Genomic Biorepository for Genetic Disorders

Overseen By Lauren Olsen, MSN

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Rady Pediatric Genomics & Systems Medicine Institute

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

102000 Participants Needed

Trial Summary

What is the purpose of this trial?

Rady Children's Institute for Genomic Medicine (RCI) will collect biological samples (such as blood), derived genomic sequences (from DNA and RNA), and clinical features in a Biorepository as a standardized resource for future research studies. The purpose of the Genomic Institute Biorepository is to provide consented samples and data for basic and clinical research related to the genomic cause and treatment of childhood disease, and, in the future, as reference (Quality Control) data to improve the ability to make clinical diagnoses or clinical decisions. In addition, the Biorepository will provide a mechanism for making a diagnosis of a genetic disease. That is, once genomic sequences have been derived from biological samples, they will be immediately analyzed. If a genetic disease is identified that appears to explain an affected child's clinical features, then those results will be confirmed by the medically accepted standard, and placed in the electronic health record.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Genomic sequencing and molecular diagnostic results?

Genomic sequencing, including whole genome sequencing, has shown potential in diagnosing rare genetic disorders more effectively than traditional methods. It can identify disease-related genetic changes and provide a rapid diagnosis for conditions with genetic diversity, making it a valuable tool in clinical settings. ^{1 2 3 4 5}

Is genomic sequencing safe for humans?

The research does not provide specific safety data for genomic sequencing, but it highlights challenges in data reporting and ethical considerations. There is no mention of direct safety concerns for humans. ^{3 6 7 8 9}

How does the Genomic Biorepository treatment differ from other treatments for genetic disorders?

The Genomic Biorepository treatment is unique because it focuses on collecting and storing genetic information from patients, which can be used for personalized medicine and precision oncology. Unlike traditional treatments that directly target symptoms, this approach aims to understand the genetic basis of disorders to develop more targeted and effective therapies. ^{9 10 11 12 13}

Research Team

Stephen Kingsmore, MD, MSc

Principal Investigator

Rady Pediatric Genomics & Systems Medicine Institute

Eligibility Criteria

The Rady Children's Institute Genomic Biorepository is open to individuals of all ages, races, genders, ethnicities, and health statuses. It includes vulnerable groups such as pregnant women, neonates, fetuses, those with cognitive disabilities, children, minorities, and employees. There are no exclusion criteria.

Inclusion Criteria

I am of any age, race, gender, ethnicity, and health status.

Certain groups of people may not be eligible to participate in the study, including pregnant women, newborn babies, individuals with learning or developmental disabilities, children, people from minority groups, and employees.

Exclusion Criteria

N/A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment and Sample Collection

Enrollment of healthy and affected subjects to collect samples and data for a pediatric genomic Biorepository. Data includes genomic sequencing and resultant molecular diagnostic results, if any.

Ongoing

Initial visit for consent and sample collection

Data Analysis and Reporting

Genomic sequences are analyzed to identify genetic diseases. Results are confirmed and placed in the electronic health record.

Ongoing

Follow-up

Participants are monitored for changes in medical condition and new symptoms are collected longitudinally.

40 years

Treatment Details

Interventions

• Genomic sequencing and molecular diagnostic results

Trial Overview This trial involves collecting biological samples for genomic sequencing to research the genetic causes and treatments of childhood diseases. The data may also be used in future as a reference for improving clinical diagnoses or decisions.

Participant Groups

Group I: Enrollees Experimental Treatment 1 Intervention

Enrollment of healthy and affected subjects to collect samples and data for a pediatric genomic Biorepository. Data includes genomic sequencing and resultant molecular diagnostic results, if any.

Who Is Running the Clinical Trial?

Rady Pediatric Genomics & Systems Medicine Institute

Lead Sponsor

Trials

10

Recruited

214,000+

Findings from Research

Human genomic sequencing can provide valuable insights for diagnosis, prognosis, and treatment across various medical fields, but its widespread use is limited by a lack of evidence showing improved patient outcomes in those without specific testing indications.

The paper reviews clinical outcome studies in genomic medicine, highlighting the challenges of generating robust evidence to support the integration of next-generation sequencing into standard patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. Peterson, JF., Roden, DM., Orlando, LA., et al.[2020]

Clinical diagnostic genome sequencing using next-generation sequencing technology allows for faster and higher volume molecular testing, providing a wealth of genetic information.

Despite its potential to significantly enhance the diagnostic process, the interpretation of the results poses challenges due to the complexity of the data and the need for careful clinical correlation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology. Schrijver, I., Aziz, N., Farkas, DH., et al.[2023]

The identification of genes responsible for rare genetic diseases allows for important clinical applications such as accurate diagnoses, genetic counseling, and opportunities for carrier and prenatal testing.

Successful partnerships between research labs and certified clinical diagnostic laboratories can effectively translate gene discoveries into clinical practice, demonstrating that testing for rare diseases can be both high-quality and financially sustainable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular genetic testing for ultra rare diseases: models for translation from the research laboratory to the CLIA-certified diagnostic laboratory. Das, S., Bale, SJ., Ledbetter, DH.[2022]

Exome sequencing significantly outperforms traditional Sanger sequencing in diagnosing heterogeneous conditions like deafness, blindness, mitochondrial disease, and movement disorders, indicating a higher diagnostic yield.

