Blok 2 casus 01

Autosomal recessive disorder affecting water and salt transport.
Genetic mutation on the CFTR gene on chromosome 7, most commonly (85%) a dF508 deletion (processing mutant mutation).
Carrier rate: 1 in 20; Incidence of CF: 1 in 3600.
Six classes of mutations exist in CF patients.
Loss or dysfunction of CFTR protein impairs chloride channels in epithelial cells of the bile ducts, pancreas, intestines, lungs, skin, and genitals.

Heel prick screening can diagnose CF via gene analysis early for better prognosis.
Further diagnostics include:
1. Immunoreactive Trypsinogen (IRT) test - elevated in pancreatic damage, common in CF patients.
2. Pancreas Associated Protein (PAP) - often elevated in CF patients.
3. Sweat test - most commonly used diagnostic method.

Medications include Kaftrio and Orkambi, improving CFTR protein function and folding.
Kalydeco increases chloride channel conductivity in class 3 mutations.
Symptomatic treatment:
- Nebulization for lung function.
- PEP mask breathing (Positive Expiratory Pressure) aids in breathing.
- Enzyme pills improve digestion in pancreatic insufficiency.

Autosomal dominant inheritance shows in every generation, mutated gene causes disease.
Autosomal recessive inheritance means the patient is homozygous for the mutated genes. In heterozygous carriers:
- 25% chance of affected offspring (homozygous).
- 50% chance that offspring will be carriers.
- 25% chance of healthy offspring.

Lysosomes: break down waste in cells.
Golgi apparatus: labels and modifies proteins for their destination.
Rough endoplasmic reticulum: contains ribosomes for RNA translation to proteins.
Mitochondria: have their own DNA, responsible for producing ATP for energy-requiring processes.

Transcription begins at a promoter on DNA, converting DNA to mRNA.
Translation begins at a start codon on mRNA, ribosomes with tRNA synthesize proteins from amino acids.

Synonymous or Silent Mutations: Change in DNA base pair without altering amino acid codon, causing no defect.
Missense Mutation: One nucleotide replaced by another, changing amino acid incorporated into protein.
Nonsense Mutation: Original codon changes to a stop codon, producing shorter non-functional protein.
Insertions and Deletions: Can cause frameshifts, altering the reading frame for mRNA translation.
Splice Mutations: Introns remain in mRNA, can lead to frameshifts and defective protein products.

In heterozygous dominant inheritance:
- 25% chance of disease in offspring.
- 50% chance offspring become carriers.
- 25% chance of no inheritance.

Inbreeding increases chance that both parents carry the same genetic mutation leading to autosomal recessive disorders.

DNA: double helix made of pyrimidines (Cytosine and Thymine) and purines (Adenine and Guanine).
Adenine-Thymine pairs form one hydrogen bond; Cytosine-Guanine pairs form two bonds.
DNA replication occurs by separating the double helix, forming replication forks.
DNA synthesis proceeds from 5' to 3' direction, is bidirectional.
Leading strand runs 5' to 3' continuously synthesized; lagging strand runs 3' to 5' discontinuously.
Okazaki fragments are short DNA strands on lagging strand for daughter strand formation.

Mechanisms like mismatch repair, proofreading, and base selection correct replication errors.

Genotype: DNA composition of an individual.
Phenotype: Physical appearance influenced by genotype and environmental factors.
Promoter on DNA marks the start of transcription.