What is Cystic Fibrosis? The Science behind the genetic condition

CF population Distribution
CF population Distribution

Cystic Fibrosis (CF) is a genetic condition, primarily affecting the lungs among other organs. In this article I will go into some detail into the process of genetic inheritance that determines whether or not someone will have CF.

Straw Flower 1 Photo Credit : Nico Cavallotto (Flickr)
Straw Flower 1 Photo Credit : Nico Cavallotto (Flickr)

The Experiment

There is an experiment you can try at home that’s fun and easy. You don’t need any beakers or fancy expensive equipment. All you need is a clothes peg and an ordinary drinking straw.

Step 1: Close the peg on your nose tightly.

Step 2: Hold the straw in your mouth.

Step 3: Breathe.

The premise seems simple; but how long until you’re uncomfortable? One minute? Maybe two? When your body is starved of oxygen your brain begins to panic. That mounting feeling of unease and discomfort is your brain telling your body to increase the airflow.

What happens when that feeling becomes unbearable? You simply remove the straw. What if you can’t? The straw experiment is used to help people understand living with Cystic Fibrosis (CF). CF is a genetic (inherited) lung condition affecting thousands of people every day.

The Numbers

There are estimates of up to 100,000 diagnosed CF patients worldwide. The true number may be higher with many people being misdiagnosed. There are a majority of countries with CF patients that have no registries and thousands of CF patients are treated for symptoms without ever being diagnosed.

CF is Ireland’s most common genetic condition, with one in 19 people being carriers of the defective gene. The CF defect is a recessive gene meaning it takes two defective genes to be diagnosed with CF. Genes are located on the chromosome, in effect genetic inheritance is determined by the chromosomes.

Each body contains 23 pairs of chromosomes, one of each pair is inherited from each parent independently. If both parents are carriers of the defective gene any children they might have will follow the principles of Mendelian inheritance.

The Principle

The principle of Mendelian inheritance, named after Gregor Mendel, states there are two laws governing genetic inheritance when applied to recessive defects such as CF. The first law of segregation states that the two contributed pairs of chromosomes will separate so that the child receives one from each parent.

The second law of independent assortment states that after being segregated the individual chromosomes can be paired in any of the potential pairings, essentially operating under the rules of chance. There is a third law of dominance which is concerned with which one of the pair of chromosomes is expressed over the other but this does not apply to recessive genes.

The end result for children born to CF carrier parents are as follows:

-25% chance of CF diagnosis        -50% chance of CF carrier             -25% chance of non-carrier

As Demonstrated by the figure below.

Recessive Gene Inheritance
Recessive Gene Inheritance

The Diagnosis

The defective gene from which CF gets its name is the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The CFTR gene codes for a protein also known as CFTR. The CFTR protein resides in the surface of epithelial cells which line the lungs, digestive system and sweat glands.

The symptoms of CF are caused by the inability of the CFTR to release chloride (salt) leading to the production of thick, sticky mucus in specific organs. The organs that are typically involved in CF are the skin, pancreas and lungs.

To date more than 1800 different mutations in the CFTR gene have been identified to cause CF. Most of these mutations either substitute one DNA base – the building material of DNA – for another, or delete a small number of DNA bases altogether. The alteration of DNA bases is called a delta. Critically, however, most of these mutations are rare with only seven accounting for almost 90% of Irish CF patients.

The most common mutation of the CFTR gene, accounting for approximately 70 percent of CF patients worldwide, is called F508del. This delta is caused by the deletion of three base pairs of the CFTR gene that lead to the loss of an essential amino acid in the CFTR protein.

CF population Distribution
CF population Distribution

The Treatment

Treatments for CF are largely concentrated on symptom relieving remedies. The most common treatment plans involve the use of a nebuliser. The nebuliser converts liquid medicines into an inhalable gas.

CF treatment plans are highly individualised and multi-faceted. Common approaches to treatment regimens include the use of antibiotics to battle chronic infections, pancreatic enzymes to aid digestion and chest physiotherapy sessions to loosen secretions.

The most effective treatment for CF, used only in the most extreme circumstances, is to undergo a lung transplant. The availability of donor lungs for transplant and the inherent risks associated with such a delicate procedure limits patients access to treatment.

Following a transplant the patient is subject to strenuous medications to offset the effects of organ rejection. For this reason lung transplants have often been described as trading one disease for another, albeit with much higher quality of life.

There is hope in the future that medication can regulate the source of complications arising due to CF with new treatments, Kalydeco providing relief for a section of the CF population and Orkambi currently in the approval process.

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