Genetic Disorders

Question 1

Classify genetic disorder

Answer 1

Mutations underlie these disorders:

Genetic mutations (xterised by single gene mutations of large effects)

With classic mode of inheritance (Mendelian disorders)

OR

Non-classic mode of inheritance

• Complex multigenic Disorders-(Complex multifactorial disorders)
• Chromosomal (cytogenetic) Disorders

Question 2

What’s mutation and the types?

Answer 2

Mutation is defined as apermanent change in theDNA that are transmitted toprogeny cells.

Point mutation

Frameshift mutations

Trinucleotide repeat mutation

Question 3

Explain the types

Answer 3

Definition: Substitution of a single nucleotide base by a different base.

Frameshift Mutations:

Definition: Result from the deletion or insertion of one or two base pairs, leading to a shift in the reading frame of the DNA.

Trinucleotide Repeat Mutations:

Definition: Involves the repetition of a sequence of three nucleotides multiple times. This type of mutation can lead to genetic disorders when the number of repeats exceeds a normal threshold

Question 4

Disorders like Huntington’s disease and fragile X syndrome are caused by what type of mutation

Answer 4

Trinucletide Repeat M

Question 5

Non classical single gene mutation involves

Answer 5

Genetic imprinting
Trinucletide repeats
Mitochondrial genes

Question 6

Define these terms
Penetrance
Complete penetrance
Incomplete penetrance

Answer 6

Penetrance refers to the percentage of individuals who possess a particular gene and exhibit the phenotype associated with that gene.
Complete Penetrance: Every individual with the gene manifests the phenotype.
Incomplete Penetrance: Some individuals with the mutant gene do not show the phenotype.

Question 7

What’s Variable Expressovity and an example of it

What’s polymorphism

Answer 7

Variable Expressivity:

Definition: A genetic trait seen in all individuals carrying the mutant gene, but the degree of expression varies among individuals.

Example: Neurofibromatosis (NF), where symptoms range from mild skin spots to severe tumors.

Polymorphism:

Definition: A genetic variant that has at least two alleles and occurs in at least 1% of the population.

Question 8

Single Gene Disorders of Large Effects (Mendelian Disorders):

Caused by mutations in a single gene.
What’s the Inheritance patterns of single gene mutations

Answer 8

Inheritance patterns include autosomal dominant, autosomal recessive, and sex-linked (X-linked).

Question 9

Causes and examples of
Complex multigenic & chromosomal dx

Answer 9

Complex Multigenic Disorders:

Result from the interaction of multiple genes and environmental factors.

Examples include many common diseases such as diabetes, hypertension, and heart disease.

Chromosomal Disorders:

Caused by abnormalities in chromosome number or structure.

Examples include Down syndrome (trisomy 21), Turner syndrome (45,X), and Klinefelter syndrome (47,XXY

Question 10

What’s autosominal D dx and it’s characteristics

Answer 10

Autosomal Dominant (AD):

A single copy of the mutant gene (from either parent) can cause the disorder.

Characteristics:

50% chance of an affected parent passing the disorder to offspring.

Males and females are equally likely to be affected.

Delayed onset of symptoms is common.

Clinical features can vary due to incomplete penetrance and variable expressivity.

New mutations can occur, leading to cases with no family history.

Question 11

What are the Examples of Autosomal Dominant Disorders:

Answer 11

Nervous System: Huntington disease, Neurofibromatosis, Myotonic dystrophy, Tuberous sclerosis.

Urinary System: Polycystic kidney disease.

Gastrointestinal: Familial polyposis coli.

Hematopoietic: Hereditary spherocytosis, von Willebrand disease.

Skeletal: Marfan syndrome, Ehlers-Danlos syndrome (some variants), Osteogenesis imperfecta, Achondroplasia.

Metabolic: Familial hypercholesterolemia, Acute intermittent porphyria.

Question 12

What’s AR mutation and it’s characteristics

Answer 12

Autosomal Recessive (AR):

Two copies of the mutant gene (one from each parent) are necessary to cause the disorder.

Characteristics:

Parents are typically carriers and are not affected.

