Untitled Quiz

Genetic diseases are conditions caused by abnormalities in genes.
Hereditary disorders are passed down from one parent, carried in the gametes through generations, and are often familial.
Congenital diseases are present at birth. Not all genetic diseases are congenital, and not all congenital diseases are genetic. Congenital syphilis is an example.
Mutations are permanent changes in DNA. Germ cell mutations are transmitted to offspring, causing inherited diseases. Somatic cell mutations are not passed to offspring but can cause cancers and some congenital malformations.

Point mutation: A single nucleotide base is substituted by another. This can result in the replacement of one amino acid in the protein. Sickle cell anemia is an example, where a change in a nucleotide triplet encoding glutamic acid changes it to valine, causing the missense mutation.
Nonsense mutation: A point mutation that changes an amino acid codon to a chain termination codon (stop codon). This prematurely terminates protein synthesis, and the resulting protein is rapidly degraded.
Frameshift mutation: Deletion or insertion of one or two base pairs alters the reading frame of DNA, affecting protein synthesis. A three-base deletion is not a frameshift mutation.

Three-base deletion: A mutation in which three bases are deleted, this does not lead to a frameshift mutation but results in loss of a specific amino acid (e.g., phenylalanine in cystic fibrosis) because the deletion occurs in multiples of three.
Four-base insertion: An insertion of four bases in a gene that alters the reading frame. The addition or removal of nucleotides in groupings that are not multiples of three results in a frameshift mutation.
Trinucleotide repeat mutations: Mutations characterized by amplification of a sequence of three nucleotides—e.g., fragile X syndrome, which has 250-4000 CGG repeats within the FMR-1 gene. In normal individuals, the number of repeats is usually around 29.

Mendelian disorders: Resulting from mutations in a single gene. These are approximately 1% of all adult and 6-8% of pediatric hospital admissions. They are further classified as autosomal dominant, autosomal recessive, and X-linked.
Complex disorders: Involve multiple genes and environmental factors (multifactorial inheritance). Examples include diabetes mellitus.
Chromosomal disorders: Result from structural or numerical alterations in the autosomes or sex chromosomes.
Heterogeneous disorders: involve a single gene but do not follow typical Mendelian inheritance patterns.

At least one affected parent is needed.
Males and females are equally affected.
If one affected parent and one unaffected parent have a child, there is a 50% chance the child will inherit the disorder.
Some patients don't have affected parents. This could mean a new mutation in the egg or sperm of non-affected parents.
Clinical features may be modified by reduced penetrance or variable expressivity.
- Reduced penetrance: some individuals inherit the mutant gene but are phenotypically normal (i.e. have the mutation but don't exhibit the disease.)
- Variable expressivity: the trait is seen in all who carry the mutant gene but is expressed differently among individuals (i.e. some individuals are more severely affected than others).
The symptoms may not appear until adulthood.
A 50% reduction in normal gene products is linked to clinical symptoms

Both parents are often carriers (unaffected).
Affected individuals inherit two copies of the abnormal gene—one from each parent.
Affected children have a 25% chance of inheritance for each pregnancy.
Consanguinity is more common (likely).
Expression of the defect is more uniform than autosomal dominant.
Symptoms often appear early in life.
50% reduction in normal gene products may accompany clinical symptoms.

Primarily carried on the X chromosome, thus affecting mostly males.
Affected males inherit the mutation from their heterozygous mothers.
Affected males do not transmit the disorder to their sons; all of their daughters are carriers.
Sons of heterozygous mothers have a 50% chance of inheriting the disorder.
X-linked dominant disorders are less common and are characterized by transmission of the disease to 50% of sons and daughters of an affected heterozygous female.

Marfan syndrome: An autosomal dominant connective tissue disorder caused by a mutation affecting the fibrillin gene. This causes abnormalities in the skeleton, eyes, and cardiovascular system.

Familial hypercholesterolemia: An autosomal dominant disorder. Heterozygotes often have 2-3 times the normal plasma cholesterol levels. Symptoms usually only appear in adulthood - such as xanthelasma, and premature coronary artery disease. Homozygotes are often much more severely affected, and show signs of xanthelasma in childhood, and can die from myocardial infarction by age 15.

Phenylketonuria (PKU): An autosomal recessive inborn error of metabolism resulting from a deficiency in the enzyme phenylalanine hydroxylase. Affected infants appear normal at birth but in few weeks to 6 months, phenylalanine in plasma increases, causing severe mental retardation and other issues. Treatment includes restricting the intake of phenylalanine.

Prader-Willi syndrome & Angelman syndrome: Both arise from a deletion on chromosome 15, but with different clinical feature.

Genetic analysis, prenatal or postnatal analysis may use techniques such as karyotyping analysis, fluorescent in situ hybridization (FISH), molecular diagnostics (PCR), or a combination, to study cells and chromosomes to detect abnormalities.
- Karyotyping analysis: A technique used to visualize or study chromosomes, to identify structural and numerical abnormalities.
- FISH: Technique that uses fluorescent probes to detect or study genes or chromosomal locations.
- PCR: A technique used to amplify certain segments of DNA (or RNA). It is more sensitive than FISH for detecting mutations.
Prenatal testing: Testing for diseases or conditions in a fetus to detect abnormalities such as neural tube defects, Down syndrome, chromosomal abnormalities, genetic diseases, etc before birth.
Amniocentesis: A prenatal test done in the 15-17th weeks of pregnancy involving inserting a needle into the amniotic sac to obtain a sample for examination.
Chronic villus sampling: A method for screening or testing an embryo / fetus using placenta biopsy (Chorionic villi tissue).
Maternal blood tests: These tests involve sampling maternal blood to screen for certain birth defects like Down syndrom.e

Mitosis: Cell division resulting in two identical daughter cells.
Meiosis: Cell division resulting in four haploid daughter cells.
- Non-disjunction: Error during meiosis leading to an extra or missing chromosome.
Cytogenetic disorders: Disorders involving chromosomal abnormalities, including numerical abnormalities (aneuploidy) with a chief cause of non-disjunction of homologous chromosome pairs in the first meiotic division or a failure in sister chromatids to separate during second meiosis.
- Loss of chromosomal material can lead to more severe defects than the gain of chromosomal material.
Sex chromosome imbalances: Usually tolerated better than similar autosome imbalances.
De Novo mutations: Changes in genes or cells that occur unexpectedly or spontaneously in an organism.