Informed Consent Form
1. Purpose of the corporation
Merogenomics Inc. is an independent, privately owned company whose purpose is to help individuals obtain access to their genome sequence and its potential interpretation for their private use (hereafter also referred to as the “Client”). This is achieved by providing access to third party service providers that can deliver such services at the highest level of quality.
Through the collection of available data, Merogenomics Inc. aims to:
1) Educate the general public regarding the potential benefits, risks, and uncertainties posed by the use of genomic technologies;
2) Investigate potential commercial developments associated with genomic technologies;
3) Expand the knowledge base of genomic information linked to human traits.
Genomic information generated from sequencing and data analysis is for private (Client) use, will be kept confidential until delivered to the Client, and will not be divulged to any public body, database, or institution unless the disclosure is requested by the Client. Third party access to a Client's genome will be solely for the purpose of data generation and/or analysis.
Once generated data are delivered to the Client, it will be completely removed from all databases within two weeks (14 days) by all parties involved in the procedure, unless otherwise indicated. The Client’s genomic information will be released to additional third parties after an agreement is signed by the Client and:
1) A licensed healthcare practitioner is authorized by the Client to use the information for the Client’s benefit;
2) The Client’s genome will be stored in the digital repository for private future access;
3) Scientifically relevant information derived from the Client’s genomic sequencing and/or subsequent treatment is submitted for publication.
2. Purpose of the Consent Form
This informed consent form (hereafter referred to as the “Consent Form”) describes eligibility requirements, a description of the genome sequencing procedure, and potential risks and benefits to the Client associated with whole genome sequencing. Whole genome sequencing is the detection of the nature and precise order of nucleotides in the genome, or the entire DNA content in an individual. By deciphering the genome sequence, one can learn how individual DNA sequence varies from the sequence commonly found in the population, and how such variation in the DNA sequence relates to function of person’s biological processes, including predicted outcomes on health and physical characteristics.
By entering into the Terms of Agreement with Merogenomics Inc., Client agrees that he or she understands the concepts described herein and the additional supporting material available at Merogenomics Inc. website, and based on information provided by Merogenomics Inc., the Client desires to have his or her genome or the genome of a dependent sequenced and analyzed for personal use. The Client also agrees that such information does not constitute a medical assessment and is not meant to replace a medical assessment by a healthcare professional.
3. Limitation of the Consent Form
The Consent Form cannot provide full disclosure of all of the conditions tested by the whole genome sequencing procedure due to the quantity of possible variants discovered and possible conditions analyzed. This is further underscored by the dynamic nature of genomic sciences, where new information is continuously being added. The possibility exist that novel information of important medical value to the Client will be discovered that is currently not included in the scientific databases information.
4. Procedure to obtain genome sequencing
Merogenomics Inc. will collect the Personal Information necessary to process the transaction. Health Information (if applicable, depending on the type of analysis required, or on a voluntary basis) will be collected and the results of two questionnaires to measure potential psychological risk factors of genome sequencing impact will be documented (hereafter referred to as the “Safety Assessment Questionnaires”). Appropriate collaborating third parties will collect tissue samples in the form of either saliva or blood (depending on the type of analysis required) from the individual who will undergo the genome sequencing procedure (hereafter referred to as the “Subject”) and will generate the appropriate data from the collected tissue samples.
The Client will receive research data (via a secure web portal) in the form of a whole genome DNA sequence and a data interpretation report based on his or her individual genome sequence (hereafter referred to as the “Analysis Report”). The information the Client receives by agreeing to participate in the procedure, including DNA sequence data and the Analysis Report interpreting the DNA sequence data, is not meant to be interpreted as medical advice or a diagnosis but only as auxiliary information for the Client’s educational use. Data and information received from Merogenomics Inc. or third parties are not intended to replace professional medical advice, diagnosis, or treatment. Information or data received from Merogenomics Inc. or third parties should be analyzed and confirmed by a licensed healthcare professional before being used for a medical purpose.
Participants can withdraw at any time with a full refund minus the Merogenomics Inc. processing fees and the cost of the procedure component already undertaken, if any. Steps to obtain a whole genome sequence and its interpretation are described in more detail in sections 4.2.—4.6.
4.2. Genome sequencing procedure considerations
4.2.1. Mandatory information filing
In order to participate in a genome sequencing procedure, the Client will be required to certain sensitive information necessary. In a secure web portal, the Client will submit his or her name, contact information, and payment information. Additional Personal Information and/or Health Information will be voluntary unless it is required by the procedure chosen by the Client (see section 18.104.22.168.). The Client will be required to read and sign agreement forms, including the Terms of Agreement and additional forms required by the third parties involved in the genome sequencing and its analysis. Once the Client is familiarized with the concepts of the genome sequencing procedure, he or she will be asked to choose genome analysis preferences (see below in 4.2.6.).
The Consent Form includes Client agreement to the following points:
1) The information provided is accurate, and corresponds to an individual whose genome will be sequenced;
2) The tissue sample and the information that have been provided belong to the person for which the genome sequencing will be performed;
3) The individual (Subject) whose genome will be sequenced does not have an identical twin (the existence of an identical twin requires that the twin agree that his or her sibling will undergo genome sequencing and that the twin signs a Consent Form for such procedure).
4.2.2. Communication with family members
Family members of the Subject whose genome will be sequenced do not need to sign the Terms of Agreement. The sole exception to this is the existence of an identical twin of the Subject (see section 4.2.3.(A)). However, information received from Merogenomics Inc. or third parties (including DNA sequence data and the Analysis Report that interprets the DNA sequence data) could have important consequences to the Subject’s blood-related family members. Therefore, Merogenomics Inc. encourages the Client to discuss the decision to sequence a genome with family members who have a close genetic relationship with the Subject (parents, siblings, offspring) as they will be the most impacted by the information provided. Merogenomics Inc. also recommends that Clients consider preprocedure counseling to prepare for potential psychological familial implications as a result of undergoing the genome sequencing procedure. Finally, Merogenomics Inc. suggests that the Client review topics on family communication of genetic information at the Merogenomics Inc. website and elsewhere. We believe that these considerations should not be left till the results of a genome sequencing procedure are received.
4.2.3. Additional recipients considerations
(A) 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.
