Cystic Fibrosis: Genetics and CFTR

Cystic Fibrosis

• Cystic fibrosis is caused by a defective gene on chromosome 7q31.2, called CFTR (cystic fibrosis transmembrane conductance regulator).
• The CFTR gene produces a protein that helps salt (sodium chloride) move in and out of cells.
• If the protein doesn't work correctly, an abnormally thick and sticky mucus is produced on the outside of the cell, clogging the airways in the lungs and increasing the risk of infection by bacteria.
• The cells most seriously affected by this are the lung cells.
• Over 2,000 mutations have been described that affect the CFTR gene in different ways.
• The most common CFTR mutation is a deletion of three DNA nucleotides, leading to the deletion of an amino acid (phenylalanine) at position 508 of the protein sequence, denoted as ΔF508.
• ΔF508 is found in around 90% of CF patients.
• Some conditions caused by two CFTR mutations might cause only mild lung disease with or without affecting the pancreas, and can be described as "atypical CF".
• Cystic fibrosis is an inherited disease, and both parents must be carriers of the gene for a child to inherit it.
• 25% of children of carrier parents will have cystic fibrosis.
• Boys and girls are equally likely to get the disease.
• About 10 million Americans carry the gene and do not know it.
• More whites get the disease than do people of other races.

Sweat Test

• In cystic fibrosis, mutations affect the composition of the mucus layer lining the epithelial surfaces in the lungs and pancreas.
• The disruption of ion transport affects the salt concentration in sweat, which is used in the CF "sweat test".

Inheritance

• For someone to get cystic fibrosis, both parents must be carriers of the gene that causes it.
• Boys and girls are equally likely to get the disease.
• About 10 million Americans carry the gene and do not know it.
• More whites get the disease than do people of other races.

Asthma

• Asthma is a chronic lung disease that causes wheezing, breathlessness, chest tightness, and coughing.
• According to the Centers for Disease Control and Prevention, approximately 1 in 12 adults and 1 in 11 children have asthma.
• Bronchial asthma is the most common chronic disease affecting children and young adults.
• It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment.
• Having a family history of asthma or allergies increases the chance of developing asthma.
• Other risk factors for asthma include smoking or breathing in tobacco smoke, pollution, and obesity.

Alpha-1 Antitrypsin Deficiency

• Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency.
• Those with the SZ combination have an increased risk of developing lung diseases (such as emphysema), particularly if they smoke.
• Worldwide, it is estimated that more than 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ).
• Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs.
• People with MZ alleles have a slightly increased risk of impaired lung or liver function.