25% chance of affected offspring if both parents are carriers.

Males and females are equally affected.

Often shows early onset.

Question 13

Examples of AR

Answer 13

Metabolic: Cystic fibrosis,Phenylketonuria,Galactosemia,α1-Antitrypsin deficiency, Wilson disease,Hemochromatosis,Glycogen storage diseases

Hematopoietic: Sickle cell anemia,Thalassemias

Endocrine: Congenital adrenal hyperplasia

Skeletal: Ehlers Danlos syndrome (some variants), Alkaptonuria

Nervous: Neurogenic muscular atrophies, Friedreich ataxia, Spinal muscular atrophy

Question 14

Why are females carriers and expressed I’m males

Answer 14

X-linked recessive disorders are caused by mutations in genes on the X chromosome. Since males have only one X chromosome, a single mutated gene can cause the disorder. Females, with two X chromosomes, usually must have mutations in both copies of the gene to be affected, making these conditions much more common in males.

Question 15

Two copies of the mutant gene are needed for females, but only one for males.
Characteristics:
Males are more frequently affected.
Carrier females have a 50% chance of passing the gene to sons (affected) and daughters (carriers
Examples of this x chromosome dx

Answer 15

Examples of X-Linked Recessive Disorders: Hemophilia A and B, Duchenne muscular dystrophy, Red-green color blindness.

Question 16

What’s the Transmission Patterns of x linked dx

Answer 16

Affected males do not transmit the disorder to their sons, but all daughters become carriers.

Heterozygous females (carriers) usually do not express the disease because they have a normal allele on the other X chromosome.

Sons of heterozygous women have a 50% chance of inheriting the mutant gene and expressing the disorder

Question 17

What’s Lyonization in x chromosome dx

Answer 17

Lyonization (X-Chromosome Inactivation):

In females, one of the X chromosomes is randomly inactivated in each cell, leading to variability in disease expression.

If the X chromosome carrying the normal allele is inactivated in most cells, a heterozygous female might fully express the disorder, though this is rare.

Question 18

Examples of x chromosome dx in males

Answer 18

Musculoskeletal:

Duchenne Muscular Dystrophy

Blood:

Hemophilia A and B

Chronic Granulomatous Disease

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Immune System:

Agammaglobulinemia

Wiskott-Aldrich Syndrome

Metabolic:

Diabetes Insipidus

Lesch-Nyhan Syndrome

Question 19

X-Linked Dominant Disorders

These disorders are rarer and occur due to dominant disease alleles on the X chromosome. It’s Transmission patterns is?

With an example

Answer 19

Transmission patterns include:

An affected heterozygous female transmits the disorder to half of her sons and half of her daughters.
An affected male transmits the disorder to all his daughters but none of his sons if the female parent is unaffected.
Example:

Vitamin D-resistant rickets.

Question 20

Types of Genetic Disorders
List examples of Single-Gene Disorders

Answer 20

Enzyme Defects:

Lead to lysosomal storage diseases such as Gaucher Disease and Niemann-Pick Disease.

Membrane Receptor and Transport System Defects:

Example: Familial Hypercholesterolemia.

Alterations in Non-Enzyme Proteins:

Example: Hemoglobinopathies such as Sickle Cell Anemia.

Pharmacogenetic Mutations:
Result in unusual drug reactions, such as G6PD Deficiency.

Question 21

Complex Multigenic Disorders
These result from the interaction between multiple genes and environmental factors, with an additive effect of genetic components

List it’s xteristic and examples

Answer 21

Characteristics:

Low penetrance and small effects from individual genes.

The more deleterious genes inherited, the more severe the disease expression.

Examples:

Common diseases such as diabetes, hypertension, and heart disease.

Cleft lip or cleft palate (or both)

Congenital heart disease

Coronary heart disease

Hypertension

Gout

Diabetes mellitus

Pyloric stenosis

Question 22

30-41

Question 23

What’s Euploidy and Aneuploidy

Answer 23

Euploidy: The condition of having a complete set of chromosomes, typical for a species. For humans, this means having 46 chromosomes (23 pairs).

