DNA Repository
Several years ago the Vietnam Era Twin Registry (VETR) Scientific Advisory Committee recommended as a new initiative the collection and maintenance of DNA samples collected from Registry twin pairs. As the VETR is a national resource for studies investigating genetic and non-genetic influence on health and disease in middle age men, this initiative will enhance the value of the information collected from twins to the medical research community.
The accuracy of DNA testing makes it the best
method for determining zygosity in twins (identical
versus non-identical). When there are no differences
found in the genes being compared in a test of
zygosity, the chances are less than 1 in 100 that
the twins are dizygotic (DZ – non-identical), in
other words, the twins are more than 99% certain
to be monozygotic (MZ - identical). The use of
DNA for zygosity testing is only performed when
both members of the pair agree. Therefore twins
are explicitly told that this aspect of the test
requires both members to consent. If one member
of the pair is willing while the other is not,
then the testing cannot be conducted. If the twins
wish to be informed of the results of zygosity
testing, the VETR will provide this to them by
mail after testing is complete. The vast majority
of twins already have an excellent grasp of their
own zygosity and studies have indicated that self-assessment
is over 95% accurate. In most cases the twins in
the VETR already know their zygosity, but there
will be some twins who either do not know or have
incorrectly assessed their zygosity.
Besides zygosity
testing, the DNA Repository will be used for other
specific testing that is part
of an approved study protocol. For example, in
a recently approved longitudinal study examining
the cognitive ability of VETR twins, the protocol
requires the assay of the apolipoprotein * e 4
genotype which has been suggested to be involved
in Alzheimers disease.
The VETR has developed a general system of protocols for the collection
and storage of twin DNA that assures confidentiality for all
participants. The genetic samples are stored at
VA Puget Sound Health Care System in Seattle under
the direction Dr. Schellenberg, a geneticist at
the University of Washington (UW) and VA Puget
Sound. His lab processes and stores all DNA samples
and it is important to note that Dr. Schellenberg
and all staff in his lab have absolutely no phenotypic
information about the twins, as his lab is completely
blinded to the identity, disease characteristics,
and lifestyles and behaviors of the twins. Coded
and password protected genetic information is transmitted
directly to VETR staff, who then link phenotype
and genotype information and forward these data
to investigators for analyses.
Before
a twin decides whether to participate in the
DNA repository, the procedures, confidentiality safeguards,
and potential risks are explained in great detail.
To be able to accommodate the wishes of the highest
number of twins, a so-called layered consent
process is used which allow twins to choose from several
options with regard to how their DNA is used
in current or future research studies. Such options
include: 1) not having their samples used for
any testing beyond the immediate goals of the study;
2) allowing for future testing of their samples
restricted to the study for which they provided
the sample; or 3) allowing unrestricted future
research use of their samples. In any of these
cases, twins are informed that any future use
of their samples would have to be approved by the
VETR plus an outside Human Subject Committee.
Confidentiality safeguards include code number identifiers as opposed
to name or other personal information on all
DNA
samples, and withholding of personal information
from investigators who use these data. Only VET
Registry staff are able to link DNA to a personal
identifier.
DNA testing for specific genes will
not necessarily involve providing the participants
with test results.
This is because many of the genes identified
by investigators in DNA analysis have unknown
or uncertain consequences for the future health of the individual.
The decision to disclose genetic marker information
to study subjects is made based on the general
guidelines outlined in the National Bioethical
Advisory Committee (NBAC) report, which indicates
that all of the following conditions should
apply before disclosure to study participants:
- findings are scientifically valid and confirmed,
and
- findings have significant implications
for the subject's health, and
- a course of action or treatment is available,
and
- appropriate medical advice or referral is provided.
Each study involving genotype testing beyond
zygosity testing will
be reviewed for the following conditions and
decisions will be made accordingly.
The VETR Policies and Procedures now require all clinical studies to incorporate
the collection of DNA from participants. This policy will permit the gradual
collection of DNA samples from twins who wish to participate in this project
over time.
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