Genes and Disease

Most diseases are related in some way to our genes. The information contained in our genes is so critical that simple changes can lead to a severe inherited disease, make us more inclined to develop a chronic disease, or make us more vulnerable to an infectious disease.

The majority of diseases involve both genetics and the environment.

Scientists currently believe that single gene mutations cause approximately 6,000 inherited diseases. These diseases are called single gene or monogenic diseases because a change in only one gene causes the disease.

These conditions include a number of lung and blood disorders, such as cystic fibrosis, sickle cell anemia, and hemophilia. Although rare, as a group, they still affect millions of people worldwide.

The rules that underlie the inheritance of major common diseases are not as straightforward. These diseases include heart disease, diabetes, Alzheimer disease, psychiatric disorders, and osteoarthritis.

These diseases affect many millions of people, and their treatment and prevention consumes the majority of health care resources in developed countries.

These common diseases result not just from a change in one or a few genes, but from a combination of the effects of the environment and a number of susceptibility genes.

Susceptibility genes contribute to an individual's risk of developing a specific disease, but usually are not enough to cause the disease. Susceptibility genes may influence the age of onset of a disease, contribute to its rate of progression, or help to protect against it. Understanding the rules of their inheritance and their roles in disease is not a simple task.

Different alleles may be associated with different degrees of susceptibility, or risk. The APOE gene on chromosome 19 is one example of a disease susceptibility gene. An individual who has two copies of one variant allele of APOE is more likely to develop Alzheimer disease at an earlier age than an individual with a different APOE genotype.

Hunting for Genes

Comparing sections of DNA code is a very slow and labor intensive method of searching.

To find a gene that is involved in a specific disease, scientists must search for DNA changes that are present more often in people who have a particular disease compared to people who do not have the disease.

One approach to this is to start with a gene whose function is known and that is suspected of playing a role in the disease, then compare the DNA of people who have the disease with those who do not to see if that gene is associated with the disease.

Another is to look in areas of the genome that are thought to be associated with the disease, then see if there are similarities among people who have the disease.

Yet another approach is to examine the DNA of large numbers of people with and without the disease and search the whole genome for areas that differ between the two groups.

Searching randomly through three billion base pairs of DNA for tiny changes that may be linked to disease has been difficult, time-consuming and expensive.

Scientists believe that the major common diseases are caused by alternative forms of many genes that interact with each other and with the environment, with each gene making a contribution to the disease. It has been difficult for scientists to trace the effects of these genes, even when they study many large families that include affected individuals.

SNPs

Using SNPs as "signposts" cuts down the time needed to locate nearby genes.

A new kind of genetic map, called a high-density single nucleotide polymorphism (SNP or "snip") map, has the potential to speed up this research.

SNPs are single-base differences in the DNA sequence that can be observed between different individuals in the population. They are the simplest and most common form of DNA polymorphism.

SNPs are present throughout the human genome with an average frequency of 1 per 1,000 base pairs. The frequency, stability and relatively even distribution of SNPs in the genome make them particularly valuable as genetic markers.

A marker is like a signpost on the genetic highway — a spot that is observed in everyone and that can be used as a reference point among people. The marker itself (a SNP, for example) may or not cause the disease, medicine response or other phenotype that is being examined. In some cases, it may be directly linked to the phenotype, but it is useful as a signpost in either case.

Using the information SNPs provide, it may be possible to predict your genetic risk of developing a certain disease, to diagnose a disease more accurately, or to predict how you most likely will respond to a medicine.

How might a doctor's knowledge of your genetic data affect your everyday life in the future?

Just as you carry your medical insurance card with you, you may also one day carry a wallet-sized card that has your genetic data coded on it. Doctors would be able to use this data to predict your risk of developing a disease and your likely response to a medicine before they prescribe it for you.