The Client can request a genome sequence procedure for an individual other the Client only if the Client is a legal custodian of such an individual, and such individual is a legal dependent of the Client. In such circumstance, the legal dependent is the Subject of the procedure while the Client is responsible for the commercial transaction and receipt of data resulting from the genome sequence procedure.
Merogenomics Inc. can offer services to an individual under the age of 18 only with the authorization of a guardian adult (parent or legal custodian), and only by direct request and on behalf of a guardian adult who acts as the Client of Merogenomics Inc.
Merogenomics Inc. will immediately terminate services to minors who are discovered to represent themselves as 18 years of age or older, or Clients who represent themselves as legal custodians of individuals who are not their dependants.
(C) Next of kin recipient
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 the Terms of Agreement, less the obligation to pay for the services if the Client’s account is current with Merogenomics Inc.
(D) Healthcare provider
The genome sequencing procedures that are offered to private consumers by Merogenomics Inc. can also be requested by a healthcare provider on behalf of a patient. In such instance, Merogenomics Inc. recommends that blood sample be drawn at a medical clinic, rather than using a saliva sample.
No Client medical records are needed to initiate a genome sequencing order for a Client by a healthcare provider. A third party service provider can send a sample collection kit to the ordering physician or to the preferred laboratory to obtain the Subject’s blood, saliva, or a cancer biopsy sample. The Analysis Report based on the genome sequencing tests will be delivered to the Client and to the ordering physician. The Client will receive a digital copy of the genome sequence.
4.2.4. Choice of genome sequence procedure type
The Client will determine what type of genome sequencing he or she desires, depending if it is for asymptomatic individuals (people expected to be healthy), or persons with disease symptoms. The options selected can impact both the genome sequencing procedure and the data analysis. The following options are provided:
22.214.171.124. Genome sequencing procedures for individuals with symptoms
(A) Genome sequencing for cancer profiling
Individuals diagnosed with cancer can undergo genome sequencing of the cancer specimen to obtain molecular understanding of affected biological pathways and possible target treatment options.
Cancer sample can be analyzed on its own but for enhanced results, cancer and normal tissue should be sequenced. Such normal/tumor pairing allows for more accurate determination of mutations that arose in the cancer sample only. For normal tissue sequencing, a blood sample will be required.
Additional diagnostic tools, such as RNA transcriptomics (measures expression of the genome in cancer cells) and proteomics (measures production of proteins as a result of genome expression), can be employed in helping understand the molecular nature of the cancer that could indicate FDA-approved or developmental treatment options, or therapies to which the cancer may be resistant.
If treatment course is discovered that includes experimental medication, the Client and his or her oncologist will be informed of relevant clinical trials. Tests are not a guarantee of successful outcome.
The whole genome sequence will be analyzed for additional informative DNA variations unrelated to cancer and provided in a customizable Analysis Report along with a digital copy of the entire genome DNA sequence.
(B) Genome sequencing for disease diagnosis
If an individual suffers from a rare disease that has not been successfully diagnosed, he or she can attempt to seek the genomic cause(s) of the condition. When a diagnosis is the purpose of the genome sequencing, personal Health Information additional to what is indicated for a simple analysis, described in section 126.96.36.199.(D), is required and certain family members must have their genomes sequenced for comparison. The supervision of a clinical geneticist is required, and can be arranged by the Client or by Merogenomics Inc. Individuals are encouraged to consider the potential impact of not obtaining any meaningful information, or discovering a disease for which there is no current treatment. As such a procedure will require additional resources to have information of interest validated, the financial aspect can be considerable.
188.8.131.52. Genome sequencing procedures for asymptomatic individuals
(C) Prenatal fetus/mother genome sequencing
A pregnant mother who desires to sequence the genome of her fetus using a noninvasive procedure must supply a blood sample. The blood can be drawn by a trained healthcare professional and delivered in appropriate fashion by the healthcare institution where the blood sample was taken to the genome sequencing facility. The genomes of the mother and the fetus will be sequenced from the same blood sample in order to deliver the genome sequence of the fetus. No consent from an individual other than the mother of the fetus is required. However, as the information generated could have important health implications for the father of the fetus (the fetus might have inherited a variant of important health consequence from the father), Merogenomics Inc. encourages the mother to discuss the genome sequencing plan with the father of the fetus prior to the procedure. The Client is encouraged to consider potential psychological consequences of the genome sequencing of the fetus, including discovery of undesired health information about the father, or even that the biological father is different than expected.
(D) Individual genome sequence procedure
When the genome of an individual Subject is sequenced, only the Client who instigates the procedure will obtain the genome sequencing data. This procedure requires a saliva or blood sample from the Subject, depending on the Client’s preference.
4.2.5. Choosing genome analysis preferences
The Client can receive the genome DNA sequence data alone, or the genome sequence data plus the Analysis Report. If the Analysis Report is requested, the Client can choose the kind of information included in the report, as some information could be disruptive to the emotional well-being of the Client or the Client’s family. The types of information that the Client can choose for delivery include:
(A) Pathogenic but nonactionable (untreatable) [e.g., Huntington disease, spinal muscular atrophy]
A pathogenic variant is a mutation with direct consequences to human health. A pathogenic variant is considered “nonactionable” if the condition resulting from the pathogenic mutation is untreatable. Knowledge of nonactionable pathogenic variants can prepare the Subject of genome sequencing for a possible condition, but such foreknowledge can involve significant psychological and social challenges. Therefore, a Client must carefully consider whether the receipt of nonactionable pathological information is warranted. To help with decision making, Merogenomics Inc. offers a complementary Safety Assessment Questionnaire prior to the whole genome sequencing procedure to help assess Client’s potential psychological risk factors. The likelihood of such incidental finding (~1-5% for all pathogenic variants) also needs to be considered, and that the discovery of pathogenic variant does not guarantee a disease development.
(B) Pathogenic and actionable (treatable) [e.g., cystic fibrosis, phenylketonuria]
“Actionable” incidental findings are mutations that are either pathogenic or likely to be pathogenic where intervention can be undertaken. This includes the 56 genes published by the American College of Medical Genetics and Genomics as the minimum standard for patient notification. However, Merogenomics Inc.’s recommendations will depend on the most up to date information presented in available public databases.
