Genotype:

Answer 22

Topic 2: Single Gene Disorders

Genotype: The genetic makeup of an individual.

Question 23

Topic 2: Single Gene Disorders

Phenotype:

Answer 23

Topic 2: Single Gene Disorders

Phenotype: Observable traits resulting from genotype-environment interactions.

Question 24

Topic 2: Single Gene Disorders

Homozygous:

Answer 24

Topic 2: Single Gene Disorders

Homozygous: Possessing two identical alleles (e.g., AA or aa).

Question 25

Topic 2: Single Gene Disorders Heterozygous:

Answer 25

Topic 2: Single Gene Disorders Heterozygous: Possessing two different alleles (e.g., Aa).

Question 26

Topic 2: Single Gene Disorders Dominant:

Answer 26

Topic 2: Single Gene Disorders Dominant: A trait expressed with one allele (e.g., Aa or AA).

Question 27

Topic 2: Single Gene Disorders Recessive:

Answer 27

Topic 2: Single Gene Disorders Recessive: A trait expressed only with two identical alleles (e.g., aa).

Question 28

TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance Autosomal dominant: Examples: Recurrence risk: 50% if one parent is affected.

Answer 28

TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance Autosomal dominant: Requires only one mutated allele for the phenotype. Examples: Marfan syndrome, Huntington’s disease. Recurrence risk: 50% if one parent is affected.

Question 29

TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance Autosomal recessive: Examples: Recurrence risk:

Answer 29

TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance Autosomal recessive: Requires two mutated alleles for the phenotype. Examples: Cystic fibrosis, sickle cell anemia. Recurrence risk: 25% if both parents are carriers.

Question 30

TLO 2.3: X-linked inheritance X-linked dominant: Examples: .

Answer 30

TLO 2.3: X-linked inheritance X-linked dominant: Affects males and females. Examples: Rett syndrome, hypophosphatemic rickets.

Question 31

TLO 2.3: X-linked inheritance X-linked recessive: Examples: Recurrence risk:

Answer 31

TLO 2.3: X-linked inheritance X-linked recessive: Affects males more severely; females are carriers. Examples: Hemophilia A, Duchenne muscular dystrophy. Recurrence risk: Sons of carrier mothers have a 50% chance of being affected.

Question 32

TLO 2.4: Properties of mitochondrial inheritance Examples:

Answer 32

TLO 2.4: Properties of mitochondrial inheritance Inherited exclusively from the mother. Affects tissues requiring high energy (e.g., brain, muscles). Examples: Leber hereditary optic neuropathy (LHON), MELAS syndrome.

Question 33

TLO 2.5: Define incomplete penetrance and pleiotropy Incomplete penetrance: Pleiotropy:

Answer 33

TLO 2.5: Define incomplete penetrance and pleiotropy Incomplete penetrance: Not all individuals with a mutation exhibit symptoms (e.g., BRCA1 mutation carriers). Pleiotropy: A single gene mutation impacts multiple systems (e.g., Marfan syndrome affects connective tissue, heart, and eyes).

Question 34

TLO 2.6: Describe genetic imprinting and uniparental disomy Genetic imprinting: Uniparental disomy: Examples: Prader-Willi syndrome: Angelman syndrome:

Answer 34

TLO 2.6: Describe genetic imprinting and uniparental disomy Genetic imprinting: Differential expression of genes depending on their parental origin. Uniparental disomy: Both chromosomes come from one parent. Examples: Prader-Willi syndrome: Paternal deletion on chromosome 15 or maternal uniparental disomy. Angelman syndrome: Maternal deletion on chromosome 15 or paternal uniparental disomy.

Question 35

Topic 3: Population Genetics TLO 3.1: Define and Calculate Genotype Frequency and Allele Frequency Genotype Frequency

Answer 35

Genotype frequency refers to the proportion of individuals in a population with a specific genotype (e.g., homozygous dominant, heterozygous, or homozygous recessive). It is expressed as a fraction or percentage of the total population. Mathematically: f(Genotype)=Number of individuals with a specific genotypeTotal number of individuals in the populationf(Genotype)=Total number of individuals in the populationNumber of individuals with a specific genotype

Question 36

Topic 3: Population Genetics TLO 3.1: Define and Calculate Genotype Frequency and Allele Allele Frequency

Answer 36

Allele Frequency Allele frequency is the proportion of a specific allele (e.g., dominant or recessive) among all alleles at a particular locus in the population. Allele frequency is important because it measures genetic diversity within a population. For a population with two alleles (A and a): f(A)=2(AA)+(Aa)2N,f(a)=2(aa)+(Aa)2Nf(A)=2N2(AA)+(Aa),f(a)=2N2(aa)+(Aa) Where: * NN is the total number of individuals in the population.

