FAQs for Genetics Patients

Several types of genetic testing are available, including DNA   testing (known as molecular analysis), chromosome testing, chromosome microarray, and biochemical testing.  The type of genetic testing that may be recommended will vary depending on the reason for the genetics evaluation and from patient to patient.  

Learn more about genetic testing at the Centers for Disease Control & Prevention (CDC) - Genetic testing

DNA is a molecule inside our cells that contains the genetic information (genes) that provide instructions for the development and normal function of the cells and structures of our body. DNA is built from a specific combination (sequence) of four smaller molecules called nucleotides, the genetic blueprint for our development. Genetic disorders result from abnormal changes in the sequence of these nucleotides, which affect normal development and function. Those changes can be inherited from one or both parents or occur for the first time in an egg or sperm. Humans have about 20,000 pairs of genes.  We inherit one of each pair from our mother and one from our father.  

DNA testing involves examining DNA extracted from a person’s blood cells or other body tissues such as saliva.  A DNA test examines the sequence of the nucleotides in one or many genes to identify abnormal changes that can be associated with a person’s symptoms. It's like finding a typo or error in the sequence of one of those genes, which could explain why someone has a specific health problem.

DNA tests can be limited or large in scope, depending on the reason for the genetics evaluation.  For some people, testing may be restricted to the DNA sequence analysis of only a single gene (known as single gene testing). For others, analyzing the DNA sequence of more than one gene (panel testing) or the sequence of all a person’s DNA (whole exome or whole genome sequencing) may be recommended.   The scope of ordered DNA testing depends on your or your child’s medical condition. More about those tests is explained below.

The genomic testing that your healthcare provider has ordered is for clinical purposes and is not a research study. Consent is not required for clinical testing, but your healthcare provider may wish you to sign a form indicating that you received the information about the testing process.  

Learn more about molecular diagnosis

Whole exome sequencing (extended gene analysis) involves analysis of the DNA sequence contained in the exons of all our genes.  Exons are the part of our genes that code for proteins.  Proteins are complex molecules in our cells required for normal development and maintenance of normal function of the body’s tissues and organs.   The exons comprise only 1-2% of our DNA but play the most significant role in our health and development. All of a person’s exons together are called the exome, instead of analyzing all of our DNA. WES involves only analyzing 1-2% (the exome) of our DNA. Whole exome sequencing is typically used when it is unclear what specific genes might be causing a person’s symptoms.

Learn more about Whole Exome Sequencing (WES)

Limited panel testing looks for abnormal changes (variants) in the exons of more than one gene.  Limited panel testing is used when changes in a specific group of genes could explain a person’s symptoms.  The number of genes in a limited panel includes those known to cause symptoms consistent with the patient’s symptoms and can range from two to many hundred genes.  For example, hearing loss can be caused by an abnormal variant in one of a few hundred genes. 

A single gene test is a molecular DNA-based test that searches for variants in the exons of a specific gene. Testing of a single gene (instead of analysis of many different genes) is used when a person has symptoms that strongly suggest a specific genetic disorder and where the symptoms of that disorder only occur due to abnormal DNA changes (variants) in one specific gene.

This method analyzes the entire DNA sequence, including all the exons and non-protein coding portions of our genes).  This test provides the most information about a person’s DNA sequence.  Its use is restricted to cases where a genetic disorder is strongly suspected, but whole exome sequencing has not identified an underlying cause.

Learn more about Whole Genome Sequencing (WGS)

Single gene analysis, gene panel testing, and whole exome sequencing involve analysis of the exons, which are the protein-coding portions of our genes.  About 85% of abnormal changes in the DNA sequence that cause genetic conditions are present in the exome.   The remainder is not located in the exome and thus is undetectable by these testing methods. In addition, some abnormal gene changes in the exome may not be detectable by current sequencing technology. 

No variant is identified [negative (normal) report]: No genetic change (variant) was found to explain the patient's medical condition. This result reduces but does not eliminate the possibility that the medical condition has a genetic basis.  It is still possible that an abnormal change in the DNA sequence is present but cannot be detected by current testing methods. Additional testing using other testing methods or future re-analysis of the data from the current test may be recommended. Interpretation of a normal result depends on your specific situation. 

A pathogenic variant is identified [positive (abnormal) report]: One or more abnormal gene variants are identified causing the patient's medical condition or predict the patient has an increased risk of developing a medical condition. This type of genetic test result can be used to diagnose and make decisions about patient care, including treatment and surveillance.

A likely pathogenic variant is identified [a qualified positive (abnormal) report]: The genetic test result gives sufficient evidence to justify using it in clinical decision-making combined with other evidence for the disease to make the best decision about the patient’s medical care (e.g., X-ray studies or other laboratory tests).  

A variant of uncertain significance: A DNA sequence change was identified. However, there is insufficient information to determine whether it is disease-causing or represents normal human variation. Changes in the DNA sequence (variants) are common in all our genes. A substantial proportion of uncertain significance variants prove normal as more data becomes available.  Variants of uncertain significance should not be used in clinical decision-making.  Sometimes, testing other family members can provide more information about the clinical importance of a variant of uncertain significance.

Incidental findings: Because many genes are examined in genetic panel testing, this analysis may uncover a different genetic disorder unrelated to the medical condition being tested.  This is known as an incidental finding.  Genetic disorders that can be treated ("actionable incidental findings") are reported, following the standards of care recommended by medical societies.  Incidental findings often relate to treatable heart or treatable conditions that might increase cancer risk.  Incidental genetic findings are less common than incidental findings in many other routine medical tests, such as CT scans and MRIs. Depending on the type of genetic testing you or your child is having, we will discuss with you the option of receiving incidental findings.  

Chromosomes are the structures inside cells that contain our DNA. A chromosomal test analyzes whole and large pieces of chromosomes to determine whether there are significant genetic changes, such as an extra copy of a chromosome or a large missing or extra piece of chromosome, that can cause a genetic condition.  A chromosome test is usually performed on blood cells; it can also be performed on cells obtained from other tissues in the body, including amniotic fluid cells, cells from the placenta, and saliva.

This technology can find missing or extra pieces of genetic material on the chromosomes that are too small to be detected by the basic chromosome test but could cause a genetic disorder.  A chromosome microarray can be performed on DNA obtained from blood cells and on DNA from cells obtained from other tissues in the body, such as saliva.

A protein or enzyme test is a biochemical test that studies the amount or activity level of the product of a gene rather than the gene itself. Abnormalities in the amount or activity of an enzyme can indicate an underlying genetic disorder. A protein or enzyme test can usually be performed using blood cells. Occasionally, skin cells might be required.

• Autosomal recessive
• Autosomal dominant 
• X-linked recessive