General Principles Week 3 Flashcards
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:
The central dogma is summarized as:
DNA → RNA → Protein.
Topic 1: The Genetic Code and Mutations
Replication:
DNA is duplicated to ensure genetic material is inherited by daughter cells during cell division.
Topic 1: The Genetic Code and Mutations
Transcription:
DNA is transcribed into RNA (specifically, mRNA) by RNA polymerase.
Topic 1: The Genetic Code and Mutations
Transcription occurs in the nucleus and involves:
Promoters:
Exons:
Introns:
Promoters: Regions of DNA that signal RNA polymerase to start transcription.
Exons and introns: Exons are coding regions of mRNA; introns are spliced out.
Topic 1: The Genetic Code and Mutations
Translation:
mRNA is translated into proteins at the ribosome.
- Translation: mRNA is translated into proteins at the ribosome. This process involves:
tRNA:
Ribosomes:
Codons:
tRNA: Delivers amino acids.
Ribosomes: Facilitate peptide bond formation between amino acids.
Codons: Groups of three nucleotides in mRNA that encode specific amino acids.
TLO 1.2: Describe the genetic code and codons
Genetic Code:
A set of rules dictating how nucleotide sequences in mRNA are translated into proteins.
TLO 1.2: Describe the genetic code and codons
Codons:
Triplet nucleotide sequences (e.g., AUG) that code for amino acids or regulatory signals.
TLO 1.2: Describe the genetic code and codons
- Start codon:
- Stop codons:
- Start codon: AUG (methionine) initiates protein translation.
- Stop codons: UAA, UAG, UGA terminate translation.
TLO 1.2: Describe the genetic code and codons
Universal:
Degenerate:
Non-overlapping: .
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.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Mutation:
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.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Point mutations:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Point mutations: A single nucleotide substitution.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Silent mutation:
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).
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Missense mutation:
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.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Nonsense mutation:
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).
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Frameshift mutations:
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.
TLO 1.4: Describe trinucleotide repeat disorders
Examples:
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.
TLO 1.5: Define anticipation with disease examples
Anticipation:
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.
Topic 2: Single Gene Disorders
Gene:
Topic 2: Single Gene Disorders
Gene: A DNA sequence encoding a protein or functional RNA.
Topic 2: Single Gene Disorders
Locus:
Topic 2: Single Gene Disorders
Locus: A gene’s location on a chromosome.
Topic 2: Single Gene Disorders
Allele:
Topic 2: Single Gene Disorders
Allele: Variant forms of a gene.
Topic 2: Single Gene Disorders
Genotype:
Topic 2: Single Gene Disorders
Genotype: The genetic makeup of an individual.
Topic 2: Single Gene Disorders
Phenotype:
Topic 2: Single Gene Disorders
Phenotype: Observable traits resulting from genotype-environment interactions.
Topic 2: Single Gene Disorders
Homozygous:
Topic 2: Single Gene Disorders
Homozygous: Possessing two identical alleles (e.g., AA or aa).
Topic 2: Single Gene Disorders
Heterozygous:
Topic 2: Single Gene Disorders
Heterozygous: Possessing two different alleles (e.g., Aa).
Topic 2: Single Gene Disorders
Dominant:
Topic 2: Single Gene Disorders
Dominant: A trait expressed with one allele (e.g., Aa or AA).
Topic 2: Single Gene Disorders
Recessive:
Topic 2: Single Gene Disorders
Recessive: A trait expressed only with two identical alleles (e.g., aa).
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal dominant:
Examples:
Recurrence risk: 50% if one parent is affected.
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.
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal recessive:
Examples:
Recurrence risk:
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.
TLO 2.3: X-linked inheritance
X-linked dominant:
Examples: .
TLO 2.3: X-linked inheritance
X-linked dominant:
Affects males and females.
Examples: Rett syndrome, hypophosphatemic rickets.
TLO 2.3: X-linked inheritance
X-linked recessive:
Examples:
Recurrence risk:
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.