(C) Pharmacogenetic information [e.g., warfarin dosing]
Pharmacogenomics is a study of the correlation between the variations observed in the DNA sequence of an individual and the reaction of that individual to treatment with a drug; that is, whether the effect of the drug is adverse or efficacious. The pharmacogenomics science attempts to tailor a drug to fit an individual patient based on the patient’s genome information. Furthermore, the optimal drug dose can be chosen to match the individual metabolism phenotype, while avoiding adverse effects associated with toxicity or lack of efficacy. Therefore genetic differences known to affect response to medications can be used to predict drug effectiveness for a specific individual.
(D) Carrier status for recessive conditions [e.g., thalassemia]
Variants that we inherit from our parents can be either homozygous (meaning identical variant copy was inherited from both mother and father) or heterozygous (meaning the DNA inherited from one parent in that location is different from the one inherited from the second parent). For many of inherited disease to be exhibited, they need to be inherited in a homozygous state, where deleterious variant was obtained from each parent. This means that heterozygous combination of variants might have no obvious clinical manifestation whereas a homozygous state could lead to disease. Therefore an otherwise healthy individual can be a heterozygous carrier of variants that can lead to disease in future generations. Current estimates suggest that 0.5–1% of the random couples will be carriers of same disease variants. Such couples are at 25% risk of having an affected offspring (one in four chance because each parent also is a carrier of a non-deleterious variant). Foreknowledge of carrier status can impact reproduction decisions.
(E) Adult onset conditions [e.g., breast cancer]
There is a considerable ethical debate in the scientific community about the need to and right to inform minors of genetic indications that could impact their future health (i.e., conditions that are adult onset) as obtained from genomic sequencing. The stance taken by the American College of Medical Genetics and Genomics is that no age limitation should be set on the return of incidental findings that suggest a future health risk, as such results are likely to have important implications for other family members. The Canadian College of Medical Geneticists’ guidelines state that adult-onset genetic conditions should not be communicated unless disclosure could prevent serious harm to the health of other family members, and unless such disclosure is desired by the parents. The Client is encouraged to consider potential psychological consequences of disclosure of such information to the Subject and other family members.
(F) Risk for multifactorial common diseases conditions [e.g., diabetes]
Common diseases such as heart disease and diabetes are polygenic in nature; that is, they comprise hundreds and even thousands of DNA variants whose interplay toward disease development is unclear.
Such variants can explain about 10% of the genetic component of the disease at best, even if the impact of all associated variants is combined, and therefore they have low predictive value. As these variants currently have either no clinical validity or unclear validity, testing for them is not typically offered in a clinical setting.
This information can be presented to the Client for future reference while recognizing the limitations of such information.
(G) Nonmedically related traits and information [e.g., ancestry, hair loss]
Nonmedical information can also be obtained, such as heritage background, nonhealth related trait information, or information with indirect medical impact, such as a predisposition to obesity.
By mapping the pattern of inheritance among different groups of people around the world, ancestry relationships can be established. When a person has his or her genome sequenced, the pattern of shared DNA can point to the person’s ancestral origin. Such insights could have health-related implications however, as different ethnic groups are carriers of different health impacting variants.
The Client’s decision to omit specific types of information in the Analysis Report is subject to change if such decision takes place prior to data being destroyed. The Client has the option of having the genome in question reanalyzed at a future date (described in section 4.2.10.).
4.2.6. Special considerations for an Analysis Report based on cancer sample
The cancer sample analysis is presented in a format distinctive from that of saliva and blood samples. It might include information from the normal tissue to demonstrate data analysis outcomes that are unique to the cancer sample. The following information can be expected in an Analysis Report based on a cancer tissue sample.
(A) Somatic mutations
Somatic variants are variants that have not been inherited and are produced after conception. Such mutations can appear in the genome of any cell in the body at any time during a person’s lifespan. Some mutations can affect cell cycle regulation leading to a cancerous phenotype.
Many somatic mutations can be expected in a cancer sample. These can be grouped into five categories:
1) Variants involved only in the Subject’s cancer sample;
2) Variants affected in many cancers;
3) Variants involved in specific cancer types;
4) Variants listed in cancer related databases but not associated with cancer;
5) Other somatic mutations.
(B) Prediction of drug response
Variants are listed that are associated with cancer sensitivity to or resistance to FDA-approved or investigational therapeutics. The information provided in the Analysis Report does not recommend any specific treatment, but can suggest personalized treatment options that might be undertaken with medical oversight. Clinical trial information for experimental drugs in development is provided with relevant contact information.
(C) Prediction of toxicity
Variants that have been associated with drug toxicity according to FDA labeling are listed. This information can be used to select optimal medication, dosing amount, and treatment duration. This information can be combined with the Subject’s normal tissue variants (germline variants meaning variants that have been inherited) to obtain a more detailed background.
Variants are listed that have been previously associated with clinical outcomes; for example, overall survival or recurrence-free survival. Information with positive or negative prognostic implications is included.
4.2.7. Choosing a validation option for pathogenic variants
In the unlikely event that the Subject’s genome sequence analysis reveals any pathogenic variants (actionable or not), the Client has an option of having the genetic information verified with additional technologies to ascertain that it is accurate. Validation makes the genome sequence clinically valid and therefore available for medical interpretation toward potential treatment (if the discovered pathogen is actionable). Choice of the validation option will generate an additional Analysis Report specifically tailored for healthcare professionals, which includes a statement describing the information that was discovered, how the information was obtained, proof of the validated sequence, and the identity of the institution responsible for the information generated.
The information that a verified pathogenic variant was located in the genome sequence can be shared with a medical doctor who will integrate this information with the Subject’s personal and family medical history and suggest appropriate surveillance or treatment. Confirmation with secondary technology is necessary prior to consultation with a medical professional to rule out a potential technical anomaly.
4.2.8. Storing 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.
4.2.9. 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.
4.2.10. Payment obligation and withdrawal conditions
Signing an agreement with Merogenomics Inc. will result in payment processing for the services rendered by Merogenomics Inc. The payment to Merogenomics Inc. is independent of and in addition to the fees collected by third parties who prepared the tissue samples for genome sequencing, performed the whole genome sequencing or generated genome data analysis.
The Client is free to withdraw from the procedure at any time. Withdrawal from the procedure prior to involvement of any third parties will be subject to a full refund minus the portion of the fee payment that applies to services rendered by Merogenomics Inc. Payment to Merogenomics Inc. is permanent and nonrefundable.
