Considerations After Genome Sequencing

Receipt of Data

All of the DNA tests endorsed by Merogenomics require a physician to sign the test requisition form before the DNA sequencing procedure can be purchased by the client. The only exception are the pharmacogenomic tests, which can also be ordered for the client by a pharmacist.

For this reason, the client will not be directly receiving the results of the DNA test. Instead, it will be the ordering physician that will obtain the data (both the Analysis Report based on the decoded DNA sequence of the subject of the test, as well as a digital copy of the DNA data). To ensure the safety of the client and the subject of the test (if they are different from the client), this process allows the ordering physician to review the results and determine the appropriate course of action that would most benefit the client. Appropriate surveillance of, or intervention with, conditions revealed through genome sequencing should be considered only by a medical professional. 

Prior to ordering the test, the client needs to determine if she or he would like to obtain information related to untreatable conditions. The receipt of any pathogenic results, that is DNA results linked to a human disease, can be challenging to handle. This can be even more so in the case of a disease to which there is no known treatment available. It is recommended that the client be as prepared as possible for the receipt of the results, especially if the client has agreed to obtain information related to untreatable conditions. Such preparation could include ensuring that someone close is available for support after the information is disclosed, or to perhaps even accompany the client to the meeting with the doctor.

However, the likelihood of obtaining a genetic diagnosis for an untreatable condition is small. The likelihood of obtaining a pathogenic result is estimated between 1-5%. Within the scope of possible pathogenic results, the highest likelihood will be linked to a hereditary cancer predisposition. But full genome sequencing tests for literally hundreds of possible diseases in one test, including all known diseases with established genetic links, the number of which is expanding every year for both the number of conditions as well as documented causative DNA mutations, so that possibility is likely to increase.

The likelihood of discovery that the client is a carrier of a disease is very high, with the vast majority of people in the population expected to be carriers. If a couple planning to have children screened themselves for carrier status with the same service provider at the same time, their results will be analyzed in tandem to flag any potential issues of reproductive consequences.

The likelihood of obtaining pharmacogenomic information is also very high, with nearly everyone tested obtaining results relevant to drug response.

Only one Analysis Report is provided per client (with the exception of family-based reports when comparing the carrier status between two prospective parents). Service providers of DNA testing will not update or supplement the Analysis Report unless the client agrees to purchase a new one. Some service providers might allow one complimentary update of the data. If available, Merogenomics recommends waiting two or more years between data analysis dates to allow for the ample accumulation of new medical understanding about the genome sequence. A new Analysis Report is generated based on the DNA sequence data that was previously generated for the client. If the client's DNA data is not already stored by the service provider, the client’s DNA sequence will be uploaded via a secure website portal for the new Analysis Report.

 

Pathogenic Variants Verification

All DNA tests endorsed by Merogenomics are clinical and are not to be considered for research purposes only. This means that the laboratories performing the DNA test follow the highest established standards to ensure the delivery of accurate information that is then presented to the healthcare provider. This also means that the Analysis Report that the doctor obtains is ready to use for medical interpretation in the context of patient’s medical history.

However, no medical test is infallible from errors and diagnostic errors can and do occur. In the case where the results point to medical management options with a serious impact potential on the patient, such as surgical intervention, the same caution of examining the evidence is required as with any other diagnostic medical testing. In such cases, the diagnosed condition can be confirmed with additional testing, which can include tests completely independent of DNA, and/or re-testing for a specific DNA alteration with an alternate DNA sequencing technology.

This ensures that the information obtained is valid and not due to rare a sequencing error. The client can obtain pathogenic variant verification in one of the following ways:

  • Pathogenic variant verification can be performed in the laboratory where the genome sequence data was produced, using the same sample that was used for genome sequence data generation within the time period that the tissue sample is maintained by the sequencing laboratory
  • The client can send a new tissue sample to the laboratory where the genome sequence data was produced and request pathogenic variant verification, or the client can request pathogenic variant verification from another laboratory
  • The client can discuss the available choices for pathogenic data verification with his or her healthcare provider

 

Communication with Family Members

If pathogenic variants with health risk consequences are discovered in an individual, such results are likely to have important implications for other family members. This provides an opportunity for other family members to undergo screening tests to determine who might be at risk, potentially bringing benefit to otherwise unsuspecting individuals. However, all information might not be welcomed by all relatives, and even if family members are open to sharing results, some information could be disruptive to their emotional well-being. Caution should be taken when approaching family members about the possibility of disclosing genome sequencing results if such results might also have implications for the family member.

