Whole Genome Medical Sequencing for Genome Discovery
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/21/2018 |
| Start Date: | February 17, 2010 |
| Contact: | Julie Sapp |
| Email: | sappj@mail.nih.gov |
| Phone: | (301) 435-2832 |
Whole Genome Medical Sequencing for Gene Discovery
Background:
- A number of rare inherited diseases affect only a few patients, and the genetic causes of
these conditions remain unknown. Researchers are studying the use of a new technology called
whole genome sequencing to learn which gene or genes cause these conditions. Understanding
the genes that cause these diseases is important to improve diagnosis and treatment of
affected patients.
Objectives:
- To identify the genetic cause of disorders that are difficult to identify with existing
techniques.
- To develop best practices for the medical and counseling challenges of whole genome
sequencing.
Eligibility:
- Individuals who have one of the rare disorders under consideration in this study. These
conditions are generally those in which the genetic cause of the disorder is unknown.
The eligibility of most individual participants will be decided on a case-by-case basis
by the researchers.
- Family members of affected individuals, if that family member (often a parent) may
provide genetic information.
Design:
- Participants in this study will have at least one and in some cases several of the
following procedures:
- A medical genetics evaluation.
- Other tests that may include x-rays, magnetic resonance imaging (MRI) exams, and
consultations with other doctors. Not all studies are necessary for each person, but the
information from the tests may be required to proceed with some of our gene sequencing
studies.
- Clinical photographs to document certain aspects of the disorder.
- Blood and skin biopsy samples, or other tissue samples, as required by the study
doctors.
- Genetic testing, as decided by the researchers. However, most participants in this study
can expect to undergo whole genome sequencing, which is a technique to study all of a
person s genes.
- Some participants may be asked to take part in a telephone interview and/or a web-based
survey.
- Participants will have choices about what kinds of results from whole genome sequencing
they wish to learn.
- After the tests have been completed and the results of the genetic studies are known,
participants will be offered a return visit to the National Institutes of Health to
learn these results. During this visit, participants will be asked to complete surveys
and participate in interviews related to their decisions to participate in the study and
to learn individual genetic test results.
- A number of rare inherited diseases affect only a few patients, and the genetic causes of
these conditions remain unknown. Researchers are studying the use of a new technology called
whole genome sequencing to learn which gene or genes cause these conditions. Understanding
the genes that cause these diseases is important to improve diagnosis and treatment of
affected patients.
Objectives:
- To identify the genetic cause of disorders that are difficult to identify with existing
techniques.
- To develop best practices for the medical and counseling challenges of whole genome
sequencing.
Eligibility:
- Individuals who have one of the rare disorders under consideration in this study. These
conditions are generally those in which the genetic cause of the disorder is unknown.
The eligibility of most individual participants will be decided on a case-by-case basis
by the researchers.
- Family members of affected individuals, if that family member (often a parent) may
provide genetic information.
Design:
- Participants in this study will have at least one and in some cases several of the
following procedures:
- A medical genetics evaluation.
- Other tests that may include x-rays, magnetic resonance imaging (MRI) exams, and
consultations with other doctors. Not all studies are necessary for each person, but the
information from the tests may be required to proceed with some of our gene sequencing
studies.
- Clinical photographs to document certain aspects of the disorder.
- Blood and skin biopsy samples, or other tissue samples, as required by the study
doctors.
- Genetic testing, as decided by the researchers. However, most participants in this study
can expect to undergo whole genome sequencing, which is a technique to study all of a
person s genes.
- Some participants may be asked to take part in a telephone interview and/or a web-based
survey.
- Participants will have choices about what kinds of results from whole genome sequencing
they wish to learn.
- After the tests have been completed and the results of the genetic studies are known,
participants will be offered a return visit to the National Institutes of Health to
learn these results. During this visit, participants will be asked to complete surveys
and participate in interviews related to their decisions to participate in the study and
to learn individual genetic test results.
