Cystic fibrosis is a rare genetic disorder carried on a recessive allele. It affects the lungs and other organs. It interrupts the normal self-cleaning mechanism of the lungs because mucus becomes too thick and sticky to move easily. Genetic disorders like this can be traced through families using a pedigree chart.

Why this is important…Pedigrees are a useful way to track disorders, or other rare traits, through families. It allows genetic counselors to predict the chances of the disorder showing up again.

Foundations

Pedigrees track phenotypes rather than genotypes. When we worked out genetic problems using Mendelian genetics, we focused on genotypes of just two parents. Pedigrees track the phenotypes of many individuals in a family. The information can be used to determine genotypes of individuals, which is useful in genetic counseling. This is relevant if a couple is considering having a child, but are worried because of a family history of certain genetic disorders in one or both families.

Key terms

Pedigree – chart tracing certain phenotypes through a family tree

Mucus – gel-like fluid composed of water, salts, glycoproteins, and anti-microbial proteins (adj: mucous – usually used to describe membranes that make mucus)

Cilia – short projections of fibers from the cell membrane used to create movement

Details

Pedigrees are a genetic family tree. Each shape represents a person. People are connected by lines to show family relationships (Figure 4-10). Shapes representing people with the trait are shaded to indicate they have the disorder or trait. You don’t have to understand the genetics behind the traits in order to construct a pedigree. Pedigrees can even reveal how the inheritance works in situations where it is not known.

Pedigree of recessive trait over 3 generations. Individuals are labeled with letters to the side for identification.

FIGURE 4-11. Pedigree for cystic fibrosis. This is a recessive trait inherited on chromosome 7. (“Pedigree of recessive trait” by J. Buegge is licensed under CC BY 4.0)

Here is how the pedigree format works:

Squares represent males, circles represent females
Horizontal lines indicate two individuals mated
Vertical lines branch to each of the offspring
Each row of shapes represents one generation

Stop & Think #10: Pick a rare genetic trait in your family. Draw a simple pedigree for 2 or 3 generations.

Genotypes can be determined from pedigrees if you know the mode of inheritance. In Figure 4-10, the pedigree tracks a recessive trait – cystic fibrosis. Typically, pedigrees only track a trait that is rare. Your assumption should be that most normal individuals, especially individuals not in that family, have all normal alleles. Here is how to determine genotypes of individuals in a pedigree for a recessive trait:

Start with those showing the trait. They can only have one genotype - homozygous recessive (aa).
For those not showing the trait, you know one allele must be dominant (A_). Look at their parents. Since you know each parent contributed one allele, seeing the phenotypes of parents should reveal possibilities for the second allele.
If an individual has offspring, look at the phenotypes of offspring. If both parents are normal but at least one child has the disorder, then you can conclude that each parent carried the recessive allele.

The process is similar for dominant alleles, just remember that the allele is usually rare.

Stop & Think #11: From Figure 4-10, what is the genotype of individual labeled D?

Cystic fibrosis makes individuals unable to regulate the consistency of mucus. That may not sound serious, but it is. A thin coat of mucus lines our trachea and bronchioles. Dust particles stick to the mucus, creating a natural air filtration system. Once filled with dust and bacteria, the mucus needs to get out of the lungs. It is moved up the trachea by short, hair-like projections (cilia) of the cells lining the respiratory tract (Figure 4-11). These act like microscopic oars, moving the mucus up to the throat where it can be swallowed. Individuals with cystic fibrosis have unusually thick, sticky mucus that is hard to move up the airways. Instead, it settles down in the lungs causing a variety of problems like pneumonia and poor oxygen exchange.

Diagram of respiratory system. Closeup of cells lining tubes shown in detail. Emphasis is placed on cilia, hair-like projections on surface of cells.

Figure 4-12. Cilia of airways. The cells lining the airways of the lungs have hair-like projections (cilia) that sway. This moves mucus up and out of the airways. ("Ciliated Epithelium" by BruceBlaus is licensed under CC BY 3.0)

Mucus is normally a thin, watery fluid. This type of mucus can be moved easily by cilia. This is accomplished in a similar way to how sweat glands produced sweat – salts are pumped into the mucus by the cells lining these airways. Once salt moves into the mucus, water follows it from the tissues below. (The idea of water following salt is called osmosis, which we will study in later chapters.)

Individuals with cystic fibrosis received the wrong genetic instructions for this salt pump. That is why their mucus remains thick and sticky – it doesn’t get diluted with water. On a cellular level, our bodies control water movement by controlling where salt goes.

Optional: For more information about cystic fibrosis and how lungs clear out debris, read the online article: Moving Mucus Matters for Lung Health.

Treatments are necessary for individuals with cystic fibrosis to get mucus out of their airways. This can involve a variety of ways to vibrate their chest cavity to help the mucus move out. Also, since a thicker layer of mucus builds up in the alveoli, diffusion of oxygen is slowed. (The thicker the membrane, the slower diffusion.) Oxygen treatments are often necessary to increase the oxygen gradient and supply the blood with sufficient oxygen to sustain the body.

Learning objectives

Interpret pedigrees to determine gender, generations, relationships and traits.
Analyze a pedigree to determine the genotype or phenotype of individuals.
Identify cilia and describe their function.

Stop & Think Questions Explained

10. Your pedigree should resemble the example provided. The main idea is to recreate the format yourself. See if you can identify siblings, cousins, uncles, etc.

11. The individual labeled D, along with her partner, must be carriers (heterozygous) for cystic fibrosis.