RARE Toolkits

Below is a list of all of our current RARE Toolkits.

Genetic Testing
Genetic Testing

Genetic Testing

Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of these tests can confirm or rule out suspected genetic conditions.

If costs were not a limiting factor, every baby’s whole genome could be sequenced (and analyzed) immediately after birth. This would provide all of the baby’s genetic information and make it possible to treat and potentially prevent any diseases that arise. Sequencing every baby’s genome, however, is not currently desirable due to several reasons, including the extremely high cost of testing the entire genome and the fact that most of the genome is still not well understood.

Indications for Genetic Testing

Not every person will need to undergo whole genome sequencing. However, some families may choose to undergo this or other types of genetic testing. Some reasons to consult with a healthcare provider about these types of tests include:

● Personal and/or family history of genetic disease
● Multiple family members with similar symptoms/features without a specific diagnosis
● Symptoms that elude doctors and cannot be diagnosed through continuous testing
● Multiple congenital anomalies/birth defects
● A newborn screening result that indicates a possible genetic disease
● A history of multiple miscarriages and/or stillbirths
● An unexplained infant death
● General developmental delay/intellectual disability

Genetic Testing Options

As shown in the comparison chart below, there are many genetic testing options for individuals with rare diseases. Some of the most commonly used tests are described within this toolkit.


Exome Sequencing

There are several different types of genetic tests available to physicians. A patient’s symptoms and results from prior tests will determine the appropriate one. If prior tests have not revealed conclusive results, a doctor may recommend a whole exome sequencing test.

Quote Mark

"Many of our patients have come in with other genetic tests that have been inconclusive or negative. Sometimes families went on a diagnostic odyssey looking for answers for years because ‘there wasn’t a technique to make the diagnosis.’ Now we have that ability with exome sequencing. We needed a technology to say, ‘Aha, this is the diagnosis!'"


Dr. Ada Hamosh

Professor, Department of Pediatrics and Institute of Genetic Medicine at John Hopkins University School of Medicine

What is Exome Sequencing?
Eric Green, Director of the National Human Genome Research Institute (NHGRI), explains what exome sequencing looks at.

This test sequences the exons of about 20,000 genes in the human genome that are responsible for making proteins and contain 85 percent of all known disease-causing mutations. To begin the process, DNA is collected, typically by a blood draw. If a blood draw is difficult, DNA can also be extracted from saliva or a cheek swab. Prior to sample collection, be sure to ask your doctor about preserving the donated sample for future testing. This could help reduce the amount of blood draws, and allows the sample to be used for multiple purposes. Also, inquire as to your rights to a copy of your exome– you should be able to get a copy for your own re-use later.

“People are very generous when they are asked to provide samples for researchers, especially in the rare disease community. However, donating a biological sample such as blood or tissue multiple times can become challenging; it can be a hassle. Through Biobanks, biorepositories that store various biological samples and associated information, these samples can be held and used in current and future research studies. It’s a more efficient way to conduct research, and it minimizes the burden on the person donating the sample.”

Liz Horn, Principal, LHC Biosolutions

Results from an exome sequencing test are typically not available for several weeks or months due to the large amount of data the test yields. The results are given to the ordering physician in a report interpreting the sequence information and confirming the presence of any disease causing mutations. This test may or may not be covered by insurance companies.

Quote Mark

"About one in three [affected individuals] benefit from exome sequencing, and this test should be used to complement the work performed by the doctor. Blood work, physical/clinical symptoms, family history, etc. should be analyzed first. Genetics are not the whole picture—just part of the picture."


Gary Jackson

Senior Clinical Account Manager at Illumina, a leading developer and manufacturer of genetic sequencing technologies

Whole Genome Sequencing

If the exome sequencing failed to explain any of the symptoms or features, then whole genome sequencing can be performed. This test will sequence all 3 billion base pairs in the human genome. It also requires DNA to be extracted, preferably through a blood draw. This test is typically only available on a research basis at this time, given the expensive nature of the test and the large amount of data it generates.

Results can take several months or even years. Once results are ready, they are returned to the ordering physician in a report containing clinical interpretation of the sequencing data. As with exome sequencing, make sure to ask for a copy of your genome – it’s your data!

Physicians will order this test for patients who have exhausted all other forms of genetic testing. One should note that getting insurance reimbursement for this test is often more difficult than for exome sequencing.

How to Sequence a Genome
This animated video presents all the essential steps in sequencing a genome.