Outline of disease gene hunting approaches in the Millennium Genome Project of Japan

To capture the potentially enormous and vital opportunity in the post sequence era of human genome research, the Japanese government on December 19, 1999 drew up the basic outlines of the 5-year Millennium Genome Project (MGP). The "Disease Gene" Team of MGP aims to establish genome-based personalized medical care and to seed a revolutionary drug development inspired by the new information and technology, which the genome research provides. Five disease categories have been chosen as project targets: dementia, cancer, diabetes, hypertension and asthma, which are manifesting a major impact on the health and welfare of the rapidly graying Japanese society. These so-called "common diseases" are etiologically multifactorial, and the genetic components, if any, are considered polygenic with relatively high disease allele frequencies in the population. In the first year, 2000, a consortium or "Subteam" was established for each disease category, and several hypothesis-driven candidate gene approaches were launched. In 2001, a complementary strategy of disease gene hunting, a statistics-based genome-wide approach, was initiated. The Disease Gene Team decided to employ a genome-wide, gene-based SNP scan through close collaboration with another arm of MGP, the "Human Genome Variation" Team, which discovered 194,393 SNPs as of December 25, 2002 from genome of the Japanese people. Each Subteam reached a consensus regarding eligibility criteria and research protocols, which were reviewed by the institutional review boards in accordance with the new Ethics Guidelines For Human Genome/Genetic Analysis Research promulgated by the government on April 1, 2001. The Subteams organized a multi-institutional consortium, which in 2001 collaborated in the collection of quality germline DNA samples and clinical and life-style related information. In 2002, the third year of MGP, the genome scan started at two typing centers using the high-throughput SNP typing system established by RIKEN. The premise and prospect of the approach will be discussed.