NIAID Centralized Sequencing Protocol

Investigators at the National Institute of Allergy and Infectious Diseases (NIAID) use next-generation sequencing technologies to help determine genetic contributions to immune diseases. These efforts have increased rates of molecular diagnosis for a subset of NIAID

participants as well as uncovered fundamental insights into the cellular and signaling pathways in host defense and immune regulation.

Despite these successes, analysis and interpretation of genomic data remain a substantial challenge. Simply, researchers do not understand the functional and clinical consequences of most human genetic variation. This is true at NIAID and across the intramural research program. Making progress in this area requires a coordinated, systematic, and transparent approach to clinical genomics research.

This protocol is specific to genetic testing and explicitly aims to both strengthen clinical care and enhance research throughout participating programs at the NIH. Probands will provide biological specimens for genetic testing and will be required to be enrolled on a primary protocol, which will execute the primary clinical and research evaluations. This protocol serves as a vehicle for a

programmatic effort that includes standardized phenotyping, test ordering through the Clinical Research Information System (CRIS), sample collection and isolation, nucleic acid analysis, bioinformatics, clinical interpretation, reporting in CRIS, genetic counseling, and supporting effective use of genomics as a research tool throughout the intramural program. Genetic testing results and data (upon request) will be shared with the research teams for protocols on which a given participant is co-enrolled. Overall, increased process standardization will support data integrity and efficiency while still accommodating the need for investigator flexibility.

• PARTICIPANT INCLUSION CRITERIA:
• Must fulfill one of the following criteria:

• Proband participants: must be individuals under investigation by another NIH protocol on which they are co-enrolled, or are referred from the GDMCC protocol "Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults" (NCT04702243). Probands may have a disease under investigation or be healthy volunteers
• Biological relatives: biologically related to a proband participant.
• Aged 0-99 years.
• Participants must be willing to undergo genetic testing.
• Participants must be willing to allow samples to be stored for future research.
• Participants must be willing to have their de-identified genomic data shared, for example in a controlled access databases like the Database of Genotypes and Phenotypes (dbGaP).
• To complete surveys and interviews:

• Proficient with the English language.
• Able to provide informed consent.
• Adult healthy volunteers must be able to provide informed consent.

PARTICIPANT EXCLUSION CRITERIA:

Any condition that, in the opinion of the investigator, contraindicates participation in this study is a reason for exclusion.