Basic Genetics

When someone says that a disease is "genetic," this means that there is a change in a gene.

But what is a gene? How can a change in a gene cause disease?

Our bodies are made of trillions of different cells which make up all our tissues (hair, teeth, nails, muscles, blood, bones, etc.).

Almost every cell has a nucleus inside that contains genetic material called DNA. DNA is unique material that makes us different from each other.

Inside the nucleus, the DNA is divided into 23 pairs of thread-like structures, called chromosomes. The first 22 pairs are numbered 1–22, and the 23rd pair is our sex chromosomes. They determine if we will be male (XY) or female (XX). See diagram of male chromosomes below.

For every pair, one chromosome is from the mother, and one is from the father. This means that half of our unique genetic material comes from each parent.
 
Each chromosome contains many genes. Together, our genes are like an "instruction manual." They tell our bodies how to grow and function properly. For example, there are hundreds of genes that tell our hearts how to function.
 
Sometimes a change (or error) can occur in a gene. A change in a gene is called a mutation or variant. A variant is like a misspelled word in the "instruction manual" and can cause the gene to stop working properly, which may lead to disease.

To learn more information about chromosomes and genes please click here.

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If something is said to be "inherited," it means it is passed on from one or both parents to the child. Eye color, for example, is a trait that we inherit from our parents. Pathogenic (disease-causing) variants causing conditions like rasopathies, hearing loss, and cardiomyopathy, and respiratory disease, also can be inherited.

There are four major ways that variants can be passed on:

• Autosomal Dominant
• Autosomal Recessive 
• Mitochondrial 
• X-linked

Autosomal Dominant Inheritance

Autosomal refers to the fact that the pathogenic variant (mutation) is located on one of the numbered chromosomes (e.g., chromosome 5). When a pathogenic variant is passed in a dominant way, only one pathogenic variant is enough to cause the condition, such as in HCM. Therefore, if a person has one dominant pathogenic variant, he or she will have HCM. That also means that every child of that person will have a 50% (or 1 in 2) chance of getting the variant and having HCM. The diagram below shows this relationship.

Facts about dominant conditions:

• One pathogenic variant is enough to cause disease. 
• The disease is typically seen in every generation (e.g., grandparent, parent, child). 
• When one parent has a dominant pathogenic variant, every child has a 50% chance of having the disease (due to one pathogenic variant).

 

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Autosomal Recessive Inheritance

Autosomal still refers to the fact that the pathogenic variant (mutation) is located on one of the numbered chromosomes (e.g., chromosome 5). However, unlike a dominant variant, one recessive pathogenic variant is not enough to cause disease, such as in cystic fibrosis (CF) or some forms of hearing loss. When an individual has just one recessive variant, he or she is called a carrier and does not have CF.

The diagram below shows how CF is passed on.

Facts about recessive conditions:

• Two recessive pathogenic variants are required to cause disease. 
• The disease may appear to skip generations (e.g., grandparent, child). 
• If each parent has one recessive pathogenic variant (i.e., both parents are carriers), every child has a 25% chance of having CF and a 50% chance of being a carrier.

 

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Mitochondrial Inheritance

There are some pathogenic variants  that occur in mitochondrial genes. These genes are found inside structures called mitochondria, found within the cell.
 
Unlike nuclear genes, which are passed on by each parent, mitochondria genes are only passed on by the mother. This means that if the mother has a pathogenic hearing loss variant in her mitochondrial genes, all her children may have hearing loss as well. If the father has a pathogenic variant in his mitochondrial gene, his children will not be affected. The diagram below demonstrates this inheritance.

Facts about mitochondrial hearing loss:

• If the mother has a mitochondrial pathogenic variant, all of her children could develop the condition. 
• If the father has a mitochondrial pathogenic variant, he will not pass it onto any of his children.

 

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X-Linked Inheritance

Sometimes a pathogenic variant can occur only on a specific type of chromosome, called a sex (or gender) chromosome. Sex chromosomes are just one pair of the 23 pairs of chromosomes that we have.

This pair however, is different in men and women. There are two types of sex chromosomes, X and Y. Women have two X chromosomes, while men have one X and one Y chromosome.