Question 37

Topic 3: Population Genetics TLO 3.1: Define and Calculate Genotype Frequency and Allele Example Calculation:

Answer 37

Suppose a population consists of 100 individuals with the following genotypes: 25 AAAA, 50 AaAa, and 25 aaaa. Genotype frequencies: f(AA)=25100=0.25,f(Aa)=50100=0.50,f(aa)=25100=0.25f(AA)=10025=0.25,f(Aa)=10050=0.50,f(aa)=10025=0.25 Allele frequencies: f(A)=2(25)+50200=0.5,f(a)=2(25)+50200=0.5f(A)=2002(25)+50=0.5,f(a)=2002(25)+50=0.5

Question 38

TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication Definition of Hardy-Weinberg Equilibrium (HWE)

Answer 38

The Hardy-Weinberg equilibrium describes a theoretical state in which the allele and genotype frequencies in a population remain constant from generation to generation, provided certain assumptions are met.

Question 39

TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication Key Assumptions of HWE:

Answer 39

Key Assumptions of HWE: 1. Large population size: Prevents genetic drift. 2. No mutation: No new alleles are introduced or altered. 3. Random mating: No preference for specific genotypes in mating. 4. No natural selection: All genotypes have equal reproductive success. 5. No gene flow: No migration into or out of the population.

Question 40

TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication

Answer 40

Implications: The Hardy-Weinberg principle provides a baseline for measuring genetic variation and helps identify when evolutionary forces are acting on a population. If the observed genotype frequencies deviate from expected frequencies under HWE, one or more of the assumptions may be violated, indicating evolutionary change. Mathematically, the equilibrium condition for a single gene with two alleles (A and a) is: p2+2pq+q2=1p2+2pq+q2=1 Where: * pp is the frequency of allele AA, and qq is the frequency of allele aa. * p2p2: Frequency of homozygous dominant genotype (AAAA). * 2pq2pq: Frequency of heterozygous genotype (AaAa). * q2q2: Frequency of homozygous recessive genotype (aaaa).

Question 41

TLO 3.3: Apply the Hardy-Weinberg Equilibrium to Calculate Genotype Frequency Estimates Application

Answer 41

Given allele frequencies (pp and qq), genotype frequencies can be estimated using the HWE equation. Example: In a population, the frequency of allele AA (pp) is 0.6, and the frequency of allele aa (qq) is 0.4 (p+q=1p+q=1). Homozygous dominant (AAAA): f(AA)=p2=(0.6)2=0.36f(AA)=p2=(0.6)2=0.36 Heterozygous (AaAa): f(Aa)=2pq=2(0.6)(0.4)=0.48f(Aa)=2pq=2(0.6)(0.4)=0.48 Homozygous recessive (aaaa): f(aa)=q2=(0.4)2=0.16f(aa)=q2=(0.4)2=0.16 These frequencies can be compared to observed data to determine if the population is in HWE.

Question 42

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Mutation:

Answer 42

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Mutation Spontaneous changes in the DNA sequence introduce new alleles. Mutations are the ultimate source of all genetic variation and are critical for evolution.

Question 43

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Genetic Recombination

Answer 43

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Genetic Recombination During meiosis, homologous chromosomes exchange genetic material (crossing over), creating new allele combinations.

Question 44

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Gene Flow (Migration)

Answer 44

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Gene Flow (Migration) Movement of individuals or gametes between populations introduces new alleles, increasing genetic diversity.

Question 45

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Genetic Drift

Answer 45

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Genetic Drift Random changes in allele frequencies, especially in small populations, can lead to loss of genetic variation.

Question 46

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Natural Selection

Answer 46

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Natural Selection Differential survival and reproduction of individuals with specific genotypes can increase or decrease genetic variation, depending on selective pressures.

