AB007. Genomic medicine: impact of rare disease research on medicine and health care

Abstract: Most of rare diseases are genetic and the number of identified pathogenic genes is rapidly increasing since the introduction of next-generation sequencers. To date more than 4,500 Mendelian rare disorders with known molecular basis are listed in the OMIM database. In the past, it was believed by the majority of medical community that research on rare diseases scarcely contributes to medical science and health care in general. Sometimes rare disease research was considered to be a kind of hobby similar to collecting rare stamps or a charity activity to rescue those deserted patients. In the past decade, genome scientists searched for the genetic basis of ‘common diseases’ based on the ‘common variant hypothesis’. It turned out, however, most of the identified common variants identified by genome-wide association studies had relatively small effect on disease susceptibility. Now the genome scientists are turning to ‘rare variant hypothesis’, where each of rare variants has a strong effect on disease development. Recently rare disease research led to the discovery of important medical findings and the development of novel drugs not only for rare diseases but also for common diseases. For example, the elucidation of pathogenic genes for osteopetrosis, a rare condition in which bone mass is excessively increased, contributed the development of novel drug for osteoporosis, a common fragile bone disorder among aged people. Studies on rare familial renal glucosuria due to SGLT2 mutations gave the idea of a novel therapeutic strategy for diabetes mellitus by dumping excess sugar into urine. It is reasonable to assume that pathogenic genes responsible for Mendelian disorders are crucial for maintaining health in human beings. We need to reiterate the importance of analyzing characteristic clinical features associated with rare genetic variants, which may not be readily elucidated by basic research using cells or animals.

Keywords: Genome; rare disease; Mendelian disorders; next-generation sequencing