Therefore, withdrawal from the procedure prior to genome sequencing being commenced will be subject to a full refund of payment portion to the third parties. Once the genome sequencing is commenced by third parties, no refund for that procedure can be delivered. However, if genome data analysis was chosen and paid for by the Client, withdrawal from the procedure prior to data analysis is subject to a refund for the data analysis service. If the Client has chosen to deposit the Subject’s genome DNA sequence in a digital repository, and withdraws prior to this event, a refund for this service will be applicable if the DNA sequence has not yet been delivered to the genome digital repository. Finally, if the Client has paid for future genome data reanalysis, a refund can be obtained prior to the reanalysis procedure.
Upon the Client’s withdrawal from the procedure, all of the data associated with the Client will be deleted within two weeks (14 days) of the notice of withdrawal, unless otherwise indicated.
4.3. Collection of Health Information
When registering for the genome sequencing procedure, the Client is asked to provide additional information about the Subject of the genome sequencing via secure website portal, and which may include Health Information.
The type of Health Information submitted is voluntary unless it is required for the genome sequencing procedure chosen by the Client (genome sequencing for diagnosis, see section 184.108.40.206.). Typical Health Information include date of birth (month and year), prescribed medications, personal and family medical history, family pedigree, race/ethnicity/ancestry, vital signs (height, weight, blood pressure), and lifestyle traits (e.g., nutritional patterns, exercise habits, smoking), but can vary depending on the third party providing the genome sequencing service.
Information submitted by the Client, except information that could identify an individual, will be used by Merogenomics Inc. to promote understanding of genomic sciences. Merogenomics Inc. retains the right to publish collective summaries of such information (including frequencies of identified variants in the analyzed population that could be associated with specific trait information). All such voluntary information can help us to understand genome function, and might contribute to future data analyses. Unless agreed upon by the Client, information that is required for the procedure will remain private and will not be divulged to a public or private third party except one involved in data generation.
4.4. In-person interview
Each prospective Client will have an opportunity to have an in-person interview via Skype, or phone, 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 genetic counseling session. Prospective Merogenomics Inc. Clients are encouraged to undergo a preprocedure counseling session to gain insight into the potential benefits and limitations of the genome sequencing procedure. 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 the Health Information (if applicable), and to provide an opportunity for the Client to ask questions.
4.5. Tissue collection
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. For genome sequencing for cancer profiling, tumor biopsy sample will be required via a doctor's order.
(A) 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).
(B) 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).
(C) 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.
Once whole genome sequence data is successfully generated, remaining tumor sample will be permanently destroyed within two weeks (14 days), or returned to pathology laboratory for continued storage, as requested by the Client or the Client’s treating physician.
4.6. DNA sequence data generation and interpretation
Merogenomics Inc. does not guarantee the accuracy or completeness of procedures performed by third parties associated with genome sequence data generation or interpretation. The partners involved are of the standard sought by academic and industry research institutions, and the same quality of performance is expected to be realised by a private Client.
4.6.2. Signing third parties’ Consent Forms
Consent Forms from third parties involved in the genome sequencing procedure will need to be signed by the Client and their content will depend on the services requested. Merogenomics Inc. was not involved in the generation of these forms, and takes no responsibility for the accuracy and thoroughness of the information presented. Merogenomics Inc. representatives are ready to discuss questions the Client might have regarding third party consent forms.
4.6.3. How DNA sequence data are generated
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 typical 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.
4.6.4. Receipt of Client DNA sequence data
When the genome DNA analysis is complete, the Subject’s genome DNA sequence and the Analysis Report based on it (see section 4.2.6.—4.2.7.) will be available via a password protected website. The DNA sequence and the analysis data will remain private and confidential unless the Client consents to its publication (discussed further below in section 4.6.7.).
Merogenomics Inc. cannot guarantee that the genome DNA sequence is accurate or complete. Technological limitations exist that preclude a guarantee that every single base in the human genome will be identified correctly, and that all segments of the genome will be sequenced to completion. However, the standard sought is greater than 95% of the genome being sequenced with 95% or greater accuracy. This level of identification and analysis provides a reliable basis for useful interpretation.
Once it is confirmed that the Subject's genome sequence and the Analysis Report based on it has been downloaded by the Client, these data will be deleted within two weeks (14 days) by Merogenomics Inc. and by associated third parties involved in the data generation. Long term storage can be achieved by storage at a secure genome digital repository.
4.6.5. How an Analysis Report is generated
Analysis of the sequencing results in asymptomatic Clients of Merogenomics Inc. is performed outside of a clinical setting and relies on automated bioinformatic methodologies. In a clinical setting, an additional manual oversight of generated data can be expected (software generated data is inspected by medical genetics doctors). When appropriate, Merogenomics Inc. will aid Client access to clinical management, such as in the case of genome sequencing for disease diagnosis, or cancer treatment.
Interpretation of the genome sequence is performed by specialized computer programs that compare the obtained Client DNA sequence with information available in databases that have been built with information published in the scientific literature, or observed in a clinical setting. Such programs also analyze the DNA sequence of variants that might be suspected to be pathogenic in nature based on the predicted damage caused by the mutation relative to the biological importance of the gene or genome location affected. Because this latter form of information is without supporting evidence, it should be considered only as a guide for the assessment of a qualified medical geneticist who could establish correlating evidence.
The results the Client receives have not been interpreted or analyzed by a clinical geneticist, nor are the results confirmed by additional methods. In the absence of a phenotype or family history, the predicted outcomes of observed variants are less clear than they would be if such information were available. For this reason, as recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, higher specificity thresholds are adopted, and more evidence is required to suggest that a variant is pathogenic.
4.6.6. Receipt of an Analysis Report
In addition to the whole genome DNA sequence data, the Client will be provided with an Analysis Report based on the DNA sequence and its association with Health Information that was submitted by the Client. The Analysis Report is intended to help the Client understand the potential interpretation of the Subject’s genome sequence. The Analysis Report will contain a noncomprehensive list of genetic variants (SNPs) discovered in the Subject’s DNA sequence for which a meaningful interpretation of medical interest exists. The number of variants listed can vary between Service Providers, and can include information for up to 2000 genes and genomic locations. The data will incorporate current scientific information, and will be stratified from the most to the least clinically validated.
