Consultation with a health care provider is not a prerequisite, however, it is highly recommended if the results of genomic sequencing will be used to obtain specific health related information.
A prospective client should first become familiar with the content of the Merogenomics Inc. website to learn about the genomic sequencing procedure and its purpose, and to gain genetics background. Merogenomics Inc. staff are available to provide information that cannot be obtained at the website. The client will choose one of four related procedures and additional supporting products. Genetic counseling should be seriously considered prior to undergoing a genome sequencing procedure.
The client can purchase the whole genome sequencing procedure of choice after signing a website-based Informed Consent and a User Agreement. Relevant personal information and client payment information will be obtained.
In the first step a voluntary website-based psychological health assessment questionnaire is filled out. The questionnaire is used to assess the potential psychological risks that the client might experience if serious health hazard is determined by the sequencing. The client has the option to decide against obtaining such sequencing results or against the sequencing procedure entirely if the results of the questionnaire show that such a finding could harm the mental state of the client.
In the second step a DNA Swab Kit is sent to the client to obtain a saliva sample which will be used for DNA isolation and sequencing. If the genome sequencing procedure is requested by a healthcare provider on behalf of the client, a blood sample collection kit will be provided. For prenatal genome sequencing, a sample of the mother’s blood is necessary as it contains DNA of both mother and child. The blood sample must be drawn and sealed in a sterile container by appropriately trained health care personnel.
The third step is DNA analysis of the obtained specimen. The DNA analysis comprises known and validated health risks and this information is delivered to the client along with the determined DNA sequence. Report information will be organized from most scientifically validated to least validated. Only information regarded to have sufficient scientific validation can be considered “clinically actionable". Access to genetic counselors can be requested to aid the client in data interpretation. Any “clinically actionable” information can be delivered to the healthcare provider of choice.
The client has an option of storing their genome sequence at a secure and private digital repository with an additional option for future genome reanalysis.
Follow-up psychological health assessment is administered three months after genomic sequencing to measure possible client anxiety. Such information can help us to gauge the risks of use of this technology and can suggest ways to modify information delivery for population benefit.
Each prospective client will have an opportunity to have an in-person interview via Skype with Merogenomics Inc. representative Dr. Mikolaj Raszek free of charge for a duration of 30 minutes to answer questions regarding the genome sequencing procedure. This should not be viewed as a genomic counseling session. Once the agreement with Merogenomics Inc. is signed by the client, an additional 30 minute in-person interview will be scheduled to confirm that the client is familiar with the genome sequencing procedure protocols, to confirm the identity of the client (and that of the subject if the subject is different from the client), to confirm the accuracy of collected data, and to provide an opportunity for the client to ask questions.
Payment for services offered by Merogenomics Inc. must be processed by fund transfer to the Merogenomics Inc. bank account.
Additional Participants Consideration
As part of the signed agreement form, the client is asked to provide the following information:
- Identical (monozygotic) twin consent obligation
Identical twins share the same DNA sequence, therefore, information obtained by genome sequencing reveals private information of more than one individual. If the subject has a living sibling who is an identical (monozygotic) twin, then the consent of the twin is required for the genome sequencing procedure.
- Optional next of kin recipient consideration
Details regarding a next of kin recipient of the genome sequencing results can be provided by the client in case the client is unavailable to receive the results or in the event of client death. The chosen next of kin recipient must be aware of the genome sequencing procedure undertaken by the subject and must be aware that the results of the test could implicate the health of related individuals; therefore, the next of kin recipient is required to sign a consent form.
Safety Assessment Questionnaires
The client is asked to complete two online assessments, one prior to the genome sequencing procedure and one after the Analysis Report has been received by the client. Direct-to-consumer whole genome sequencing is relatively new and the potential psychological and social risks of participation are not fully known. Consequently, Merogenomics Inc. offers a Safety Assessment Questionnaire prior to whole genome sequencing, described below in section 1), an assessment of psychological risk factors to measure the potential impact of the genome sequencing results on the well-being of the client. A second Safety Assessment Questionnaire, described below in section 2), is applied after the genomic sequencing is complete and the Analysis Report has been received by the client. It is anticipated that this questionnaire will identify unforeseen consequences of the procedure.
1) Questionnaire prior to whole genome sequencing procedure
This part of the assessment can identify high-risk individuals who might not handle negative information—for example, the revelation of an untreatable condition—with equanimity. The questions give the client an opportunity to evaluate his or her temperament and encourage the client to build an appropriate support network. This part of the Safety Assessment Questionnaire allows clients to choose data analysis preferences and helps them to decide whether they should take the genome sequencing procedure.
