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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5041-5048.
Prepublished online as a Blood First Edition Paper on September 22, 2008; DOI 10.1182/blood-2008-07-171678.
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Submitted July 31, 2008
Accepted August 27, 2008
HapMap scanning of novel human minor histocompatibility antigens
Michi Kamei, Yasuhito Nannya, Hiroki Torikai, Takakazu Kawase, Kenjiro Taura, Yoshihiro Inamoto, Taro Takahashi, Makoto Yazaki, Satoko Morishima, Kunio Tsujimura, Koichi Miyamura, Tetsuya Ito, Hajime Togari, Stanley R Riddell, Yoshihisa Kodera, Yasuo Morisima, Toshitada Takahashi, Kiyotaka Kuzushima, Seishi Ogawa, and Yoshiki Akatsuka*
Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan
Departments of Hematology/Oncology, University of Tokyo, Tokyo, Japan
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Department of Information and Communication Engineering, Graduate School of Information Science, University of Tokyo, Tokyo, Japan
Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
Department of Pediatrics, Higashi Municipal Hospital of Nagoya, Nagoya, Japan
Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Japan
Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Saitama, Japan
Department of Pediatrics and Neonatology, Nagoya City University, Graduate School of Medical Science, Nagoya, Japan
Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan
Aichi Comprehensive Health Science Center, Aichi Health Promotion Foundation, Chita-gun, Japan
The 21st century COE Program, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
* Corresponding author; email: yakatsuk{at}aichi-cc.jp.
Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity, associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial anti-tumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T-cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunological assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with >3,000,000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating two novel mHags as well as one previously identified example. The HapMap data set represents an invaluable resource to investigate human variation, with obvious applications in genetic mapping of clinically relevant human traits.

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