About Baylor-Hopkins Center for Mendelian Genomics
Johns Hopkins and Baylor College of Medicine have received NIH-NHGRI grant support for the creation of a Center for Mendelian Genomics (CMG) to help “solve” Mendelian disorders for which the genetic etiology is presently unknown. The Baylor-Hopkins Center for Mendelian Genomics (BHCMG) is funded to provide DNA sequencing, data analysis, interpretation and infrastructure for dbGaP submission, ELSI (consent) review and publication. Only submissions from health care providers will be accepted. Patients interested in their particular condition are referred to clinical genetics services that could be useful.
Submission Process
You should make electronic submission of your case(s) for consideration through the BHCMG instance of PhenoDB. We will consider both single families with the ability to track segregation and also cohorts of patients with same the phenotype, with or without the ability to track segregation. In order for your project to be accepted for sequencing in the BHCMG, at least 2 approvals are required. One is by the Phenotype Review Committee (PRC) that will assess the appropriateness of your case(s) for this research effort based on the phenotype, demonstrated inheritance pattern, and family history. The second is determination that the subject has been appropriately consented. This can be done prospectively, using our consent process, or using your consent, previously signed, which will require review and approval by our ELSI (Consent Review) Committee.
PRC Review: The PRC will review each case to determine the likelihood that a result is obtainable, given the phenotype and the available samples. You will be notified of the committee’s decisions. We are reviewing families and cohorts in which the condition is likely inherited as a single gene disorder (Mendelian disorder) including:
- Previously-defined syndromes (omim.org) for which the responsible gene has not been identified
- Previously-identified syndromes for which some genes have been identified but some patients do not have a mutation in the known genes (any gene that accounts for >= 25% of the cases of the syndrome should have been ruled-out prior to consideration for this project)
- New syndromes that are segregating as a single gene disorder
ELSI (Consent) Review: If samples are already collected and informed consent has been obtained under a separate research protocol, the submitter will provide the ELSI Committee with all iterations of consent forms used in obtaining informed consent for research. These should be blank templates. The ELSI committee will review the consent forms to determine whether samples can be submitted to the BHCMG and whether data can be submitted to dbGaP. The submitter will receive a letter of determination following the review. If the original consent is determined not to be adequate for use in the BHCMG, or if the subject has consented but not yet provided a biological sample, then the subject should be re-consented using the IRB-approved research consent form for the Mendel project.
For questions on the submission process, please contact Dr. Reid Sutton at Baylor or Corinne Boehm at Johns Hopkins.
For questions on Phenotype Review, please contact the chair of the PRC, Dr. Ada Hamosh.
For questions about the Consent Review policy, please contact the chair of the ELSI Committee, Dr. Debra Mathews.
The Principal Investigators can be contacted as follows: Dr. David Valle and Dr. James Lupski.
(Contact information is only available to registered users.)
Who is Eligible to Submit Samples?
We are eager to consider proposals to study any unexplained Mendelian phenotype including single cases, single families, or cohorts of unrelated individuals with a particular diagnosis. Any healthcare professional may submit a proposal for consideration. Submissions are easy using the BHCMG instance of PhenoDB.
Data Analysis
The study has funding for analysis of the sequence data and will take however large a role in the analysis and interpretation of the data that you prefer. You will have access to whatever level of data you want, including BAM files if you desire. If we are involved in the analysis, you can expect one of three outcomes:
- We may be able to identify the gene and causative variant
- We may identify a short list of candidate genes and variants that will require additional work to find the responsible gene
- We may conclude that we are not able to solve the case with the data in-hand. We anticipate that we may return to these “unsolved cases” in the future when we have more information about Mendelian disorders, sequencing strategy and analysis of sequence data.
Validation & Confirmatory Studies
Follow-up studies, such as targeted genotyping of additional family members or subjects with the same phenotype, will likely be required. This work is not funded in this study and will be your responsibility. However, if your resources do not permit this additional work, we may be able to identify researchers with whom you can collaborate.
Data Sharing
Following return of the final results to you, we will submit them to a controlled access database, e.g. dbGaP. Details on data access for dbGaP studies can be found here. The results will not be submitted to dbGaP for at least 6 months after you have received the final results. This interval is meant to allow you to write up and submit your results.
Publication Agreements and Acknowledgements
The BHCMG and NHGRI should be acknowledged in any publication that results from data generated by this project. The BHCMG must be listed as a ‘banner authorship’ (see below), but each individual member need not be listed unless a substantial contribution was made. For each member of the BHCMG who had a significant role in the analysis and interpretation of the data or a role in writing or editing a manuscript, that contribution should be acknowledged as in any scientific collaboration with potential co-authorship on the manuscript.
How to cite the BHCMG as an author:
Baylor-Johns Hopkins Center for Mendelian Genomics
How to acknowledge the BHCMG and NHGRI:
Funding for this study was provided by the Baylor-Hopkins Center for Mendelian Genomics through National Human Genome Research Institute grant 5U54HG006542