The genome analysis information that the Client can expect to receive in the Analysis Report can include the following (some of which might be important for interpretation by licensed healthcare professionals):
1) Variant information, including:
(A) Genomic location;
This information identifies the specific chromosomal location where the variant is found.
(B) Variant identification number (dbSNPrs#);
The variant identification number is a variant identification tag that is listed in a public archive of all identified genetic variations collected by the National Center for Biotechnology Information. Variant identification numbers can be obtained at https://www.ncbi.nlm.nih.gov/SNP/.
(C) Risk/protective allele designation;
The risk/protective allele designation provides the scientific background that has been collected on the variant outcomes, including risk of disease development. References to scientific reports will be included.
(D) Allele frequencies within the population;
Allele frequencies within the population denotes an estimated percentage of the population (subcategorized by ethnicity if such information is available) that carry the indicated variant. The more frequent a variant is, the less likely it is to be responsible for a damaging biological effect.
(E) Estimated accuracy and read depth;
The “estimated accuracy” provides the odds that a variant was identified correctly by a sequencing platform. The “read depth” depicts how many independent times a DNA strand containing the indicated variant was sequenced by a sequencing machine (i.e., the coverage). The higher the coverage, the higher the probability that the nucleotides were called correctly in that DNA sequence.
2) Genotype with qualitative interpretation;
Interpretation of the combined effect of inheritance from both parents of the specific genomic location that includes identified variant of interest. A variant outcome can be different depending on what DNA sequence has been inherited from either of the parents.
3) A brief overview of the condition associated with discovered variant(s) and U.S. incidence rates when available.
Summative risks of different SNPs toward a given condition will not be provided due to current lack of definitive evidence on how such SNP associations can be accurately combined to estimate risk (unless scientific evidence to the contrary exists); instead, risks will be listed individually for each SNP.
Additional information can include estimated genomic ancestry and information on nonmedically relevant traits.
The report will also include background information on the data generation procedure, potential technical limitations, and information intended to help the Client make an informed decision about whether to publish information based on the DNA sequence data to a public website and database (described in section 4.6.7.).
The databases, published scientific knowledge, and bioinformatics tools that are used to generate the Analysis Report are not comprehensive, can contain errors, and are subject to change. Therefore, Merogenomics Inc. cannot guarantee that the Analysis Report is accurate or complete. All information will be supplemented with citations of key studies providing current evidence for the disclosed information.
Only one Analysis Report is provided per Client. Merogenomics Inc. will not update or supplement the Analysis Report unless the Client agrees to purchase a new one (described below in section 4.6.8.).
The Analysis Report is not intended to represent or substitute professional medical advice, diagnosis, or treatment. The information presented in the Analysis Report cannot be used for any medical or clinical purpose unless first interpreted and confirmed by a licensed healthcare professional. A Client with a medically informative Analysis Report can book an appointment with a genetic counselor (also available through Merogenomics Inc. at extra cost) to answer health related questions.
The Analysis Report represents only a minor fraction of the entire genome sequence. It is an interpretation of the sequence based on the current state of scientific knowledge, which can be expected to change at a rapid pace. For this reason Merogenomics Inc. recommends storing personal genome DNA sequence data in a digital repository for future reanalysis as new scientific data emerges.
4.6.7. Decision to publish DNA sequence data
It is possible that the DNA data analysis will uncover novel information of value to the medical community. Merogenomics Inc. can request the third party involved in DNA data analysis to inform the Client in such instance and 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 Subject’s DNA sequence data, Merogenomics Inc. or the involved third party will make the DNA sequence data plus any personal trait data that might be critical for interpretation of the DNA data 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. 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.
4.6.8. Updating the analysis of DNA sequence data and obtaining a new Analysis Report
A Client may wish to obtain new Analysis Report for additional cost. To access this service the Client must either:
1) Store the genome DNA sequence in a genome biobank digital repository and choose an option of future reanalysis (there is a cost for storage);
2) Reload the Subject’s genome at a secure website portal for additional analysis.
4.6.9. Nonreceipt of data
The Client has a period of 30 days to accept the return of genome sequencing data and the Analysis Report from the moment of first contact informing the Client that the data are available for upload. If no communication with the Client is achieved, the next of kin will be contacted. If the Client or the next of kin does not accept the test results within 30 days of the first communication, the data might be permanently destroyed without recourse to a refund for performed services, or a daily storage fee might be incurred, as determined by the third party service provider.
Once the whole genome sequence and the Analysis Report are delivered to the Client, the Subject’s data will be removed from all databases, the Client’s private contact information will be deleted, and the contact with Merogenomics Inc. will be severed, unless:
1) The Subject’s genome is deposited in the digital repository for future reanalysis;
2) Merogenomics Inc. is requested to provide information on the latest services available that may include the following:
- Have the genome reanalyzed according to the latest available scientific information;
- Receive promotional offers used towards services offered by Merogenomics Inc.;
- Receive information about novel services available for the benefit of the Client;
- Participate in research studies or scientific undertakings that might be coordinated by Merogenomics Inc.
5. Potential harm
Direct-to-consumer whole genome sequencing is a relatively new technology available to the public; therefore, the scope of potential risk and resulting psychosocial discomfort to the general public has not been fully evaluated. Merogenomics Inc. will update its website with current scientific information about the potential psychosocial risks of the genome sequencing procedure whenever it becomes available.
Prospective genome sequencing Clients can complete a Safety Assessment Questionnaire to identify psychosocial risk factors that could be faced if the procedure uncovers negative information (see section 4.2.4.). The Client should discuss with the immediate family the potential risks, including the possibility that other family members can be affected by the information derived from the Subject’s genome. Merogenomics Inc. can connect the Client with a genetic counselor if desired.
5.1. Potential discomforts prior to the receipt of data
(A) Physical discomfort
There are no known discomforts or side effects associated with providing saliva samples. Collection of the blood sample may result in a small amount of pain, and will require the collection of blood into the sample collection receptacle. Temporary bruising, swelling, and/or infection at the site of puncture could occur.
(B) Time inconvenience
It is estimated that up to 5 hours will be required to read online educational background materials and additional content supplied by Merogenomics Inc., study the genome sequencing Consent Form and agreement terms of involved service providers carefully, and complete the Safety Assessment Questionnaires. The time spent in family discussion of the genome sequencing procedure and its impact will vary with the Client. Inappropriate sample collection by the Client, inability of the provided sample to meet sufficient DNA quality and quantity standards for genome sequencing procedure, or use of a defective kit could add to the time required to submit a sample.
