CF Genetics: The Basics

A person must inherit two copies of a defective CF gene -- one copy from each parent -- to have the disease. People who inherit only one copy are considered CF carriers and do not have the disease, but they can pass their copy of the defective gene on to their children.

Our Genetic Encyclopedia

Genes provide the body with coded instructions to make proteins, which affect everything from the color of our hair and eyes to our body's growth and health.

Every cell in our body contains genetic information -- a complete set of instructions for how the body looks, develops and works.

You can think of your genetic information as an encyclopedia with 23 volumes. Each volume contains thousands of entries or topics and is made up of billions of letters.

Each of us has a full genetic encyclopedia in every one of our cells. The genetic information is the same, whether the cell is a blood cell, skin cell or hair cell.

Genetic information is stored in chromosomes. These are the different volumes of our genetic encyclopedia. Humans have 23 pairs of chromosomes. Each pair is made up of a copy of a chromosome from the mother and the father.

Women have two X chromosomes, and men have one X and one Y chromosome. Eggs and sperm have only a single copy of each chromosome, rather than the pairs found in other cells in the body. A child inherits one copy of every "volume" of the encyclopedia from each parent.

Each chromosome is further divided into genes, which are the entries, or topics, in the encyclopedia. The genes supply the body with instructions for making proteins.

All of this genetic information is in code and stored as a chemical called deoxyribonucleic acid (DNA). The DNA code is made up of letters that spell out the entries of our genetic encyclopedia.

If we all shared 100 percent of our genetic material then we would all be as alike as identical twins are. But not every single letter in the genetic encyclopedia is the same in all of us, which helps to explain why we are not all exactly alike.

How Changes in the CF Gene Affect the Body

Different types of changes, or mutations, in our genes affect the body in different ways.

In people with CF, mutations in a certain gene can disrupt the normal production or functioning of a protein found in the cells of the lungs and other parts of the body.

Within our genetic encyclopedia, there are small differences in our genes. Sometimes the differences are minor or do not affect a person's health -- like two encyclopedia entries that are worded in slightly different ways, but still say the same thing and have the same meaning. In these cases, people's genes may differ or the protein made by the gene is slightly different, but the genes and the proteins work correctly.

At other times, the change in a gene may cause the protein to not work or not be made at all. Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein is responsible for regulating the flow of salt and fluids in and out of the cells in different parts of the body.

In people with CF, mutations in the CF gene cause the CFTR protein to malfunction, leading to a buildup of thick mucus, which in turn leads to persistent lung infections, destruction of the pancreas in most individuals with CF and complications in other organs.

The CF gene was discovered in 1989 on chromosome pair 7 -- volume 7 in our genetic encyclopedia -- by researchers supported by the CF Foundation.

Cystic fibrosis is an example of a recessive disease. That means a person must have a mutation in both copies of the CF gene to have CF. If someone has a mutation in only one copy of the CF gene and the other copy is normal, he or she does not have CF and is a CF carrier. About 10 million people in the United States are CF carriers.

CF carriers can pass their copy of the CF gene mutation to their children. Each time two CF carriers have a child together, the chances are: 

  • 25 percent (1 in 4) the child will have CF
  • 50 percent (1 in 2) the child will be a carrier but will not have CF
  • 25 percent (1 in 4) the child will not be a carrier of the gene and will not have CF

Children of two carriers may be healthy CF carriers like their parents. In a family with four children, it is possible that none of the children, some of the children or all of the children will have CF. Each baby has the same chance to inherit CF mutations from both parents, no matter whether any of the other siblings are carriers or have CF.

Different Types of CF Mutations

There are more than 1,800 mutations in the CF gene. While some CF mutations are common, others are rare and found in only a few people. Genetic testing can help identify the gene mutations of an individual with CF.

Genetic testing can be used to tell if a person carries a mutation of the CF gene. The test looks at a person's DNA, which is taken from cells in a blood sample or from cells that are gently scraped from inside the mouth. 

Through genetic testing, a person's genetic information can be used to help diagnose CF. Genetic information can also be used for genetic counseling, but it cannot be used to tell you how healthy or sick an individual with CF will be.

All 50 states and the District of Columbia conduct newborn screening for cystic fibrosis. If a newborn screening test is positive, the baby should have a sweat chloride test to find out whether he or she has CF.

More than 1,800 different mutations have been identified in the CF gene, and more continue to be found. These mutations can be grouped into different types, based on how confident scientists are that the change in the gene actually causes the CF disease. 

  • CF-causing mutations. When a person inherits two mutations of this type, he or she will always have CF. In laboratory tests, these genetic mutations show clearly that the CFTR protein does not work. The CF Foundation is supporting a project, called CFTR2, that is collecting information on all confirmed CF-causing mutations. On the CFTR2 website, you can search for a specific CF gene mutation to learn if it causes the disease.  

  • Mutations of Unknown Significance. These mutations have been reported in people with CF, but have not been confirmed to always cause CF.

  • Mutations of Varying Clinical Consequence. We do not know if these mutations cause CF. These mutations can be further broken down into:
    • Mutations that sometimes cause CF, but sometimes do not.
    • Mutations that have not been found often enough through genetic testing to know definitively if they do or do not cause CF
    • Mutations linked with having one or more symptoms related with CF. When people who had one or two of the clinical signs of CF (for example, chronic pancreatitis, sinus disease or male infertility) but did not have full CF disease were examined, certain CF mutations were found. Sometimes these mutations are also seen in people with CF. They can be called CF-related mutations and often overlap with the "mutations of unknown significance" group.

  • Non CF-Causing Mutations. Mutations in this group are genetic changes that do not cause CF.

When Genetic Testing Results Are Not Clear

Reading a genetic test result -- especially one for a healthy newborn baby -- is not always simple and it can be difficult to determine what, if any, CF mutations a person has.

Even after a genetic test is completed, it is sometimes hard to be completely certain whether a person has CF. Some people may be told they have CFTR-related metabolic syndrome (CRMS) and will need to be followed over time by a care team at a CF Foundation-accredited care center to see if they develop CF symptoms.

When a person has signs or symptoms of CF (such as lung infections, weight loss or an inability to gain weight), he or she should be seen at a CF Foundation-accredited care center for a sweat testing and full CF evaluation. 

Watch Webcasts on CF Genetics

Learn more about CF genetics, including CF gene mutations and genetic counseling: