Huntington’s Disease (HD) is a fatal, inherited disorder that causes the progressive deterioration of nerve cells in the brain, leading to motor, cognitive, and psychiatric symptoms. This neurodegenerative disease is passed down through families according to specific genetic rules. To visualize and track the inheritance of HD within a family, healthcare professionals and genetic counselors use a standardized graphical tool called a pedigree chart. This chart serves as a family tree, allowing individuals to map the disorder across multiple generations to understand their own genetic risk.
Understanding the Pedigree Tool
A pedigree chart is a visual map of a family’s genetic history, using universal symbols to represent individuals and their biological relationships. Geneticists use a square to represent a male and a circle to represent a female. If the sex of an individual is unknown, a diamond shape is used instead.
Relationships are depicted through horizontal and vertical lines connecting these shapes. A horizontal line between a male and a female indicates a mating or partnership. A vertical line drops from the mating line to the sibship line, from which the couple’s children branch off.
To organize the family over time, each generation is assigned a Roman numeral (I, II, III), starting with the oldest generation at the top. Individuals within the same generation are numbered sequentially with Arabic numerals, moving from left to right. The most important visual cue is the shading of the shapes. A completely shaded square or circle indicates an individual affected by the disorder being tracked. An unshaded shape represents an unaffected individual, which is a straightforward way to see who has the disease across the family structure.
The Autosomal Dominant Inheritance Pattern of HD
Huntington’s Disease is categorized as an autosomal dominant disorder, which dictates a specific pattern of inheritance seen on the pedigree chart. The disease is caused by a mutation in the HTT gene, located on an autosome (not a sex chromosome). This location explains why the disorder affects both males and females with roughly equal frequency, a characteristic easily observed in the pedigree.
The term “dominant” means that a person only needs to inherit one copy of the altered gene to develop the disorder. Every person has two copies of the HTT gene, and inheriting just one mutated copy is sufficient for the disease to manifest. Therefore, in a pedigree for an autosomal dominant condition like HD, an affected individual will almost always have at least one affected parent.
The genetic change in the HTT gene involves a sequence of three DNA building blocks—cytosine, adenine, and guanine (CAG)—that is repeated too many times. While a normal HTT gene has a short CAG sequence, a person with HD has a significantly expanded number of these repeats. This expansion leads to the production of an abnormal huntingtin protein, which is toxic to nerve cells and causes the progressive neurodegeneration characteristic of the disease.
Because the trait is dominant, the disease typically appears in every generation of a family, a hallmark pattern visible in the pedigree. The only exception to an affected person having an affected parent is the rare case of a new, or de novo, mutation, where the genetic change occurs spontaneously. Otherwise, the pattern will not skip generations, which helps distinguish HD from other genetic conditions.
Interpreting HD Risk Using the Pedigree
The primary purpose of analyzing an HD pedigree is to calculate the probability of inheriting the gene. Because HD is an autosomal dominant disorder, the risk of transmission from an affected parent to each child is 50%. This is because the affected parent has one normal gene copy and one mutated gene copy, and each child has an equal chance of inheriting either one.
To determine the risk for a specific child, you must first identify which parent is affected (shaded on the chart). If one parent is affected and the other is unaffected (unshaded), the probability for each offspring to inherit the gene is 50%. This 50% risk is constant and applies to every pregnancy individually, regardless of how many siblings are already affected or unaffected.
The pedigree also allows for the identification of individuals who have a 0% risk of passing the gene on. If a person has an affected parent but is unaffected (unshaded symbol), they could not have inherited the dominant, disease-causing gene copy. Since they do not carry the mutated gene, their children face no risk of inheriting HD from that side of the family. This clear distinction between a 50% risk and a 0% risk for offspring of at-risk individuals is a practical application of the HD pedigree.
Tracing inheritance through generations helps clarify risk for extended family members, such as a grandchild of an affected individual. If the child of the affected grandparent is unaffected, the grandchild’s risk of inheriting the gene is zero. If the child is affected, the grandchild’s risk returns to 50%. Analyzing the pattern of shaded and unshaded shapes is the method used to assess genetic risk for future generations.