How genes can lead to disease

As you have learned, the information encoded in genes is vital to every process of living. Therefore, it is not surprising that changes in genes can sometimes lead to disease. There are some differences in the DNA between individual people, in the form of multiple alleles for many genes, which do not result in disease. These differences are the basis of of genetic diversity among people. Other changes in DNA can be very detrimental to our health. This page offers an overview of the ways in which genes can contribute to disease. For more information on these topics, see the section on Links - Information on genetic diseases.

Mutations

The term mutation can refer to any type of change in DNA. Some examples of mutations are missing or inserted base pairs or alterations in the sequence of a gene. Mutations prevent the gene from giving proper instructions to the cells, which can therefore not function normally. Mutations in one or more genes can lead to disease. Many of the genetic conditions that have been identified result from mutations in just one gene; these are called single gene disorders. Some examples of single gene disorders are listed below:

Cancer

In Cystic Fibrosis and other inherited diseases, the disease-causing mutation is present at birth and in every cell in the body has a mutation. Cancer usually arises later in life from a mutation in a small number of cells. There are many types of cancer which affect different parts of the body, but all cancers result from mutations which cause cells to multiply much more quickly than usual. These cells usually lose their original function and can damage the surrounding tissue in a variety of ways, such as by forming an obstructive mass or by depriving other cells of nutrients. The mutations that cause uncontrolled growth can result from exposure to radiation or chemicals, or just by chance as the body ages.

While the majority of cancers result from mutations which occur in just a few cells, some cancers can be inherited. In these cases, every cell in the body starts with a mutation, which on its own does not cause disease. However, because the DNA has already been damaged, the cells are more vulnerable to subsequent mutations. Therefore, people with an inherited mutation have a much higher risk of getting cancer compared to the general population. They also usually get cancer at a younger age. For example, 5-10% breast cancer cases are thought to be due to inherited mutations. Many childhood cancers are caused by inherited mutations.

Chromosomal Abnormalities

In some cases, diseases result not from changes in individual genes but in changes in the number or arrangement of chromosomes. For example, people with Down Syndrome have three copies of chromosome 21, instead of the usual two. There are not very many examples of conditions arising from major chromosomal abnormalities, because most cases of fetuses with chromosomal abnormalites are not able to survive past the earliest stages of development. Most examples of conditions with altered numbers of chromosomes involve the sex chromosomes. There are also conditions involving abnormally arranged chromosomes, such as two chromosomes fused together or large deletions and insertions. Some examples of conditions resulting from chromosomal abnormalities are listed below:

To see photographs of karyotypes with chromosomal abnormalities, link to The Cytogenetics Gallery at the University of Washington.

Polygenic disease

The prefix 'poly-' means 'many.' Most diseases that appear to be inherited are not caused by mutations in a single gene. Rather, combinations of alleles of various genes contribute to the phenotype. For example, the risk of having diabetes or heart disease appear to be influenced by genetics in some cases, but the increased risk results from the interaction of a variety of genes. Each of the contributing alleles on their own are not disese-causing, so the method of identifying and studying the genetics of these diseases is quite different from the study of mutations in single genes.

Note: Human genetics is an extremely complex topic. This website is meant only as an introduction and overview. If you are concerned about how genetics may affect your health, always consult your physician.