Question 47

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Non-Random Mating

Answer 47

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Non-Random Mating Assortative mating or inbreeding affects genotype frequencies and reduces heterozygosity.

Question 48

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Population Size

Answer 48

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Population Size Larger populations tend to maintain more genetic variation due to reduced effects of genetic drift.

Question 49

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Environmental Factors

Answer 49

TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation: Environmental Factors Selective pressures, such as climate, predators, or food availability, influence which genotypes are advantageous.

Question 50

Topic 4: Cytogenetics (Chromosomal Abnormalities) TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature Karyotype:

Answer 50

Topic 4: Cytogenetics (Chromosomal Abnormalities) TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature Karyotype: A display of an individual’s complete set of chromosomes arranged in pairs and sorted by size, centromere position, and banding pattern. Chromosomes are visualized using stains (e.g., Giemsa stain for G-banding). A normal karyotype includes 22 pairs of autosomes and 1 pair of sex chromosomes.

Question 51

Topic 4: Cytogenetics (Chromosomal Abnormalities) TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature Chromosome nomenclature: Example:

Answer 51

Topic 4: Cytogenetics (Chromosomal Abnormalities) TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature Chromosome nomenclature: The total chromosome number, sex chromosomes, and any abnormalities are noted. Example: 46,XX: Normal female. 47,XX,+21: Female with trisomy 21 (Down syndrome). 46,XY,t(9;22): Male with translocation between chromosomes 9 and 22 (Philadelphia chromosome, associated with chronic myeloid leukemia).

Question 52

TLO 4.2: Discuss numerical chromosomal abnormalities Numerical abnormalities: Euploidy: Aneuploidy:

Answer 52

TLO 4.2: Discuss numerical chromosomal abnormalities Numerical abnormalities: Variations in chromosome number due to errors in cell division (nondisjunction or anaphase lag). Euploidy: A normal set of chromosomes (e.g., 46 in humans). Aneuploidy: Gain or loss of chromosomes.

Question 53

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of autosomal aneuploidies: Trisomy 21 (Down syndrome): Trisomy 18 (Edwards syndrome): Trisomy 13 (Patau syndrome):

Answer 53

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of autosomal aneuploidies: Trisomy 21 (Down syndrome): * Three copies of chromosome 21. * Clinical features: Intellectual disability, hypotonia, characteristic facial features, congenital heart defects. Trisomy 18 (Edwards syndrome): * Three copies of chromosome 18. * Clinical features: Severe developmental delays, overlapping fingers, rocker-bottom feet. Trisomy 13 (Patau syndrome): * Three copies of chromosome 13. * Clinical features: Microcephaly, cleft lip/palate, polydactyly, congenital heart defects.

Question 54

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of sex chromosome aneuploidies: Turner syndrome (45,X): Clinical features:

Answer 54

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of sex chromosome aneuploidies: Turner syndrome (45,X): Monosomy of the X chromosome in females. Clinical features: Short stature, gonadal dysgenesis, webbed neck.

Question 55

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of sex chromosome aneuploidies: Klinefelter syndrome (47,XXY): Clinical features:

Answer 55

TLO 4.2: Discuss numerical chromosomal abnormalities Examples of sex chromosome aneuploidies: Klinefelter syndrome (47,XXY): Extra X chromosome in males. Clinical features: Tall stature, hypogonadism, gynecomastia, infertility.

Question 56

TLO 4.3: Describe the most common cause of numerical chromosomal abnormalities Cause: Nondisjunction:

Answer 56

TLO 4.3: Describe the most common cause of numerical chromosomal abnormalities Cause: Most numerical abnormalities result from nondisjunction during meiosis. Nondisjunction: Failure of homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to separate. This results in gametes with an extra or missing chromosome, leading to aneuploidy after fertilization.

Question 57

TLO 4.4: Describe structural chromosomal abnormalities Structural abnormalities: Translocation: Robertsonian translocation: Deletion: Inversion: Paracentric inversion: Pericentric inversion: Ring chromosome: Example:

Answer 57

TLO 4.4: Describe structural chromosomal abnormalities Structural abnormalities: Result from chromosomal breakage and improper repair. Translocation: Exchange of segments between non-homologous chromosomes. Robertsonian translocation: Fusion of two acrocentric chromosomes (e.g., t(14;21) associated with hereditary Down syndrome). Deletion: Loss of a chromosome segment. Example: Cri-du-chat syndrome (5p deletion). Inversion: A chromosome segment is reversed end-to-end. Paracentric inversion: Does not involve the centromere. Pericentric inversion: Includes the centromere. Ring chromosome: A circular chromosome formed when the ends fuse after breakage. Example: Turner syndrome (ring X chromosome).