5.2. Risks associated with the receipt of data
5.2.1. Data quality is not guaranteed
Due to limitations of technology and its interpretation, Merogenomics Inc. cannot guarantee that the information presented, including the genome DNA sequence data and the Analysis Report, are accurate and correct. Merogenomics Inc. will provide information regarding the limitations of the procedure, for example, the coverage depth of the sequence, or the level of quality of DNA nucleotide identification.
Potential limitations of genome sequencing technology include the following:
(A) Analytical validity
How accurately and reliably genome sequencing measures genome variants is termed “analytical validity.” Analytic validity depends on how many times a nucleotide base is read by the sequencing platform during the sequencing process. The more times a particular base is read, the higher the accuracy that it was measured, or “called,” correctly at that particular position. The number of times a particular base is called is the “read depth” or “coverage depth.” The coverage depth can be affected by the quantity and quality of DNA available for sequencing, as well as the computational capabilities of the software selected to determine the DNA sequence. A certain minimum coverage depth is required as the acceptable threshold to be confident that the nucleotide base was called correctly.
Because the DNA is not read at uniform coverage across the genome, it is possible that segments of the genome could be read below the minimum coverage depth. If the depth coverage is not sufficient, it is possible that a base will be identified that is not actually present in a person’s genome. For example, if a mutation that leads to a disease is mistaken for a normal gene (a false negative), the person could think they have been successfully tested for a condition and found to be “negative” for it, whereas that might not be the case. Conversely, a gene could be misread as a mutation that is expected to lead to an adverse condition, whereas in reality, the person is not harbouring such a mutation in their genome (a false positive). A small fraction of the genome might not be sequenced if it reads below the minimum coverage depth.
It is therefore important to remember that information obtained from genome sequencing is not to be used for medical interpretation unless it is validated by additional means. It is the first step only in unravelling biological information from personal DNA.
In summary, genome depth coverage varies throughout, and the lower the depth, the lower the probability that base was measured correctly. Conversely, the higher the coverage, the higher the probability of accurate base calling. The current standard expected is a minimum of 95% of the genome being sequenced with 95% or greater accuracy.
(B) Structural variants
While technologies used to sequence DNA are highly accurate at deciphering the sequence, the majority of available technologies have limited scope in being able to determine so called structural variants. These are alterations that affect large segments of DNA at a time, such as duplications, deletions, and inversions. Such structural variants can still have important impact on health, but due to the limited scope in determining such structural genomic rearrangements by current sequencing technologies, such biological events might not be interpretable for the benefit of a Client. Instead, current genome sequencing allows for analysis of potential impact of individual base changes. The American College of Medical Genetics and Genomics guidelines for mandatory returns of incidental findings have also been set up with this limitation in mind, and the guidelines do not advise a search for structural variants in the list of genes they recommend.
Although genome sequencing has the potential to reduce morbidity and mortality by enabling early identification of risk factors for various health conditions, and to aid identification of an appropriate treatment course, it is not an all-encompassing screen for every possible disease. The interpretation of sequencing results is limited by the current state of medical knowledge, and can range from almost certain clinical significance to almost certainly no significance. In some instances the data might even present contradictory evidence. Even if the interpretation of genome sequencing results is straightforward, such information might not lead to a useful ameliorative intervention for a specific condition or disease. However, since the human genome we are born with is static (it does not change unless influenced by environmental factors, for example, in the development of many cancers), it means that obtained sequence can always be reinterpreted in the future as the scientific potential expands.
A related issue is that the amount of data that need to be analyzed and curated prior to a genome sequence being delivered to a Client requires considerable computer and human resources. The bioinformatics capabilities of genome sequence analysis are continuously improving by incorporating new information, and the process is increasingly automated. As the demand for clinical interpretation of the genome increases, so does the demand for appropriate platforms to deliver a higher performance standard. However, without human oversight, there is no guarantee that such automated algorithms will always be accurate, as no database is error-free.
(D) Clinical validity and utility
Another often cited limitation is the lack of clinical validity and utility for systematic mass scale use of genomic sequencing technology for public’s benefit, and is only being currently investigated at clinical research institutions around the world. Currently there is no gold standard against which the performance of population genomic screening can be judged. Whether application of next generation sequencing will reduce mortality and morbidity in the population the way it has been demonstrated in individual studies is yet to be established. Numerous large scale population studies have been undertaken throughout the world to examine this issue. Increasing number of academic medical centers performing genome sequencing for human diagnostics under a Clinical Laboratory Improvement Amendments licence highlights the expanding role of genomics in medical practice. Development of metrics that measure the healthcare outcomes of genomic sequencing to validate the clinical utility of genomic medicine toward effective patient care currently remains a top challenge and a priority.
(E) Test failure
Factors outside the control of the service provider tasked with isolation and sequencing of DNA can negatively influence the quality of the genome sequence and therefore its interpretation. This can include the quality of the DNA sample provided for analysis, such as low quantity, high bacterial contamination, or sample degradation. Such factors can even prevent the procedure from being undertaken. In such a circumstance, the Client might be obliged to deliver a new sample.
(F) Additional limitations of prenatal tests
In postnatal genome sequencing the DNA is isolated from cells present in a saliva or blood sample. In a prenatal genome sequencing test, the sequencing must be performed on DNA fragments that are circulating cell-free in the mother’s blood sample. Accurate determination of the fetal genome depends on the amount of DNA in the mother’s blood sample, and the test can fail if sufficient fetal DNA is not present in the mother’s blood sample. A 2% chance of test failure due to genome quality control failure can be expected (necessitating retest or resampling from the Client), and past studies suggest that only in 0.1% of cases test is not possible due to inability to reach the minimum required quality control standards.
Fetal cell-free DNA is derived from the placenta and therefore might not accurately represent the genomic information of the fetus. Extraembryonic tissue mosaicism, or a vanishing twin/cotwin demise are events that result in a mixture of genomes, which can lead to false results. Maternal chromosome abnormality, or maternal metastatic disease can also complicate interpretation of the genomic data and lead to false results.
The mother’s blood sample can harbor cell-free DNA released from cancerous cells. Such DNA contains identifiable mutant variant signatures. Therefore, women undergoing prenatal testing run a risk of incidental finding of cancer discovery.