TLO 2.4: Properties of mitochondrial inheritance
Examples:
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.
TLO 2.5: Define incomplete penetrance and pleiotropy
Incomplete penetrance:
Pleiotropy:
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).
TLO 2.6: Describe genetic imprinting and uniparental disomy
Genetic imprinting:
Uniparental disomy:
Examples:
Prader-Willi syndrome:
Angelman syndrome:
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.
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Frequency
Genotype Frequency
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
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Allele Frequency
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.
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Example Calculation:
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
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
Definition of Hardy-Weinberg Equilibrium (HWE)
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.
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
Key Assumptions of HWE:
Key Assumptions of HWE:
- Large population size: Prevents genetic drift.
- No mutation: No new alleles are introduced or altered.
- Random mating: No preference for specific genotypes in mating.
- No natural selection: All genotypes have equal reproductive success.
- No gene flow: No migration into or out of the population.
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
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).
TLO 3.3: Apply the Hardy-Weinberg Equilibrium to Calculate Genotype Frequency Estimates Application
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.
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:
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.
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
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.
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)
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.
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
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.
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
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.
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
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.
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
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.
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
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.
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Karyotype:
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.
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Chromosome nomenclature:
Example:
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).
TLO 4.2: Discuss numerical chromosomal abnormalities
Numerical abnormalities:
Euploidy:
Aneuploidy:
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.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of autosomal aneuploidies:
Trisomy 21 (Down syndrome):
Trisomy 18 (Edwards syndrome):
Trisomy 13 (Patau syndrome):
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.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Turner syndrome (45,X):
Clinical features:
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.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Klinefelter syndrome (47,XXY):
Clinical features:
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.
TLO 4.3: Describe the most common cause of numerical chromosomal abnormalities
Cause:
Nondisjunction:
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.
TLO 4.4: Describe structural chromosomal abnormalities
Structural abnormalities:
Translocation:
Robertsonian translocation:
Deletion:
Inversion:
Paracentric inversion:
Pericentric inversion:
Ring chromosome:
Example:
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).
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:
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).
TLO 5.2: Describe the multifactorial threshold model
Threshold model:
Example:
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.
TLO 5.3: Discuss the assessment of recurrence risk for multifactorial diseases
Recurrence risk depends on:
Example:
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.
Topic 6: Genetic Analysis
TLO 6.1: Describe genetic analysis and different methods used
Cytogenetic techniques:
Molecular techniques:
Biochemical analysis:
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.
TLO 6.2: Describe different blotting techniques and their implications in diagnosis
Southern blot:
Northern blot:
Western blot:
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.
TLO 6.3: Describe the polymerase chain reaction (PCR) and its use in genetic analysis
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).
TLO 6.4: Discuss different genetic diseases routinely screened in fetuses and newborns
Prenatal screening:
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.
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?
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
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?
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%
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?
a.0%
b.100%
c.50%
d.25%
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?
a.Acceptation
b.Mutation
**c.Anticipation **
d.Assumption
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?
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%)
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?
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
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?
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
Huntington’s disease is due to which of the following mutations?
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
Which of the following techniques involves the application of distinct DNA sequences resulting in manyidentical copies sufficient for analysis?
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)
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?
a.Electrophoresis
b.Autoradiography
c.Hybridization
d.Addition of primer
e.Probing
What is the central dogma of genetics?
a.protein–>RNA–>DNA
b.DNA–>mRNA–>protein
c.RNA–>DNA–>protein
d.mRNA–>DNA–>protein
e.DNA–>protein–>mRNA
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?
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
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?
a.Trisomy 21
b.Neural tube defects
c.Turner syndrome
d.Omphalocele
e.Fetal alcohol syndrome
The correct answer is:
Trisomy 21
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:
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
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?
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
Non-invasive prenatal screening (NIPS) is a highly accurate screening test. What does it measure?
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
Which of the following statements is CORRECT regarding autosomal recessive inheritance?
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
