Pedigree Analysis and Polygenic Traits

A pedigree is a family tree that shows how a trait is inherited through generations, and polygenic inheritance describes traits, such as height and skin color, that are controlled by many genes and are also shaped by the environment. In brief: in a pedigree, squares represent males, circles represent females and shaded symbols represent affected individuals. By studying the pattern, you can often tell whether a trait is dominant or recessive and whether it is autosomal or X-linked. Polygenic traits show a continuous range of phenotypes that forms a bell-shaped distribution.

Pedigrees are the main tool of genetic counseling for human families, because humans cannot be crossed experimentally. This guide explains the symbols and rules of pedigree analysis, shows a method for working out the inheritance pattern, introduces polygenic and environmental effects, works through an example pedigree and corrects common mistakes.

What do pedigree symbols mean?

A pedigree is a chart showing the members of a family over several generations and who has a particular trait. The standard conventions are:

• A square is a male, and a circle is a female.
• A filled (shaded) symbol is an individual with the trait. An unfilled symbol does not show it.
• A half-filled symbol or a dot inside the symbol is often used for a carrier, if known.
• A horizontal line connects two partners, and a vertical line leads to their children, who are drawn in order of birth from left to right.
• Generations are labeled with Roman numerals (I, II, III) and individuals within a generation with Arabic numbers (1, 2, 3).
• A diagonal line through a symbol shows a deceased person. A double line between partners shows a marriage between relatives.

How do you identify the pattern of inheritance?

The aim is to decide whether the trait is dominant or recessive, and autosomal or X-linked. Use these clues.

Step 1: Dominant or recessive?

• If two unaffected parents have an affected child, the trait is recessive, and both parents must be carriers. This is the single clearest sign.
• If every affected person has at least one affected parent, and the trait appears in every generation, it is probably dominant. Two affected parents can have an unaffected child only if the trait is dominant, and both parents are heterozygous.

Step 2: Autosomal or X-linked?

• If an affected daughter has an unaffected father, the trait cannot be X-linked recessive, because a daughter would have to inherit the recessive allele on her X chromosome from her father as well as from her mother.
• If the trait affects many more males than females, and skips generations through females, it is probably X-linked recessive.
• If an affected father always has affected daughters and never affected sons through him, the trait may be X-linked dominant.
• If males and females are affected about equally, it is probably autosomal.

Inheritance patterns compared

Worked example: analyzing a pedigree

Consider a family with this description. Generation I: a man (I-1) and a woman (I-2), both unaffected. Generation II: they have three children: an affected daughter (II-1), an unaffected son (II-2) and an unaffected daughter (II-3). II-3 marries an unaffected man (II-4), and they have one affected son (III-1) and one unaffected daughter (III-2).

1. Dominant or recessive? Two unaffected parents (I-1 and I-2) have an affected daughter (II-1). Therefore, the trait is recessive, and I-1 and I-2 are both heterozygous carriers.
2. Autosomal or X-linked? The affected person in generation II is a daughter. For an X-linked recessive trait, an affected daughter must have an affected father (she needs the recessive allele on both X chromosomes, and one comes from her father). The father I-1 is unaffected, so the trait is not X-linked. It is autosomal recessive.
3. Genotypes (A is normal, a is the recessive allele): I-1 and I-2 are Aa. II-1 is aa. II-2 and II-3 are unaffected, so they are AA or Aa.
4. Chance that II-3 is a carrier: from Aa × Aa, the outcomes are 1 AA : 2 Aa : 1 aa, and II-3 is known to be unaffected, so the probability that she is Aa is 2/3.
5. Check with generation III: II-3 has an affected child (III-1, aa), so she must be Aa, and II-4 must also be a carrier (Aa). The probability for the next child to be affected is 1/4.

The method shows how information on later generations changes the earlier estimates. At first the chance that II-3 was a carrier was 2/3, but the birth of an affected child proves that she is. When the trait is rare, the unrelated partner is less likely to be a carrier, so affected children usually appear in families with consanguinity (marriage between relatives), who are more likely to carry the same rare allele.

What is polygenic inheritance?

Many traits do not have just two or three clear categories. Height, skin color, eye color shades, body mass and blood pressure vary continuously. These traits are polygenic: they are controlled by the combined effects of many genes, each with a small effect, often with additive alleles. A person’s height, for example, is influenced by hundreds of genetic variants identified so far.

A simple model illustrates this. Suppose three genes, each with two alleles (a “tall” allele that adds 2 cm and a “short” allele that adds nothing). There are 6 alleles in total, so height varies between 0 and 12 cm above a baseline, in steps of 2 cm. A cross of two individuals heterozygous for all three genes gives a distribution of 7 classes in a ratio of 1 : 6 : 15 : 20 : 15 : 6 : 1, which are the binomial coefficients for 6 alleles. The distribution is bell-shaped, with most offspring in the middle class and few at the extremes. With more genes and environmental effects, the distribution is smooth and closely resembles a normal distribution.

How does the environment affect phenotype?

The phenotype is the result of genotype and environment together. Environmental effects include diet, exercise, light, temperature, disease and chemicals. A person with genes for tall stature may be shorter if malnourished in childhood. Identical twins raised in different environments differ in some features, which makes them a valuable tool in research on the effects of heredity and environment.

Examples in other organisms: the hydrangea changes the flower color with the pH of the soil (blue in acid soil, pink in alkaline), the Himalayan rabbit grows dark fur only on the cooler areas of its body, and the Arctic fox changes its coat color with the seasons. Many human diseases, including heart disease and type 2 diabetes, are multifactorial: they result from several genes and lifestyle factors.

How have pedigrees and polygenic traits been studied?

Francis Galton, a cousin of Charles Darwin, studied the inheritance of height and other traits in families in the 1880s, and he found that the offspring of very tall parents tended to be closer to the average, a phenomenon he called regression. Ronald Fisher showed in 1918 that continuous variation can be explained by Mendelian inheritance of many genes. Genome-wide association studies since the 2000s have identified thousands of variants that contribute to polygenic traits.

Which mistakes are common?

Mistake 1: Calling a trait dominant because it is common

Use the pattern of inheritance. Unaffected parents with an affected child indicate a recessive trait.

Mistake 2: Assuming every unaffected person is a carrier or is not a carrier

The genotype may be uncertain. Use probabilities, such as 2/3 for an unaffected child of two carriers.

Mistake 3: Saying that polygenic traits are controlled by a single gene

They involve many genes and the environment, which explains the continuous variation.

Mistake 4: Ignoring the environment

Even a trait with a strong genetic basis can be changed by diet, health or other conditions.