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Transcript
Genome Informatics 11: 464–465 (2000)
464
A Security System for Human Genome Information
Encoded by Chemicals, Not by Electronic Codes
Yumi Kawazoe1
Toshikazu Shiba1
[email protected]
[email protected]
Masahito
Yamamoto2
[email protected]
1
2
Azuma Ohuchi2
[email protected]
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Division of Systems and Information Engineering, Graduate School of Engineering,
Hokkaido University, Sapporo 060-8628, Japan
Keywords: genome information, gene diagnosis, security system
1
Introduction
With the increasing discoveries of new genes, it has become necessary to establish a security system
for personal genome information. Although many security systems for electronic information stored
in computers have been developed, there is still no security system for information that is encoded by
chemicals like DNA, RNA and proteins. Thus, an effective security system for human genome information, rather than simply reliance on the guidelines regarding ethics of human genome information
utilization, is needed.
Nowadays, many blood samples and other medical samples are collected in medical facilities and
used for diagnoses by biochemical and cytological tests. These samples include personal information
encoded in DNA or RNA. Since there is no security system to protect the genome information included
in these samples, anybody can easily obtain personal information analyzing DNA or RNA sequences
in these samples. It would be almost impossible to compel all medical facilities to keep strict charge of
these samples. With the continuing development of human genome analysis, it is possible that leakage
of personal genome information from these medical samples will become a big social problem.
In order to prevent the leakage of personal genome information from medical samples, we have
constructed a security system that prevents gene analysis from these samples. In this system, PCR
analysis of human genome information is prevented by placing dummy DNAs and/or RNAs with excess
information into the tubes containing blood samples. If the dummy DNAs and/or RNAs contain excess
wild-type genes, it is impossible to detect mutant genotypes of original DNA information, because these
dummy molecules are not only dominantly purified through genome DNA or RNA preparations form
blood samples but also dominantly amplified by PCR. As a result, the PCR-amplified DNA fragments
are derived from the dummy molecules, not from the original blood samples. Using these dummy
molecules, we succeeded to completely “lock” the original genome information of blood samples.
If the personal genome information of blood samples must be “unlocked”, the original DNA information can be analyzed by removing dummy molecules using molecular-tagging techniques. Dummy
DNAs and/or RNAs have been tagged by certain chemicals or special oligonucleotides for which information has not been made publicly available. Only authorized facilities know which tags have
been appended to the dummy DNAs and/or RNAs and can remove the tagged-dummy molecules by
affinity trapping. If dummy DNAs have been tagged by digoxigenin (DIG), it is easy to remove these
molecules by anti-DIG antibody affinity trapping.
In this report, we describe a security system we have constructed for personal genome information that is based on the concept that information in chemicals is equally important to manage as
information in electronic binary codes.
A Security System for Genome Information
465
Figure 1: DNA sequencing analysis of PCR amplified c-Ki-ras gene of a locked sample (A) and an
unlocked sample (B).
2
Materials and Methods
In order to construct model systems of a genome information security system, we employed the human
c-Ki-ras gene as a target gene to lock and unlock.
Locking of genomic DNA information Four kinds of dummy DNAs (128 bp) that contain different mutations at codon 61 of c-ki-ras [1] were put into the sample tubes for blood sampling.
These dummy DNA fragments were tagged by DIG at each 5’ end. Human blood was collected
into sample tubes that contains dummy DNAs, and genomic DNA of each blood sample was
purified. Using the purified genomic DNA as a template, the c-Ki-ras gene was amplified by
PCR. The DNA sequence of the amplified DNA fragment was determined.
Unlocking of genomic DNA information To remove the DIG-tagged dummy DNA, purified genomic DNA from each blood samples was mixed with an anti-DIG polyclonal antibody and
incubated at 37◦ C for 10 min. Protein G sepharose was added to the mixture and further
incubated for 10 min. After centrifugation, the supernatant was used as a template for PCR
to amplify the original c-Ki-ras gene. The DNA sequence of the amplified DNA fragment was
analyzed to confirm unlocking of the original DNA information.
3
Results and Discussions
Fig. 1A shows the results of DNA sequencing of the locked sample. The DNA sequence that corresponds to codon 61 was not determined and is indicated as N. Since the ras gene of original genomic
DNA is wild-type, the original sequence should be TTG (CAA). However, it is impossible to detect the
original sequence because some peaks derived from excess amount of dummy DNAs were overlapped
and masked the original sequence. After the removal of dummy DNAs by affinity trapping, the DNA
sequence of original blood sample was clearly detected as CAA (Fig. 1B).
These results indicate that original DNA information derived from blood samples can be locked
by dummy DNAs and unlocked by removing dummy DNAs. However, variations of molecules for
DNA tagging must be designed to ensure effective locking of DNA information, since combinations
of several tagged molecules would make unexpected unlocking of the information difficult. By using
this security system, information encoded by chemicals will be able to be managed in the same way
as electronic information.
References
[1] Chang, E.H, Gonda, M.A., Ellis, R.W., Scolnick, E.M., and Lowy, D.R., Human genome contains
four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses,
Proc. Natl. Acad. Sci. USA, 79(16):4848–4852, 1982.