 

Communication with Healthcare Providers

The ordering physician of the DNA test will be the primary recipient of the DNA test data and interpretation. A doctor who is familiar with the client’s health history will ideally be in a position to integrate the genome sequence information with her or his personal medical history, along with their family medical history, and evaluate whether further examination is required to obtain supporting evidence of pathogenic mutations.

However, the utility of the DNA test results should not end after the receipt of the original Analysis Report. The DNA data can provide value for the remainder of the life of the subject of the test. Thus, the ordering physician should periodically review the information within the context of the patient’s changing medical history. Available genome sequence data should be reviewed in the following situations:

  • New and serious symptoms materialize in the patient
  • Atypical symptoms are observed in a closely-related family member
  • The sudden death of a family member without a clear explanation behind the cause
  • New medications are to be prescribed for the patient

In addition, the client could have additional doctors involved in her or his care, any of which could potentially benefit from DNA data interpretation in their medical management of the patient. Therefore, after receiving the genome sequence information, the client should consider sharing the results with any doctor involved in their care prior to making any medical decisions or taking action. Some of the medical specialists will wish to analyze the DNA test results prior to their management of a condition, and may request specific genetic testing. In such circumstances, the client can inform the doctor that DNA testing has taken place in the past and inform them of the results. If the past DNA test undertaken by the client was full genome sequencing, it might be of greater value for such data to be reanalyzed than to undergo a new test as a full genome sequence could offer a more complete investigation.

 

Decision to Publish DNA Sequence Data

All DNA tests endorsed by Merogenomics are for clinical purposes and the service providers of the tests deposit any pathogenic variant findings, along with the corresponding patient symptoms, into public databases that are used worldwide for further medical understanding of the human genome. The client’s personal information is safeguarded and is not revealed in the process.

However, the client also has an option to publish their genomic data elsewhere, whether through participation in a research project or through the use of commercial third-party tools in a bid to better understand the meaning of their own genome. Whereas participation in a research project usually comes with the strict protection of a client’s privacy rights, and information use and distribution is under scrupulous oversight, the use of commercial third-party tools might not guarantee the safekeeping of client information confidentiality. Therefore, Merogenomics recommends that genome sequence information be kept private by minimizing third-party access to the genomic data unless a genuine benefit for the client can be identified, and is backed up by a thorough investigation of the third-party’s data protection practices.

An example of the type of research that the client might want to participate in includes the development of polygenic risk scores, which predict negative health outcomes based on many different DNA mutations found in the genome. Such risk scores are usually for very common health conditions, but due to their complex genetic nature, they have not been previously well understood. Participation in such studies can help progress the scientific understanding of the genome while obtaining access to unique information that might not be commercially available for years to come.

An example of the type of commercial third-party tools that one may wish to utilize is one for analyzing one’s genome for ancestral or ethnic background information.

Caution should always be exercised when delivering your own genomic data to other third parties.

 

Inheritance of Genomic Data

Collecting personal genome sequence data and its interpretation informs the subject of the test about the potential health risks associated with DNA alterations. However, the DNA sequence also has the power to inform one about the potential or actual genetic makeup of other close relatives. Approximately 50% of one’s genome is identical to those of their parents, siblings, and offspring. Each successive generation will reduce that genetic inheritance in half. In other words, each person’s genome sequence will be 50% identical to that found in their biological children, 25% to that in their grandchildren, 12.5% to that in their great-grandchildren, and so on. These numbers can be cut in half for the relationship with one’s nieces and nephews and the subsequent offspring generations.

Heritability of the DNA code across generations is important because it allows for the tracking of medical outcomes as related to DNA mutations. This means that one’s genome sequence data can be of importance to future generations within the family, long after the passing of the subject of the test. For example, if one is a carrier of a currently unrecognized DNA mutation towards the development of a specific disease, and such information is propagated in the family for several generations, a future union of one of the carrier descendants with another carrier of the same mutation could produce a child with a disease. Having access to the DNA data of any additional closely-related family members, living or dead, could significantly increase the chances of identifying the DNA mutations causing the condition. Thus, one’s DNA data might assist in the medical management of family members, perhaps even several generations down the line.

For this reason, Merogenomics recommends that each client considers who should have access to their DNA data after their death or in the event that they lose their own capacity to make decisions, and then proceed to codify such information in appropriate legal documents such as wills. Each family should aim to maintain the privacy and ownership of all of the genetic information of its members, past and present.

 

Additional Products

  • genome sequencing
  • genomic counseling
  • digital biobank storage

 

Related Information

Types of Genome Sequencing Procedures

DNA Tests for Health Risks

Cancer DNA Tests

Prenatal DNA Tests

Undiagnosed Diseases DNA Tests

Genomic Education


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