Before DNA testing

This post explains the different DNA testing options available to patients/consumers who seek to discover potential genetic causes of an already existing condition. The testing also applies to a person who wants to screen before any clinical symptoms of a condition become apparent.

There are many options and considerations so this can be a confusing area to wade through, hence Merogenomics recommends studying this information very carefully before a DNA test selection. First off, the DNA tests described are clinical, and when aiming to use a DNA test for medical diagnostic purposes, finding other commercial options without a participating doctor’s oversight (tests referred to as direct-to-consumer DNA tests) is not recommended. Clinical DNA tests that require a doctor’s involvement are different than direct-to-consumer test in that they are guaranteed to be offered through regulated laboratories and follow stringent guidelines ensuring patient/consumer safety thus Merogenomics recommends avoiding any and all of the inferior direct-to-consumer DNA tests for health, including those used only for screening (when no apparent symptoms are present but the family history implies a possible inheritance of a condition). In short, always rely on clinical tests that involve a doctor’s participation if you want a dependable health-related analysis as the goal of your DNA test.

Genetic counselling before and after clinical DNA testing is always recommended. Merogenomics strives to ensure you have access to the best genetic counsellors. Reach out if you need help. Studying the Merogenomics site gives you a strong educational head start in preparation for your first interaction with any healthcare professionals in medical genetics. This is one of the most valuable services offered by Merogenomics and it is free! We recommend it for doctors and patients alike who are interested in clinical DNA testing.

Using clinical DNA testing to identify a condition

For basic discovery processes, when trying to find out possible genetic mutation(s) (the more clinical term is variants) causing a condition, there are a few options available:

• Chromosomal microarray (Note: Merogenomics does not need to offer this – see below, under our Sequencing graphic for more details – but we can help with access to this type of test.) This process, where genetic information is looked at on a general or broad scale, seeks to identify if entire segments of chromosomes are either missing or duplicated. These are referred to as structural variants mutations affecting a large amount of DNA). A chromosomal microarray is a cheap and rapid way to see if a genome is affected by structural variants, but it does not provide any DNA sequence information (actual DNA coding information). Think of this as looking at your genetic material with only a magnifying glass. However, the use of this technology, when combined with the power of DNA sequencing (typically by using gene panel testing – see below for definition), does become the current the gold standard for DNA analysis in medicine.

• There are other technologies that can be used to provide a subset of information of a chromosomal microarray test. One of these includes multiplex ligation-dependent probe amplification (MLPA), which is a simple test to analyze if a specific gene of interest could be present in multiple copies since some diseases are produced as a consequence of a gene, or a portion of a gene, having multiplied itself. This form of structural variant is specifically referred to as copy number variation.

• DNA sequencing. (These are the services that Merogenomics promotes) - This is a process where the DNA code is actually determined, down to single point mutations. Think of this as looking at your genetic material with a microscope. It can be further subdivided as described below.

The rule of thumb is that the more comprehensive a DNA sequencing test is, the more expensive it is, but comprehensive also ensures vital genetic information of interest is not overlooked.

Tests listed from the least to most investigative go like this: gene panels (pre-selected genes of interest are investigated) to exome (all the coding genes in the DNA code are investigated, approximately 2% of all of your DNA) to full genome (all of the DNA – coding, non-coding, and mitochondrial- is investigated).

When it comes to current clinical experiences though, the most experience lies with just specific gene panels and the least experience is with a full genomic test. This is because gene panels are cheaper so in clinical medicine they have been used the most. With full genome tests, they produce such a large amount of data that they are routinely found in the discovery process of completely new disease conditions or new types of variants, and this requires very significant expertise and resources.

Merogenomics’ vision about the role that DNA testing plays (and will continue to play) in medicine is quite clear - DNA sequencing will continue demonstrating increased cost utility along with clear advantages for proactive use (DNA sequencing prior to an onset of condition symptoms) rather than reactive use.

Interestingly, sometimes the type of information that can be identified with a chromosomal microarray (large chunks of DNA code either missing or being duplicated – structural variants) can be completely missed with gene panels or exome sequencing. A full genome sequencing can capture this information, depending on the quality of the analysis, but it requires sophisticated interpretation of the data. The company that Merogenomics works with are experts in this area and this explains why the additional technology of chromosomal microarrays is unnecessary when choosing tests recommended by Merogenomics.

