How Genetic Disorders Are Inherited

Genetic disorders are diseases caused by an abnormal gene, often described as a mutation. When such diseases are inherited (rather than the result of a random mutation), it means they are passed along to a child from one or both parents, often according to certain patterns of inheritance.

These patterns are determined by the way the mutation causes disease, whether only one or both parents have the gene, which chromosome it is on, and other factors. The presence of a mutation doesn't always translate to the disease it's associated with. For example, Huntington's disease, breast cancer, and autoimmune diseases are associated with specific genes, but a person who inherits them won't necessarily develop these conditions.

On the other hand, some genetic mutations, such as those linked to hemophilia, will always manifest the disorder. Furthermore, the environment can have an effect on the degree to which a gene mutation is expressed, which explains why in some cases family members with the same genetic mutation may experience an inherited disorder somewhat differently.

Patterns of Inheritance

The various patterns of inheritance are attributed to Austrian scientist Gregor Mendel, who discovered them while working with garden pea hybrids in the 1800s. Mendel sometimes is referred to as the father of modern genetics; likewise, the patterns of inheritance for single-gene diseases are often described as Mendelian.

According to Mendel's work, there are five distinct patterns of inheritance: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.

Dominant and Recessive Genes

A genetic mutation is a change In a genetic code.

Because of the altered genetic code, the body might:

• Lack a normal protein, such as an enzyme, and this absence of a normal function can cause a disease to develop.
• Make an abnormal protein that causes harm to the body and leads to disease.

Typically, a mutation that causes an abnormal protein will result In dominant inheritance, while a mutation that causes the body to lack a protein will have a recessive disease inheritance pattern.

That's because an abnormal product can cause harm even if the other chromosomes codes for a normal product. And if the problem with a genetic mutation is that it doesn't code for a protein that the body needs, the normal gene on the other chromosome will usually code for the protein.

Autosomal Dominant

In autosomal dominant disorders, only one copy of a mutated gene is necessary for the disease to develop, and males and females are equally likely to be affected.

Children who have a parent who has an autosomal dominant disorder have a 50% risk of inheriting the mutated gene and developing the disorder. Examples of autosomal dominant disorders include Huntington's disease and Marfan syndrome.

Sometimes, however, these disorders result from a new mutation and happen in people with no family history.

Autosomal Recessive

In autosomal recessive disorders, both copies of a mutated gene—one from each parent—must be present for a person to develop the disease. A person with only one abnormal copy will be a carrier, but will not have the disease.

Carriers will not have any signs or symptoms of the disorder. Carriers have a 50% chance of passing the mutation to their children.

If families in which both parents carry the mutation for an autosomal recessive disorder, the odds of the children having the disorder are as follows:

• 25% risk of inheriting both mutations and having the disorder
• 50% risk of inheriting only one copy and becoming a carrier
• 25% risk of not inheriting the mutation at all (they will not be carriers either)

Examples of autosomal recessive disorders include cystic fibrosis, sickle cell disease, Tay-Sachs disease, and phenylketonuria (PKU).

X-Linked Dominant

X-linked dominant disorders are caused by mutations in genes on the X (female) chromosome. Females have two X chromosomes and will have the disorder if either of the X chromosomes carries the mutation.

In males (who have one X chromosome and one Y chromosome), a mutation in the X chromosome will cause the disorder.

Most times, males have more severe symptoms of an X-link disorder than females. However, one feature of X-linked inheritance is that fathers cannot pass on these traits to their sons. Fragile X syndrome is an example of an X-linked dominant disorder.

X-Linked Recessive

In X-linked recessive disorders, the mutated gene occurs on the X chromosome. Because males have one X chromosome and one Y chromosome, a mutated gene on the X chromosome is enough to cause an X-linked recessive disorder.

Females, by contrast, have two X chromosomes, so a mutated gene on one X chromosome usually has less effect on a female because the other X chromosome carries the normal gene.

However, a female with a genetic mutation on one X chromosome is a carrier of that disorder. From a statistical standpoint, this means 50% of her sons will inherit the mutation and develop the disorder, while 50% of her daughters will inherit the mutation and become a carrier. Examples of X-linked recessive disorders are hemophilia and red-green color blindness.

Mitochondrial

Mitochondria are structures called organelles that exist in each cell of the body, where they convert molecules into energy. Each mitochondrion contains a small amount of DNA: A mutation of that DNA is responsible for mitochondrial disorders.

Mitochondrial disorders are passed down from mothers to their sons or their daughters. Only females can share mitochondrial mutations with their offspring because egg cells contribute mitochondria to the developing embryo; sperm cells do not.

Conditions resulting from mutations in mitochondrial DNA can appear in every generation of a family and can affect both males and females. An example of a mitochondrial inherited disorder is Leber hereditary optic neuropathy, a form of sudden vision loss.

Other Inheritance Patterns

In addition to the five main patterns of inheritance, there are a few others.

Y-Linked Disorders

Because only males have a Y chromosome, only males can be affected by and pass on Y-linked disorders. All sons of a man with a Y-linked disorder will inherit the condition from their father. Some examples of Y-linked disorders are Y chromosome infertility and cases of Swyer syndrome in which a male's testicles do not develop normally.

Codominance

Codominant inheritance involves a relationship between two versions of a gene. Each version of a gene is called an allele. If the alleles inherited by a parent don't match, the dominant allele usually will be expressed, while the effect of the other allele, called recessive, is not expressed.

In codominance, however, both alleles are dominant and therefore phenotypes of both alleles are expressed. An example of a codominance condition is alpha-1 antitrypsin deficiency.