Prenatal testing cannot be used to obtain the following information: evaluation of placental dysfunction, preterm delivery risk, fetal growth restriction, preeclampsia, placental abruption, intrauterine fetal demise, and perinatal death.
(G) Additional limitations of cancer sample tests
Cancer biopsy samples are typically a mixture of normal cells and cells at different stages of cancer development. Therefore, variable amounts of cancerous DNA might be available for genome sequencing in a cancer sample, increasing the chance of test failure. Depending on the cancer type and sequencing procedure, > 10% of samples might contain an inadequate mass of DNA to obtain a reliable DNA sequence. Up to 20% of these samples can require either multiple attempts at preparation or sequencing to obtain sufficient depth coverage of DNA. Such difficulties can delay results and increase costs, and in some cases more sample must be provided. The final depth coverage determines the degree to which different genomic alterations can be identified.
The test results can provide no information of value if molecular profiling does not indicate a personalized therapy that can perform beyond standard treatment options.
5.2.2. Psychosocial impact
Genome sequencing can uncover data that have potential negative psychological consequences to the Client and the Client’s family. Some examples of data that fit this description are: the discovery of a pathogenic variant, the receipt of indecisive results with regard to certain health conditions, difficulty assimilating information that contradicts prior beliefs, and the information that the Subject of the genome sequencing is not biologically related to family members as previously believed. Sharing discovered information with other individuals, especially with family members, can be an additional source of distress if all individuals are not adequately prepared.
In rare instances, potentially harmful genetic variants could be discovered in the Client’s DNA sequence. Whether discovery of such information leads or does not lead to actionable treatment, the information is likely to cause anxiety or stress. The severity and duration of the discomfort will vary among individuals. The knowledge that a Subject carries a genomic variant(s) that predisposes him or her to a life-threatening condition can enhance the level of chronic distress, even in asymptomatic individuals.
As a result, the Client should seek genetic counseling with a professional who is best equipped at navigating the psychological and familial impacts of receipt of adverse genetic news, and who can recommend an appropriate course of action. The Client should verify the accuracy of the DNA sequence and its interpretation with a qualified healthcare professional. Merogenomics Inc. can provide access to a genetic counselor (for an additional fee) to answer medical questions the Client might have regarding the Subject’s genome information. Merogenomics Inc. can assist the Client in validating Subject’s identified pathogenic variants with appropriate secondary technology (see section 4.2.8.).
5.2.3. Data use for medical care
The clinical importance of most of the human genome is still unknown. While scientific understanding of the relationship between genes and trait expression is growing rapidly, the clinical utility of much of the developing knowledge remains uncertain in the general population.
For these reasons, Merogenomics Inc. takes no responsibility for a Subject’s medical care or consequences to a Subject’s health status. The information provided by Merogenomics Inc. should be applied to a medical or clinical objective only after an overview and confirmation by a licensed healthcare provider.
5.3. Risks of public disclosure of data
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.
5.4. Client miseducation
Studies indicate that the general public can be misinformed about the clinical utility and the accuracy of disease risk prediction of direct-to-consumer genomic testing. The public over emphasizes the importance of genetics in health and disease, and under emphasizes the significance of environmental and lifestyle factors. The misconception that the genome is the cause of all biological conditions can lend genetic information a higher impact than it deserves in some cases. The Client runs a risk of misunderstanding the meaning of the genome sequence and its interpretation in the Analysis Report. Merogenomics Inc. attempts to allay misconceptions with the educational content provided, and recommends genetic counseling prior and after the genome sequencing procedure.
6. Potential benefits of genome sequencing
6.1. Benefits to the Client
(A) Scientific information with potential medical implications is obtained
The primary purpose of sequencing one’s genome is to obtain information of medical value for future care. Genomic sequencing can provide information on genetic variants that can lead to disease or can increase the risk of disease development, even in asymptomatic people. Thus genomic sequencing has the potential to increase the ability to act preemptively prior to disease development or commence treatment for a disease that has not yet been diagnosed. Another advantage of genome sequencing is that information regarding drug efficacy or adverse effects of drug use can be obtained. The relationship between drugs and the genome is called pharmacogenomics.
Information that can be garnered through genome sequencing can vary between each individual but may include the following:
1) Predisposition to different conditions of medical interest, such as disease development;
2) Carrier status of conditions that might lead to disease development in offspring;
3) Potential pharmacogenomic information;
4) Information related to health, such as predisposition to obesity;
5) Additional trait information;
6) Ancestral information.
The contents of the Analysis Report are based on current scientific information, with clear distinctions made between information that has been clinically validated and information that has potential interest only due to a paucity of supporting evidence. While the information presented in the Analysis Report is meant for private education only, each Client has an opportunity to act proactively to treat potential health complications or to reduce the impact of negative outcomes through the guidance of a healthcare practitioner.
(B) Single complete test in a lifetime
As your genome is the same throughout all the cells in your body, and is specific to each individual, accurate whole genomic sequence need be obtained only once (genome sequence does not change unless influenced by environmental factors, for example, in the development of many cancers); it is a repository of biological information that will never have to be resequenced. Genomic information is available for interpretation in perpetuity, providing an opportunity to learn new information as more scientific knowledge of the genome emerges.
Whole genome sequencing is different from genotype screening tests or sequencing of individual genes. Whole genome sequencing looks at the entire DNA whereas genotyping or sequencing a panel of desired genes looks only at chosen fragments of the genome. Such fragments are selected to obtain specific information about a physical trait, but can run a risk of missing information important for appropriate analysis. It is also biased towards predetermined choice of which segments should be analyzed. Therefore, another important benefit of genome sequencing over genotyping is the discovery of rare or novel variants that otherwise would not be found. Access to a genome sequence reduces or removes the trial and error that frequent diagnostic tests that search for clues for undesirable and elusive health conditions and drug prescriptions that seek to alleviate such conditions. Thus, genome sequencing can result in substantial cost saving, especially when measured over the lifespan of an individual.
(C) Technical accuracy
The genome sequencing procedure and the data interpretation are performed according to the highest standards available to public consumers. Human genome sequencing is an innovative and state-of-the-art technology, and novel discoveries in improving data quality are constantly being made. Merogenomics Inc. selects service providers that can generate data of the highest quality based on the latest published supporting records. Merogenomics Inc. provides third party appraisal to ensure that these stringent criteria are met.