If a variant is said to be X-linked, it occurs only on the X chromosome. Since women have two X chromosomes, a pathogenic variant on one X chromosome would not result in conditions such as Danon disease or ectodermal dysplasia, because the second X chromosomes without a variant would act as a backup copy of the gene. However, in men, the Y chromosome cannot make up for the pathogenic variant on the X chromosome, so they will have the condition. The diagram below shows how an X-linked pathogenic variant is passed on.

Facts about X-linked conditions:

• Conditions resulting from an X-linked pathogenic variant are usually only seen in males. 
• If the mother has a pathogenic variant on one side of her X-chromosomes, each female child has a 50% chance of being a carrier (but will not have the condition) and each male child will have a 50% chance of having the condition.

 

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What is a genetic test?

A genetic test is when selected genes in the DNA are analyzed to see if they have variants (mutations) in them. A genetic test is like a "spell-checker" that looks for misspellings/changes in genes. This test may help determine whether a disease is genetic.

This information may allow better treatment and management of the disease. It can also help predict the chance that future children and family members will inherit the disease. Although a blood sample is preferred and the most reliable, a genetic test may be done using saliva or cheek cells.

To learn more in-depth information about genetic testing, please refer to our test menu and disease-specific information.

How much does a genetic test cost?

The cost of a genetic test depends on what test is ordered.

Genetic testing is usually covered by insurance if there is a medical reason for the test. At this time, our lab does not bill insurance companies. However, patients may try to obtain pre-approval for a test from an insurance company prior to genetic testing or seek reimbursement after the testing process has been completed. Some insurance companies require that a letter of medical necessity be submitted prior to granting pre-approval or reimbursement.

What are the benefits & limitations of a genetic test?

Benefits of Genetic Testing:

• Finding a pathogenic variant may help to establish a diagnosis, even in at-risk family members who have no signs or symptoms of the disease. 
• Finding a pathogenic variant may guide physicians in patient management and screening. 
• It can identify at-risk family members who did not inherit the pathogenic variant, freeing them from unnecessary follow up and worry. 
• Family members may be able to determine the chance of having future children with the disease.

Who should I talk to about genetic testing?

Your physician may or may not be knowledgeable about genetics. Therefore, it is often recommended that you also talk to a genetics professional.

These professionals may include:

• Genetic Counselor - a person who holds a master's degree in genetics. He/she helps patients and families understand genetic diseases. A genetic counselor can help interpret genetic test results and discuss the chance for a disease in future family members. Click here to find a genetic counselor in your area or contact an LMM genetic counselor.
• Clinical Geneticist - a medical doctor who has training in genetics. He/she can help diagnose genetic diseases, help interpret genetic test results, and discuss the chance for disease in future family members. 
• Clinical Molecular Geneticist - usually a person with a PhD in genetics. He/she oversees genetic testing in the laboratory and reports test results to a counselor or a physician.

What is familial testing?

If previous genetic testing has identified a variant(s) known to cause disease (pathogenic) in your family, then you or your family members can have testing specifically for that/those variant(s). This test is called a familial variant test and because this test looks only for the specific variant(s) identified in your family, is different from the original test. Testing will allow you or your family members to determine if anyone has inherited the variant(s) and are at risk to develop the disease.

What can the test tell me?

Testing for a familial variant will tell you whether or not you inherited the disease present in your family.

If the result of the test is negative, then you do not have the variant and are now at the same risk as the general population to develop the disease.

If the result is positive, it means you were found to have the variant. For instance, a person found to have a variant causing an autosomal dominant disease like dilated cardiomyopathy in their family, is now at increased risk to develop the disease and has a 50% (or 1 in 2) chance to pass this same variant onto his/her children. In recessive conditions like cystic fibrosis and some forms of hearing loss, a person found to have only one disease-causing variant is a carrier for that condition. Carriers are not at risk to develop the condition. If a person is found to have two disease-causing variants, then they have the condition.

A positive result does not always mean that an individual will develop the disease. The severity of some diseases is affected by other factors, such as diet or other environmental exposures. To understand the meaning of a positive test result, please contact the lab and speak with a genetic counselor.

Sample can be blood or saliva. Please refer to the sample requirements page of our website for more information on how to send a sample.