Question 58

Topic 5: Genetics of Common Diseases TLO 5.1: Discuss multifactorial inheritance and its influential factors Multifactorial inheritance: Examples of multifactorial diseases: Type 2 diabetes: Hypertension: Congenital diseases:

Answer 58

Topic 5: Genetics of Common Diseases TLO 5.1: Discuss multifactorial inheritance and its influential factors Multifactorial inheritance: Results from the combined effect of multiple genes (polygenic) and environmental factors. Examples of multifactorial diseases: Type 2 diabetes: Influenced by genetic predisposition and lifestyle factors (e.g., obesity, diet). Hypertension: Genetic susceptibility combined with environmental triggers (e.g., salt intake, stress). Congenital diseases: Cleft lip/palate, neural tube defects (e.g., spina bifida).

Question 59

TLO 5.2: Describe the multifactorial threshold model Threshold model: Example:

Answer 59

TLO 5.2: Describe the multifactorial threshold model Threshold model: Explains the likelihood of developing a multifactorial disease. Disease occurs when the combined genetic and environmental factors surpass a certain threshold. The threshold varies between sexes and populations. Example: Pyloric stenosis occurs more frequently in males, indicating a lower threshold for expression.

Question 60

TLO 5.3: Discuss the assessment of recurrence risk for multifactorial diseases Recurrence risk depends on: Example:

Answer 60

TLO 5.3: Discuss the assessment of recurrence risk for multifactorial diseases Recurrence risk depends on: Number of affected relatives. Severity of the condition in the proband. Closeness of the familial relationship. Population prevalence. Example: Risk of neural tube defects decreases with folic acid supplementation but increases with maternal history of the defect.

Question 61

Topic 6: Genetic Analysis TLO 6.1: Describe genetic analysis and different methods used Cytogenetic techniques: Molecular techniques: Biochemical analysis:

Answer 61

Topic 6: Genetic Analysis TLO 6.1: Describe genetic analysis and different methods used Genetic analysis involves studying DNA, RNA, and protein to identify mutations and chromosomal abnormalities. Cytogenetic techniques: Karyotyping, fluorescence in situ hybridization (FISH). Molecular techniques: PCR, next-generation sequencing (NGS), microarrays. Biochemical analysis: Enzyme assays to detect metabolic abnormalities.

Question 62

TLO 6.2: Describe different blotting techniques and their implications in diagnosis Southern blot: Northern blot: Western blot:

Answer 62

TLO 6.2: Describe different blotting techniques and their implications in diagnosis Southern blot: Detects specific DNA sequences. Used for large gene rearrangements (e.g., Duchenne muscular dystrophy). Northern blot: Analyzes RNA to study gene expression. Example: Detection of gene silencing in Fragile X syndrome. Western blot: Detects specific proteins. Example: Diagnosing HIV through detection of viral proteins.

Question 63

TLO 6.3: Describe the polymerase chain reaction (PCR) and its use in genetic analysis

Answer 63

TLO 6.3: Describe the polymerase chain reaction (PCR) and its use in genetic analysis PCR amplifies specific DNA sequences using primers and a thermostable DNA polymerase (e.g., Taq polymerase). Steps: Denaturation: DNA strands separate at high temperature. Annealing: Primers bind complementary sequences. Extension: DNA polymerase synthesizes the target sequence. Applications: Detecting mutations (e.g., BRCA1/2 mutations in breast cancer). Pathogen detection (e.g., HIV, SARS-CoV-2).

Question 64

TLO 6.4: Discuss different genetic diseases routinely screened in fetuses and newborns Prenatal screening:

Answer 64

TLO 6.4: Discuss different genetic diseases routinely screened in fetuses and newborns Prenatal screening: Non-invasive tests: Ultrasound for structural abnormalities. Cell-free DNA (cfDNA) for detecting trisomies (e.g., trisomy 21, 18, 13). Invasive tests: Amniocentesis: Analyzes fetal karyotype. Chorionic villus sampling (CVS): Detects genetic disorders.