We aim to use whole-genome medical sequencing (WGMS) to discover causative molecular lesions
for a set of rare, severe phenotypes hypothesized to be caused by either somatic mutations,
germline de novo heterozygous mutations, germline inherited recessive, or germline inherited
dominant mutations in currently unknown or uncharacterized genes. The goal of this research
is threefold: to identify causative sequence variants for disorders whose molecular etiology
was previously unknown, to apply this insight to both the rare disorders under study and more
common phenotypes, and to enhance the study of mutation on a genome-wide level.
We plan to recruit approximately three to six affected individuals along with both parents
for each phenotype under study. Prospectively recruited trios will be brought to the NIH
Clinical Center for brief clinical evaluations and molecular evaluation. Each trio will be
consented to whole genome sequencing with the option to learn clinically relevant results,
that is, those that explain the disorder in question (what we refer to as the primary variant
) as well as other clinically relevant findings discovered incidentally as part of the WGMS
process (what we refer to as secondary variants ). Participants will be offered a return
visit to NIH to learn these results, and will be asked to complete surveys and participate in
interviews related to their decisions about participation in the study and to learn
individual genotype results.
The NIH Intramural Sequencing Center (NISC) will screen for sequence variants that conform to
the hypothesized inheritance pattern. These variants will be validated, for example by using
trios for de novo phenotypes, or with additional cases. We have started developing analytic
algorithms to distinguish potentially pathogenic genetic alterations from normal variation.
All sequence variants deemed clinically relevant will be validated in a CLIA-certified
laboratory and the results returned to that participant, should they choose to learn these
findings. This protocol is being designed in a way that will provide the long-term potential
for pursuing many different clinical projects.
for a set of rare, severe phenotypes hypothesized to be caused by either somatic mutations,
germline de novo heterozygous mutations, germline inherited recessive, or germline inherited
dominant mutations in currently unknown or uncharacterized genes. The goal of this research
is threefold: to identify causative sequence variants for disorders whose molecular etiology
was previously unknown, to apply this insight to both the rare disorders under study and more
common phenotypes, and to enhance the study of mutation on a genome-wide level.
We plan to recruit approximately three to six affected individuals along with both parents
for each phenotype under study. Prospectively recruited trios will be brought to the NIH
Clinical Center for brief clinical evaluations and molecular evaluation. Each trio will be
consented to whole genome sequencing with the option to learn clinically relevant results,
that is, those that explain the disorder in question (what we refer to as the primary variant
) as well as other clinically relevant findings discovered incidentally as part of the WGMS
process (what we refer to as secondary variants ). Participants will be offered a return
visit to NIH to learn these results, and will be asked to complete surveys and participate in
interviews related to their decisions about participation in the study and to learn
individual genotype results.
The NIH Intramural Sequencing Center (NISC) will screen for sequence variants that conform to
the hypothesized inheritance pattern. These variants will be validated, for example by using
trios for de novo phenotypes, or with additional cases. We have started developing analytic
algorithms to distinguish potentially pathogenic genetic alterations from normal variation.
All sequence variants deemed clinically relevant will be validated in a CLIA-certified
laboratory and the results returned to that participant, should they choose to learn these
findings. This protocol is being designed in a way that will provide the long-term potential
for pursuing many different clinical projects.
- INCLUSION CRITERIA:
- An individual who is affected with a disorder under study. We have provided a list of
exemplar disorders in Appendix A. As stated above, these individuals will generally
represent simplex cases with rare phenotypes whose molecular etiology is unknown.
- A family member of an affected individual where that family member (often a parent) is
potentially informative or useful for linkage or other bioinformatic analyses of
genetic variants. Probands who are minors or decisionally-impaired adults are eligible
if they have a parent or legal guardian who has authority to sign a consent form on
their behalf.
EXCLUSION CRITERIA:
- Probands who are adults and decisionally-impaired are ineligible if they do not have a
legal guardian who has authority to sign a consent form on their behalf.
- Subjects who have known, significant affective or psychiatric disorders that, in the
judgment of the team, may impair their ability to understand and appropriately use
complex medical and genetic information will be considered decisionally-impaired and
will be ineligible unless they have appointed (or, in the case of minor children, are
in the custody of) an appropriate surrogate decision-maker.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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