2) Questionnaire post whole genome sequencing procedure
To uncover longer-term consequences of the genome sequencing procedure, this questionnaire is filled out by the client three months after delivery of the Analysis Report. This part of the assessment can help determine steps that might avoid negative impacts on future clients.
Together, the assessment questionnaires inform the larger context of the genome sequencing impact on the population. The Safety Assessment Questionnaires are not mandatory. The client can forgo the questionnaires upon signing an agreement that he or she understands the risks associated with not taking the assessment, and bears full responsibility for such a decision (part of the original agreement). The Safety Assessment Questionnaire will be provided via the Merogenomics Inc. website. The identity of the respondents to the Safety Assessment Questionnaires is confidential. Answers to the questions are used to assess whether the client is at risk for emotional distress. As the questionnaire is website-based, and without supervision of a qualified psychologist, it is used only as an additional tool to determine whether there is a safety concern, and to mitigate potential adverse reactions. Collected data may be used to alter the type of services offered by Merogenomics Inc., to influence company policies, or to modify the consent form or user agreement for the purpose of risk management. Information gathered from the Safety Assessment Questionnaires may also be used to identify growing trends in the genome sequencing industry for public education.
Genome sequencing can be performed on a sample of blood or saliva, the sole exception being prenatal whole genome sequencing which requires a blood sample. A blood sample is preferable to a saliva sample as blood furnishes higher quality data. Although a saliva sample is a simpler option, saliva is susceptible to bacterial contamination, which can impact the accuracy of the genome sequence. For blood sample collection, kits need to be provided in a clinical setting via a doctor's order.
Blood sample collection
If blood is to be collected at medical center, approximately 5 ml of blood will be drawn by venesection by a trained medical professional, and sent to the sequencing facility. If a portion of the blood sample is not used in the procedure, it will be frozen and saved at the biorepository of the sequencing facility to act as a back-up for further genome sequence data generation in case the primary procedure fails. Once whole genome sequence data is successfully generated, remaining blood sample will be permanently destroyed within two weeks (14 days).
Saliva sample collection
For the majority of genome sequencing procedures, a saliva sample is sufficient to obtain the required DNA (although a blood sample is preferred). A sample vial, a sterile swab, instructions for use, and an identification code for the subject of the genome sequencing will be sent to the client. The swab is used to collect a saliva sample from inside the subject’s mouth, and will be sent to a third party in an envelope provided. A small portion of the saliva sample will be frozen and saved at the biorepository of the sequencing facility to act as a back-up for further genome sequence data generation in case the primary procedure fails. Once whole genome sequence data is successfully generated, remaining saliva sample will be permanently destroyed within two weeks (14 days).
Cancer biopsy sample collection
Protocols and collection kits for cancer biopsy samples can vary among service providers. Paraffin embedded cancer samples are the most common, but alternatives will be suggested if they are deemed beneficial to the quality of the genome sequencing outcome.
Cancer biopsy samples are usually stored at the pathology laboratory that harvest the sample from a patient. The treating physician or oncologist can arrange for the pathology laboratory to deliver the sample to the genome sequencing facility, provided that sufficient quality and quantity standards are met. Otherwise a new biopsy sample may be required for the genome sequencing procedure.
Genome Sequence Generation and Interpretation
DNA isolation, DNA sequencing, and the interpretation of a subject’s genomic DNA are performed by third parties partnered with Merogenomics Inc. These firms have set technical competency standards and demonstrated procedural analytical validity, and collaborate with leading academic and industry research institutions.
The procedure of whole genome sequencing commences with DNA isolation from the sample collected from the subject. The isolated DNA is broken up into millions of small fragments. Each fragment is joined to a specific tag and placed in a flow cell in a sequencing machine. The flow cell is populated with tags that are complementary to the tags on the DNA fragments, allowing DNA fragments to attach to the flow cell. Each individual DNA fragment is then multiplied (for enhanced signal measurement) into a population of identical pieces of DNA. Each DNA fragment is sequenced by providing one of four different possible DNA nucleotides that make up DNA, a single nucleotide at a time. Each nucleotide is attached to a specific fluorescent molecule to identify its presence on the DNA fragment being sequenced. All of the millions of small fragments are sequenced simultaneously. The decoded fragments are then pieced together into a whole genome sequence with a computer program and delivered to the client.
The higher the number of independent times a particular nucleotide base is read, the higher the accuracy that it was measured (also termed “called”) correctly at that location. This is also referred to as “read depth” or “coverage depth.” A certain minimum coverage depth is required as the acceptable threshold to be confident that the nucleotide base was called correctly.
