HDSA Center of Excellence at Hennepin County Medical Center

Genetic Testing

Genetics and the Inheritance of Huntington's Disease

What is Huntington’s Disease (HD) and how it is passed on? This information is important to people who have HD. It is important to the children, friends, and caregivers of people who have HD. Understanding genetics is also important if someone you know is considering having a genetic test for HD.

Introduction

Huntington’s Disease (HD) is a neurologic disease that affects mood, memory,

and movements.

HD is not contagious

HD cannot be passed from one person to another by touching, kissing, or sexual contact. HD is not caused by excessive drinking, drug use, smoking, head injury, or any other events that happen during a lifetime. However, some of these things may make the symptoms of HD worse.

HD is a hereditary disease

HD is caused by a change in one particular gene that is important in protecting the cells of the brain.

The gene change is present from the moment a person is conceived; there is nothing anyone can do before or after birth to "put the gene back to normal" in a person who is destined to develop HD.

Cells and chromosomes

Our bodies are made up of millions of CELLS. The cells have many different parts. Some of the parts are special for a particular cell, to help it perform its special jobs in the body. Other parts are found in all cells. For example, every cell has a NUCLEUS, which contains genetic information. The genetic information determines what a person looks like, blood type, and many other things that can be inherited (such as color-blindness or high cholesterol).

Chromosomes are inside cells

The genetic information in the nucleus is packaged into parcels called CHROMOSOMES. A chromosome looks like a little string. Chromosomes come in pairs; one member of each pair came from the mother and the other member of that pair came from the father. Humans have 23 pairs of chromosomes. One of the chromosome pairs determines the sex of the child, and the other 22, called autosomes, contain the rest of the genetic information.

Cells, nuclei, and chromosomes are too small to see with your eyes, but they can easily be seen with a microscope. What you cannot see even with the most powerful microscope are GENES, which are lined up along the chromosomes. Because we cannot see the genes, we must do special chemical tests to find out about them.

Genes

Genes are locted on the chromosomes

There are about 50,000 genes lined up like beads on a string along the 23 chromosome pairs in each cell. Each chromosome contains about 2,000-3,000 genes. A gene is a recipe, telling the cell how to make an important protein or compound to run the body’s systems. Signals within the gene also tell the cell when to make the protein and how to modify it after it is made. Because our cells have two copies of each chromosome, there are also two copies of each gene in each cell.

Some mistakes or changes within a gene are normal and do not cause a disease. These changes are called "polymorphisms." But sometimes, the instructions within a gene are incorrect or changed in such a way that the protein that is produced is too large or too small or not able to function properly.

When a gene is altered in such a way that it fails to work properly and causes symptoms of a disease, then we call it a "disease gene."

How genes are passed on

We said earlier that all cells of the body carry two copies of each gene. There is one exception: the egg and sperm cells. The egg and sperm cells have only one copy of each chromosome, and therefore, only one copy of each gene. When the egg and the sperm meet to form the first cell of the new human embryo, their nuclei join together so that the new embryo has the usual two copies of each chromosome, and two copies of each gene. One copy came from the mother’s egg, and the other copy came from the father’s sperm. In that way, each person has an even mixture of genes from both parents.

Disease genes

Genes sometimes have mistakes.

You can imagine that with 50,000 genes inside each of the millions of cells in our bodies, we all carry some genes with errors in them. It is to our advantage, therefore, that there are two copies of each gene. For many genes, having one normal copy of a gene allows the body to function normally, even if the second copy has an error in it and does not work properly. In this case, only if BOTH copies of the gene have errors does a person notice symptoms of a disease. Diseases that are recognized only when both gene copies are not functioning properly are called RECESSIVE diseases.

On the other hand, some diseases appear when only one disease gene is present, even when the other copy of the gene is normal. For these diseases, the disease gene seems to dominate over the normal gene. These diseases are called DOMINANT diseases, or dominantly inherited diseases. If the disease-causing gene is a dominant gene, only people who have two copies of a normal gene will be free of the disease.

HD is a dominantly inherited disease.

HD is an autosomal dominant disorder. That means that the gene that causes HD is located on one of the 22 chromosomes called the autosomes, not on the one pair of sex-determining chromosomes. For that reason, HD is equally likely to affect individuals of either sex. And because HD is a dominant disease, only one copy of the disease gene must be present to cause the disease.

Anyone who has the HD disease gene will eventually develop symptoms of HD. Most people affected with HD have one HD disease gene and one normal gene. Any child of a person with the HD disease gene has a 50 percent chance of inheriting the HD disease gene.

The HD gene

The location of the HD gene on the chromosomes was first discovered in 1983 by Dr. James Gusella and his collaborators. It was not until 10 years later, in 1993, that the HD gene itself was identified. The gene does not look like any other genes that are already known, and it is not yet understood exactly what the protein made by the gene does in the cell. It is known how the HD gene changes to cause HD. The normal gene contains 10-35 copies of a certain "word," (called "CAG repeat"). An HD disease gene contains 36 or more CAG repeats. Although HD genes with 36-39 CAG repeats are abnormal and can cause HD, occasionally a person with CAG repeat numbers in this range will live free of symptoms even into his or her 80s or 90s.

A simple blood test can determine how many CAG repeats are present within a person’s two HD genes. However, even knowing how many CAG repeats someone’s HD gene has, it is impossible to predict when symptoms will begin. At the Hennepin County Medical Center HD Clinic, we have seen affected persons first exhibit symptoms at ages as young as 7 years and as old as 84 years.

Special Note: We would like to acknowledge and thank the HCMC Service League for providing grant funds to help maintain these web pages.