If more than one individual in a family is afflicted with a disease, it is a clue that the disease may be inherited. A doctor needs to look at the family history to determine whether the disease is indeed inherited and, if it is, to establish the mode of inheritance. This information can then be used to predict recurrence risk in future generations.
A basic method for determining the pattern of inheritance of any trait (which may be a physical attribute like eye color or a serious disease like Marfan syndrome) is to look at its occurrence in several individuals within a family, spanning as many generations as possible. For a disease trait, a doctor has to examine existing family members to determine who is affected and who is not. The same information may be difficult to obtain about more distant relatives, and is often incomplete.
Once family history is determined, the doctor will draw up the information in the form of a special chart or family tree that uses a particular set of standardized symbols. This is referred to as a pedigree. In a pedigree, males are represented by squares and females by circles . An individual who exhibits the trait in question, for example, someone who suffers from Marfan syndrome, is represented by a filled symbol or . A horizontal line between two symbols represents a mating . The offspring are connected to each other by a horizontal line above the symbols and to the parents by vertical lines. Roman numerals (I, II, III, etc.) symbolize generations. Arabic numerals (1,2,3, etc.) symbolize birth order within each generation. In this way, any individual within the pedigree can be identified by the combination of two numbers (i.e., individual II3).
Dominant and recessive traits
Using genetic principles, the information presented in a pedigree can be analyzed to determine whether a
given physical trait is inherited or not and what the pattern of inheritance is. In simple terms, traits can be either dominant or recessive. A dominant trait is passed on to a son or daughter from only one parent. Characteristics of a dominant pedigree are: 1) Every affected individual has at least one affected parent; 2) Affected individuals who mate with unaffected individuals have a 50% chance of transmitting the trait to each child; and 3) Two affected individuals may have unaffected children.
Recessive traits are passed on to children from both parents, although the parents may seem
perfectly "normal." Characteristics of recessive pedigrees are: 1) An individual who is affected may have parents who are not affected; 2) All the children of two affected individuals are affected; and 3) In pedigrees involving rare traits, the unaffected parents of an affected individual may be related to each other.
The reason for the two distinct patterns of inheritance has to do with the genes that predispose an
individual to a given disease. Genes exist in different forms known as alleles, usually distinguished one from the other by the traits they specify. Individuals carrying identical alleles of a given gene are said to be homozygous for the gene in question. Similarly, when two different alleles are present in a gene pair, the individual is said to be heterozygous. Dominant traits are expressed in the heterozygous condition (in other words, you only need to inherit one disease-causing allele from one parent to have the disease). Recessive traits are only expressed in the homozygous condition (in other words, you need to inherit the same disease-causing allele from both parents to have the disease).
Penetrance and expressivity
Penetrance is the probability that a disease will appear in an individual when a disease-allele is present. For example, if all the individuals who have the disease-causing allele for a dominant disorder have the disease, the allele is said to have 100% penetrance. If only a quarter of individuals carrying the disease-causing allele show symptoms of the disease, the penetrance is 25%. Expressivity, on the other hand, refers to the range of symptoms that are possible for a given disease. For example, an inherited disease like Marfan syndrome can have either severe or mild symptoms, making it difficult to diagnose.
Not all diseases that occur in families are inherited. Other factors that can cause diseases to cluster within a family are viral infections or exposure to disease-causing agents (for example, asbestos). The first clue that a disease is not inherited is that it does not show a pattern of inheritance that is consistent with genetic principles (in other words, it does not look anything like a dominant or recessive pedigree).