Pedigree Analysis

In genetics, a pedigree is a diagram of a family tree showing the relationships between individuals together with relevant facts about their medical histories. A pedigree analysis is the interpretation of these data that allows a better understanding of the transmission of genes within the family. Usually, at least one member of the family has a genetic disease, and by examining the pedigree, clues to the mode of inheritance of the disorder and the potential risk to other family members can be obtained.

Pedigree analysis can also allow estimation of gene penetrance and gene expressivity. Penetrance is defined as the probability that a disease sate will manifest in an individual who carries an allele cusing the disease is present. For example, if one-half of all individuals who carry a dominant allele eventually manifest the associated disease, the allele has 50% penetrance. Expressivity describes the range of symptoms and degree of sevety associated with different disease states.

The pedigree is initiated by using a symbol to represent the proband or individual seeking counseling. immediate family members (parents, siblings, spouse, children) are added next, followed by aunts, uncles, cousins, grandparents, and others in the proper orientation. Males are indicated as squares and females as circles. The square or circle is filled in for any affected individuals to reflect their disease status. When two people marry or have children together, a single line is drawn between them. A vertical line descends from this marriage line and then connects to another horizontal line, the sibship line. Short vertical lines descend from the sibship line, one for each of the children of this union. All members of one generation are shown adjacent to one another in a A three-generation pedigree analysis. Illustration by Argosy. The Gale Group.
row, with preceding generations above and later generations below. There are special symbols to denote consanguineous marriages (a double marriage line), identical twins (a single line from the sibship line that bifurcates for each twin), fraternal twins (an inverted V drops from the sibship line), divorce and remarriage (cross hatches on the marriage line to show discontinuity between the divorced partners and a second marriage line to the new partner), and so on.

Each generation is labeled at the left with a Roman numeral beginning with the first generation. The members of each generation are consecutively numbered left to right with Arabic numbers, always starting each generation with one. In this way, each person can be specifically identified. For example, the second person in the first generation would be individual I-2, and the sixth person in the fourth generation would be IV-6.

Once the family members are properly arranged, important medical facts can be added. Proper interpretation of the pedigree is dependent upon obtaining accurate information about each individual in a pedigree. The first step in pedigree analysis is to observe the number and relationships of all individuals who express the same or similar clinical features. From this, it should be possible to determine if the disorder is dominant or recessive, autosomal or X-linked by looking for the typical patterns of inheritance. For example, an autosomal disease can usually be distinguished by seeing male-to-male transmission of the mutation, but since males pass only the Y chromosome to their sons, there should never be father to son transmission of an X-linked gene. Males will be most commonly affected in an X-linked disease, whereas males and females should be equally affected in autosomal disorders. In general, a dominant disease will be seen in approximately half of the individuals in each generation, but recessives occur very rarely. If the mutation is in the mitochondrial genome, affected mothers will pass the trait to all of their children, but none of the offspring of an affected male should have the disease.

Once the inheritance pattern of the disorder is determined, the status of family members in the pedigree can be evaluated. By carefully observing the position of affected individuals, mutation carriers may be identified. From this data, the risk of carrier status for other family members or the chance that a couple may have an affected child can be estimated.

Pedigrees are also maintained for many animals, though the purpose of pedigree analysis is somewhat different. The data contained in the pedigree are generally utilized to select individuals with specific characters for breeding purposes. Animals with unfavorable traits are eliminated from consideration so that the next generation will include individuals with more of the preferable traits. For each species, the characters of choice will vary. In the thoroughbred world, pedigree analysis tries to combine speed with stamina and a will to win that will yield winning racehorses. For cows, sheep, and pigs, such characteristics as high milk production, higher muscle content, or better wool are desirable. Even some plants have pedigrees as researchers strive to find drought and pest resistant species with high crop yields.

In medicine, pedigree analysis is an essential part of a complete medical work up for a genetic disease. The information obtained is an important aid in understanding the disorder and providing the best counseling to the family. For other plant and animal species, pedigree analysis is also a useful tool, though the goal is usually for gene selection rather than risk assessment.