Aneuploidy: The condition of having an abnormal number of chromosomes, not in complete sets. Examples include trisomy (an extra chromosome) and monosomy (a missing chromosome).

Question 24

What are they types of chromosome).

Chromosome Banding

& definition and uses

Answer 24

Q-Banding: A method of staining chromosomes with quinacrine dye, which fluoresces under UV light, highlighting regions rich in adenine-thymine base pairs.

G-Banding: Involves treating chromosomes with trypsin and then staining with Giemsa dye, which produces a series of light and dark bands, useful for identifying chromosomal abnormalities

Question 25

Chromosome Structure

p Arm: The short arm of a chromosome.

q Arm: The long arm of a chromosome.

Question 26

What’s the Mechanisms Leading to Aneuploidy

Answer 26

Anaphase Lag: Occurs when a chromosome or chromatid is left behind during cell division, leading to one daughter cell with a missing chromosome. And it results in one normal cell and one monosomy

Non-Disjunction: The failure of homologous chromosomes or sister chromatids to separate properly during cell division, resulting in gametes with an abnormal number of chromosomes

Causing monosomy & trisomy

Question 27

Whts the Consequences of Aneuploidy

Answer 27

Monosomy: The presence of only one copy of a particular chromosome instead of the usual two.

Trisomy: The presence of an extra chromosome, resulting in three copies of a particular chromosome.

Question 28

What’s Mosaicism

Answer 28

Mosaicism: The presence of two or more populations of cells with different chromosomal complements in the same individual, arising from a mutation early in development.

Question 29

What’s Disorders Involving Autosomes

Answer 29

Down Syndrome (Trisomy 21):

Incidence: 1 in 700 live births.

Karyotypes: 47,XX,+21 or 47,XY,+21; Robertsonian translocation in 4% of cases.

Symptoms: Mental retardation, congenital heart defects, increased risk of leukemia, and Alzheimer’s disease in older patients.

Associated Factors: Strongly linked to maternal age.

Patau Syndrome (Trisomy 13):

Incidence: 1 in 20,000 live births.

Symptoms: Severe mental retardation, heart and organ defects, polydactyly, cleft lip and palate, rocker-bottom feet, often leading to death by age one.

Cri du Chat Syndrome (5p Deletion):

Karyotype: 46,XX or 46,XY, 5p-.

Symptoms: Cat-like cry, microcephaly, severe mental retardation, heart defects.

Edwards Syndrome (Trisomy 18):

Incidence: 1 in 10,000 live births.

Symptoms: Severe mental retardation, small facial features, organ malformations, typically leading to death by age 2-3.

Question 30

List Disorders Involving Sex Chromosomes

Answer 30

Disorders Involving Sex Chromosomes

Turner Syndrome (45,X):

Incidence: 1 in 2000 live births.

Symptoms: Hypogonadism, short stature, webbed neck, infertility.

Klinefelter Syndrome (47,XXY):

Symptoms: Hypogonadism, tall stature, gynecomastia, infertility.

Super Male (47,XYY):

Symptoms: Generally normal physical appearance, may have taller stature and learning difficulties.

Super Female (47,XXX or 49,XXXX):

Symptoms: Generally mild, may include tall stature, learning difficulties, and reduced fertility.

Hermaphroditism and Pseudohermaphroditism:

Hermaphroditism: Presence of both ovarian and testicular tissue.

Pseudohermaphroditism: Discrepancy between external genitalia and gonadal sex (e.g., individuals with testes but female external genitalia

Question 31

Acquired germline mutation causes skip generation why?

Question 32

Chromosomal (cytogenetic) Disorders
Can be classified into

Answer 32

Disorders involving Autosomes

Disorders involving Sex chromosomes

Question 33

The Structural abnormalities of chromosome can be:

Answer 33

Quantitative-abnormal number or

Qualitative- alteration in structure,

…of one or more chromosomes

Question 34

What are the Types of Structural Chromosomal Disorders and explain them

Answer 34

1,Translocations:

Balanced Translocation: The exchange of chromosome segments between two chromosomes without any genetic material gain or loss. Generally does not cause abnormalities in carriers but can cause issues in offspring.