Question 65

Sickle cell anemia is caused by a missense mutation resulting in defective formation of a globin protein.In this condition, Glutamic acid is replaced by which of the following amino acids?

Answer 65

a.Phenylalanine b.Proline c.Arginine **d.Valine** e.Lysine Sickle cell anemia is a condition due to missense mutation where Glutamic acid is replaced by Valine.Hydrophilic amino acid is replaced by hydrophobic amino acid in the outer surface of protein resultingin abnormal hemoglobin. It is an autosomal recessive disease caused by a point mutation in thehemoglobin beta gene (HBB) found on chromosome 11p15.5. Carrier frequency of HBB variessignificantly around the world, with high rates associated with zones of high malaria incidence, sincecarriers are somewhat protected against malaria. About 8% of the African American population arecarriers. A mutation in HBB results in the production of a structurally abnormal hemoglobin (Hb), calledHbS. Hb is an oxygen carrying protein that gives red blood cells (RBC) their characteristic color. Undercertain conditions, like low oxygen levels or high hemoglobin concentrations, in individuals who arehomozygous for HbS, the abnormal HbS clusters together, distorting the RBCs into sickled shapes.These deformed and rigid RBCs become trapped within small blood vessels and block them, producingpain and eventually damaging organs. The correct answer is: Valine

Question 66

A man who is affected with hemophilia A (X-linked recessive) mates with a woman who is aheterozygous carrier of this disorder. What proportion of this couple's daughters will be affected, and what proportion of the daughters will be heterozygous carriers?

Answer 66

a.0%; 100% **b.50%; 50% ** c.100%; 0% d.0%; 50% e.2/3; 1/3 Because the man transmits his X chromosome to all of his daughters, all of the daughters must carry atleast one copy of the mutation. The mother will transmit a mutation-carrying X chromosome half thetime and a normal X chromosome half the time. Thus, half of the daughters will be heterozygouscarriers, and half will be affected homozygotes, having received a mutation from both parents. The correct answer is: 50%; 50%

Question 67

A woman who has a heterozygous genotype for the gene variant causing Phenylketonuria (PKU), mateswith an unrelated man homozygous for the normal gene variant. What is the risk that their child willhave PKU?

Answer 67

**a.0%** b.100% c.50% d.25%

Question 68

Which of the following terms is used to describe a disease that, from generation to generation, shows adecrease in the age of onset and an increase in the severity of symptoms?

Answer 68

a.Acceptation b.Mutation **c.Anticipation ** d.Assumption

Question 69

Look at the pedigree below. If the male shown by the arrow in the fourth generation was to mate with ahomozygous normal female, what is the risk of their child also having the disease?

Answer 69

a.25% b.75% **c.0%** d.100% e.50% In these situations, try to identify the pattern of inheritance first. The pattern shown here is autosomalrecessive because we can see that in generation I, the male parent is affected, whereas the femaleparent is normal. In the progeny, the sons and daughters are affected with an approximately equalfrequency. This shows it to be an autosomal trait. It is not an X-linked trait, because the father contributes the X chromosome only to the daughter, not tothe son. Similarly, the Y chromosome is passed down to the son, not the daughter. Since the affectedfather has affected both the son and daughter, it is not a sex-linked trait, rather it is an autosomal trait. Had it been a dominant trait, all the progeny would have been affected. Here we can see that ingeneration II, a son is normal. Also, in the next generation we can see the trait skipping a generation.This happens in case of a recessive trait. Recessive traits require two identical alleles for their expression.An affected child can have unaffected parents. Hence, we can conclude that the given pedigree represents the transmission of an autosomal recessivetrait. Now draw the punnett square based on what the question is asking. Here the male is affected so in AR for them to be affected they should be homozygous for the disease;you can give any nomenclature to the allele but remember what nomenclature or color you are givinghere I will give ‘a’ for affected and ‘A’ for unaffected allele. So, the male’s genotype is aa. Now for thefemale it says homozygous and normal so her genotype is AA. If the question had said heterozygousnormal/carrier then it would have been Aa. But let’s go back to our scenario and draw a Punnett square. a (male) a (male) A (female) Aa Aa A (female) Aa Aa As it is AR we need both affected allele’s to be inherited for the disease to be phenotypically visible orfor the individual to be affected. Hence the affected individual recurrence risk ratio is 0/4= 0% But the risk of the child being a carrier for the disease is 4/4= 100% Answer: (0%)

Question 70

A 25-year-old man experiences severe intolerance to certain medications. On 2 occasions, his reactionsto various drugs have necessitated hospital admission. His family pedigree with respect to this conditionis shown below, with the red arrow indicating his position within the family. Assume that this conditiondemonstrates complete penetrance and is rare in the general population. This condition most likelyexhibits which of the following inheritance patterns?

