Laboratories

Laboratory of functional Genomics Does not recruit students for the academic year 2019

Associate Professor Manabu WATANABE
TEL: +81-3-5449-5343
E-mail: wata{at}k.u-tokyo.ac.jp

Introduction

【Key Words】 dogs, cats, comparative genomics, genome diagnosis, clinical trials for companion animals, circular translational research

“For dogs, for cats, for life”

Establishing a canine and feline disease analysis platform

 Dogs and cats were domesticated thousands of years ago – at least 15,000 years ago for dogs and about 10,000 years ago for cats – and are now considered to be irreplaceable partners as companion animals to humans. The behavior of pets that live closely with humans is very intriguing, and at the same time, their illnesses are worrisome problems. In our research group, we aim to elucidate and overcome these problems through canine and feline genomic and genetic studies. We have thus far created a network of genome, blood, and disease resources from healthy and sick dogs and cats by amalgamating a number of human and academic fields such as zoology, veterinary medicine, genomics, and information sciences, and independently built pet-specific analytical tools ranging from genome sequencing using next-generation sequencers to a series of genomic analyses using computers. As the only research group in Japan that has established a series of these analytical platforms, we are working enthusiastically to elucidate the traits as well as the mechanisms of genetic diseases and cancer in dogs and cats.

Canine and feline genomic analysis: their traits, genetic diseases, and cancer

 We are currently storing and managing thousands of samples we have collected from 56 dog breeds and hundreds of samples from 20 cat breeds, both healthy and diseased. Using these biological resource bases, we are conducting correlation analyses between genomic polymorphism and breed traits such as the characteristic personalities and body type by comparing common gene polymorphisms between various dog breeds. We are also searching for causative genomic polymorphisms of genetic diseases such as neuroaxonal dystrophy in Papillon dogs, Vogt-Koyanagi-Harada disease in Akita dogs, narcolepsy with cataplexy in dogs and neuropathy in cats. Moreover, with the aim of directly linking cancer genome studies with veterinary practice, we are moving forward with the analysis of actual cancer biopsies and conducting genomic analyses of various types of canine cancer, such as breast cancer, liver cancer, and lung cancer, and common feline cancers, such as breast cancer and squamous cell carcinoma.

The application and social contribution of canine and feline genomic studies

 In addition to previous artificially induced animal disease models that utilize mice and other animals, there has been increased interest recently in dogs and cats as the next-generation animal disease models since they live in the same environment as humans and spontaneously develop various diseases. From the perspective of comparative genomic studies of diseases, it would be possible to elucidate the mechanism of diseases with unknown etiology by examining the universality of the onset between similar diseases or by extrapolating candidate disease genes. This can be achieved by comparing the causative genomic changes between humans and other animal species regarding the diseases that we have investigated. We believe such elucidation will contribute to the clarification of molecular pathology beyond the boundaries of a specific species
 As clinical veterinary and medical application of genomic analysis technology, we also combine multiplex polymerase chain reactions with next-generation sequencing. With this combination, the target region of a disease-derived genome from a ~10 ng sample can be amplified in a single tube using a few thousand pairs of primers. Subsequently, rapid genomic analysis can be completed in approximately 24 hours using a system that requires only trace amounts of cancer specimen. We are promoting its application in actual genomic diagnostics.
 In addition, to facilitate the application of molecularly targeted clinical drugs that have been shown to exhibit marked anti-cancer effects in dogs and cats, we have sought assistance from the Veterinary Medical Center, Faculty of Agriculture, the University of Tokyo, and are currently conducting a veterinary trial of molecularly targeted lapatinib in dogs and cats with breast cancer.
 Furthermore, the genomic analysis of guide dogs could enhance the success rate of guide dog training. By examining the cause of diseases and preventing them, it would be possible to provide assistance in training and nurturing healthy and reliable guide dogs that are not susceptible to disease and also possess the necessary qualities of a guide dog, thereby contributing to society.
 Through such research activities, we are developing a system of “circular translational research (information and problem sharing translational research)” that shares requests and information required by everyone from diverse backgrounds involved with dogs and cats. It is our aim that this system will extend the mutual cooperation, achievements, and information to all parties.
 As a veterinary pathologist, I have treated many dogs and cats and handled body donations, and this valuable experience has also been the starting point for these research activities. Endeavoring to save even one life that could not have been saved before and to contribute to the enrichment of society through our research activities, we are advancing our research “for dogs, for cats, for life.”


Reference

Manabu WATANABE
Current status, issues, and perspectives in genome research of dogs - The origin, characters, hereditary diseases, and tumors - The Journal of Animal Genetics (2016) 44, 69–85.

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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