Heredity and Disease

What you’ll learn to do: Explain the conventions of a family pedigree and predict whether a disease will be passed through a family in one of three modes

Over the years, we’ve seen that some diseases are hereditary. In this outcome, we’ll learn just how some diseases can be passed through a family line.

Family pedigrees and diseases can also be used to solve “mysteries,” such as the case of the Tsar of Russia and the missing Princess Anastasia. In this case, haemophilia within European royalty figured prominently in identifying the bodies of the murdered Russian royals (but not Princess Anastasia).

A family tree charting haemophilia in the descendants of Queen Victoria. Queen Victoria had three children: Princess Alice of the UK, Prince Leopold Duke of Albany, and Princess Beatrice of the UK. Of Queen Victoria's children, only Prince Leopold had haemophilia. Princess Alice had three children: Princess Irene, Prince Friedrich, and Alexandra Feodorovna. Of Princess Alice's children, only Prince Friedrich had haemophilia. Princess Irene had two sons, Prince Waldemar and Prince Heinrich, both of whom had haemophilia. Alexandra had one son, Alexy Nikolaevich, who had haemophilia. Queen Victoria's son Prince Leopold had one daughter, Princess Alice, who did not have haemophilia. Princess Alice had one son, Prince Rupert, who had haemophilia. Queen Victoria's daughter Princess Beatrice had three children: Victoria Eugenie, who did not have haemophilia, and two sons, prince Leopold of Battenberg and Prince Maurice of Battenberg, who both had haemophilia. Beatrice's daughter Victoria Eugenie had two sons, Alfonso of Spain and Infante Gonzalo of Spain, both of whom haemophilia.

Figure 1

Learning Outcomes

  • Understand why geneticists use pedigrees to track human diseases
  • Understand how a pedigree analysis is used to identify the inheritance pattern of a genetic disorder

Pedigrees and Disease

Health care professionals have known for a long time that common diseases—like heart disease, cancer, and diabetes—and even rare diseases—like hemophilia, cystic fibrosis, and sickle cell anemia—can run in families. If one generation of a family has high blood pressure, it is not unusual for the next generation to have similarly high blood pressure. Therefore, family history can be a powerful screening tool and has often been referred to as the best “genetic test.”

Both common diseases and rare diseases can run in families. Therefore, family history can be a powerful screening tool. Family history should be updated on each visit and patients should be made aware of its significance to their health.

Importance of Family History

Family history holds important information about an individual’s past and future life. Family history can be used as a diagnostic tool and help guide decisions about genetic testing for the patient and at-risk family members. If a family is affected by a disease, an accurate family history will be important to establish a pattern of transmission. In addition, a family history can even help to exclude genetic diseases, particularly for common diseases in which lifestyle and environment play strong roles. Lastly, a family history can identify potential health problems that an individual may be at increased risk for in the future. Early identification of increased risk can allow the individual and health professional to take steps to reduce risk by implementing lifestyle changes and increasing disease surveillance.

Notwithstanding the importance of family history to help define occurrence of a genetic disorder within a family, it should be noted that some genetic diseases are caused by spontaneous mutations, such as for single gene disorders like Duchenne muscular dystrophy and hemophilia A, as well as for most cases of Down syndrome, chromosomal deletion syndromes, and other chromosomal disorders. Therefore, a genetic disorder cannot be ruled out in the absence of a family history.

How to Take a Family Medical History

A basic family history should include three generations. To begin taking a family history, start by asking the patient about his/her health history and then ask about siblings and parents. Questions should include:

  1. General information such as names and birthdates
  2. Family’s origin or racial/ethnic background
  3. Health status
  4. Age at death and cause of death of each family member
  5. Pregnancy outcomes of the patient and genetically-related relatives It may be easier to list all the members of the nuclear family first and then go back and ask about the health status of each one. After you have taken the family history of the patient’s closest relatives, go back one generation at a time and ask about aunts, uncles, grandparents, and first cousins.

Pedigrees

One way to record a family history is by drawing a family tree called a “pedigree.” A pedigree represents family members and relationships using standardized symbols (see below). As patients relate information to you about their family history, a pedigree can be drawn much quicker than recording the information in writing and allows patterns of disease to emerge as the pedigree is drawn. Since the family history is continually changing, the pedigree can be easily updated on future visits. Patients should be encouraged to record information and update their family history regularly.

A Chart indicating common symbols on pedigree charts. A square indicates a male. A circle indicated a female. A dotted line with a second outline around the shape indicated the individual was adopted. A slash through the shape indicates the individual is deceased. A small triangle indicates a pregnancy loss. If the number of weeks is known, it is included. A still birth is indicated in the same way as a death. A slash through a connecting line indicates a divorce. If you do not know names of individuals, but do know the number of male and female children, you can indicate this with the number of children inside a square and a circle. For example, the number 5 in a square would indicated five sons. If you do not know the gender of children but you do know the number of children, you can indicate this by recording the number of children inside a diamond.

Figure 2

The sample pedigree below contains information such as age or date of birth (and, for all deceased family members, age at death and cause of death), major medical problems with age of onset, birth defects, learning problems and mental retardation, and vision loss/hearing loss at a young age. For family members with known medical problems, ask whether they smoke, what their diet and exercise habits are if known, and if they are overweight.

A sample pedigree chart. The father’s side of the family is from Mexico. The paternal grandfather died at 65 from a heart attack. The maternal grandmother is 85 years old. They had three children: the father, an aunt, and an uncle. There was also a pregnancy loss at eight weeks. The uncle is 62, married, and has 3 sons and 2 daughters in their 30s or 40s. The aunt is 47, married, and has one daughter who is 23. The mother’s side is from England and Germany. The maternal grandfather died in his 60s from colon cancer. The maternal grandmother died in her 70s from breast cancer. She was diagnosed at 68. They had one daughter (the mother) and adopted a son. The adopted uncle is 47, married, and has two non-identical twins, who are 20. The mother is 49, has high blood pressure, and has a child from a previous marriage. The half-sister is 24, same mother, different father. The father is 50 and has high cholesterol. The mother and father had three children: brother, sister, and you. The brother is 22, married, and has two children: a son and a daughter. The sister is 18, unmarried, and has club foot. You are 15.

Figure 3

Genetic Disorder and Pedigrees

Watch this video to understand the basics of conducting a pedigree analysis of a human genetic disorder. At the end, you should feel comfortable with the basic steps used to conduct a pedigree investigation.


Check Your Understanding

Answer the question(s) below to see how well you understand the topics covered in the previous section. This short quiz does not count toward your grade in the class, and you can retake it an unlimited number of times.

Use this quiz to check your understanding and decide whether to (1) study the previous section further or (2) move on to the next section.