Answer 70

**a.X-linked recessive** b.X-linked dominant c.Autosomal dominant d.Mitochondrial e.Autosomal recessive The pedigree shows that only males are affected by the drug intolerance. Specifically, male offspring ofunaffected parents are affected. There is no evidence of male-to-male transmission. This pattern is mostconsistent with X-linked recessive inheritance from an asymptomatic carrier female in the firstgeneration. In X-linked recessive inheritance: 1. Affected males will always produce unaffected sons and carrier daughters. 2. Carrier females have a 50% chance of producing an affected son or carrier daughter. G6PD deficiency,which causes acute hemolytic anemia on exposure to oxidant drugs, follows an X-linked recessivepattern of inheritance. The correct answer is: X-linked recessive

Question 71

While examining a family pedigree for a condition you notice that none of the affected males have sonsthat are affected. What is the inheritance pattern of the condition?

Answer 71

a.The phenomenon is due to incomplete penetrance b.Autosomal dominant **c.Mitochondrial** d.The phenomenon is due to imprinting e.Autosomal recessive The correct answer is: Mitochondrial

Question 72

Huntington's disease is due to which of the following mutations?

Answer 72

a.Silent mutation b.Nonsense mutation **c.Trinucleotide repeat** d.Missense mutation e.Chromosomal deletion HD is an autosomal dominant disease caused by degeneration of striatal neurons and characterized bya progressive movement disorder and dementia. Jerky, hyperkinetic, sometimes dystonic movementsinvolving all parts of the body (chorea) are characteristic; affected individuals may later developbradykinesia and rigidity. The disease is relentlessly progressive and uniformly fatal, with an averagecourse of about 15 years. The gene for HD, HTT, located on chromosome 4p16.3, encodes a 348-kDprotein known as huntingtin. In the first exon of the gene, there is a stretch of CAG repeats that encodesa polyglutamine region near the N terminus of the protein. Normal HTT genes contain 6 to 35 copies ofthe repeat; when the number of repeats is increased beyond this level, it is associated with disease. The correct answer is: Trinucleotide repeat

Question 73

Which of the following techniques involves the application of distinct DNA sequences resulting in manyidentical copies sufficient for analysis?

Answer 73

a.Northern blot b.Southern blot c.Dot blot d.Western blot **e.Polymerase chain reaction (PCR)** PCR provides a means of amplifying distinct DNA sequences, starting with incredibly tiny amounts ofDNA and resulting in large amounts of identical copies sufficient for analysis. PCR is sensitive enough toamplify the DNA from a single cell to yield amounts sufficient for analysis. PCR requires prior knowledgeof sequence information at the two ends of the target sequence. PCR needs primers to start DNAsynthesis, which means that some DNA sequence in or close to the region of interest must be known. The correct answer is: Polymerase chain reaction (PCR)

Question 74

To analyse DNA, first, we need to remove the histones and do DNA fragmentation. Within thefragments is the gene or sequence of our interest. What is the next immediate step in the blottingtechnique after the DNA fragments are generated by restriction enzymes?

Answer 74

**a.Electrophoresis** b.Autoradiography c.Hybridization d.Addition of primer e.Probing

Question 75

What is the central dogma of genetics?

Answer 75

a.protein-->RNA-->DNA **b.DNA-->mRNA-->protein** c.RNA-->DNA-->protein d.mRNA-->DNA-->protein e.DNA-->protein-->mRNA

Question 76

The incidence of Duchenne muscular dystrophy in North America is about 1/3,000 males. Based on this,what is the gene frequency of this X-linked recessive mutation?

