Genetic Disorders Flashcards
Classify genetic disorder
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
What’s mutation and the types?
Mutation is defined as apermanent change in theDNA that are transmitted toprogeny cells.
Point mutation
Frameshift mutations
Trinucleotide repeat mutation
Explain the types
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
Disorders like Huntington’s disease and fragile X syndrome are caused by what type of mutation
Trinucletide Repeat M
Non classical single gene mutation involves
Genetic imprinting
Trinucletide repeats
Mitochondrial genes
Define these terms
Penetrance
Complete penetrance
Incomplete penetrance
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.
What’s Variable Expressovity and an example of it
What’s polymorphism
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.
Single Gene Disorders of Large Effects (Mendelian Disorders):
Caused by mutations in a single gene.
What’s the Inheritance patterns of single gene mutations
Inheritance patterns include autosomal dominant, autosomal recessive, and sex-linked (X-linked).
Causes and examples of
Complex multigenic & chromosomal dx
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
What’s autosominal D dx and it’s characteristics
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.
What are the Examples of Autosomal Dominant Disorders:
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.
What’s AR mutation and it’s characteristics
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.
Examples of AR
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
Why are females carriers and expressed I’m males
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.
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
Examples of X-Linked Recessive Disorders: Hemophilia A and B, Duchenne muscular dystrophy, Red-green color blindness.
What’s the Transmission Patterns of x linked dx
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
What’s Lyonization in x chromosome dx
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.
Examples of x chromosome dx in males
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
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
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.
Types of Genetic Disorders
List examples of Single-Gene Disorders
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.
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
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
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What’s Euploidy and Aneuploidy
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).
What are they types of chromosome).
Chromosome Banding
& definition and uses
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