Keep in mind, that every genetic test in the world will always risk missing some information. Thus this is all about minimizing risk of neglecting to discover mutations of interest.

Types of DNA sequencing tests

The tests below are listed from most clinical use experience but least amount of information investigated, to the most comprehensive tests which suffer from lowest level of experience (although companies that are involved in this are definitely experts).

These are the categories of tests Merogenomics recommends when someone is trying to discover their genetic information related to an existing symptomatic condition(s), or in the process of attempting to discover a genetic predisposition prior to any symptoms being present:

• Condition-specific gene panels – selected genes (range of genes investigated can be from just a few to over thousand, as long as the genes are known to play a role in a specific medical area of interest). Merogenomics works with one of the best medical DNA testing companies in the world, with largest and longest technical experience in this field.

  Advantages: very high experience with medical use and interpretation. Genes are selected based on the past data regarding impacts and that are well validated.

  Disadvantages: can miss information if a mutation is outside the selected regions being tested. Technology is not suitable for finding any large-scale mutations – structural variants, and would then need to be supplemented with additional testing (the chromosomal microarray).

• Exome sequencing – all of the coding genes are investigated of the genome.

  Advantages: it is estimated that at least 80% of all human diseases stem from mutations in genes, hence this test has a very high chance of uncovering mutations related to known genetic diseases or discovering new information.

  Disadvantages: less clinical experience compared to gene panels. Can miss information if a mutation is outside the selected regions being tested. Technology is not ideal for finding large-scale mutations, the structural variants.

• Full genome – at least 95% of your DNA investigated (this includes the nuclear and mitochondrial DNA), covering the widest scope of information possible.

  Advantages: some disease-causing mutations can be outside of the genes which would always be missed with previous tests. Technology suitable for finding large scale mutations, the structural variants. The only DNA test needed in a lifetime as all of information is captured with this test.

  Disadvantages: slow and complicated analysis. Least medical experience available thus requiring excellent quality teams for this purpose.

To learn more about the types of DNA tests in general, below are helpful playlists of Merogenomics YouTube videos categorized by target groups serviced by Merogenomics.

At Merogenomics we firmly believe that background education is the most helpful and important aspect prior to purchasing a DNA test.

Pharmacogenetic (PGx) DNA testing

One specific test worth bringing up (a specific version of gene panels) is pharmacogenetic testing which is a help determine how medications should be used by a patient based on their personal genetics. This test helps identify some medicines that could be toxic, or especially help to identify the correct dosage of a medication to take. If a person's medication is on the list of the ~300 medications that are currently already verified to be linked to personal genetics, it can be worthwhile investigating with pharmacogenetic tests. In theory, full genome sequencing would capture all of the DNA information that can also be obtained from a pharmacogenetic test. However, the full genome test would not include the scope of analysis that a stand-alone pharmacogenetic gene panels do (different full genome tests could offer different levels of interpretation). Importantly, nearly everyone can uncover important personal pharmacogenomic information with this type of test! This could be especially critical for patients (and their medical professionals) already dealing with a condition and dependent on medication use.

The two medical specialties that benefit the most from this test are cancer and mental health conditions (psychiatry) with currently around 50 medications in each category linked to personal genetics. But medications related to many other medical specialties and/or the management of many conditions or their symptoms are also part of pharmacogenetic testing. The use of pharmacogenetic DNA testing can potentially alleviate the trial-and-error searching for the correct medication to use, or can provide very valuable information related to personalized dosing of medication.

To see if a medication important to you is on the list, please watch the video below (last section of this educational content lists all the drugs).

Finally, this article has encompassed nearly all of the different clinical DNA testing options Merogenomics recommends that would be relevant to those individuals wanting to uncover their genetic information related to existing conditions, or their predisposition to a future condition - with a spotlight example that shows how genetic testing can directly impact the use of medications when dealing with an existing condition.

It is very important to consider DNA testing options carefully, as ultimately it should be the patients/consumers who decide what DNA test they should select. It is a consideration involving the factors of risking missing some information while considering how much clinical experience each test has and also the relative cost of the test. Merogenomics hopes this article is of aid in making this decision, and we wish you successful DNA sequencing!

This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

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