Genetic Disease

Medical Authors and Editors: Barbara K. Hecht, Ph.D. and Frederick Hecht, M.D.

What is a genetic disease?

A genetic disease or disorder is any disease that is caused by an abnormality in an individual's genome. The abnormality can range from minuscule to major -- from a discrete mutation in a single base in the DNA of a single gene to a gross chromosome abnormality involving the addition or subtraction of an entire chromosome or set of chromosomes.

What are the different types of inheritance?

There are a number of different types of genetic inheritance, including the following four modes:

1. Single gene inheritance -- Also called Mendelian or monogenic inheritance. This type of inheritance is caused by changes or mutations that occur in the DNA sequence of a single gene. There are more than 6,000 known single-gene disorders, which occur in about 1 out of every 200 births.

   Some examples of single gene inheritance are cystic fibrosis, sickle cell anemia, Marfan syndrome, Huntington's disease, and hemochromatosis. Single-gene disorders are inherited in recognizable patterns: autosomal dominant, autosomal recessive, and X-linked.

2. Multifactorial inheritance -- Also called complex or polygenic inheritance. This type of inheritance is caused by a combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on chromosomes 6, 11, 13, 14, 15, 17, and 22. Some common chronic diseases are multifactorial disorders.

   Examples of multifactorial inheritance include heart disease, high blood pressure, Alzheimer's disease, arthritis, diabetes, cancer, and obesity. Multifactorial inheritance also is associated with heritable traits such as fingerprint patterns, height, eye color, and skin color.

3. Chromosome abnormalities -- Chromosomes, distinct structures made up of DNA and protein, are located in the nucleus of each cell. Because chromosomes are the carriers of the genetic material, abnormalities in chromosome number or structure can result in disease.

   For example, Down syndrome or trisomy 21 is a common disorder that occurs when a person has three copies of chromosome 21. There are many other chromosome abnormalities including Turner syndrome (45,X), Klinefelter syndrome (47, XXY), the cat cry syndrome (46, XX or XY, 5p-), and so on.

4. Mitochondrial inheritance -- This type of genetic disorder is caused by mutations in the nonchromosomal DNA of mitochondria. Mitochondria are small round or rod-like organelles that are involved in cellular respiration and found in the cytoplasm of plant and animal cells. Each mitochondrion may contain 5 to 10 circular pieces of DNA.

   Examples of mitochondrial disease include an eye disease called Leber's hereditary optic atrophy; a type of epilepsy called MERRF which stands for Myoclonus Epilepsy with Ragged Red Fibers; and a form of dementia called MELAS for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes.

What is the human genome?

The human genome is the entire "treasury of human inheritance." The sequence of the human genome provides the first holistic view of our genetic heritage. While not yet complete, continued refinement of the data bring us ever closer to a complete human genome reference sequence. The 46 human chromosomes (22 pairs of autosomal chromosomes and 2 sex chromosomes) between them house almost 3 billion base pairs of DNA that contains about 30 to 40,000 protein-coding genes. The coding regions make up less than 5% of the genome (the function of the remaining DNA is not clear) and some chromosomes have a higher density of genes than others.

Most genetic diseases are the direct result of a mutation in one gene. However, one of the most difficult problems ahead is to find out how genes contribute to diseases that have a complex pattern of inheritance, such as in the cases of diabetes, asthma, cancer and mental illness. In all these cases, no one gene has the yes/no power to say whether a person has a disease or not. It is likely that more than one mutation is required before the disease is manifest, and a number of genes may each make a subtle contribution to a person's susceptibility to a disease; genes may also affect how a person reacts to environmental factors.