Radiation Effects Research Foundation five year strategic research plan and program management, 1997-2001 Page: 25 of 152
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777
778 Two-dimensional electrophoresis (2-DE) methods
779
780 The Biochemical Genetics Laboratory has developed a 2-DE technique based on 3P-
781 labeled DNA digests created with three sets of restriction enzymes. This method produces three
782 gels per individual having a total number of roughly 2000 spots (fragments) that are suitable for
783 D/I/R mutation detection. A study using DNA samples from 200 BALB/c mice derived from
784 irradiated spermatogonia, conducted primarily to prove that the 2-DE technique is capable of
785 detecting mutations, will be completed within a year. This study will be followed by an
786 investigation of DNA from the 200 pilot study families. It is expected that this pilot study will
787 take at least five years to complete. If the spontaneous mutation rate is 1x105 / fragment /
788 generation, we would expect to detect five mutations in the 120 children of the 100 control
789 families.
790
791 The study (even in its preliminary phase) involves collaboration of a number of groups,
792 including: the Cytogenetics Laboratory for efforts to localize putative mutations and their normal
793 counterparts using FISH or other techniques, the Information Technology Department for help
794 in data management and software conversion/development, the Department of Statistics in dealing
795 with the pattern recognition and other problems arising in the analyses of these complex data.
796 RERFs long-term collaboration with the University of Michigan is also an essential component
797 of this program.
798
799 Genetic markers of hypertension
800
801 In accordance with the recommendations of the Blue Ribbon Panel, a protocol is being
802 developed for a pilot study to assess markers for genes potentially associated with hypertension.
803 This study, which will include 200 AHS participants (100 normal and 100 with hypertension as
804 defined by the 1993 WHO/ISH guidelines), will make use of DNA from lymphocytes obtained
805 during the routine AHS examination.
806
07 F, mail survey and health study feasibility
08
09 In response to the recommendations of the Blue Ribbon Panel, we are preparing detailed
10 plans to carry out a mail survey of all surviving members of the F, cohort and to conduct a small
11 scale study of the feasibility of an ongoing program for ascertainment of disease and disability in
12 the cohort. The mail survey will provide data that can be used to obtain baseline (self-reported)
13 information on health status and serve as a source of risk factor data that can be used in future
14 analyses of cancer mortality and incidence in this cohort. The small clinical study (500 people)
15 will include biochemical genetic studies of several genes related to common diseases (e.g.,
16 hypertension and diabetes). The mail survey and clinical feasibility study will last about two years
17 and will be followed by a workshop to determine what additional studies, if any, should be carried
18 out by RERF.
19
20 Genetic epidemiology (family studies)
21
22 Efforts are currently underway to define a database of family relationships within the LSS,
23 in-utero, and F, cohorts. The initial focus is on the families of breast cancer patients in order to18
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Radiation Effects Research Foundation five year strategic research plan and program management, 1997-2001, report, October 31, 1997; Washington D.C.. (https://digital.library.unt.edu/ark:/67531/metadc716813/m1/25/: accessed July 16, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.