OLYMPUS TECHNOZONE Vol.48 2001-01

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The Search for Genes Has Begun -involving with common diseases of humans

Sumio Kawai Fluorescence image of DNA microarray.
Sumio Kawai
Fluorescence image of DNA microarray.
Sumio Kawai
Mr. Makino: 
What are your feelings about global trends for genome research in the 21st century?

Dr. Oishi: 
From now on, it will be necessary to focus on the genetic differences among individuals. In the case of humans, it is believed that the differences at base pair level occur at a rate of 1 base(nucleotide) in 1,000 bases (nucleotides). Consequently, there should be about 3 million different bases in the total of total 3 billion bases. In practical sense, it is important to establish methods to identify the differences quickly, accurately and economically .

Mr. Makino: 
In other words, the work from now on will focus on detecting differences in base pairs which are termed single nucleotide polymorphism (SNP). These SNPs will be the basis to find genes responsible for major diseases.

Dr. Oishi: 
Of the 3 million SNP people are said to have, already approximately 2 million have been determined. Celera Genomics says that they have already gone through the genomes of nearly 10 people and that they have already found 2 million SNPs. However, ten people are not enough to understand all the differences. This research, however, will contribute to identify the genes that cause common diseases of people.

Mr. Makino: 
How exactly is the Kazusa DNA Research Institute tackling the issue of DNA based medicine or pharmacogenomics?

Dr. Oishi: 
We believe that there are several stages as far as human genome research is concerned. First is the use of genome informationof people to find the genes that are responsible for common diseases or lifestyle related diseases, such as heart disease, high blood pressure, diabetes, rheumatism and Alzheimer's. The reason these haven't been found so far is because they are not caused simply by a single gene.

There are already several thous and cases known as monogenic hereditary diseases like Huntington's disease and cystic fibrosis and genes responsible for these diseases have already been found. This is because they can generally be found by tracking down with a help of genealogies. However, in the case of common diseases, they are caused by the defects among several or more genes. Thus we call them polygenic diseases. Generally they are hidden in their youth when the body is strong enough to overwhelm defects but appear when one gets old. The competition to find these genes has begun.

Assuming that people have about 60,000 genes (a recent estimate is - 35,000), it is said that about one percent (300) of these genes are related to familiar common diseases. If we identify the gene responsible for an illness, we can at least guess the nature of the product of the gene, a protein, and we can figure out how its defect causes the illness.

Mr. Makino: 
If the gene and its defect that causes diabetes can be determined, then the function of the gene will be clarified. We are then able to determine where this illness begins.

Dr. Oishi: 
Of course, this in only the beginning. We next have to confirm it by introducing the same defective gene in mouse genome to find out whether the introduction causes the same symptom as that of human's.

Mr. Makino: 
The important aspect for technology is how to accurately, quickly and inexpensively discern changes in genes.

By the way, aren't the hurdles for obtaining samples for genetic analysis too high in Japan compared to the West?

Dr. Oishi: 
Yes, they are. In U.S., things are not so simple like one phone call does it all, but you can solicit for 500 healthy people by much easier ways. You have donors who provide blood and pay them on the condition that donors cannot be identified.

Mr. Makino: 
We already have an anonymous donor system in place. Unfortunately, it isn't working because of very high hurdles to clear. I'm afraid we might be getting a slow start once again.

Dr. Oishi: 
Objectively speaking, it is clear that U.S. took the lead in the first round concerning information technology and biotechnology of the latter half of the 20th century. Why did this happen? It's because both are new technologies based upon new concepts. When something new emerges in Japan, people tend to sit back and wait until they can at least get some image of it. This attitude is shutting outnew possibilities. On the other hand, since the future market of biotechnology will be enormous, andthere will be countless business chances, we have to realize that competitions among industrial countries will continue for several generations.

As I've mentioned a little while ago, Japan should make use of most of her current advanced technologies. That, I believe, is the strong point of Japan although I may sound a little boastful. We can fight the battle against U.S. if we effectively utilize our strengths.

In addition, the level of molecular biology in Japan is considerably high. Moreover, Japan has been leading the world in fermentation technology, breeding technology, enzyme production technology, quality control and so on.
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