Robertsonian Translocation: A type of balanced translocation involving the fusion of long arms of two acrocentric chromosomes. Commonly involves chromosomes 13, 14, 15, 21, and 22. Can lead to conditions like Down syndrome when chromosome 21 is involved.

2,Isochromosome: A chromosome with identical arms due to the loss of one arm and duplication of the other.

3,Inversions:

Paracentric Inversion: Involves the chromosome segment excluding the centromere.

Pericentric Inversion: Includes the centromere within the inverted segment.

4,Deletions: Loss of a chromosome segment, leading to conditions such as Cri du chat syndrome.

5,Ring Chromosomes: Formed when a chromosome undergoes two breaks and the ends of the chromosome arms fuse to form a ring.

Question 35

What are the incidence & causes of some Disorders Involving Autosomes

Answer 35

Involving Autosomes

Down Syndrome (Trisomy 21):

Incidence: 1 in 700 live births in the US.

Causes: 95% due to trisomy 21, 4% due to Robertsonian translocation, 1% mosaicism.

Risk Factor: Strong correlation with increased maternal age.

Symptoms: Congenital heart disease, dysmorphic features, mental retardation, predisposition to leukemia, neurodegenerative changes, abnormal immune response.

Edwards Syndrome (Trisomy 18):

Incidence: 1 in 10,000 live births.

Symptoms: Severe mental retardation, small facial features, organ malformations, typically leading to early death.

Patau Syndrome (Trisomy 13):

Incidence: 1 in 20,000 live births.

Symptoms: Severe mental retardation, heart defects, polydactyly, cleft lip and palate, rocker-bottom feet, leading to death within the first year of life.

Cri du Chat Syndrome (5p Deletion):

Karyotype: 46,XX or 46,XY, 5p-.

Symptoms: Cat-like cry, microcephaly, severe mental retardation, heart defects

Question 36

Between Autosomal & sex chromosome disorder which is more common?

Answer 36

Sex chromosome disorders are more common than autosomal disorders

Question 37

Differentiate between Klinefelter Syndrome & Turner Syndrome

Hint: symptoms & incidents

Answer 37

Klinefelter Syndrome

Incidence: 1 in 850 male births.

Symptoms: Tall stature, hypogonadism, lack of secondary male characteristics, gynecomastia, principal cause of male infertility.

Turner Syndrome

Incidence: 1 in 3,000 female births.
Karyotype Heterogeneity: Includes pure monosomy X, mosaicism, and other complex karyotypes.
Symptoms: Short stature, webbed neck, cardiovascular abnormalities, lack of secondary sex characteristics, streak ovaries due to accelerated loss of oocytes.

Question 38

What’s Klinefelter Syndrome & Turner Syndrome logo😂😂

Answer 38

Klinefelter Syndrome (47, XXY):

Turner Syndrome (45, X):

Question 39

What are the Types and Rates of Mutation

Answer 39

Genome Mutation

Mechanism: Chromosome missegregation (e.g., aneuploidy)

Frequency: 10−210^{-2}10−2 per cell division

Chromosome Mutation

Mechanism: Chromosome rearrangement (e.g., translocation)

Frequency: 6×10−46 \times 10^{-4}6×10−4 per cell division

Gene Mutation

Mechanism: Base pair mutation (e.g., point mutation, small deletion, or insertion)

Frequency: 10−1010^{-10}10−10 per base pair per cell division or 10−5−10−610^{-5} - 10^{-6}10−5−10−6 per locus per generation

Question 40

What’s the full meaning and use of RFLP Linkage Analysis

Answer 40

RFLPs (Restriction Fragment Length Polymorphisms): Useful markers for all human chromosomes. They help in mapping disease genes by searching for linkage between an RFLP and the disease phenotype.

Question 41

Diagnosis of Genetic Disorders

Screening for Carriers

Preimplantation Genetic Diagnosis

Prenatal Diagnostic Testing

Newborn Screening

Presymptomatic Testing: For predicting diseases and assessing risk for adult-onset conditions.

Confirmational Diagnosis: For symptomatic individuals.

Forensic/Identity Testing