Pedigree analysis

Definition

A pedigree is a family tree or chart made of symbols and lines that represent a patient's genetic family history. The pedigree is a visual tool for documenting biological relationships in families and the presence of diseases. Pedigree analysis is an assessment made by a medical professional about genetic risk in a family.

Purpose

Pedigrees are most often constructed by medical geneticists or genetic counselors. People are referred to genetic professionals because of concern about the presence of a genetic condition in a family member. Pedigree analysis can help identify a genetic condition running through a family, aids in making a diagnosis, and aids in determining who in the family is at risk for genetic conditions. During pedigree construction, the family's beliefs about the cause for a genetic disease or emotional issues related to a diagnosis may be revealed. For instance, family members may experience guilt or shame about passing on a genetic trait. Thus, the communication process involved in taking the family history may allow the health care provider to identify areas in which the patient may need reassurance, education, or emotional support.

Creating a pedigree

Pedigree symbols

A standard set of symbols has been established for use in creating pedigrees. Some of the most commonly used symbols are shown in this entry. When a person is affected with a birth disorder, mental retardation, or other health problems, the individual is shaded or marked. If more than one condition is present in a family, different identifying marks should be made. A key to decipher these markings should also be included on the pedigree. The meaning of each horizontal and vertical line is also shown.

Information obtained

A typical pedigree is made of information about three generations of a family. The consultand is the person seeking genetic evaluation, counseling or testing. The proband in a family is the person in a family affected with a genetic disease. Beginning with the consultand, questions should be asked about the health of first, second, and third degree relatives. First-degree relatives are children, parents and siblings. Second-degree relatives are half siblings, nieces, nephews, aunts and uncles, grandparents, and grandchildren. Third-degree relatives are first cousins. Important information to obtain on both sides of the family includes:

• ages or dates of birth
• presence of any birth disorders, learning problems, chronic illnesses, surgeries, or medical treatments
• presence of specific features of a disease if the condition is suspected in the family
• genetic testing results if previously performed in the family
• cause of death for deceased family members
• pregnancy losses, stillbirths or infant deaths and causes

• infertility in the family
• ethnic background of the families
• consanguinity

It is important to establish the accuracy of information given by patients. Therefore, medical records are often requested in order to provide accurate risk assessment.

Pedigree patterns

Autosomal dominant inheritance

Pedigree 1 illustrates the occurrence of an autosomal dominant disorder called neurofibromatosis (NF). NF is characterized by growths under the skin called neurofibromas, dark spots on the skin called café au lait spots, and an eye finding called Lisch nodules. NF is caused by a single dominant gene on chromosome 17. Each person who is affected with NF has a 50% chance to pass the gene on to each child. The symptoms of NF are variable so that some family members are affected more seriously than others. The pedigree shows that in autosomal dominant inheritance , multiple generations of a family are affected. This is called vertical transmission of a trait through a family. Males and females are equally likely to be affected. In a particular sibship, about half of the siblings are affected.

Autosomal recessive inheritance

Pedigree 2 illustrates the occurrence of an autosomal recessive disorder called cystic fibrosis (CF) in a family. CF is a chronic respiratory disease characterized by digestive problems and a shortened life span. A person with CF has two genes for the condition on chromosome 7. Each parent is an obligate carrier of a gene for the condition. When both parents are carriers, there is a one in four or 25% chance that each child they have together will be affected. In autosomal recessive inheritance, siblings are most often affected rather than people in successive generations. Since siblings are affected, this is called horizontal transmission of a disease in the family. Males and females are equally likely to be affected in this type of inheritance and others in the family have an increased chance to be unaffected carriers of the disease.

X-linked recessive inheritance

Pedigree 3 illustrates the occurrence of an X-linked disorder called hemophilia . Hemophilia is characterized by excessive bleeding and bruising. Depending on the type of hemophilia, a particular blood-clotting factor is deficient. In X-linked recessive inheritance, males are affected with the condition while females are unaffected carriers. In X-linked recessive inheritance, vertical transmission of the disease is seen, with skipping of generations. There is no male-to-male transmission of a disease in this type of inheritance. This is because males pass their Y chromosome to each son, instead of the X chromosome with the disease gene. Each daughter of an affected male is an obligate carrier of the disease since they will always inherit his X chromosome. There is a 50% that each son of a carrier woman will be affected. There is a 50% chance that each daughter of a carrier female will be a carrier.

Resources

BOOKS

Baker, Diane. A Guide to Genetic Counseling. New York: A. Wiley and Sons, Inc. 1998.

Harper, Peter S. Practical Genetic Counseling. Oxford: Butterworth Heinmann 1998.

Rose, Peter, and Anneke Lucassen. "Taking a Family History." In Practical Genetics for Primary Care. Oxford: Oxford University Press, 1999.

PERIODICALS

Bennett, Robin et al. "Recommendations for Standardized Human Pedigree Nomenclature." The Journal of Genetic Counseling (December 1995): 267–79.

Sonja Rene Eubanks, MS, CGC