Identifying novel disease genes and revealing the pathomechanism of monogenic diseases

Diseases are caused by genetic and/or environmental factors. It is important to understand the pathomechanism of monogenic diseases that are caused only by genetic factors, especially prenatal‐ or childhood‐onset diseases for pediatricians. Identifying “novel” disease genes and elucidating how genomic changes lead to human phenotypes would develop new therapeutic approaches for rare diseases for which no fundamental cure has yet been established. Genomic analysis has evolved along with the development of analytical techniques, from Sanger sequencing (first‐generation sequencing) to techniques such as comparative genomic hybridization, massive parallel short‐read sequencing (using a next‐generation sequencer or second‐generation sequencer) and long‐read sequencing (using a next‐next generation sequencer or third‐generation sequencer). I have been researching human genetics using conventional and new technologies, together with my mentors and numerous collaborators, and have identified genes responsible for more than 60 diseases. Here, an overview of genomic analyses of monogenic diseases that aims to identify novel disease genes, and several examples using different approaches depending on the disease characteristics are presented.