Decision to Publish DNA Sequence Data
It is possible that the DNA data analysis will uncover novel information of value to the medical community. The client can decide whether to release the critical DNA sequence data to the public or keep it private. If the client elects to publish the DNA sequence data, the DNA sequence data plus any personal trait data that might be critical for interpretation of the DNA data will become available on a public website and database. The privacy of the client will continue to be protected. Information garnered from sequenced genomes allows scientists to ever more accurately interpret future human genomes. Merogenomics Inc. can aid the client in the data publication process.
Merogenomics Inc. recommends that a client seek the opinion of a licensed healthcare practitioner and/or a genetic counselor before deciding whether to publish data derived from the subject's genome sequence, and that only partial and relevant genome information is made available to the public in order to protect the identity of the client.
Data published to a public website or database will no longer be confidential. Depending on the scope of the published information, it is possible that a third party may discover the identity of the client. Generally, such identification could occur only by comparing published data with another source of data, for example, a biological sample obtained from the same individual. Therefore, Merogenomics Inc. recommends that genome sequence information be kept private unless a genuine public benefit (such as a variant that can be correlated to a specific diagnosis) can be identified.
The choice to publically disclose the DNA sequence data and other information associated with it, will result in its delivery to an openly available scientific website and database, and therefore make it accessible to third parties. Reproduction, analysis, or even modification of such information could then occur without consent from either the client or Merogenomics Inc. Therefore, Merogenomics Inc. recommends that when choosing to publicly disclose a subject’s genomic information for social benefits or any other reason, only information essential to the objective be released to protect anonymity.
Public disclosure of genetic and/or trait data associated with a subject’s personal identity could result in employment, insurance, or financial discrimination, and could negatively impact social interactions, including those between family members. Such disclosure could expose the subject and his or her family to media attention.
Public disclosure of a subject’s entire genome, even without access to personal identity, could result in genetic identity theft. Genetic identity theft could lead to:
1) Real or fictional claims to family relation status from other individuals
2) Impediments to employment status, insurability, education, health access, or financial services
3) The planting of synthetic DNA at a crime scene
4) The revelation of genetic information that was not desired to be known
The clients also needs to consider such potential implications in case the subject’s genomic or personal information is maliciously stolen during the whole genome sequencing procedure.
The risk (and its severity) of public disclosure (or theft) of the entire genome sequence data (or partial genome information in association with personal identity) cannot be predicted. Merogenomics Inc. encourages the client to discuss with his or her immediate family members the potential hazards of disclosure or theft and the fact that not all hazards can be anticipated.
Storing DNA a Genome Sequence in a Digital Repository
The client can choose to deposit the subject’s genome sequence in a digital repository for safekeeping and for future reanalysis as new scientific data emerges. Long term multigenerational family genomic information can extend medical value to future generations. For a yearly renewal fee, a third party can provide DNA digital cloud storage with data encryption and password access.
Reanalysis of DNA Sequence Data
Genome sequence reanalysis based on new scientific data and techniques can be performed every 6 months or every 12 months (as preferred by the client) after the original Analysis Report is issued. A cost will apply for each updated Analysis Report.
Merogenomics Inc. will take all reasonable efforts to protect the privacy of the information and samples provided by the client and the confidentiality of the data generated. All data and information will be encrypted, password protected, and stored in a cloud. All tissue samples will be stored in a safe biorepository until they can be safely discarded. Merogenomics Inc. will not distribute private and sensitive information to third parties without the agreement of the client.
Merogenomics Inc. cannot absolutely guarantee the confidentiality of client information and genome sequencing and analysis data in the event of unintended data breaches such as hacking or other unforeseen events. To minimize the chance of private information being accessed by undesired third parties, all protected data will be erased within two weeks (14 days) of delivery to the client. Client contact information can be kept for future reference in the Merogenomics Inc. database with the agreement of the client.
A statistical database containing all the information accumulated by Merogenomics Inc., including genomic data statistics, will be maintained for informative and developmental purposes. Such information will be without reference to and cannot be utilized to identify any individual. Examples of the type of information included in the database are: the number of pathogenic variants identified among clientele, the average age of clientele, frequency of male vs. female purchases. Collected data from many persons might be published or used for teaching purposes for the propagation of scientific knowledge without revealing any information that could lead to individual identification. Data from a single individual will be published only with approval from that person, and in a way in which the published information cannot lead to an identification of the individual involved.