What Causes Genetic Disease?

In reality, there is no easy answer to this question. Genetic disease is just as complicated as any other medical condition. Put simply, though, genetic disease is caused by a combination of environmental factors and some kind of genetic abnormality. In general, there are four different types of genetic disorders: 1) single gene, 2) multifactorial, 3) chromosomal, and 4) mitochondrial.

Single Gene Disorders

Single gene disorders are caused by mutations to the DNA sequence in one gene. Mutations are simply changes to the genetic information. A disease-causing mutation usually disrupts the protein normally coded for in some way. It may be that the protein's size or shape changes so dramatically that it cannot function as it is supposed to. It could be that the amount of protein made is inappropriate; too much or too little of a protein can have negative effects. At any rate, the mutation in the one gene alters its protein product enough to cause a disease. There are over 6,000 known single gene disorders, though many are quite rare. It is estimated that a single gene disorder occurs in 1 of every 200 births.

Single gene disorders are inherited in recognizable, predictable patterns: autosomal dominant, autosomal recessive, and sex-linked. More information on each of these is available in the Basic Concepts section. These patterns are often called Mendelian patterns of inheritance, named after Gregor Mendel, who first recognized and defined them.

Although the genetic mutation is necessary for a disorder to occur, some kind of interaction with the environment is often required for many of the symptoms to appear. For example, there is a single gene disorder called phenylketonuria (PKU). PKU is the result of a mutation in the gene that codes for an enzyme called PAH. As a result of this mutation, the body is not able to break down proteins in food properly and certain amino acids can accumulate in the body. This accumulation leads to symptoms such as mental retardation. PKU can be successfully treated by restricting proteins in the food. If an individual with PKU follows this treatment, the symptoms of PKU will never appear. Thus, the symptoms of PKU are present only if there is a mutation for the PAH enzyme and the person eats foods with proteins. The mutation is a genetic factor. The food is an environmental factor. PKU is a classic example of a single gene disorder that is characterized by an interaction between genetic and environmental factors.

Other examples of single gene disorders include cystic fibrosis, achondroplasia, sickle cell anemia, neurofibromatosis, galactosemia, Huntington disease, Marfan syndrome, and Duchenne muscular dystrophy.

Multifactorial Inheritance

Multifactorial conditions are sometimes called complex genetic disorders, owing to the great number of factors that play a role in their development. There are many conditions which have known genetic factors; often times, scientists have even been able to locate one or several genes directly involved in the development of the condition. However, the environment and/or random factors play just as big (if not a bigger) role in the appearance of symptoms. Multifactorial conditions can involve the interactions of many genes and chromosomes, as well as many environmental triggers. As such, it is much more difficult to predict the inheritance and appearance of multifactorial conditions.

Many “common� conditions are now known to involve genetics in some way, and thus are examples of multifactorial disorders. These include cancer, heart disease, Alzheimer's disease, arthritis, diabetes, and obesity. Many birth defects are considered multifactorial, including cleft lip, cleft palate, heart defects, and neural tube defects like spina bifida.

Chromosomal Abnormalities

When the structure of a chromosome is altered in some way, the genetic material it carries can be affected, too. Abnormalities like extra, missing, or disordered segments of one or more chromosomes can lead to disease. There are many ways in which the structure of a chromosome can change; some are changes that are passed down from parent to child, some are not. Some chromosome changes can have little or no effect on a person, but most have very serious consequences. Many chromosomal disorders are detected by looking at and analyzing a karyotype, or picture of a person's chromosomes:

This is an example of a karyotype. The chromosomes are paired, numbered, and put in order. The 23 rd pair, the sex chromosomes, is always placed last in a karyotype. As you can see, this is a karyotype for a male, since there is one X chromosome and one Y chromosome. A female karyotype would show the X chromosomes as a pair just like every other chromosome pair, and no Y chromosome.

This is an example of a karyotype. The chromosomes are paired, numbered, and put in order. The 23 rd pair, the sex chromosomes, is always placed last in a karyotype. As you can see, this is a karyotype for a male, since there is one X chromosome and one Y chromosome. A female karyotype would show the X chromosomes as a pair just like every other chromosome pair, and no Y chromosome.

Examples of chromosomal disorders include Down syndrome (the presence of an extra chromosome 21), Klinefelter syndrome (a male who has an extra X chromosome and so is XXY), Turner syndrome (a female missing an X chromosome and so is X0), and Cri du Chat syndrome (part of chromosome 5 is missing).

Mitochondrial Disorders

Mitochondrial disorders are fairly rare conditions that involve the mitochondria of a cell. The mitochondria have their own genes and DNA, separate and completely independent from the genetic material found on chromosomes. The genetic information located in the mitochondria is mostly used to keep the mitochondria functioning, and to aid in their role of cellular respiration. Cellular respiration is the method by which cells produce energy. That energy is used by the cells, and by the entire body. Mitochondria are especially important in cells that require a lot of energy, like those of the brain, heart, and muscles. A mutation in mitochondrial DNA often leads to problems in those particular organs, but any area of the body can be affected. Symptoms vary among conditions, but there are some common ones: muscle weakness, poor growth, vision and hearing problems, increased risk of infection, neurological problems, and learning disabilities.

Mitochondrial inheritance can become quite complicated if examined closely. Basically, though, mitochondrial disorders are always inherited from the mother. Mitochondria and the genetic information they hold are always passed down to children through the egg; sperm cells are usually too small to carry any mitochondria. Mothers can pass down mutations in mitochondrial DNA to both male and female children. However, the severity of the condition caused by the mutation will vary from person to a person, even in members of the same family. This is because there are many mitochondria in one cell and they are not identical in the genetic information carried; the replication of genetic material in mitochondria is not nearly as neat and orderly as in chromosomes. Some mitochondria may carry the mutation, others may not. As such, some people may be mildly affected with a mitochondrial condition, while others may be more severely affected. Also, not all cells carry the same number of mitochondria. Some cells may have very few, others may have a lot. The more mitochondria a cell has, the more likely it is that at least one will carry the mutation.

Some examples of mitochondrial disorders include LHON (Leber Hereditary Optic Neuropathy), Kearns-Sayre syndrome, MELAS (Mitochondrial Encephalopathy Lactic Acidosis with Stroke-like episodes), Leigh syndrome, and MERRF (Myoclonic Epilepsy with Ragged Red Fibers).

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