We inherit genomic DNA from our parents. About 0.1% of its sequences vary between individuals. Some of these individual differences cause not only physical traits like body size and athletic ability but also susceptibility to various diseases. By unraveling the relationship between these individual differences in genomic sequences and susceptibility to diseases, we could gain deeper insights into disease mechanisms and ultimately connect these findings to treatment and prevention. To achieve this, we have developed experimental techniques capable of analyzing tens of thousands of individuals and our lab members with diverse backgrounds are collaborating to advance this research and our research scope is expanded beyond humans to include dogs and cats.
“Rare variants” is a key term in our laboratory. Some rare variants significantly alter gene function and greatly influence disease onset. Therefore, they become crucial for personalized medicine using genomic information. However, we need to perform sequencing analysis in a large number of DNAs to obtain reliable results about the impact of rare variants. To address this, we have developed own experimental techniques enabling efficient analysis and we have analyzed more than 400,000 samples provided by Biobank Japan and other biobanks and cohorts.
For more details: Rare Variants Analysis
Both genetic and environmental factors are important in cancer development, but cancers caused by a specific germiline pathogenic variant in the genome are called hereditary cancers. This became widely known in 2013 when actress Angelina Jolie underwent a preventive double mastectomy. The BRCA1 and BRCA2 genes are well-known causes of such cancers. Today, drugs targeting these genes have been developed and several precision-medicine approaches are covered by health insurance in Japan. Our laboratory has analyzed data from over 100,000 individuals and participated in international consortia, publishing Japanese data that has been incorporated into clinical practice guidelines. Furthermore, we have demonstrated that both BRCA1 and BRCA2 genes increase the risk of gastric, esophageal, and biliary tract cancers, which are more common in Japan. We also showed that the gastric cancer risk significantly increases in the presence of Helicobacter pylori infection but remains largely unchanged without infection. Through these findings, we are conducting research aimed at advancing personalized medicine.
For more details: Cancer Research
Alongside cancer, dementia is a major social issue in Japan. Genetic factors play a significant role, accounting for about 70% of the heritability. This proportion is higher than in many other diseases. It is also well-known that developing new drugs for dementia is extremely difficult. To contribute to both these challenges, we are conducting analyses focusing on rare variants in dementia. We expect the time will come when personalized medicine, utilizing genomic information appropriately, becomes available for dementia, just as it has for hereditary cancers. Furthermore, based on the findings from our genomic analysis research, we are also conducting studies where we introduce genetic variants associated with disease onset into iPS cells to elucidate the unknown mechanisms underlying dementia onset or, conversely, resistance to its development.
For more details: Dementia Research
Companion animals like dogs and cats have been bred through inbreeding, pairing individuals with traits valued by humans. In dogs, this has led to breeds ranging from Chihuahuas weighing a few kilograms to breeds exceeding 100 kilograms, creating a difference of dozens of times. As a result, it is well known that certain breeds have become predisposed to specific diseases. Furthermore, compared to well-known laboratory animals like mice and rats, these animals are closer to humans. They not only share many diseases but also exhibit highly similar behaviors and cognitive functions, making them potentially better models. Therefore, it is crucial to reduce breed-specific diseases in dogs and cats while also conducting research using them as better models for human diseases. However, using commonly seen dogs and cats as research subjects is challenging, requiring cooperation from many pet owners and veterinarians. Leveraging the fact that our laboratory has four researchers with veterinary licenses, we are conducting unique research in collaboration with Veterinary Medical Center of the University of Tokyo, aiming to benefit both human and veterinary medicine.
For more details: Dog and Cat Genome Research
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