Answer 76

a.2/3,000 b.1/9,000 c.1/6,000 d.(1/3,000)2 e.1/3,000 Because males have only a single X chromosome, each affected male has one copy of the disease-causing recessive mutation. Thus, the incidence of an X-linked recessive disease in the male portion of a population is a direct estimate of the gene frequency in the population. The correct answer is: 1/3,000

Question 77

Triple test performed on a pregnant woman at 18 weeks of gestation reveals low levels of alpha-fetoprotein (AFP). Amniocentesis confirms these findings. The mother is a known alcoholic and smoker. Low AFP levels are associated with which of the following conditions?

Answer 77

**a.Trisomy 21** b.Neural tube defects c.Turner syndrome d.Omphalocele e.Fetal alcohol syndrome The correct answer is: Trisomy 21

Question 78

A single missense mutation in the gene coding for cystathionine beta-synthase causes a variety ofphenotypic manifestations including skeletal deformities, mental retardation and vascular thromboses. This phenomenon is referred to as:

Answer 78

a.Polyploidy b.Variable penetrance c.Segregation d.Imprinting **e.Pleiotropy** Cystathionine beta-synthase deficiency is the enzyme defect present in classic homocystinuria.Homocystinuria is characterized clinically by ectopia lentis, mental retardation, marfanoid habitus andosteoporosis in addition to vascular problems. Pleiotropy is the occurrence of multiple phenotypicmanifestations, often in different organ systems, as a result of a single genetic defect. Pleiotropydescribes instances where multiple phenotypic manifestations result from a single genetic mutation.Most syndromic genetic illnesses exhibit pleiotropy. Polyploidy occurs when more than two completesets of homologous chromosomes exist within an organism or partial hydatidiform mole, for example,there are cells of nonstandard ploidy (typically 69XXX, 69XXY or 69 XYY). The chromosomes in this caseare derived from one haploid maternal set and two haploid paternal sets of chromosomes. Penetrancerefers to the proportion of individuals with a given genotype that express the associated phenotype. Inincomplete penetrance, less than 100% of individuals with a given genotype express its associatedphenotype. The law of segregation (Mendel's first law) describes the phenomenon wherebygametogenesis within the parent organism results in the separation of paired chromosomes and thusthe separation of paired 31 genes so that each offspring inherits only half of each parent's geneticcomposition Parental imprinting refers to the preferential transcription of genes from one or another ofa homologous pair of chromosomes depending on the parental origin of the chromosome. The correct answer is: Pleiotropy

Question 79

In studying a large number of families with a small deletion in a specific chromosome region, it is noted that the disease phenotype is distinctly different when the deletion is inherited from the mother as opposed to the father. What is the most likely explanation?

Answer 79

a.Mitochondrial inheritance b.X-linked recessive inheritance c.Sex-dependent penetrance **d.Imprinting** e.X-linked dominant inheritance Imprinting refers to the differential transcriptional activity of genes inherited from the father versus themother. Under mitochondrial inheritance, only an affected mother can transmit the disease phenotype;the offspring of affected males are always unaffected. The other modes of inheritance can influence therelative proportions of affected individuals who belong to one gender or the other (e.g., more affectedmales under X-linked recessive inheritance, more affected females under X-linked dominantinheritance), but they do not involve any differences in expression depending on the transmittingparent. The correct answer is: Imprinting

Question 80

Non-invasive prenatal screening (NIPS) is a highly accurate screening test. What does it measure?

Answer 80

**a.cfDNA of the fetus** b.Maternal DNA c.The presence of neural tube defect d.Amniotic fluid e.The gestational age Non-invasive prenatal screening (NIPS), used for common autosomal and sex chromosomeaneuploidies possible, with sensitivities and specificities approaching 99% for trisomy 21. After 9-10weeks post LMP, the serum of a pregnant woman contains fetal DNA that is not contained in thenucleus of a cell but is floating freely in the maternal circulation. Significant proportion (5 - 50 %) of allcfDNA found in maternal plasma. Short pieces of DNA. Commercial kits and PCR to isolate and prepareDNA for analysis. The correct answer is: cfDNA of the fetus

Question 81

Which of the following statements is CORRECT regarding autosomal recessive inheritance?

Answer 81

a.Male are more frequently affected than females b.Females are more frequently affected than males **c.Affected individuals are not seen in every generation** d.Clinical expression results from heterozygous allele inheritance The correct answer is: Affected individuals are not seen in every generation