niaid centralized sequencing protocol

Conditions: Atopy; Primary Immunodeficiency; Autoimmunity; Autoinflammation

Summary: background: genetic testing called "sequencing" helps researchers look at dna. genes are made of dna and are the instructions for our bodies to function. we all have thousands of genes. dna variants are differences in genes between two people. we all have lots of variants. most are harmless and some cause differences like blue or brown eyes. a few variants can cause health problems. objective: to understand the genetics of immune disorders various health conditions, as well as outcomes of clinical genomics and genetic counseling services performed under this protocol. eligibility: participants in other nih human subjects research protocols - either at the nih clinical center (cc) or at children s national health system (cnhs) - (aged 0-99 years), and, in select cases, their biological relatives design: researchers will study participant s dna extracted from blood, saliva, or another tissue sample, including previously collected samples we may have stored at the nih. researchers will look at participant s dna in great detail. we are looking for differences in the dna sequence or structure between participants and other people. participants will receive results that: * are important to their health * have been confirmed in a clinical lab * suggest that they could be at risk for serious disease that may affect your current or future medical management. some genetic information we return to participants may be of uncertain importance. if genetic test results are unrelated to the participant s nih evaluations, then we will not typically report: * normal variants * information about progressive, fatal conditions that have no effective treatment * carrier status (conditions you don t have but could pass on) the samples and data will be saved for future research. personal data will be kept as private as possible. if future studies need new information, participants may be contacted.

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.

Eligibility criteria:
* 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.

Keywords: phenotyping genetics sequencing inborn errors of immunity genomics natural history