(D) Privacy of information
Protecting the privacy of genetic information and access to informed consent are viewed as important by the general public, and are key influencing factors in public interest in direct-to-consumer genomic testing. Private ownership of one’s genome sequence allows the Subject of such procedure to determine and control how such sensitive biological information is handled and disclosed.
(E) Cascade testing to other family members
If a variant with potential health implications is revealed in an individual, such information will have direct impact on closely related family members. Other family members can undergo a screening test to determine if they are at risk. This is one of the most positive effects associated with direct-to-consumer genome testing in presymptomatic individuals. Secondary testing can lead to the identification of other family members that have the variant in question.
(F) Multi-generational impact
A whole genome sequencing procedure produces data that can be analyzed and interpreted in perpetuity. Once a genome is decoded it becomes a multigenerational repository of information.
Merogenomics Inc. recognises the value of long term multigenerational storage of genomic information in the family for the superior improvement in the medical care of future generations. Therefore each Client should also consider how the data generated from the Subject’s genome sequence should be handled long term, including after he or she has passed on. Merogenomics Inc. considers genomic data extremely valuable, and inheritance of such data from one generation to another of important significance.
6.2. Benefits to society
Whole genome sequencing is a novel technology available to the public, and its contribution to understanding how genome variation contributes to physiology or disease is a rapidly growing area of scientific research.
Merogenomics Inc. aims to contribute to society’s education about the benefits and limitations of genomic technologies and to commercial developments surrounding the use of genomic technologies.
Merogenomics Inc. aims to propagate the value of ownership and control of access to one’s genomic data. As we enter the age of genomic information, Merogenomics Inc. intends to educate society about potential economic, ethical, and legal implications of genome sequencing, as greater understanding of these concepts arrives. Public mass participation in genome sequencing is bound to lead to important discoveries that can positively influence medical knowledge of human biology in health and disease, furthering the development of novel diagnostics and therapeutics.
7.1. Preserving confidentiality
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, unless otherwise specified. Client contact information can be kept for future reference in the Merogenomics Inc. database with the agreement of the Client.
7.2. No confidentiality after publication
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.
7.3. Disclosure to healthcare provider
Merogenomics Inc. will not share Client information, DNA sequence data, or the Analysis Report with a healthcare provider unless specifically requested to do so by the Client. Merogenomics Inc. recommends that only the pertinent information contained in the Analysis Report be shared with a third party. The exception to this rule is if the Client is undergoing a procedure that requires the oversight of a clinical geneticist with access to the whole genome sequence. In such instance Merogenomics Inc. cannot guarantee the Client information will remain confidential.
7.4. Replies to Safety Assessment Questionnaires
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 web-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 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.
7.5. Publication of research results
A statistical database containing all the information accumulated by Merogenomics Inc., including de-identified 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.
8. Alternatives to the genome sequencing procedure
A prospective Client should be aware that alternatives to whole genome sequencing exist that might fulfil his or her purpose with less expense of time and money and less risk of loss of privacy. Although the list is not exhaustive, several options are presented below.
(A) Professional medical advice
Knowledge of direct-to-consumer genetic and genomic tests is continuously increasing among healthcare practitioners. Many licensed healthcare providers are equipped to provide suitable advice especially in the context of available medical records.
(B) Genotyping test
Genotyping tests are available direct-to-consumer or via medical care. Such tests screen for thousands of variants at precise locations along the genome. As only a fraction of the genome is analyzed (only the most informative type of variants are sought), genotyping tests can be provided at a much lower cost than whole genome sequencing.
(C) Specific gene panel test
Genes known to be involved in specific health conditions can be tested, for example, genes involved in cancer development. Such tests are typically offered in a clinical setting when dealing with the diagnosis of specific diseases.
(D) Exome sequencing
Exome sequencing is similar to whole genome sequencing, except that it targets the portion of the genome that codes for proteins. The exome comprises of only 1–2% of the whole genome, therefore exome sequencing is a cheaper option than whole genome sequencing, and the vast majority of all disease causing variants are found in the exome.
(E) Paternity and ancestry kits
Low cost alternatives are publically available for individuals who are not interested in the potential medical benefits of genome sequencing but are curious about other advantages of such technology, such as identification of paternity status, or ancestral heritage.
In addition, alternative whole genome sequencing companies exist with specific appeal to individual needs. An individual can also obtain whole genome sequencing within a clinical setting. This option is recommended for a person with an undiagnosed disease or cancer because of the professional care and diligence that is offered in such a setting.
By entering into the Terms of Agreement for Merogenomics Inc.’s service in which “procedure” refers to the genome sequencing procedure, the Client agrees that:
1) The Client is of legal age (18 years or older) and is signing this document only on his or her behalf, or on behalf a legal dependent;
2) The concepts of whole genome sequencing procedure and this Consent Form have been diligently explained;
3) The Client is aware of the educational material available on the Merogenomics Inc. website, and that Merogenomics Inc. can provide access to genetic counselors to answer questions and gain proficient understanding of genetic literacy;
4) The possible harms and benefits of the procedure have been explained. The Client understands that no benefits can be derived if no informative results are obtained;
5) The Client understands that clinically relevant variants may be present in Subject’s genome that are not reported due to technical limitations of the genome sequencing procedure or scientific databases used to interpret the genome, or variants may be reported that might not exist;
6) The Client is fully aware of his or her right to forgo the procedure and seek an alternative course of action;
7) The Client knows of his or her right to stop participating in the procedure at any time;
8) The Client is free to ask questions about the procedure, prior to commencement and during the procedure;
9) The Client is aware that his or her Personal Information or Health Information, whether collected from the Client or generated through genome sequencing, will be kept private except as described to the Client;
10) The Client understands that no Personal Information or Health Information about the Client will be provided to a third party without first obtaining the Client’s permission;
11) The Client understands and consents that anonymized and de-identified information resulting from the genome sequencing procedure may be used and disclosed as described to the Client;
12) The Client agrees that the biological sample provided for the whole genome sequence procedure belongs to the Subject of the genome sequencing on whose behalf the Client signs, and does not belong to anyone else;
13) The Client has read and understood all of the pages of this Consent Form, and agrees to take part in the whole genome sequencing procedure.
Effective Date: December 10, 2016