The objectives of this project are to support the goals of the Undiagnosed Diseases Network (UDN) by continuing our work during Phase I as the sequencing core facility to provide exome and genome sequencing for the network. The extramural opportunity ?Clinical Sites for an Undiagnosed Diseases Network? created a consortium of institutions that built common protocols to improve patient access to state-of-the-art diagnostic methods, and to promote discovery and innovation in diagnosing and treating patients. Important to this coordinated effort is the use of common diagnostic modalities such that data can be readily shared among the sites. Therefore, the continued funding of a sequencing core facility that will provide state-of-the-art exome and genome sequencing for the network has been proposed. Baylor College of Medicine and the Baylor Genetics laboratory was selected as one of two sequencing cores for the UDN Phase I project performing whole exome sequencing for approximately 50% of the UDN participants. Baylor Genetics is a CAP and CLIA certified laboratory that developed whole exome sequencing as a clinical test in October 2011. Baylor Genetics has sequenced, analyzed, and provided final clinical reports of exome sequencing for over 11,000 patients with approximately 30-40% of cases receiving a molecular diagnosis. Our molecular clinical interpretation service comprises 16 ABMGG certified clinical molecular geneticists and four certified genetic counselors. To date, during UDN Phase I, the Baylor core performed exome sequencing for 256 probands and their family members for a total of 757 exomes. Whole exome sequencing comprised approximately 36% of the diagnoses made during UDN Phase I for patients and family members In response to the directives of the RFA, we will perform exome sequencing for probands and family members (3.5 individuals per proband) and deliver raw sequence reads and quality control metrics to the network within a two-week period followed by a clinical report. In addition, the Baylor core is now able to offer whole genome sequencing, analysis and clinical reporting in our CAP and CLIA certified laboratory, also with deposition of raw sequence reads within 2 weeks. In addition, we propose the option of RNASeq on a research basis for individuals with a non-diagnostic exome or genome analysis. These sequencing options can be weighed by the Steering Committee to provide the most efficient and cost-effective pathway to a molecular diagnosis for patients enrolled in this program.
The objective of this project is to continue our work as the sequencing core for the Undiagnosed Diseases Network during Phase II of the project by providing whole exome sequencing, whole genome sequencing, and RNASeq to the network. The network clinicians and researchers can choose the sequencing modality that is best suited to each patient. Through state-of-the-art DNA sequencing, it is hoped that the specific genetic change leading to the disorder can be discovered and communicated to the patients and their families.
| Splinter, Kimberly; Adams, David R; Bacino, Carlos A et al. (2018) Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med 379:2131-2139 |
| Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle et al. (2018) Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder. Am J Hum Genet 102:494-504 |
| Reuter, Chloe M; Brimble, Elise; DeFilippo, Colette et al. (2018) A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network. J Pediatr 196:291-297.e2 |
| Ramoni, Rachel B; Mulvihill, John J; Adams, David R et al. (2017) The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease. Am J Hum Genet 100:185-192 |
| Gahl, William A; Wise, Anastasia L; Ashley, Euan A (2015) The Undiagnosed Diseases Network of the National Institutes of Health: A National Extension. JAMA 314:1797-8 |
