homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients纯合性映射在纯合性单体型分析检测隐性致病基因从一个小数量的无关,远的病人.pdfVIP

Homozygosity Mapping on Homozygosity Haplotype Analysis to Detect Recessive Disease-Causing Genes from a Small Number of Unrelated, Outbred Patients 1 2 1 1 1 Koichi Hagiwara *, Hiroyuki Morino , Jun Shiihara , Tomoaki Tanaka , Hitoshi Miyazawa , Tomoko 1 3,4 3,4 5 2 Suzuki , Masakazu Kohda , Yasushi Okazaki , Kuniaki Seyama , Hideshi Kawakami 1 Department of Respiratory Medicine, Saitama Medical University, Moroyama, Saitama, Japan, 2 Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Hiroshima, Japan, 3 Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan, 4 Division of Translational Research, Research Center for Genomic Medicine, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan, 5 Department of Respiratory Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan Abstract Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical- by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type a1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1