Investigation of the susceptibility gene for COPD by homozygosity fingerprinting method

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The elucidation of the responsible gene for the multigene diseases is a difficult but an important subject. In this area, the whole genome association approach is frequently employed. However, the method is applicable only to diseases of which frequency is high, and the result often lacks reproducibility. We have invented the Homozygosity Fingerprinting method that targets multigene diseases. It is a non-parametric method applicable to recessive genes. We have determined several parameters for the method using Haldane's Poisson process model for the recombination of the chromosome, and established theoretical background for the identification of recessive genes that are derived from a small number of ancestors and now spread into the population. Using the parameter, we analyzed 6 patients with alpha-1 antitrypsin deficiency, with 45 HapMap Japanese data as a control. Although the 6 patients were from different areas of Japan, we could identify the location of alpha1-antitrypsin gene from their genotyping data. With the use of 1000k GeneChip recently available, we are able to identify genes derived from common ancestors who lived 600 years ago. The method is applicable even to the diseases that are caused by several genes, and thus is considered to be useful for the identification of such genes.The method has already approved Japanese patent (No. 4059517) and now being transferred to international phase.