Project Identifier: LLNL-95-110
Project Title:
Molecular Genetics of DNA Repair
Principle Investigator:
Dr. Christine A. Weber
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 22, 1995
IRB Approval Number: 95-110
Number of Human Subjects in the Last Reporting Period for this Project: 8
(Reporting periods vary.)
Type of Human Subjects Involvement:
A. Objectives: Our primary objective is to gain an understanding of the genetic and biochemical bases of the genetic disorders resulting from defects in the DNA repair and transcription factor gene ERCC2 (trichothiodystrophy and xeroderma pigmentosum group D) and why one disorder is cancer-prone and the other is not. To achieve this objective, cells from trichothiodystrophy and xeroderma pigmentosum group D patients and family members are used for genetic analysis of the mutations in the ERCC2 gene and in studies of the DNA repair characteristics of the cells. The data generated provide information that is useful both to our research (greater numbers of patients increase our ability to identify commonly occurring mutations and to correlate specific alterations in the protein with the specific clinical presentation) and to the clinicians and families (confirmation of diagnosis, information on degree of photosensitivity of the cells, knowledge of specific mutations in that family useful for future prenatal diagnosis).
B. Methodology: We receive cultures of archived material established in other laboratories (either clinical or research) along with case histories. We request that no identifying information be provided to us. Patient confidentiality is ensured by blacking out any identifying information received and, whenever possible, duplicating the item and destroying the original. Once received in our laboratory, a code designation is assigned (disorder name, number, and 2-letter city abbreviation) and the samples are both grown for experimental use (e.g., survival curves, mutation analysis) and frozen for future studies. All experimental notes and materials use only the code designation. The code database (showing clinician names, their sample identification, and our corresponding code designations), patient photographs, and any original documents with blacked out identifying information that must be maintained are kept in a locked file. Experimental results are then provided to the clinician and are published. Publications typically include case histories (sometimes referencing an already published case history) as well as experimental data. In some cases, recognizable photographs may be included. In such cases, the clinicians are co-authors and obtain consent for publication from the parents, legal guardian, or patient, as appropriate to each case (the patients are typically minors).
C. Human subjects are not exposed to any chemical or radioactive substances or ionizing radiation under this project.
D. Involvement of human subjects
1. Archived cell cultures from trichothiodystrophy and xeroderma pigmentosum
group D patients and family members are used for UV-survival studies, DNA repair
assays, and preparation of RNA and DNA samples for genetic analysis of the
mutations in the ERCC2 gene. No cell samples are collected specifically for this
project.
2. Since only archival materials are used, the only risks to which human
subjects are exposed under this project involve loss of privacy. Steps for
ensuring confidentiality are outlined in B above.