Case 3 1. Explain the biochemical basis of the patients condition.

Cystic fibrosis is the most common lethal autosomal recessive disease affecting the Caucasian population. The protein affected is the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride ion channel. The mutations lead to (1) defective or decreased protein production, (2) defective processing of the protein, (3) protein that is defective in the regulation of the chloride channel, or (4) defect in the transport of chloride ions. The most common mutation, a deletion of a phenylalanine residue at amino acid position 508 (F508), results in misfolding of the protein; it consequently does not traffic to the membrane. Defects in the CFTR decrease the ability of cells to transport Cl- in a number of tissues, particularly the pancreas, airway epithelia, and sweat glands. When Cl- transport is defective in the pancreas, it leads to decreased HCO3- secretion and decreased hydration that leads to thick secretions that block the pancreatic ducts and destruction of the organ. In the lungs, the decreased absorption of Cl- ions is thought to increase the absorption of the airway surface liquid thus increasing the viscosity of mucous, decreasing mucociliary clearance and increasing the incidence of airway infections. In sweat glands, defects in CFTR prevent the reabsorption of Cl- in the sweat gland duct, thusincreasing the concentration of NaCl in sweat.Thus, leading to leading to respiratory infections, gastrointestinal obstruction, pancreatic enzyme dysfunction leading to malabsorption of nutrients, and excessive electrolyte secretion.

2. Explain the role of electrophoresis in the diagnosis of the patients condition. Gel electrophoresis can be applied as a method for detection of genetic diseases such as Cystic fibrosis (CF). Larger deletions in the cystic fibrosis transmembrane conductance regulator (CFTR) gene will cause it to move differently than the full-length wild type gene. In most cases, the DNA sample of the patient is amplified by a polymerase chain reaction (PCR) using specific primers. After the electrophoresis of the PCR samples the bands are visualized under ultraviolet (UV) light using ethidium bromide staining.