Lessons from Genome-Wide Search for Disease-Related Genes with Special Reference to HLA-Disease Associations

The relationships between diseases and genetic factors are by no means uniform. Single-gene diseases are caused primarily by rare mutations of specific genes. Although each single-gene disease has a low prevalence, there are an estimated 5000 or more such diseases in the world. In contrast, multifactorial diseases are diseases in which both genetic and environmental factors are involved in onset. These include a variety of diseases, such as diabetes and autoimmune diseases, and onset is caused by a range of various environmental factors together with a number of genetic factors. With the astonishing advances in genome analysis technology in recent years and the accumulation of data on human genome variation, there has been a rapid progress in research involving genome-wide searches for genes related to diseases. Many of these studies have led to the recognition of the importance of the human leucocyte antigen (HLA) gene complex. Here, the current state and future challenges of genome-wide exploratory research into variations that are associated with disease susceptibilities and drug/therapy responses are described, mainly with reference to our own experience in this field.