Despite the lower yield for microsatellite-stable colorectal cancer, exome sequencing captures a larger number of genes, leading to better diagnostic outcomes at a reduced cost compared to single-gene testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-hoc comparison of the utility of sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases. Neveling, K., Feenstra, I., Gilissen, C., et al.[2022]

Next-generation sequencing (NGS) technologies allow for a more comprehensive approach to genetic diagnosis, moving from a traditional gene-by-gene method to broader techniques like diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS).

These NGS methods can be cost-effective for diagnosing rare genetic disorders with high variability, and they have the potential to identify new disease-related genes that were not previously associated with human diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Clinical Application of Next-Generation Sequencing. Ki, CS.[2021]

Clinical gene sequencing is becoming more important and cost-effective, with a 25% increase in the number of genes linked to diseases over the past two years, which can help guide drug selection and predict health risks.

Current reporting methods for gene sequencing results are inadequate, often omitting crucial data and reference information, which can lead to data loss and complicate integration into electronic medical records. Standardized electronic reporting is needed to improve data preservation and accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of clinical gene sequencing data reporting and associated risks for information loss. Mitchell, DR., Mitchell, JA.[2009]

Next-generation sequencing (NGS) is creating confusion regarding the return of results, as there is currently no clear policy guidance on how to handle findings, including incidental ones, across different populations.

The lack of established scientific and professional standards is causing hesitation among researchers and clinicians about returning NGS results, highlighting the need for practical policies in Europe, Canada, and the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing and the Return of Results. Knoppers, BM., Nguyen, MT., Sénécal, K., et al.[2018]

Next-generation sequencing is revolutionizing genomic medicine by enabling faster, cheaper, and more precise genetic testing, which is particularly beneficial for diagnosing rare genetic conditions in symptomatic children.

The implementation of these advanced technologies raises important ethical issues related to test design, patient consent, and the communication of results, highlighting the need for real-world deployment to fully understand these challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic medicine: evolving science, evolving ethics. Soden, SE., Farrow, EG., Saunders, CJ., et al.[2021]

The National Institutes of Health Genetic Testing Registry (GTR) is a comprehensive online resource that provides detailed information about genetic tests available worldwide, including their purpose, methods, and validity.

The GTR allows for easy access to information about genetic testing, helping healthcare providers and patients make informed decisions about genetic disorders, as all data is voluntarily submitted and regularly updated by test providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. Rubinstein, WS., Maglott, DR., Lee, JM., et al.[2021]

Biobanks, especially those collecting human specimens, are crucial for advancing research in diagnostics, forensics, and biomedical studies by providing rich genetic information.

The rise of DNA banking is significantly enhancing precision oncology and personalized medicine, reflecting a growing awareness and implementation of biobanking practices globally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA banking, its current awareness and national status in biomedical research in India, a survey. Mohanty, A., Chhabra, N., Sharma, A., et al.[2022]

The Sample Confirmation Testing (SCT) method, used in the eyeGENE Network, has successfully ensured the integrity of DNA samples from nearly 3000 participants, identifying significant laboratory errors in only 0.4% of cases.

By implementing SCT, the NEI has enhanced the quality of genetic testing data returned to individuals with inherited eye conditions, setting a standard for quality assurance in biorepositories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sample Confirmation Testing: A Short Tandem Repeat-Based Quality Assurance and Quality Control Procedure for the eyeGENE Biorepository. Parrish, RS., Garafalo, AV., Ndifor, V., et al.[2018]

Genotator is a real-time aggregation tool that compiles genetic data from 11 different clinical genetics resources, providing comprehensive coverage and reliable rankings of genes related to specific diseases, such as Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease.

In tests, Genotator successfully identified at least 75% of the top-ranked genes for these diseases, achieving a 90% concordance with the top 40 ranked candidates for Alzheimer Disease, demonstrating its effectiveness in integrating diverse genetic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotator: a disease-agnostic tool for genetic annotation of disease. Wall, DP., Pivovarov, R., Tong, M., et al.[2022]

A modified version of Spark SQL has been developed to efficiently handle genomic data, achieving over 50 times faster performance in processing genomic interval joins compared to traditional methods.

This improvement not only speeds up data retrieval for large-scale genomic studies but also significantly reduces the amount of code needed for querying, making it easier for researchers to access and analyze genetic data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GenAp: a distributed SQL interface for genomic data. Kozanitis, C., Patterson, DA.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Molecular genetic testing for ultra rare diseases: models for translation from the research laboratory to the CLIA-certified diagnostic laboratory. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A post-hoc comparison of the utility of sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Recent Advances in the Clinical Application of Next-Generation Sequencing. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Status of clinical gene sequencing data reporting and associated risks for information loss. [2009]

7. United States pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing and the Return of Results. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Genomic medicine: evolving science, evolving ethics. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

DNA banking, its current awareness and national status in biomedical research in India, a survey. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Sample Confirmation Testing: A Short Tandem Repeat-Based Quality Assurance and Quality Control Procedure for the eyeGENE Biorepository. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Genotator: a disease-agnostic tool for genetic annotation of disease. [2022]

13. England pubmed.ncbi.nlm.nih.gov

GenAp: a distributed SQL interface for genomic data. [2018]